FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Seiler, KP Ma, Y Weis, JH Frenette, PS Hynes, RO Wagner, DD Weis, JJ AF Seiler, KP Ma, Y Weis, JH Frenette, PS Hynes, RO Wagner, DD Weis, JJ TI E and P selectins are not required for resistance to severe murine Lyme arthritis SO INFECTION AND IMMUNITY LA English DT Article ID BORRELIA-BURGDORFERI; ADHESION MOLECULES; ENDOTHELIAL-CELLS; IN-VITRO; TRANSENDOTHELIAL MIGRATION; MICE DEFICIENT; NEUTROPHILS; SUSCEPTIBILITY; DISSEMINATION; EXPRESSION AB Borrelia burgdorferi-induced arthritis in mice is characterized by tendonitis, synovitis, and inflammatory-cell infiltrate, predominantly of neutrophils. Because genetic deficiency in E and P selectins results in delayed recruitment of neutrophils to sites of inflammation, mice with this deficiency were tested for their response to infection with B. burgdorferi. E and P selectins were not required for the control of B. burgdorferi numbers, nor did deficiency in E and P selectins result in alteration of arthritis severity. C1 Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA USA. MIT, Howard Hughes Med Inst, Ctr Canc Res, Dept Biol, Cambridge, MA USA. RP Weis, JJ (reprint author), Univ Utah, Sch Med, Dept Pathol, 50 N Med Dr, Salt Lake City, UT 84132 USA. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [R01 HL053756]; NIAID NIH HHS [R29 AI043521, AI-43521, AI-32223, R01 AI043521, R01 AI032223, AI-24158, R01 AI024158, R56 AI032223] NR 19 TC 5 Z9 6 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 SEP PY 1998 VL 66 IS 9 BP 4557 EP 4559 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 113RF UT WOS:000075564500081 PM 9712820 ER PT J AU Williams, DM Grubbs, BG Darville, T Kelly, K Rank, RG AF Williams, DM Grubbs, BG Darville, T Kelly, K Rank, RG TI A role for interleukin-6 in host defense against murine Chlamydia trachomatis infection SO INFECTION AND IMMUNITY LA English DT Article ID GENITAL-TRACT INFECTION; CELL-DEFICIENT MICE; GENE KNOCKOUT MICE; GAMMA-INTERFERON; ROLE INVIVO; T-CELLS; PNEUMONIA; IMMUNITY; MOUSE; RESPONSES AB Interleukin-6-deficient (IL-6(-/-)) knockout mice Bead significantly increased Chlamydia trachomatis levels in lung tissue and increased mortality compared to B6129F(2)/J controls early after intranasal infection. Gamma interferon production and chlamydia-specific antibody levels were consistent with a decreased but reversible Th1-like response in IL-6(-/-) mice. IL-6 is needed for an optimal early host response to this infection. C1 Audie L Murphy Mem Vet Hosp, Div Infect Dis, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. RP Williams, DM (reprint author), Audie L Murphy Mem Vet Hosp, Div Infect Dis, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIAID NIH HHS [R01 AI026328] NR 29 TC 39 Z9 41 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 SEP PY 1998 VL 66 IS 9 BP 4564 EP 4567 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 113RF UT WOS:000075564500083 PM 9712822 ER PT J AU Yokoe, DS Anderson, J Chambers, R Connor, M Finberg, R Hopkins, C Lichtenberg, D Marino, S McLaughlin, D O'Rourke, E Samore, M Sands, K Strymish, J Tamplin, E Vallonde, N Platt, R AF Yokoe, DS Anderson, J Chambers, R Connor, M Finberg, R Hopkins, C Lichtenberg, D Marino, S McLaughlin, D O'Rourke, E Samore, M Sands, K Strymish, J Tamplin, E Vallonde, N Platt, R TI Simplified surveillance for nosocomial bloodstream infections SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID MORTALITY; NEED AB OBJECTIVE: To compare a surveillance definition of nosocomial bloodstream infections requiring only microbiology data to the Centers for Disease Control and Prevention's (CDC) current definition. SETTING: Six teaching hospitals. METHODS: We classified a representative sample of 73 positive blood cultures from six hospitals growing common skin contaminant isolates using a definition for bacteremia requiring only microbiology data and the CDC definition for primary bloodstream infection (National Nosocomial Infections Surveillance [NNIS] System review method). The classifications assigned during routine prospective surveillance also were noted, and the time required to classify isolates by the two methods was compared. RESULTS: Among 65 blood cultures growing common skin contaminant isolates obtained from adults, the agreement rate between the microbiology data method and the NNIS review method was 91%. Agreement was significantly poorer for the eight blood cultures growing common skin contaminant isolates obtained from pediatric patients. The microbiology data method requires approximately 20 minutes less time per isolate than does routine surveillance. CONCLUSIONS: A definition based on microbiology data alone yields the same result as the CDC's definition in the large majority of instances. It is more resource-efficient than the CDC's current definition (Infect Control Hosp Epidemiol 1998;19:657-660). C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Brockton & W Roxbury Vet Adm Med Ctr, Dept Med, W Roxbury, MA USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Dept Infect Control, Boston, MA 02115 USA. Dana Farber Canc Inst, Infect Dis Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Yokoe, DS (reprint author), 181 Longwood Ave, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 NR 10 TC 32 Z9 33 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 1998 VL 19 IS 9 BP 657 EP 660 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 131AM UT WOS:000076553600009 PM 9778164 ER PT J AU Agarwal, K Chudesokei, S Crawford, E Tran, C Goetz, MB AF Agarwal, K Chudesokei, S Crawford, E Tran, C Goetz, MB TI Prevalence of unsuspected vancomycin-resistant Enterococci (VRE) rectal colonization. SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 1998 VL 19 IS 9 MA S41 BP 702 EP 702 PG 1 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 131AM UT WOS:000076553600145 ER PT J AU Przykucki, JM Sadkowski, L Thompson, C Rinaldi, MG Patterson, JE AF Przykucki, JM Sadkowski, L Thompson, C Rinaldi, MG Patterson, JE TI Comparison of floor buffers as a source of aerosolization of fungal spores in a bone marrow transplant unit (BMTU). SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 1998 VL 19 IS 9 MA M5 BP 710 EP 710 PG 1 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 131AM UT WOS:000076553600188 ER PT J AU Hamner, MB Frueh, BC AF Hamner, MB Frueh, BC TI Response to venlafaxine in a previously antidepressant treatment-resistant combat veteran with post-traumatic stress disorder SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE post-traumatic stress disorder; antidepressants; venlafaxine; catecholamines; serotonin ID DEPRESSION AB Post-traumatic stress disorder (PTSD) is frequently treated with antidepressant medications, especially the newer selective serotonergic antidepressants which have documented efficacy in PTSD. Analagous to depression, however, some PTSD patients may not have a satisfactory response to these agents. This case report describes a PTSD patient who did not respond to several serotonergic antidepressants, but did improve with venlafaxine which has both noradrenergic and serotonergic properties. Int Clin Psychopharmacol 13:233-234 (C) 1998 Lippincott Williams & Wilkins. C1 Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Hamner, MB (reprint author), Ralph H Johnson VA Med Ctr, 116A, Charleston, SC 29401 USA. NR 9 TC 22 Z9 23 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD SEP PY 1998 VL 13 IS 5 BP 233 EP 234 DI 10.1097/00004850-199809000-00008 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 131WU UT WOS:000076598900008 PM 9817630 ER PT J AU Durante, W Schafer, AI AF Durante, W Schafer, AI TI Carbon monoxide and vascular cell function (Review) SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE carbon monoxide; heme oxygenase; vascular tone; growth; platelets; cGMP; cardiovascular disease ID NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE CELLS; HEME OXYGENASE-1 GENE; DUCTUS-ARTERIOSUS; GUANYLYL CYCLASE; PLATELET-AGGREGATION; ENDOTHELIAL-CELLS; RAT AORTA; EXPRESSION; INDUCTION AB Carbon monoxide (CO) is an endogenously generated gas that may play an important physiological role in the circulation. CO is generated by vascular cells as a byproduct of heme catabolism, in which heme oxygenase (HO) catalyzes the degradation of heme to biliverdin, iron and CO. Two distinct isoforms of HO have been identified in vascular tissue. The HO-2 isoform is constitutively expressed and likely mediates the release of CO under normal physiologic conditions. In contrast, the KO-1 isoform is strongly induced in vascular cells by various stress-associated agents and markedly increases CO synthesis during pathological conditions. The release of CO by vascular cells exerts both paracrine and autocrine effects on vascular smooth muscle cells (SMC) and circulating blood cells. CO regulates blood flow and blood fluidity by inhibiting vasomotor tone, SMC proliferation, and platelet aggregation, These vascular effects of CO are mediated via the activation of soluble guanylate cyclase and the consequent rise in intracellular guanosine 3',5'-cyclic monophosphate levels in target tissues. CO may also play a role in various cardiovascular disorders, including endotoxin shock, ischemia-reperfusion, hypertension, and subarachnoid hemorrhage. This review will focus on the recent progress made in understanding the regulation and function of CO in the vasculature. C1 Baylor Coll Med, Dept Med, Houston VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. RP Schafer, AI (reprint author), Baylor Coll Med, Dept Med, 6550 Fannin,SM MS 1423, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL36045] NR 86 TC 88 Z9 91 U1 1 U2 4 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD SEP PY 1998 VL 2 IS 3 BP 255 EP 262 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 118BW UT WOS:000075818700001 PM 9855696 ER PT J AU Teicher, BA Ara, G Chen, YN Recht, A Coleman, CN AF Teicher, BA Ara, G Chen, YN Recht, A Coleman, CN TI Interaction of Tomudex with radiation in vitro and in vivo SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE thymidylate synthase inhibitor; Tomudex; colon carcinoma cells; head and neck squamous carcinoma cells ID THYMIDYLATE SYNTHASE; CELLS; 5-FLUOROURACIL; FLUORODEOXYURIDINE; RADIOSENSITIZATION; INHIBITION; CARCINOMA AB The potential of the thymidylate synthase inhibitor, Tomudex to interact with ionizing radiation was assessed in vitro and in vivo in comparison with 5-fluorouracil. A concentration of 1 mu M Tomudex decreased the shoulder of the radiation survival curves for normally oxygenated and hypoxic human HT-29 colon carcinoma cells and human SCC-25 head and neck squamous carcinoma cells, resulting in enhancement ratios of 10 and 2.8 for normally oxygenated and hypoxic HT-29 cells at 5 Gray, respectively, and enhancement ratios of 19.5 and 2.7 for normally oxygenated and hypoxic SCC-25 cell at 5 Gray, respectively. Two schedules of Tomudex administered to animals bearing the Lewis lung carcinoma resulted in additive tumor growth delay with the fractionated radiation therapy. In nude mice bearing the HT-29 colon carcinoma grown as a xenograft, administration of Tomudex daily for 5 days on a 1 or 2-week schedule resulted in increased tumor growth delay along with fractionated radiation therapy on the same schedules. However, administration of Tomudex intermittently on a 2-week schedule appeared to be more interactive with daily fractionated radiation therapy on the 2-week schedule. In each assay, the results obtained with Tomudex were equal to or exceeded those obtained with 5-fluorouracil. These findings indicate that clinical trial of Tomudex along with fractionated radiation therapy is warranted. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Teicher, BA (reprint author), Lilly Corp Ctr, Lilly Res Labs, DC 0540, Indianapolis, IN 46285 USA. NR 17 TC 22 Z9 22 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 1998 VL 13 IS 3 BP 437 EP 442 PG 6 WC Oncology SC Oncology GA 110GL UT WOS:000075371900003 PM 9683775 ER PT J AU Smith, TJ Ryan, LM Douglass, HO Haller, DG Dayal, Y Kirkwood, J Tormey, DC Schutt, AJ Hinson, J Sischy, B AF Smith, TJ Ryan, LM Douglass, HO Haller, DG Dayal, Y Kirkwood, J Tormey, DC Schutt, AJ Hinson, J Sischy, B TI Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: A study of the Eastern Cooperative Oncology Group SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID MODALITY THERAPY; CHEMOTHERAPY; CANCER; EXPERIENCE AB Squamous carcinoma of the thoracic esophagus has an extremely poor prognosis. This study, EST-1282, was undertaken by the Eastern Cooperative Oncology Group (ECOG) to determine whether the combined use of 5-fluorouracil (5-FU), mitomycin C, and radiation therapy improved the disease-free survival and overall survival of patients with carcinoma of the esophagus, compared to those who received radiation therapy alone, Two- and 5-year survivals were 12% and 7% in the radiation alone arm and 27% and 9% in the chemoradiation arm. Patients treated with chemoradiation had a longer median survival (14.8 months), compared to patients receiving radiation therapy alone (9.2 months), This difference was statistically significant. The same pattern of survival was noted in almost all subgroups independent of whether surgical resection was performed. (C) 1998 Elsevier Science Inc. C1 Morristown Mem Hosp, Morristown, NJ 07960 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Hosp Univ Penn, Philadelphia, PA 15488 USA. Univ Pittsburgh, Pittsburgh, PA 18653 USA. Univ Wisconsin, Ctr Clin Canc, Madison, WI 53706 USA. Mayo Clin, Rochester, MN 55905 USA. Univ Rochester, Ctr Canc, Rochester, NY 11083 USA. RP Ryan, LM (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 23318, CA 25988, CA 201971] NR 24 TC 167 Z9 176 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 1998 VL 42 IS 2 BP 269 EP 276 DI 10.1016/S0360-3016(98)00232-6 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 129JM UT WOS:000076460100006 PM 9788404 ER PT J AU Shekelle, PG Chassin, MR Park, RE AF Shekelle, PG Chassin, MR Park, RE TI Assessing the predictive validity of the RAND/UCLA appropriateness method criteria for performing carotid endarterectomy SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article DE quality of care; appropriateness; carotid endarterectomy; validity ID CORONARY ANGIOGRAPHY; PRACTICE GUIDELINES; BYPASS-SURGERY; UNITED-STATES; CARE; QUALITY; MEDICINE; POPULATION AB We assessed the predictive validity of an expert panel's ratings of the appropriateness of carotid endarterectomy by comparing ratings to the results of subsequent randomized clinical trials. We found the trials confirmed the ratings for 44 indications (covering almost 30% of operations performed in 1981) and refuted the ratings for none. C1 Rand Corp, Santa Monica, CA 90407 USA. Mt Sinai Med Ctr, Dept Hlth Policy, New York, NY 10029 USA. RP Shekelle, PG (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 43 TC 88 Z9 89 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD FAL PY 1998 VL 14 IS 4 BP 707 EP 727 PG 21 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA 153PQ UT WOS:000077841800013 PM 9885461 ER PT J AU Maki, JH Prince, MR Chenevert, TC AF Maki, JH Prince, MR Chenevert, TC TI Optimizing three-dimensional gadolinium-enhanced magnetic resonance angiography - Original investigation SO INVESTIGATIVE RADIOLOGY LA English DT Article DE magnetic resonance imaging; magnetic resonance artifact; contrast enhancement; angiography ID 3-DIMENSIONAL MR-ANGIOGRAPHY; BREATH-HOLD; TIME; OPTIMIZATION; AORTOGRAPHY; ARTERIES; AORTA; ORDER AB RATIONALE AND OBJECTIVES. This primarily theoretical work examines three-dimensional gadolinium-enhanced magnetic resonance angiography (3D Gd-MRA) with the goal of understanding how to achieve the best possible images with respect to signal to noise ratio (SNR) and k-space induced artifacts. Patient variables, contrast injection schemes, and pulse sequence parameters are considered for this purpose. METHODS. A theoretical analysis, including computer simulation, describes how; contrast material injection profiles influence 3D Gd-MRA images, both in terms of intravascular signal and resultant artifacts. Further theoretical analysis of the spoiled gradient refocused pulse sequence describes how to maximize SNR, Clinical imaging complements computer modeling. RESULTS. Equations were derived relating contrast injection parameters and pulse sequence variables to SNR and artifacts. For present imaging equipment, administering contrast material over a duration of 60% to 80% of the total imaging time and using fractional echo techniques gives the best SNR without significantly sacrificing image quality. CONCLUSIONS. Three-dimensional Gd-MRA can be tailored to a specific clinical situation and imaging system through the use of proper breath-holding, bolus timing, Gd administration, and pulse sequence design. C1 Univ Michigan, Dept Radiol, Div MRI, Ann Arbor, MI 48109 USA. RP Maki, JH (reprint author), VA Puget Sound Hlth Care Syst, Dept Radiol 114, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Prince, Martin/S-6850-2016 NR 16 TC 43 Z9 45 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD SEP PY 1998 VL 33 IS 9 BP 528 EP 537 DI 10.1097/00004424-199809000-00008 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 118MT UT WOS:000075842800008 PM 9766037 ER PT J AU Yamada, CY Grygotis, LA Kaufman, J AF Yamada, CY Grygotis, LA Kaufman, J TI Gadolinium-enhanced magnetic resonance angiography of the aorta - A review SO INVESTIGATIVE RADIOLOGY LA English DT Article ID 3-DIMENSIONAL MR-ANGIOGRAPHY; BREATH-HOLD; PREOPERATIVE EVALUATION; ABDOMINAL-AORTA; RENAL-ARTERIES; THORACIC AORTA; ANEURYSMS; ARCH C1 Massachusetts Gen Hosp, Dept Vasc Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Yamada, CY (reprint author), Massachusetts Gen Hosp, Dept Vasc Radiol, 14 Fruit St, Boston, MA 02114 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD SEP PY 1998 VL 33 IS 9 BP 618 EP 627 DI 10.1097/00004424-199809000-00017 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 118MT UT WOS:000075842800017 PM 9766046 ER PT J AU Kellogg, DL Crandall, CG Liu, Y Charkoudian, N Johnson, JM AF Kellogg, DL Crandall, CG Liu, Y Charkoudian, N Johnson, JM TI Nitric oxide and cutaneous active vasodilation during heat stress in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE skin blood flow; microdialysis; laser-Doppler flowmetry ID SKIN BLOOD-FLOW; EXERCISE AB Whether nitric oxide (NO) is involved in cutaneous active vasodilation during hyperthermia in humans is unclear. We tested for a role of NO in this process during heat stress (water-perfused suits) in seven healthy subjects. Two forearm sites were instrumented with intradermal microdialysis probes. One site was perfused with the NO synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) dissolved in Ringer solution to abolish NO production. The other site was perfused with Ringer solution only. At those sites, skin blood flow (laser-Doppler flowmetry) and sweat rate were simultaneously and continuously monitored. Cutaneous vascular conductance, calculated from laser-Doppler flowmetry and mean arterial pressure, was normalized to maximal levels as achieved by perfusion with the NO donor nitroprusside through the microdialysis probes. Under normothermic conditions, L-NAME did not significantly reduce cutaneous vascular conductance. During hyperthermia, with skin temperature held at 38-38.5 degrees C, internal temperature rose from 36.66 +/- 0.10 to 37.34 +/- 0.06 degrees C (P < 0.01). Cutaneous vascular conductance at untreated sites increased from 12 +/- 2 to 44 +/- 5% of maximum, but only rose from 13 +/- 2 to 30 +/- 5% of maximum at L-NAME-treated sites (P < 0.05 between sites) during heat stress. L-NAME had no effect on sweat rate (P > 0.05). Thus cutaneous active vasodilation requires functional NO synthase to achieve full expression. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, Audie L Murphy Div, San Antonio, TX 78284 USA. Presbyterian Hosp, Inst Exercise & Environm Med, Dallas, TX 75231 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. RP Kellogg, DL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM kelloggd@uthscsa.edu FU NHLBI NIH HHS [HL-36080] NR 26 TC 181 Z9 185 U1 2 U2 9 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 SEP PY 1998 VL 85 IS 3 BP 824 EP 829 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 117KY UT WOS:000075781500007 PM 9729553 ER PT J AU Laghi, F Topeli, A Tobin, MJ AF Laghi, F Topeli, A Tobin, MJ TI Does resistive loading decrease diaphragmatic contractility before task failure? SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE transdiaphragmatic twitch pressure; twitch potentiation; carbon dioxide rebreathing ID PHRENIC-NERVE STIMULATION; VOLUNTARY CONTRACTIONS; HUMAN MOTONEURONS; FATIGUE; MUSCLES; TWITCH; BREATHLESSNESS; POTENTIATION; PRESSURE; PATTERN AB While sustaining a load that leads to task failure, it is unclear whether diaphragmatic fatigue develops progressively or occurs only at task failure. We hypothesized that incremental loading produces a progressive decrease in diaphragmatic contractility ever before task failure. Ten subjects generated 60% of maximal transdiaphragmatic pressure (Pdi(max)) for 2 min, 4 min, and until task failure. Before loading, 20 min after each period of loading, and similar to 20 h after the last period of loading, Pdi(max), nonpotentiated and potentiated Pdi twitch pressure (Pdi(tw)), and the pattern of respiratory muscle recruitment during a CO2 challenge were recorded. Sensation of inspiratory effort at the 4th min of the task-failure protocol was greater than at the same time in the preceding C-min protocol. Surprisingly, potentiated Pdi(tw) and Pdi(max) were reduced after 2 min of loading and decreased further after 4 min of loading and after task failure; nonpotentiated Pdi(tw) was reduced after 4 min of loading and after task failure. The gastric pressure contribution to tidal breathing during a CO2 challenge decreased progressively in relation to duration of the preceding loading period, whereas expiratory muscle recruitment progressively increased. A rest period of similar to 20 h after task failure was not sufficient to normalize these alterations in respiratory muscle recruitment or fatigue-induced changes in diaphragmatic contractility. In conclusion, while sustaining a mechanical load, the diaphragm progressively fatigued, ever before task failure, and when challenged the rib cage-to-diaphragmatic contribution to tidal breathing and recruitment of the expiratory muscles increased pari passu with duration of the preceding loading. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ Chicago, Stritch Sch Med, Hines, IL 60141 USA. RP Laghi, F (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 36 TC 60 Z9 60 U1 1 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 SEP PY 1998 VL 85 IS 3 BP 1103 EP 1112 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 117KY UT WOS:000075781500043 PM 9729589 ER PT J AU Dearborn, JT Harris, WH AF Dearborn, JT Harris, WH TI Postoperative mortality after total hip arthroplasty - An analysis of deaths after two thousand seven hundred and thirty-six procedures SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID VOLUME; KNEE AB We retrospectively determined the prevalence and nature of mortality as many as ninety days after 2736 primary and revision total hip arthroplasties performed in 2002 patients by one surgeon at a teaching hospital between January 1969 and December 1996. All but seventy-one of the patients had received prophylaxis against venous thromboembolic disease. There were no intraoperative deaths, and no events during the operation could be linked directly to postoperative mortality. Eight deaths (mortality rate, 0.3 per cent) occurred within ninety days after the 2736 procedures. Four deaths (mortality rate, 0.15 per cent) occurred during the initial hospitalization. The cause of seven of the deaths was determined. Three patients died as a result of preexisting disease (severe hepatorenal disease, metastatic esophageal cancer, or severe cardiac disease), and one patient died from sepsis with a gram-negative organism during a thoracotomy eight days postoperatively. A bleeding complication that occurred while the patient was receiving warfarin therapy led to the death of two other patients; one of these deaths occurred in 1974 and the other, in 1982. At the time that these patients were managed, the desired prothrombin time was considered to be twice the control value. The remaining patient, who had had a clip placed on the inferior vena cava after a pulmonary embolus occurred in 1970, died secondary to acute, severe thrombosis of this vessel after a total hip arthroplasty in 1971. The patient for whom the cause of death was not determined had had an artificial aortic valve and had been receiving chronic warfarin therapy. She died suddenly eighty-nine days postoperatively; no autopsy was performed. No patient died as the direct result of a known pulmonary embolus. No deaths related to venous thromboembolic disease or its prophylaxis or treatment occurred after 1982 (1458 operations). We attribute this, in part, to reduced levels of warfarin prophylaxis and improved management with warfarin. The ninety-day postoperative mortality rate after 2736 procedures performed over nearly three decades was low (0.3 per cent). This span of time included the period before the introduction of many current improvements in perioperative care, such as routine intubation of patients under general anesthesia, continuous monitoring of the electrocardiogram intraoperatively, and blood-gas determinations. When the patients who died as a result of known, severe preexisting disease were excluded, the mortality rate was 0.18 per cent (five of 2733). C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Hip & Implant Unit, Boston, MA 02114 USA. RP Dearborn, JT (reprint author), Fremont Orthopaed Med Grp, 38690 Stivers St, Fremont, CA 94536 USA. NR 10 TC 50 Z9 52 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 1998 VL 80A IS 9 BP 1291 EP 1294 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 124FC UT WOS:000076170600006 PM 9759813 ER PT J AU Warner, JJP Beim, GM Higgins, L AF Warner, JJP Beim, GM Higgins, L TI The treatment of symptomatic os acromiale SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB During a four-year period, fourteen individuals (fifteen shoulders) who Bled been seen at the shoulder service of our institution because of pain in the shoulder had a radiographic finding of an os acromiale. On clinical examination, the pain appeared to be due to an unstable os acromiale because the patients had point tenderness over the acromion and pain on forward elevation of the shoulder The diagnosis of an os acromiale was confirmed on radiographs, magnetic resonance images, or a bone scan. Eight patients had an associated tear of the rotator cuff, The os acromiale was located in the pre-acromion in one shoulder, the meso-acromion in eleven shoulders, and the meta-acromion in three shoulders. At the operation, the anterior aspect of the acromion was found to be unstable in all shoulders, Eleven patients (twelve shoulders) had open reduction of the os acromiale and insertion of an autogenous iliac-crest hone graft, Of those patients, four (five shoulders) had open reduction and internal fixation with a tension-band procedure with use of pins and wires. Only one of those shoulders had a solid osseous union, and the other four shoulders had a non-union that was due to a disruption of the fixation, The remaining seven patients (seven shoulders) had open reduction and internal fixation with use of cannulated screws and a tension-band construct; a solid osseous union was achieved in an but one of them. One patient had excision of the pre-acromion, which relieved the pain. Two patients who had had failed open reduction and internal fixation had excision of a grossly unstable os acromiale in the meso-acromion; both patients had pain and weakness after this procedure, Of the twelve shoulders that had open reduction and bone-grafting, seven had union of the os acromiale; the average time to radiographic and clinical union was nine weeks (range, seven to twenty weeks). We concluded that, although it is rare, symptomatic unstable os acromiale does occur and can be effectively treated with use of autogenous bone-grafting and internal fixation with a rigid tension-band construct and cannulated screws. C1 Univ Pittsburgh, Pittsburgh, PA USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Shoulder Serv, 275 Cambridge St,4th Floor, Boston, MA 02114 USA. NR 12 TC 47 Z9 48 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 1998 VL 80A IS 9 BP 1320 EP 1326 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 124FC UT WOS:000076170600010 PM 9759817 ER PT J AU Carpenter, CM Galvin, J Guy, M McGovern, BA AF Carpenter, CM Galvin, J Guy, M McGovern, BA TI Runaway pacemaker in an implantable cardioverter defibrillator SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE implantable cardioverter defibrillator malfunction; crystal oscillator failure AB Introduction: Runaway pacemaker is a potentially catastrophic complication of any permanent pacing system, Methods and Results: A 70-year-old man was found to have erratic behavior of his implantable cardioverter defibrillator (ICD) during a routine outpatient interrogation. His device was turned off, and he was hospitalized in preparation for a pulse generator replacement. During his hospitalization, his ICD unexpectedly began pacing rapidly, Despite prompt resuscitation attempts, the patient died, Postmortem examination of the device demonstrated a crystal oscillator failure, Conclusion: A previously unrecognized component malfunction is a potentially lethal complication of ICDs. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, Dept Med, Boston, MA 02114 USA. RP McGovern, BA (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, Dept Med, Boston, MA 02114 USA. NR 9 TC 10 Z9 10 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD SEP PY 1998 VL 9 IS 9 BP 1008 EP 1011 DI 10.1111/j.1540-8167.1998.tb00143.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 124QK UT WOS:000076193100014 PM 9786083 ER PT J AU Tritos, NA Mantzoros, CS AF Tritos, NA Mantzoros, CS TI Clinical review 97 - Syndromes of severe insulin resistance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID DIABETES-MELLITUS; ACANTHOSIS NIGRICANS; GLUCOSE-TOLERANCE; RECEPTOR GENE; A SYNDROME; PATIENT; FIBROBLASTS; SENSITIVITY; ACTIVATION; MECHANISMS C1 Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol, RN 325,99 Brookline Ave, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu NR 37 TC 63 Z9 70 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 SEP PY 1998 VL 83 IS 9 BP 3025 EP 3030 DI 10.1210/jc.83.9.3025 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700001 PM 9745395 ER PT J AU Newman, CB Melmed, S George, A Torigian, D Duhaney, M Snyder, P Young, W Klibanski, A Molitch, ME Gagel, R Sheeler, L Cook, D Malarkey, W Jackson, I Vance, ML Barkan, A Frohman, L Kleinberg, DL AF Newman, CB Melmed, S George, A Torigian, D Duhaney, M Snyder, P Young, W Klibanski, A Molitch, ME Gagel, R Sheeler, L Cook, D Malarkey, W Jackson, I Vance, ML Barkan, A Frohman, L Kleinberg, DL TI Octreotide as primary therapy for acromegaly SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LONG-TERM TREATMENT; SANDOSTATIN-LAR; SMS 201-995; MULTICENTER; MICROSURGERY; EPIDEMIOLOGY; MANAGEMENT AB The effects of octreotide (up to 5 yr) as primary treatment in 26 patients with acromegaly were compared with those in 81 patients with acromegaly who received octreotide as secondary or adjunctive therapy after previous surgery and/or pituitary radiation. These patients were part of a multicenter study that took place between 1989-1995. The study was divided into 3 phases beginning with a 1-month placebo-controlled treatment period followed by a 1-month washout period. In the second phase, patients were randomized to treatment with either 100 or 250 mu g octreotide, sc, every 8 h for 6 months. Octreotide was then discontinued for 1 month and reinitiated at the lower dose for a total mean treatment duration of 39 months. The dose was titrated by each investigator to improve each patient's individual response, which included improvement in symptoms and signs of acromegaly as well as reduction of GH and insulin-like growth factor I(IGF-I) into the normal range. In the second phase of the study, in which patients were randomized to either 100 or 250 mu g octreotide, three times daily, mean integrated GH and IGF-I concentrations after 3 and 6 months were equivalent in the primary and secondary treatment groups. During long term open label treatment, mean GH fell from 32.7 +/- 5.2 to 6.0 +/- 1.7 mu g/L 2 h after octreotide injection in the primary therapy group and remained suppressed for a mean period of 24 months (range, 3-60 months). The mean final daily dose was 777 mu g In the patients receiving secondary treatment, mean GH fell from 30.2 +/- 7.6 to 5.6 +/- 1.1 mu g/L after 3 months and remained suppressed for the remainder of the study (average dose, 635 mu g daily). Mean IGF-I concentrations fell from 5.2 +/- 0.5 x 10(3) U/L (primary treatment group) and 4.7 +/- 0.4 x 10(3) U/L (secondary treatment group) to a mean of 2.2 +/- 0.3 x 103 U/L in both groups after 3 months of open label treatment and remained suppressed. IGF-I was reduced into the normal range during at least half of the study visits in 68% of the primary treatment group and in 62% of the secondary treatment group. Patients whose GH levels fell to at least 2 SD below the baseline mean GH were considered responders. There was no significant difference in the percentage of responders in the primary and secondary treatment groups (70% vs. 61%), nor was there a statistical difference in the mean GH concentrations between the groups. Symptoms of headache, increased perspiration, fatigue, and joint pain were reported at baseline by 46%, 73%, 69%, and 85%, respectively, of patients in the primary therapy group and improved during 3 yr of octreotide treatment in 50-100%. Similarly, these acromegaly-related symptoms were reported by 62%, 58%, 78%, and 60% of patients in the secondary therapy group, and improvement was noted in 62-88%. Pituitary magnetic resonance imaging scans were available in 13 of 26 patients in the primary treatment group before and after 6 months of octreotide treatment. Tumor shrinkage was observed in 6 of 13 patients, with reduction in tumor volume greater than 25% in only 3. Of 6 patients with documented tumor shrinkage, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 5 patients. The degree of tumor shrinkage did not correlate with the percent reduction in IGF-I or GH. In summary, octreotide was equally effective in 26 previously untreated acromegalic patients (primary treatment group) and 81 patients previously treated with either surgery or pituitary radiation (secondary treatment group). These observations call into question the current practice of surgical resection of all newly diagnosed GH-secreting pituitary adenomas regardless of the likelihood of cure. Although surgery is the treatment of choice in patients with tumors likely to be completely resected, our results suggest that if the possibility of surgical cure is low, as in patients with large or invasive tumors, then octreotide may be a reasonable primary therapeutic modality provided that the tumor does not threaten vision or neurological function. C1 NYU, Dept Med, New York, NY 10010 USA. Vet Adm Med Ctr, New York, NY 10010 USA. Cedars Sinai Med Ctr, Div Endocrinol & Metab, Los Angeles, CA 90048 USA. NYU, Med Ctr, Dept Radiol, New York, NY 10016 USA. Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Endocrinol, Philadelphia, PA 19104 USA. Mayo Clin, Dept Med, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Northwestern Univ, Sch Med, Ctr Endocrinol Metab & Mol Med, Chicago, IL 60611 USA. Univ Texas, MD Anderson Canc Ctr, Endocrinol Sect, Houston, TX 77030 USA. Innova Med Serv, Brooklyn, OH 44144 USA. Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA. Ohio State Univ, Med Ctr, Dept Med, Columbus, OH 43210 USA. Brown Univ, Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. Univ Virginia, Med Ctr, Dept Med, Charlottesville, VA 22908 USA. Univ Michigan, Med Ctr, Dept Med, Ann Arbor, MI 48109 USA. Univ Illinois, Dept Med, Chicago, IL 60612 USA. RP Kleinberg, DL (reprint author), NYU, Dept Med, 423 E 23rd St,16043 W, New York, NY 10010 USA. OI Newman, Connie/0000-0001-9144-056X FU NCRR NIH HHS [M01-RR-00034, RR-0048, 5-MO1-RR0096-32AI] NR 27 TC 172 Z9 178 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 SEP PY 1998 VL 83 IS 9 BP 3034 EP 3040 DI 10.1210/jc.83.9.3034 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700003 PM 9745397 ER PT J AU Baum, HBA Katznelson, L Sherman, JC Biller, BMK Hayden, DL Schoenfeld, DA Cannistraro, KE Klibanski, A AF Baum, HBA Katznelson, L Sherman, JC Biller, BMK Hayden, DL Schoenfeld, DA Cannistraro, KE Klibanski, A TI Effects of physiological growth hormone (GH) therapy on cognition and quality of life in patients with adult-onset GH deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; RECOMBINANT HUMAN GH; HEALTHY OLDER MEN; BODY-COMPOSITION; TRIAL; HYPOPITUITARISM; CHILDHOOD; CHILDREN; WELL AB GH replacement of adults with acquired GH deficiency (GHD) results in body composition changes including increases in lean mass and bone mineral density. However, the effects of long-term GH therapy on cognitive function are largely unknown, and there are conflicting data regarding quality of life. We performed a randomized, double-blind, placebo-controlled study of GH replacement in adults with GHD and measured cognition and sense of well-being using standardized psychometric tests before and after therapy. Forty men (median age 51 yr, range 24-64 yr) with a history of pituitary disease were randomized to GH therapy (starting dose, 10 +/- 0.3 mu g/kg per day: mean treatment dose, 4 +/- 2 mu g/kg per day) vs. placebo for 18 months, and GH doses were adjusted according to serum insulin growth factor-I levels. At baseline, the patients displayed a full-scale intelligence quotient (IQ) score nearly 1 SD above the normal mean. Mean scores on all cognitive tests fell within normal limits, and on many tests, fell above the mean. On tests of verbal learning and delayed visual memory, mean test scores fell below the mean (although within normal limits), suggestive of a relative compromise in the area of memory performance. Following 18 months of GH replacement therapy, there were no significant changes in cognitive function or quality of life. We conclude that acquired GHD in adult men is not associated with significant alterations in cognitive function as assessed by standardized tests, and chronic low-dose GH replacement therapy does not result in significant beneficial effects on cognitive function or quality of life. Although previous studies have suggested that GH replacement in adults with acquired GHD may improve quality of life, our data do not support the use of physiological GH replacement in GHD men for this indication. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Psychol Assessment Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457,32 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066] NR 41 TC 123 Z9 124 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 SEP PY 1998 VL 83 IS 9 BP 3184 EP 3189 DI 10.1210/jc.83.9.3184 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700029 PM 9745423 ER PT J AU Chaidarun, SS Swearingen, B Alexander, JM AF Chaidarun, SS Swearingen, B Alexander, JM TI Differential expression of estrogen receptor-beta (ER beta) in human pituitary tumors: Functional interactions with ER alpha and a tumor-specific splice variant SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 5th International Pituitary Congress CY JUN 28-30, 1998 CL FT MYERS, FL ID GROWTH-HORMONE CELLS; GENE; PROLACTIN; GH; SECRETION; ADENOMAS; CULTURE; OVARY; RNA AB The mitogenic and regulatory effects of estrogen (E-2) in adenohypophysial cells are known to be mediated through the nuclear estrogen receptor (ER alpha). Expression of ER alpha and several of its messenger ribonucleic acid (RNA) alternate splice variants has been shown to be restricted to prolactinomas and gonadotroph tumors. However, little is known about gene expression patterns of the novel nuclear hormone receptor ER beta in the neoplastic pituitary. ER beta has high homology to ER alpha in the DNA- and ligand-binding domains, but encodes a distinct transcriptional activating function-1 (AF-1) domain. Using RT-PCR analysis of total RNA from 38 human pituitary adenomas, we found that ER beta messenger RNA was coexpressed with ER alpha and its splice variants in 60% of prolactinomas, 100% of mixed GH/PRL tumors, and 29% of gonadotroph tumors. ER beta gene expression was not limited to ER alpha-positive tumor subtypes, however, and was also found in 100% of null cell tumors, 80% of somatotroph tumors, and 60% of corticotroph tumors. Because ER beta is coexpressed with ER alpha and its splice variants in prolactinomas and gonadotroph tumors, we functionally characterized the potential interactions between ER beta and ER alpha. We also examined the potential cooperative effects on ER beta-mediated gene expression of a tumor-specific truncated Delta 5ER alpha splice variant that has been shown to be coexpressed in the majority of ER alpha-positive tumors. This exon 5 splice variant encodes the AF-1 domain as well as regions critical for DNA binding and nuclear localization, but lacks the Ligand-binding and AF-2 domains. Mammalian expression vectors encoding ER alpha, Delta 5ER alpha, and/or ER beta complementary DNAs were transiently transfected along with an E-2 response element promoter-luciferase (ERELuc) reporter into human ER alpha/ER beta-negative osteosarcoma U2-OS cells. ER beta was less potent than ER alpha in activating E-2-stimulated ERELuc activity (4- vs. 14-fold relative to basal control levels). However, when Delta 5ER alpha was coexpressed with ER beta or ER alpha, E-2-stimulated ERELuc activity was markedly increased to 8- and 57-fold, respectively, relative to basal control levels when each full-length isoform was expressed alone. Finally, coexpression of ERP with ER alpha did not significantly alter the E-2-stimulated ERELuc activity induced by ER alpha alone. Cotreatment with tamoxifen markedly inhibited all E-2-stimulated ERELuc responses to baseline levels. Together, these data suggest that ER beta has a minor role in mediating E-2 responses in ER alpha-positive tumors, but may be the main mediator of E-2-stimulated gene expression when expressed alone in somatotroph, corticotroph, and null cell tumors. This low, but significant, level of ER beta trans-activation potential may he enhanced by coexpression of Delta 5ER alpha in neoplastic pituitary. Therefore, E-2-mediated gene expression in normal and neoplastic pituitary appears to be highly dependent on the expression of ER alpha and ER beta isoforms, which have varying transcriptional activities. C1 Massachusetts Gen Hosp, Dept Med, Neuroendocrinol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Alexander, JM (reprint author), Beth Israel Deaconess Med Ctr, Harvard Inst Med, Room 944,330 Brookline Ave, Boston, MA 02115 USA. NR 24 TC 41 Z9 43 U1 0 U2 1 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 SEP PY 1998 VL 83 IS 9 BP 3308 EP 3315 DI 10.1210/jc.83.9.3308 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700052 PM 9745446 ER PT J AU Borrego, S Eng, C Sanchez, B Saez, ME Navarro, E Antinolo, G AF Borrego, S Eng, C Sanchez, B Saez, ME Navarro, E Antinolo, G TI Molecular analysis of the ret and GDNF genes in a family with multiple endocrine neoplasia type 2A and Hirschsprung disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RECEPTOR TYROSINE KINASE; MEDULLARY-THYROID CARCINOMA; NEUROTROPHIC FACTOR; PROTOONCOGENE MUTATIONS; GERMLINE MUTATIONS; EXON 10; MEN 2A; PHENOTYPE; NEURTURIN; LIGAND AB The clinical association between multiple endocrine neoplasia type 2 (MEN2) and Hirschsprung disease (HSCR) is infrequent. Germline mutations of the ret protooncogene are the underlying cause of the MF;NZ syndromes and a proportion of cases of HSCR. In this report, we describe a new kindred in which the MENS and HSCR phenotypes are associated with a single C620S point mutation at one of the cysteine codons of the extracellular domain of the ret protooncogene. We also speculate about the role of a silent mutation in exon 2 of this same gene (A45A), present in a homozygous state in the patient with both MEN2A and HSCR. To investigate the contribution of GDNF to the phenotype observed in this kindred, we scanned the coding region of GDNF in the patient with MEN2/HSCR, but no mutation was found. C1 Hosp Univ Virgen del Rocio, Unidad Genet Med & Diagn Prenatal, Seville 41013, Spain. Hosp Univ Virgen del Rocio, Serv Endocrinol, Seville 41013, Spain. Dana Farber Canc Inst, Dept Adult Oncol, Charles A Dana Human Canc Genet Unit, Translat Res Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge, England. RP Borrego, S (reprint author), Hosp Univ Virgen del Rocio, Unidad Genet Med & Diagn Prenatal, Ave M Siurot S-N, Seville 41013, Spain. RI IBIS, GENETICA/P-3384-2015; IBIS, REPRODUCCION/P-3399-2015; Borrego, Salud/M-6314-2015; OI Eng, Charis/0000-0002-3693-5145 NR 36 TC 52 Z9 53 U1 0 U2 1 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 SEP PY 1998 VL 83 IS 9 BP 3361 EP 3364 DI 10.1210/jc.83.9.3361 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 118LV UT WOS:000075840700061 PM 9745455 ER PT J AU Lee, SJ Anasetti, C Horowitz, MM Antin, JH AF Lee, SJ Anasetti, C Horowitz, MM Antin, JH TI Initial therapy for chronic myelogenous leukemia: Playing the odds SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW TRANSPLANTATION; CHRONIC GRANULOCYTIC-LEUKEMIA; POLYMERASE CHAIN-REACTION; INTERFERON-ALPHA THERAPY; CHRONIC-PHASE; PROGNOSTIC DISCRIMINATION; CYTOGENETIC RESPONSE; ACCELERATED-PHASE; UNRELATED DONORS C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Milwaukee, WI 53226 USA. RP Lee, SJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 57 TC 23 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1998 VL 16 IS 9 BP 2897 EP 2903 PG 7 WC Oncology SC Oncology GA 116PY UT WOS:000075734800001 PM 9738555 ER PT J AU Skapek, SX Hawk, BJ Hoffer, FA Dahl, GV Granowetter, L Gebhardt, MC Ferguson, WS Grier, HE AF Skapek, SX Hawk, BJ Hoffer, FA Dahl, GV Granowetter, L Gebhardt, MC Ferguson, WS Grier, HE TI Combination chemotherapy using vinblastine and methotrexate for the treatment of progressive desmoid tumor in children SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; AGGRESSIVE FIBROMATOSIS; JUVENILE FIBROMATOSIS; RADIATION-THERAPY; LOCAL-CONTROL; RECURRENT; TAMOXIFEN; MANAGEMENT; RADIOTHERAPY; SURGERY AB Purpose: We report the treatment of 10 children for progressive desmoid tumor not amenable to standard surgical or radiation therapy with the use of vinblastine (VBL) and methotrexate (MTX). Patients and Methods: Ten patients aged 6.4 to 18 years with primary (two patients) or recurrent (eight patients) desmoid tumor were treated with VBL and MTX for 2 to 35 months. Patients with recurrent tumors had been previously treated with surgical resection with (two patients) or without (five patients) radiation therapy or with radiation therapy alone (one patient). No patient had previously received cytotoxic chemotherapy. The tumor response was assessed at routine intervals by physical examination and magnetic resonance imaging (MRI). Results: Five patients had clinical evidence of response to therapy with complete resolution (three patients) or partial resolution (two patients) of physical examination and radiographic abnormalities. Three patients had stable disease during 10 to 35 months of treatment, two of these patients had progressive disease 9 and 37 months after treatment stopped; one patient had no progression 16 months after therapy. two additional patients with stable disease had chemotherapy discontinued after 2 and 3 months. Common side effects included mild alopecia and myelosuppression and moderate nausea and vomiting. In patients with responding tumors, MRI showed decreased tumor size and, in two patients, changes consistent with fibrosis and decreased cellularity of the tumor. Conclusion: Combination chemotherapy with VBL and MTX appears to control desmoid tumor without significant acute or long-term morbidity in most children. This may allow for further growth and development in these patients, which may decrease the morbidity of subsequent definitive therapy. J Clin Oncol 16:3021-3027. (C) 1998 by American Society of Clinical Oncology. C1 Wilford Hall USAF Med Ctr, Dept Pediat Hematol Oncol, MNPO, Lackland AFB, TX 78236 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Rhode Isl Hosp, Providence, RI USA. Childrens Hosp, Med Ctr, Dept Surg, Boston, MA USA. Childrens Hosp, Med Ctr, Dept Hematol Oncol, Boston, MA USA. Childrens Hosp, Med Ctr, Dept Radiol, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Skapek, SX (reprint author), Wilford Hall USAF Med Ctr, Dept Pediat Hematol Oncol, MNPO, 2200 Bergquist Dr,Suite 1, Lackland AFB, TX 78236 USA. EM shapek@utmscsa.edu NR 44 TC 75 Z9 77 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1998 VL 16 IS 9 BP 3021 EP 3027 PG 7 WC Oncology SC Oncology GA 116PY UT WOS:000075734800017 PM 9738571 ER PT J AU Hryniuk, W Frei, E Wright, FA AF Hryniuk, W Frei, E Wright, FA TI A single scale for comparing dose-intensity of all chemotherapy regimens in breast cancer: Summation dose-intensity SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID PHASE-II TRIAL; PROSPECTIVE RANDOMIZED TRIAL; WEEKLY IV-VINORELBINE; ADJUVANT CHEMOTHERAPY; COMBINATION CHEMOTHERAPY; SIGNIFICANTLY INCREASES; POSTMENOPAUSAL PATIENTS; 1ST-LINE CHEMOTHERAPY; RESPONSE RELATIONSHIP; COOPERATIVE GROUP AB Purpose: To construct a single scale for comparing the dose-intensity of all chemotherapy regimens in breast cancer. Materials and Methods: First line single-agent trials in metastatic disease were reviewed. The unit dose-intensity (UDI) that was required to produce a 30% complete response plus partial response (CR + PR) rate was determined for each drug. Randomized trials were then analyzed that prospectively tested dose-intensity. The dose-intensities of the drugs in each arm were expressed as fractions of their UDIs and added together. This yielded each arm's summation dose-intensity (SDI), which was then correlated with treatment outcomes. Results: In the single-agent trials, dose-response relationships were linear when the studies covered a range of dose-intensities. In the randomized trials that tested dose-intensity in metastatic disease, response rates and median survival correlated linearly with the SDIs of the treatment arms. An increment of one SDI unit increased CR + PR rate by approximately 30%, CR rate by 10%, and median survival by 3.75 months. Metastatic disease trials were negative if the difference between the arms was less than 0.54 SDI units. Adjuvant trials that tested a dose-intensity difference of less than 0.65 SDI units were also negative. Conclusion: A single agent dose-response database can be derived from historic literature that enables comparison of the dose-intensity of all combination regimens on one scale. The dose-intensity increase required to improve outcome can then be identified in earlier trials that tested that variable. SDI methodology should be tested prospectively in contemporary patients, and may be useful in guiding dosage increases beyond the conventional range. J Clin Oncol 16:3137-3147. (C) 1998 by American Society of Clinical Oncology. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Family Med, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Columbus, OH 43210 USA. RP Hryniuk, W (reprint author), Karmanos Canc Inst, 4100 John R, Detroit, MI 48201 USA. FU NCI NIH HHS [1R21CA66215] NR 104 TC 66 Z9 68 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1998 VL 16 IS 9 BP 3137 EP 3147 PG 11 WC Oncology SC Oncology GA 116PY UT WOS:000075734800032 PM 9738586 ER PT J AU Syrjala, KL Roth-Roemer, SL Abrams, JR Scanlan, JM Chapko, MK Visser, S Sanders, JE AF Syrjala, KL Roth-Roemer, SL Abrams, JR Scanlan, JM Chapko, MK Visser, S Sanders, JE TI Prevalence and predictors of sexual dysfunction in long-term survivors of marrow transplantation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; GYNECOLOGIC CANCER; WOMEN; ADJUSTMENT; LEUKEMIA AB Purpose: To describe the prevalence of sexual difficulties in men and women after marrow transplantation (MT), and to define medical, demographic, sexual, and psychologic predictors of sexual dysfunction 3 years after MT. Patients and Methods: Four hundred seven adult MT patients were assessed pretransplantation. Survivors repeated measures of psychologic and sexual functioning at 1 and 3 years posttransplantation. Results: Data were analyzed from 102 event-free 3-year survivors who defined themselves as sexually active. Men and women did not differ in sexual satisfaction pretransplantation. At 1 and 3 years posttransplantation, women reported significantly more sexual dysfunction than men. Eighty percent of women and 29% of men reported at least one sexual problem by 3 years after MT. No pretransplantation variables were significant predictors of 3-year sexual satisfaction for women, For men, pretransplantation variables of older age, poorer psychologic function, not being married, and lower sexual satisfaction predicted sexual dissatisfaction at 3 years (R-2 = .28; P < .001). Women who were more dissatisfied 3 years after MT did not receive hormone replacement therapy (HRT) at 1-year posttransplantation and were less satisfied at 1 year, but not pretransplantation (R-2 = .35; P < .001). Conclusion: Sexual problems are significant in the lives of MT survivors, particularly for women. Although HRT before 1 year posttransplantation improves sexual function, it does not ensure sexual quality of life. Intervention for women is needed to apply hormonal, mechanical, and behavioral methods to prevent sexual difficulties as early after transplantation as possible. J Clin Oncol 16:3148-3157. (C) 1998 by American Society of Clinical Oncology, C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. RP Syrjala, KL (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, FM815,1100 Fairview Ave N,POB 19024, Seattle, WA 98109 USA. FU PHS HHS [68139, 63030, 18029] NR 34 TC 43 Z9 43 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1998 VL 16 IS 9 BP 3148 EP 3157 PG 10 WC Oncology SC Oncology GA 116PY UT WOS:000075734800033 PM 9738587 ER PT J AU Mayer, RJ AF Mayer, RJ TI The state of the society: A year of continued growth SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mayer, RJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1998 VL 16 IS 9 BP 3192 EP 3198 PG 7 WC Oncology SC Oncology GA 116PY UT WOS:000075734800037 PM 9738591 ER PT J AU Bauer, MS McBride, L Chase, C Sachs, G Shea, N AF Bauer, MS McBride, L Chase, C Sachs, G Shea, N TI Manual-based group psychotherapy for bipolar disorder: A feasibility study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID GROUP-THERAPY; MAINTENANCE; MANAGEMENT; ADJUNCT AB Background: The Lift: coals Program is a structured, manual-based group psychotherapy program for biopolar disorder that seeks to improve patient participation in medical model treatment (phase 1) and assist patients in meeting functional status gears (phase 2). The goals of this initial study were (a) to determine whether the procedures could be exported from the authors to other therapists and ro) to quantify tolerability and impact of procedures on patients. Method: Four therapists across 2 sites and 29 patients from the Veterans Affairs (VA) Medical Center were studied in an open feasibility study. Therapists were trained, and subsequent compliance with manual procedures was quantified. Several process indices measuring tolerability and impact an patients were analyzed. Results: Therapists covered 90% to 96% of phase 1 psychoeducational content, indicating excellent fidelity to manual procedures. Sixty-nine percent of patients completed phase I, and participation scores were in the good to excellent range for 56%. Completion of phase 1 was associated with significant increase in knowledge about bipolar disorder. Fourteen (70%) of 20 patients enrolled in phase 2 reached their self-identified, behaviorally based goal (48% of the total sample who began phase 1 of the program). Mean +/- SD time to goal completion was 8.7 +/- 5.3 months (median [95% confidence interval] = 7 [5.1-12.3 months]; range, 2-17 months). Conclusion: The manual-based intervention can be exported viith fidelity to other therapists and sites (for phase I). Data indicate reasonable tolerability and goad achievement of process (for phases 1 and 2) for those who accept this group modality. Comparison with other manual-based psychotherapies indicates remarkable consistency regarding content for psychotherapy for bipolar disorder; major differences among the psychotherapies include mode of delivery and relative emphasis of specific components. C1 Dept Vet Affairs Med Ctr, Providence, RI 02908 USA. Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bauer, MS (reprint author), Dept Vet Affairs Med Ctr, 116A, Providence, RI 02908 USA. NR 26 TC 48 Z9 50 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1998 VL 59 IS 9 BP 449 EP 455 DI 10.4088/JCP.v59n0902 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 123FB UT WOS:000076114200002 PM 9771814 ER PT J AU Marron, JS Adak, S Johnstone, IM Neumann, MH Patil, P AF Marron, JS Adak, S Johnstone, IM Neumann, MH Patil, P TI Exact risk analysis of wavelet regression SO JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS LA English DT Article DE orthogonal series denoising; squared error ID INTEGRATED SQUARED ERROR; ESTIMATORS; SHRINKAGE; THRESHOLD; BASES AB Wavelets have motivated development of a host of new ideas in nonparametric regression smoothing. Here we apply the tool of exact risk analysis, to understand the small sample behavior of wavelet estimators, and thus to check directly the conclusions suggested by asymptotics. Comparisons between some wavelet bases, and also between hard and soft thresholding, are given from several viewpoints. Our results provide insight as to why the viewpoints and conclusions of Donoho and Johnstone differ from those of Hall and Patil. C1 Univ N Carolina, Dept Stat, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Stanford Univ, Dept Stat, Palo Alto, CA 94304 USA. Stanford Univ, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. Humboldt Univ, SFB 373, D-10178 Berlin, Germany. Univ Birmingham, Sch Math & Stat, Birmingham B15 2TT, W Midlands, England. RP Marron, JS (reprint author), Univ N Carolina, Dept Stat, Chapel Hill, NC 27599 USA. NR 35 TC 24 Z9 30 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 1061-8600 J9 J COMPUT GRAPH STAT JI J. Comput. Graph. Stat. PD SEP PY 1998 VL 7 IS 3 BP 278 EP 309 PG 32 WC Statistics & Probability SC Mathematics GA 121HY UT WOS:000076008800003 ER PT J AU Lipsitz, SR Parzen, M Molenberghs, G AF Lipsitz, SR Parzen, M Molenberghs, G TI Obtaining the maximum likelihood estimates in incomplete R x C contingency tables using a Poisson generalized linear model SO JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS LA English DT Article DE EM-algorithm; ignorable missing data; Newton-Raphson algorithm; offset AB This article describes estimation of the cell probabilities in an R x C contingency table with ignorable missing data. Popular methods for maximizing the incomplete data likelihood are the EM-algorithm and the Newton-Raphson algorithm. Both of these methods require some modification of existing statistical software to get the MLEs of the cell probabilities as well as the variance estimates. We make the connection between the multinomial and Poisson likelihoods to show that the MLEs can be obtained in any generalized linear models program without additional programming or iteration loops. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Grad Sch Business, Chicago, IL 60637 USA. Limburgs Univ Ctr, B-3590 Diepenbeek, Belgium. RP Lipsitz, SR (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. EM fm-parzen@gsbmip.uchicago.edu NR 16 TC 7 Z9 7 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 1061-8600 J9 J COMPUT GRAPH STAT JI J. Comput. Graph. Stat. PD SEP PY 1998 VL 7 IS 3 BP 356 EP 376 DI 10.2307/1390709 PG 21 WC Statistics & Probability SC Mathematics GA 121HY UT WOS:000076008800007 ER PT J AU Aquino, SL Dunagan, DP Chiles, C Haponik, EF AF Aquino, SL Dunagan, DP Chiles, C Haponik, EF TI Herpes simplex virus 1 pneumonia: Patterns on CT scans and conventional chest radiographs SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE pneumonia; lungs, diseases; lungs, infections; herpes simplex virus; computed tomography; thorax ID RESPIRATORY-DISTRESS-SYNDROME; COMPUTED-TOMOGRAPHY; INFECTION; TRACT; TRACHEOBRONCHITIS; TRANSPLANTATION; DISEASE AB Purpose: The goal of our study was to describe the herpes simplex virus type 1 (HSV 1) pneumonia patterns on CT scans and chest radiographs. Method: We retrospectively reviewed clinical records and chest radiographs of 24 patients with HSV 1 pneumonia and 10 with pneumonia from combined HSV and mixed flora infection. We also reviewed CT scans available for eight patients with HSV pneumonia and four with mixed pneumonia. Results: CT scans of eight patients with HSV pneumonia demonstrated multifocal segmental and subsegmental ground-glass opacities (n = 8), additional focal areas of consolidation (n = 6), scattered distribution (n = 6), and pleural effusions (n = 7). Chest radiographs (23 patients) showed patchy segmental and subsegmental ground-glass opacities and consolidation (n = 23), scattered distribution (n = 20), and pleural effusions (n = 12). Radiographic patterns for isolated HSV pneumonia and mixed flora pneumonia were not significantly different. Conclusion: With a growing population of at-risk immunosuppressed patients, it is important to recognize CT and chest radiography patterns consistent with, although nonspecific for, HSV 1 pneumonia. C1 Wake Forest Univ, Sch Med, Dept Radiol, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Pulm Med, Winston Salem, NC 27157 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 216,55 Fruit St, Boston, MA 02114 USA. NR 30 TC 27 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1998 VL 22 IS 5 BP 795 EP 800 DI 10.1097/00004728-199809000-00024 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 120JU UT WOS:000075953900025 PM 9754119 ER PT J AU Phipps, KR Orwoll, ES Bevan, L AF Phipps, KR Orwoll, ES Bevan, L TI The association between water-borne fluoride and bone mineral density in older adults SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE fluorides; fluoridation; bone density; osteoporosis; environmental health ID HIP FRACTURE INCIDENCE; DRINKING-WATER; WOMEN; MASS; OSTEOPOROSIS; COMMUNITIES; MEN; POPULATION AB While the benefit of fluoridation in the prevention of dental caries has been overwhelmingly substantiated, the effect of fluoride on bone mineral density is less clear. This cross-sectional study was designed to compare the bone mineral densities of older adults exposed to various levels of fluoride from community water systems. Participants were recruited from 3 rural communities with naturally occurring fluoride in their water systems at 0.03, 0.7, and 2.5 mg/L. All adults, age 60 and over, were eligible if they were ambulatory and had a long-term history (greater than or equal to 20 yrs) of ingesting city water. Bone mineral density (BMD) was measured by means of dual-energy x-ray absorptiometry at 3 anatomical sites: lumbar spine, proximal femur, and forearm. A total of 353 white non-Hispanic women and 317 white non-Hispanic men took part in the study. When the data were stratified by city of residence and gender, men and women living in the community with high levels of fluoride in their community water system had significantly higher lumbar spine BMD than their counterparts from the communities with low and moderate fluoride levels. The women in the high-fluoride community had significantly higher proximal femur BMD, but there were no statistically significant differences among men in either proximal femur or forearm BMD. Long-term exposure (greater than or equal to 20 yrs) to higher levels of fluoride appears to have a positive impact on lumbar spine and proximal femur BMD. Based on the results of this study, exposure to fluoride at levels considered "optimal" for the prevention of dental caries (from 0.7 to 1.2 mg/L) appears to have no significant impact on bone mineral density. The relationship between higher let els of fluoride exposure and bone mineral density requires further investigation. C1 Oregon Hlth Sci Univ, Sch Dent, Portland, OR 97201 USA. Oregon Pacific Area Hlth Educ Ctr, Newport, OR USA. Oregon Hlth Sci Univ, Bone & Mineral Res Unit, Sch Med, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Phipps, KR (reprint author), Oregon Hlth Sci Univ, Sch Dent, 611 SW Campus Dr, Portland, OR 97201 USA. OI Orwoll, Eric/0000-0002-8520-7355 FU NIDCR NIH HHS [R01-DE09883] NR 37 TC 13 Z9 16 U1 1 U2 7 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 1998 VL 77 IS 9 BP 1739 EP 1748 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 123EH UT WOS:000076112500010 PM 9759671 ER PT J AU Bradley, KA Badrinath, S Bush, K Boyd-Wickizer, J Anawalt, B AF Bradley, KA Badrinath, S Bush, K Boyd-Wickizer, J Anawalt, B TI Medical risks for women who drink alcohol SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE alcohol consumption; alcoholism; women ID FIRST-PASS-METABOLISM; HIGH-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; SEXUALLY-TRANSMITTED DISEASES; RANDOMIZED CONTROLLED TRIAL; UNITED-STATES ADULTS; BONE-MINERAL DENSITY; 1981 NATIONAL SURVEY; EMERGENCY ROOM DATA; ALL-CAUSE MORTALITY AB OBJECTIVE:To summarize for clinicians recent epidemiologic evidence regarding medical risks of alcohol use for women. METHODS: MEDLINE and PsychINFO, 1990 through 1996, were searched using key words "women" or "woman," and "alcohol." MEDLINE was also searched for other specific topics and authors from 1980 through 1996. Data were extracted and reviewed regarding levels of alcohol consumption associated with mortality, cardiovascular disease, alcohol-related liver disease, injury, osteoporosis, neurologic symptoms, psychiatric comorbidity, fetal alcohol syndrome, spontaneous abortion, infertility, menstrual symptoms, breast cancer, and gynecologic malignancies. Gender-specific data from cohort studies of general population or large clinical samples are primarily reviewed. MAIN RESULTS:Women develop many alcohol-related medical problems at lower levels of consumption than men, probably reflecting women's lower total body water, gender differences in alcohol metabolism, and effects of alcohol on postmenopausal estrogen levels. Mortality and breast cancer are increased in women who report drinking more than two drinks daily. Higher levels of alcohol consumption by women are associated with increased menstrual symptoms, hypertension, and stroke. Women who drink heavily also appear to have increased infertility and spontaneous abortion. Adverse fetal effects occur after variable amounts of alcohol consumption, making any alcohol use during pregnancy potentially harmful. CONCLUSIONS: In general, advising nonpregnant women who drink alcohol to have fewer than two drinks daily is strongly supported by the epidemiologic Literature, although specific recommendations for a particular woman should depend on her medical history and risk factors. C1 VA Puget Sound Hlht Care Syst, Seattle Div, Hlth Serv Res & Dev, Seattle, WA 98108 USA. RP Bradley, KA (reprint author), VA Puget Sound Hlht Care Syst, Seattle Div, Hlth Serv Res & Dev, Mailstop 152,1660 S Columbian Way, Seattle, WA 98108 USA. NR 239 TC 82 Z9 83 U1 8 U2 16 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 SEP PY 1998 VL 13 IS 9 BP 627 EP 639 DI 10.1046/j.1525-1497.1998.cr187.x PG 13 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 118RY UT WOS:000075854800009 PM 9754520 ER PT J AU Gottlieb, GL AF Gottlieb, GL TI The future of delirium research SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article C1 Massachusetts Gen Hosp, Partners Hlth Care Syst Inc, Boston, MA 02114 USA. RP Gottlieb, GL (reprint author), Massachusetts Gen Hosp, Partners Hlth Care Syst Inc, Bulfinch Bldg,Suite 370E,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD FAL PY 1998 VL 11 IS 3 BP 157 EP 158 PG 2 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 154GP UT WOS:000077881100007 ER PT J AU Offner, H Adlard, K Bebo, BF Schuster, J Burrows, GG Buenafe, AC Vandenbark, AA AF Offner, H Adlard, K Bebo, BF Schuster, J Burrows, GG Buenafe, AC Vandenbark, AA TI Vaccination with BV8S2 protein amplifies TCR-specific regulation and protection against experimental autoimmune encephalomyelitis in TCR BV8S2 transgenic mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CELL RECEPTOR PEPTIDES; T-CELL; MULTIPLE-SCLEROSIS; INCREASED SEVERITY; INTERFERON-GAMMA; LEWIS RATS; DISEASE; THERAPY AB TCR determinants overexpressed by autopathogenic Th1 cells can naturally induce a second set of TCR-specific regulatory T cells. We addressed the question of whether immune regulation could be induced naturally in a genetically restricted model in which a major portion of TCR-specific regulatory T cells expressed the same target TCR BV8S2 chain as the pathogenic T cells specific for myelin basic protein (MBP), We found vigorous T cell responses to BV8S2 determinants in naive mice that could be further potentiated by vaccination with heterologous BV8S2 proteins, resulting in the selective inhibition of MBP-specific Th1 cells and protection against experimental encephalomyelitis. Moreover, coculture with BV8S2-specific T cells or their supernatants reduced proliferation, IFN-gamma secretion, and encephalitogenic activity of MBP-specific T cells, These results suggest that immune regulation occurs through a nondeletional cytokine-driven suppressive mechanism. C1 Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland Vet Affairs Med Ctr, 3710 SW Vet Hosp Rd, Portland, OR 97201 USA. FU NINDS NIH HHS [NS23444, NS23221] NR 33 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1998 VL 161 IS 5 BP 2178 EP 2186 PG 9 WC Immunology SC Immunology GA 112UB UT WOS:000075511600014 PM 9725209 ER PT J AU Aoudjit, F Potworowski, EF Springer, TA St-Pierre, Y AF Aoudjit, F Potworowski, EF Springer, TA St-Pierre, Y TI Protection from lymphoma cell metastasis in ICAM-1 mutant mice: A posthoming event SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; MONOCLONAL-ANTIBODY; EXPRESSION; LFA-1; METALLOPROTEINASES; INHIBITORS; INTEGRINS; MIGRATION; GROWTH; STEPS AB It has been hypothesized that the intercellular adhesion receptors used by normal cells could also be operative in the spreading of circulating malignant cells to target organs. In the present work, we show that genetic ablation of the ICAM-1 gene confers resistance to T cell lymphoma metastasis, Following i.v. inoculation of LFA-1-expressing malignant T lymphoma cells, we found that ICAM-1-deficient mice were almost completely resistant to the development of lymphoid malignancy compared with wild-type control mice that developed lymphoid tumors in the kidneys, spleen, and liver, Histologic examinations confirmed that ICAM-1-deficient mice, in contrast to wild-type mice, had no evidence of lymphoid infiltration in these organs. The effect of ICAM-1 on T cell lymphoma metastasis was observed in two distinct strains of ICAM-1-deficient animals. Nonetheless, lymphoma cells migrated with the same efficiency to target organs in both normal and ICAM-1-deficient mice, indicating not only that ICAM-1 expression by the host is essential in lymphoma metastasis, but also that this is so at stages subsequent to homing and extravasation into target organs. These results point to posthoming events as a focus of future investigation on the control of metastasis mediated by ICAM-1. C1 Univ Quebec, Inst Armand Frappier, Immunol Res Ctr, Laval, PQ H7N 4Z3, Canada. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP St-Pierre, Y (reprint author), Univ Quebec, Inst Armand Frappier, Immunol Res Ctr, POB 100, Laval, PQ H7N 4Z3, Canada. EM yves.st-pierre@iaf.uquebec.ca NR 38 TC 37 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1998 VL 161 IS 5 BP 2333 EP 2338 PG 6 WC Immunology SC Immunology GA 112UB UT WOS:000075511600033 PM 9725228 ER PT J AU Abadi, J Friedman, J Mageed, RA Jefferis, R Rodriguez-Barradas, MC Pirofski, LA AF Abadi, J Friedman, J Mageed, RA Jefferis, R Rodriguez-Barradas, MC Pirofski, LA TI Human antibodies elicited by a pneumococcal vaccine express idiotypic determinants indicative of V(H)3 gene segment usage SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the American-Society-for-Microbiology CY MAY 02-08, 1997 CL MIAMI, FLORIDA SP Amer Soc Microbiol ID INFLUENZAE TYPE-B; IMMUNODEFICIENCY-VIRUS INFECTION; HUMAN MONOCLONAL-ANTIBODIES; STAPHYLOCOCCAL PROTEIN-A; CROSS-REACTIVE IDIOTYPE; CAPSULAR POLYSACCHARIDE; STREPTOCOCCUS-PNEUMONIAE; HIV-INFECTION; IGG ANTIBODY; IN-VIVO AB Human immunodeficiency virus (HIV)-infected persons manifest decreased antibody responses to pneumococcal polysaccharide vaccines, Since human antibody responses to polysaccharides are often restricted, the molecular structure of antibodies elicited by a 23-valent pneumococcal vaccine was analyzed. Anti-idiotypic reagents were used to detect V(H)1, V(H)3, and V(H)4 gene usage by antibodies to pneumococcal capsular polysaccharides in HIV-uninfected and HIV-infected subjects by ELISA, HIV-uninfected persons generated beta-mercaptoethanol-sensitive and -resistant antibodies to pneumococcal capsular polysaccharides expressing V(H)3 determinants recognized by the D12, 16.84, and B6 monoclonal antibodies; antibodies expressing V(H)1 determinants were not detected, and V(H)4 determinants were expressed by beta-mercaptoethanol-sensitive antibodies only; and HIV-infected subjects had significantly lower capsular polysaccharide-specific and V(H)3-positive antibody responses. These findings confirm decreased antibody responses to pneumococcal vaccination in HIV-infected persons and suggest that their poor responses may result from HIV-associated depletion of restricted B cell subsets. C1 Yeshiva Univ Albert Einstein Coll Med, Div Infect Dis, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Div Infect Dis, Dept Med, Bronx, NY 10461 USA. Univ Birmingham, Sch Med, Dept Immunol, Birmingham, W Midlands, England. Kennedy Inst Rheumatol, London, England. Houston Vet Adm Med Ctr, Houston, TX USA. RP Pirofski, LA (reprint author), Yeshiva Univ Albert Einstein Coll Med, Div Infect Dis, Dept Microbiol & Immunol, 1300 Morris Pk Ave,Room 402 Forchheimer Bldg, Bronx, NY 10461 USA. FU NCI NIH HHS [CA-09173]; NIAID NIH HHS [AI-35370]; Wellcome Trust NR 51 TC 40 Z9 42 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1998 VL 178 IS 3 BP 707 EP 716 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 112UL UT WOS:000075512700014 PM 9728539 ER PT J AU Shapiro, RL Altekruse, S Hutwagner, L Bishop, R Hammond, R Wilson, S Ray, B Thompson, S Tauxe, RV Griffin, PM AF Shapiro, RL Altekruse, S Hutwagner, L Bishop, R Hammond, R Wilson, S Ray, B Thompson, S Tauxe, RV Griffin, PM CA Vibrio Working Grp TI The role of Gulf Coast oysters harvested in warmer months in Vibrio vulnificus infections in the United States, 1988-1996 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 07-16, 1997 CL SAN FRANCISCO, CALIFORNIA SP Infect Dis Soc Amer ID IRON; EPIDEMIOLOGY; ASSOCIATION; SATURATION; SHELLSTOCK; DISEASE; FLORIDA; CHOLERA; SERUM AB Vibrio vulnificus infections are highly lethal and associated with consumption of raw shellfish and exposure of wounds to seawater. V. vulnificus infections were reported to the Centers for Disease Control and Prevention from 23 states. For primary septicemia infections, oyster trace-backs were performed and water temperature data obtained at harvesting sites. Between 1988 and 1996, 422 infections were reported; 45% were wound infections, 43% primary septicemia, 5% gastroenteritis, and 7% from undetermined exposure. Eighty-six percent of patients were male, and 96% with primary septicemia consumed raw oysters. Sixty-one percent with primary septicemia died; underlying liver disease was associated with fatal outcome, All trace-backs with complete information implicated oysters harvested in the Gulf of Mexico; 89% were harvested in water >22 degrees C, the mean annual temperature at the harvesting sites (P <.0001), Control measures should focus on the increased risk from oysters harvested from the Gulf of Mexico during warm months as well as education about host susceptibility factors. C1 Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, Epidem Intelligence Serv, Epidemiol Program Off, Atlanta, GA USA. Ctr Dis Control & Prevent, Biostat & Informat Management Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA USA. US FDA, Epidemiol Branch, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Bur Environ Epidemiol, State Florida Dept Hlth, Tallahassee, FL USA. State Louisiana Dept Hlth & Hosp, Epidemiol Sect, New Orleans, LA USA. Texas Dept Hlth, Infect Dis Epidemiol & Surveillance Div, Austin, TX 78756 USA. Alabama Dept Publ Hlth, Div Epidemiol, Montgomery, AL 36102 USA. RP Shapiro, RL (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Fruit St, Boston, MA 02114 USA. NR 25 TC 126 Z9 147 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1998 VL 178 IS 3 BP 752 EP 759 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 112UL UT WOS:000075512700019 PM 9728544 ER PT J AU Malley, R Stack, AM Ferretti, ML Thompson, CM Saladino, RA AF Malley, R Stack, AM Ferretti, ML Thompson, CM Saladino, RA TI Anticapsular polysaccharide antibodies and nasopharyngeal colonization with Streptococcus pneumoniae in infant rats SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the Society-for-Pediatric-Research CY MAY 02-10, 1996 CL WASHINGTON, D.C. SP Soc Pediat Res ID INFLUENZAE TYPE-B; HUMAN HYPERIMMUNE GLOBULIN; VACCINE; CARRIAGE; CHILDREN; LIFE AB To evaluate the effect of passive immunization with anticapsular antibodies on nasopharyngeal carriage, two models of Streptococcus pneumoniae colonization were developed in infant rats. In a direct inoculation model, 3- to 4-day-old infant rats were intranasally inoculated with 2 x 10(5) cfu of S. pneumoniae type 3 or 6 x 10(3) cfu of S. pneumoniae type 23F. In an intralitter transmission model, 2 infant rats were intranasally inoculated with 10(3) cfu of pneumococcus type 3 or type 19F and placed in a cage containing 10 infant rats. Pretreatment with bacterial polysaccharide immune globulin led to a significant reduction in colonization of contact animals with S, pneumoniae type 3 or 19F in the intralitter transmission model (P <.05). No effect of immune globulin could be demonstrated in the direct inoculation model. These results indicate that systemic anticapsular antibodies conferred significant protection against nasopharyngeal acquisition by intralitter spread of S, pneumoniae type 3 and 19F. C1 Childrens Hosp, Div Emergency Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Infect Dis Lab, Boston, MA 02115 USA. RP Malley, R (reprint author), Childrens Hosp, Div Emergency Med, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. NR 15 TC 29 Z9 30 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1998 VL 178 IS 3 BP 878 EP 882 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 112UL UT WOS:000075512700039 PM 9728564 ER PT J AU Argyropoulos, G Jenkins, A Klein, RL Lyons, T Wagenhorst, B St Armand, J Marcovina, SM Albers, JJ Pritchard, PH Garvey, WT AF Argyropoulos, G Jenkins, A Klein, RL Lyons, T Wagenhorst, B St Armand, J Marcovina, SM Albers, JJ Pritchard, PH Garvey, WT TI Transmission of two novel mutations in a pedigree with familial lecithin : cholesterol acyltransferase deficiency: structure-function relationships and studies in a compound heterozygous proband SO JOURNAL OF LIPID RESEARCH LA English DT Article DE high density lipoprotein; LCAT activity; polymerase chain reaction; lipoprotein [a]; substrate recognition binding site; familial LCAT deficiency; fish-eye disease ID FISH-EYE DISEASE; HIGH-DENSITY-LIPOPROTEINS; AMINO-ACID EXCHANGE; LCAT DEFICIENCY; ALPHA-LCAT; MOLECULAR DEFECT; HUMAN-PLASMA; GENE; ESTERIFICATION; ABNORMALITIES AB Two novel mutations were identified in a compound heterozygous male with lecithin:cholesterol acyltransferase (LCAT) deficiency. Exon sequence determination of the LCAT gene of the proband revealed two novel heterozygous mutations in exons one (C110T) and six (C991T) that predict non-conservative amino add substitutions (Thr13Met and Pro307Ser, respectively). To assess the distinct functional impact of the separate mutant alleles, studies were conducted in the proband's 3-generation pedigree, The compound heterozygous proband had negligible HDL and severely reduced apolipoprotein A-I, LCAT mass, LCAT activity, and cholesterol esterification rate (CER), The proband's mother and tao sisters were heterozygous for the Pro307Ser mutation and had low HDL, markedly reduced LCAT activity and CER, and the propensity for significant reductions in LCAT protein mass, The proband's father and two daughters were heterozygous for the Thr13Met mutation and also displayed low HDL, reduced LCAT activity and CER, and more modest decrements in LCAT mass. Mean LCAT specific activity was severely impaired in the compound heterozygous proband and was reduced by 50% in individuals heterozygous for either mutation, compared to wild type family members. It is also shown that the two mutations impair both catalytic activity and expression of the circulating protein. C1 Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Eye Clin, Med Grp 29, Shaw AFB, SC 29152 USA. Univ British Columbia, St Pauls Hosp, Dept Pathol & Lab Med, Atherosclerosis Specialty Lab, Vancouver, BC V6Z 1Y6, Canada. Univ Washington, NW Lipid Res Labs, Seattle, WA 98103 USA. RP Argyropoulos, G (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. FU NHLBI NIH HHS [P01 HL 55782, HL30086]; NIDDK NIH HHS [DK-47461] NR 41 TC 8 Z9 9 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 1998 VL 39 IS 9 BP 1870 EP 1876 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 115CX UT WOS:000075646900017 PM 9741700 ER PT J AU Bogdanov, MB Ramos, LE Xu, ZS Beal, MF AF Bogdanov, MB Ramos, LE Xu, ZS Beal, MF TI Elevated "hydroxyl radical" generation in vivo in an animal model of amyotrophic lateral sclerosis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE oxidative damage; free radicals; superoxide dismutase; amyotrophic lateral sclerosis; microdialysis ID ZINC SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; OXIDATIVE DAMAGE; TRANSGENIC MICE; K-M; PEROXYNITRITE; MUTATIONS; DISEASE; MUTANT; COPPER AB Mutations in the enzyme copper/zinc superoxide dismutase-1 (SOD1) are associated with familiar amyotrophic lateral sclerosis (FALS). The means by which the mutations cause FALS appears to be due to an adverse property of the mutant SOD1 protein that may involve increased generation of free radicals. We used in vivo microdialysis to measure the conversion of 4-hydroxybenzoic acid to 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of "hydroxyl radical-like" production in transgenic amyotrophic lateral sclerosis (ALS) mice with the G93A mutation as well as littermate controls. The conversion of 4-hydroxybenzoic acid to 3,4-DHBA was significantly increased in the striatum of transgenic ALS mice at baseline but not in mice overexpressing wild-type human SOD1. Following administration of 3-nitropropionic acid 3,4-DHBA generation was significantly increased as compared with baseline, and the increase in the transgenic ALS mice was significantly greater than those in controls, whereas the increase in mice overexpressing wildtype human SOD1 was significantly attenuated. The present results provide in vivo evidence that expression of mutations in SOD1 can lead to increased generation of "hydroxyl radical-like" activity, which further implicates oxidative damage in the pathogenesis of ALS. C1 Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Worcester Fdn Biomed Res, Shrewsbury, MA USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, WRN 408,32 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [P01 AG12992] NR 30 TC 141 Z9 145 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1998 VL 71 IS 3 BP 1321 EP 1324 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 112DG UT WOS:000075478400046 PM 9721759 ER PT J AU Ay, H Buonanno, FS Price, BH Le, DA Koroshetz, WJ AF Ay, H Buonanno, FS Price, BH Le, DA Koroshetz, WJ TI Sensory alien hand syndrome: case report and review of the literature SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE alien hand syndrome; posterior; ischaemic stroke; posterior cerebral artery ID ARTERY TERRITORY INFARCTION; LESIONS AB An 81 year old right handed woman developed a left alien hand syndrome characterised by involuntary movements of choking and hitting the face, neck, and shoulder. The patient showed multiple disorders of primary sensation, sensory processing, hemispatial attention, and visual association, as well as a combination of sensory, optic, and cerebellar ataxia (triple ataxia) of the left arm in the absence of motor neglect or hemiparesis. Imaging studies disclosed subacute infarction in the right thalamus, hippocampus, inferior temporal lobes, splenium of corpus callosum, and occipital lobe due to right posterior cerebral artery occlusion. This rare syndrome should be considered as a "sensory" or "posterior" form of the alien hand syndrome, to be distinguished from the "motor" or "anterior" form described more commonly. C1 Harvard Univ, Dept Neurol, Stroke Serv, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. McLean Hosp, Dept Neurol, Belmont, MA 02178 USA. RP Buonanno, FS (reprint author), Harvard Univ, Dept Neurol, Stroke Serv, Massachusetts Gen Hosp,Sch Med, VBK-802,32 Fruit St, Boston, MA 02114 USA. NR 15 TC 38 Z9 40 U1 0 U2 5 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD SEP PY 1998 VL 65 IS 3 BP 366 EP 369 DI 10.1136/jnnp.65.3.366 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 114CX UT WOS:000075592500016 PM 9728952 ER PT J AU Scrivani, SJ Keith, DA Kulich, R Mehta, N Maciewicz, RJ AF Scrivani, SJ Keith, DA Kulich, R Mehta, N Maciewicz, RJ TI Posttraumatic gustatory neuralgia: A clinical model of trigeminal neuropathic pain SO JOURNAL OF OROFACIAL PAIN LA English DT Article DE gustatory neuralgia; trigeminal neuropathy; autonomic/sensory interaction; auriculotemporal nerve ID TEMPOROMANDIBULAR-JOINT SURGERY; FREYS SYNDROME; PREAURICULAR APPROACH; COMPLICATION AB Six cases are reported in which the primary complaint was episodic, recurrent facial pain that was triggered by a taste stimulus. The pain first occurred days to weeks after head and neck surgery. Patients reported that a food stimulus placed in the mouth evoked episodic, electric shock-like pain in a preauricular location on the surgical side. The smell of food or, less reliably, emotional excitement could also trigger pain. Mandibular movement did not evoke the pain, and between lancinating attacks there was either no pain or only mild discomfort. Following an episode of pain, there was a refractory period during which the pain could not be elicited. Physical examination demonstrated a preauricular sensory loss of variable distribution. No abnormal sweating or vasomotor findings were clinically apparent. No odontogenic, muscular, salivary gland neurologic, or psychologic pathology was found to explain the clinical symptoms. The pain was not relieved with standard doses of anticonvulsants that are commonly used to treat trigeminal neuralgia. The duration of the recurrent pain symptoms in this group was 8 to 132 months without remission. Gustatory neuralgia. may be a discrete syndrome that results from abnormal interactions between salivary efferent fibers and trigeminal sensory afferent fibers in the injured auriculotemporal nerve. The unique features of the disorder make it a potentially useful clinical model for the investigation of autonomic/sensory interactions in neuropathic pain. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Craniofacial Pain Ctr, Cambridge, MA 02138 USA. Tufts New England Med Ctr, Pain Program, Boston, MA 02111 USA. Tufts Sch Dent Med, Gelb Orofacial Pain Ctr, Boston, MA USA. Tufts New England Med Ctr, Headache Clin, Boston, MA USA. RP Scrivani, SJ (reprint author), Columbia Presbyterian Med Ctr, Dept Oral & Maxillofacial Surg, Sch Dent & Oral Surg, 622 W 168th St,HP-8, New York, NY 10032 USA. NR 25 TC 7 Z9 7 U1 0 U2 0 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 1064-6655 J9 J OROFAC PAIN JI J. Orofac. Pain PD FAL PY 1998 VL 12 IS 4 BP 287 EP 292 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 136AL UT WOS:000076835400005 PM 10425975 ER PT J AU Gill, TJ Sledge, JB Ekkernkamp, A Ganz, R AF Gill, TJ Sledge, JB Ekkernkamp, A Ganz, R TI Intraoperative assessment of femoral head vascularity after femoral neck fracture SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE osteonecrosis; femoral neck fractures; internal fixation; vascularity ID INTERNAL-FIXATION; BLOOD-FLOW; COMPLICATIONS; SCINTIGRAPHY; PRESSURE; FEMUR; BONE AB Objectives: To develop an intraoperative technique to predict the development of avascular necrosis after internal fixation of femoral neck fractures. Design: Prospective study. Setting: All patients were treated at the same hospital. Patients/Participants: Sixty-four patients who presented for internal fixation of a femoral neck fracture were enrolled in the study. Intervention: A 2.0-millimeter drill was used to assess the presence and character of bleeding from the femoral head at open reduction and internal fixation of a femoral neck fracture. Main Outcome Measurements: Patients were evaluated postoperatively by history, examination, and roentgenography for the development of avascular necrosis of the femoral head fragment. A minimum two-year follow-up with radiography was required for entry into the study, with an average follow-up of 3.2 years. Results: None of the fifty-six patients with bleeding from the drill holes in the femoral head fragment developed avascular necrosis. Eight of eight patients with no bleeding after reduction developed avascular necrosis. There were no infections or nonunions. Conclusions: Intraoperative drilling of the femoral head is a highly sensitive and specific predictor for the development of avascular necrosis after femoral neck fractures. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Bern, Dept Orthoped, Bern, Switzerland. RP Gill, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, 604C,Fruit St, Boston, MA 02114 USA. NR 43 TC 39 Z9 40 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD SEP-OCT PY 1998 VL 12 IS 7 BP 474 EP 478 DI 10.1097/00005131-199809000-00008 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 124QX UT WOS:000076194300008 PM 9781771 ER PT J AU Capano, G Bloch, KJ Carter, EA Dascoli, JA Schoenfeld, D Harmatz, PR AF Capano, G Bloch, KJ Carter, EA Dascoli, JA Schoenfeld, D Harmatz, PR TI Polyamines in human and rat milk influence intestinal cell growth in vitro SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE breast milk; difluoromethylornithine (DFMO); IEC-6; infant formula; neonate; polyamine ID INFANT FORMULAS; MATURATION; SPERMIDINE; ENTEROCYTES AB Background: Polyamines are required for intestinal growth and development. In this study, we examined whether milk can supply the polyamines needed for growth of LEC-6 cells, a line on non-transformed rat intestinal crypt cells. Methods: Human, bovine, and rat milk, and cow's milk-based infant formula were studied. Human, bovine, and rat milk were defatted and sterilized by filtration. IEC-6 cells were stabilized in Dulbecco's modified Eagle's medium (DMEM) containing 0.5% fetal bovine serum, 5 mM L-glutamine, 100 U/mL penicillin and 100 mu g/mL streptomycin for 24 h at 37 degrees C. Thereafter, to initiate active growth, cells were placed in fresh DMEM containing 5% FBS (plus the other ingredients) supplemented with 5% (vol/vol) milk or infant formula. In some experiments, cells were also treated with difluoromethylornithine (2.5 mM) (DFMO), an inhibitor of polyamine synthesis, or dialyzed milk plus DFMO. After 44 hours of culture, cells were pulsed with H-3-thymidine (H-3-TdR) for 4 hours, harvested and the radioactivity incorporated into DNA was measured. Results: Human and rat milk stimulated proliferation of IEC-6 cells (p < 0.05 compared to controls); addition of DEMO did not reverse the stimulatory effect. Bovine milk and the infant formula did not stimulate proliferation or prevent the growth inhibition induced by DEMO. After dialysis, human milk had less ability to reverse the DFMO inhibition (p < 0.05). Conclusions: These experiments suggest that both human and rat milk, but neither bovine milk nor the infant formula, contain sufficient bioactive polyamines to sustain cell growth during inhibition of polyamine synthesis. C1 Childrens Hosp Oakland, Dept Gastroenterol & Nutr, Oakland, CA 94609 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Immunol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Allergy Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Univ Naples Federico II, Dept Pediat, Naples, FL USA. RP Harmatz, PR (reprint author), Childrens Hosp Oakland, Dept Gastroenterol & Nutr, 747 52nd St, Oakland, CA 94609 USA. FU NICHD NIH HHS [HD12437]; NIDDK NIH HHS [DK33506] NR 20 TC 20 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD SEP PY 1998 VL 27 IS 3 BP 281 EP 286 DI 10.1097/00005176-199809000-00002 PG 6 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 114QG UT WOS:000075619900002 PM 9740197 ER PT J AU Friedmann, AM King, KE Shirey, RS Resar, LMS Casella, JF AF Friedmann, AM King, KE Shirey, RS Resar, LMS Casella, JF TI Fatal autoimmune hemolytic anemia in a child due to warm-reactive immunoglobulin M antibody SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE autoimmune hemolytic anemia; warm-reactive IgM antibody; Evan's syndrome; in vivo hemagglutination ID IGM AUTOAGGLUTININS AB Purpose: Autoimmune hemolytic anemia (AIHA) due to warm-reactive immunoglobulin M (IgM) antibodies is rare in adults and has never been described in children. This report describes a pediatric patient with warm AIHA due to high-titer complete IgM antibody. Patients and Methods: A 9-year-old girl with a history of Evan's syndrome had severe anemia, fatigue, and skin mottling. Results: Serologic evaluation revealed a high-titer, high thermal amplitude (37 degrees C) complete IgM autoantibody. Despite aggressive management (including high dose corticosteroids, intravenous immune globulin, cyclophosphamide, mycophenolate mofetil, whole blood exchange transfusions, and cyclosporine A), the patient remained markedly anemic and developed multiorgan system failure related to diffuse in vivo hemagglutination. Her clinical course included cardiovascular collapse caused by agglutinated red blood cells in the right ventricle with outflow obstruction, cerebrovascular infarcts, hepatic failure, and infarction of her extremities. She ultimately died from disseminated Aspergillosis infection. Conclusion: This rare form of AIHA is associated with a dismal prognosis. Early, aggressive treatment is advocated, although it remains to be seen whether the clinical course can be reversed and the outcome improved. C1 Johns Hopkins Univ, Div Pediat Hematol, Baltimore, MD USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. RP Friedmann, AM (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WAC-705, Boston, MA 02114 USA. NR 7 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD SEP-OCT PY 1998 VL 20 IS 5 BP 502 EP 505 DI 10.1097/00043426-199809000-00020 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 127PC UT WOS:000076358900020 PM 9787330 ER PT J AU Stoler, JM Huntington, KS Peterson, CM Peterson, KP Daniel, P Aboagye, KK Lieberman, E Ryan, L Holmes, LB AF Stoler, JM Huntington, KS Peterson, CM Peterson, KP Daniel, P Aboagye, KK Lieberman, E Ryan, L Holmes, LB TI The prenatal detection of significant alcohol exposure with maternal blood markers SO JOURNAL OF PEDIATRICS LA English DT Article ID FETAL GROWTH; PREGNANCY; ACETALDEHYDE; CONSUMPTION; DRINKING; SERUM; TRANSFERRIN; HEMOGLOBIN; ETHANOL AB Objective: To examine the efficacy of a combination of 4 blood markers of alcohol use in detecting alcohol-abusing pregnant women. Study design: Two new markers of alcohol use, whole blood-associated acetaldehyde and carbohydrate-deficient transferrin, and 2 traditional markers of alcohol use, gamma-glutamyl transpeptidase and mean red blood cell volume, were measured in the blood of pregnant women. Each woman was interviewed about alcohol and drug use, medical and obstetric histories, and nutrition. Each infant was examined by a clinician who was blinded to exposure status. Results: All of the women who reported drinking an average of 1 or more ounces of absolute alcohol per day had at least, 1 positive blood marker. The infants of mothers with 2 or more positive markers had significantly smaller birth weights, lengths, and head circumferences than the infants with negative maternal screens. The presence of 2 or more positive markers was more predictive of infant outcome than any self-reporting measure. Conclusions: These markers, which detect more at-risk pregnant women than self-reporting methods, could lead to better efforts at detection and prevention of alcohol-induced fetal damage. C1 Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Sansum Med Res Fdn, Santa Barbara, CA 93105 USA. Boston Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. LabOne Inc, Home Off Reference Lab, Lenexa, KS USA. RP Stoler, JM (reprint author), Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, 55 Fruit St,Warren 801, Boston, MA 02114 USA. RI Peterson, Karen/E-8084-2015 OI Peterson, Karen/0000-0001-6737-8698 FU NIAAA NIH HHS [5R03AA09049] NR 33 TC 55 Z9 57 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 1998 VL 133 IS 3 BP 346 EP 352 DI 10.1016/S0022-3476(98)70267-7 PG 7 WC Pediatrics SC Pediatrics GA 117GJ UT WOS:000075772900010 PM 9738714 ER PT J AU Francesconi, CM Abad, JC Lim, JE Talamo, JH AF Francesconi, CM Abad, JC Lim, JE Talamo, JH TI Evaluation of pentoxifylline in the prevention of haze after photorefractive keratectomy in the rabbit SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article ID EXCIMER-LASER; CORNEAL HAZE; TOPICAL CORTICOSTEROIDS; PROLIFERATION; GLYCOSAMINOGLYCAN; FIBRONECTIN; INHIBITORS; COLLAGEN; STEROIDS; SURGERY AB BACKGROUND: Pentoxifylline (PTX) is a methylxanthine derivative that, besides its hemorrheologic properties, possesses multiple physiologic effects at the cellular level. It has been used in keloid prevention due to its ability to inhibit the secretion of collagen and glycosaminoglycans from activated fibroblasts. METHODS: Ten New Zealand White (NZW) rabbits underwent a -7.00 diopters, 6.0 mm diameter photorefractive keratectomy after laser ablation of the epithelium with a VISX 20/20 excimer laser. The bare stroma was stained with fresh 0.5% dichlorotriazinyl aminofluorescein (DTAF). The procedure was performed on both eyes, 4 days apart. One eye received 1% Pentoxifylline qid and the other balanced salt solution qid as a control for 4 weeks, starting the same day of surgery, Two masked observers graded the amount of haze at 2, 4, 6, and 8 weeks after surgery using slit-lamp biomicroscopy. Three rabbits were sacrificed at 2 and 4 weeks followed by two rabbits at 6 and 8 weeks. The area between the DTAF-stained collagen to the base of the epithelium was measured using a digital image analyzer. RESULTS: There was no statistically significant difference in the amount of haze either by slit-lamp microscopy or by histological analysis between the pentoxifylline-treated eyes and the controls at any time interval (Student's t-test: 0.16 to 0.92) CONCLUSION: Pentoxifylline did not seem to affect haze formation in a PRK rabbit model. As no signs of toxicity were observed, further studies might examine higher concentrations or dose frequencies. C1 Cornea Consultants, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. McGill Univ, Sch Med, Toronto, ON, Canada. McGill Univ, Sch Med, Montreal, PQ, Canada. RP Talamo, JH (reprint author), Cornea Consultants, 100 Charles River Plaza, Boston, MA 02114 USA. NR 28 TC 4 Z9 4 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA J9 J REFRACT SURG JI J. Refractive Surg. PD SEP-OCT PY 1998 VL 14 IS 5 BP 567 EP 570 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 125QX UT WOS:000076249500013 PM 9791824 ER PT J AU Carey, K AF Carey, K TI Stochastic demand for hospitals and optimizing "excess" bed capacity SO JOURNAL OF REGULATORY ECONOMICS LA English DT Article ID COST-FUNCTIONS; POLICY IMPLICATIONS; MARKET-STRUCTURE; PANEL-DATA; COMPETITION; ANTITRUST; STANDARDS; MERGER; CARE AB This paper addresses the issue of hospital bed capacity by considering the stochastic demand for United States hospitals. An equilibrium condition for the optimal number of "excess" beds is derived and applied using a cost function estimated with a panel data model for the period 1987-1992. Results indicate that it may be difficult to justify the costliness of existing levels of empty hospital beds. The Department of Justice and the Federal Trade Commission should be cognizant of the potential effects of hospital mergers on undesirable excess bed capacity. C1 US Dept Vet Affairs, Management Sci Grp, Bedford, MA 01730 USA. RP Carey, K (reprint author), US Dept Vet Affairs, Management Sci Grp, 200 Springs Rd, Bedford, MA 01730 USA. NR 37 TC 21 Z9 21 U1 3 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0922-680X J9 J REGUL ECON JI J. Regul. Econ. PD SEP PY 1998 VL 14 IS 2 BP 165 EP 187 DI 10.1023/A:1008009302343 PG 23 WC Economics SC Business & Economics GA 120ZL UT WOS:000075987700004 ER PT J AU Alterman, AI Bedrick, J Cacciola, JS Rutherford, MJ Searles, JS McKay, JR Cook, TG AF Alterman, AI Bedrick, J Cacciola, JS Rutherford, MJ Searles, JS McKay, JR Cook, TG TI Personality pathology and drinking in young men at high and low familial risk for alcoholism SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID DISORDERS; CHILDREN; HISTORY; COMORBIDITY; PREDICTORS; BEHAVIOR; VALIDITY; ABUSE AB Objective: Three groups varying in familial alcoholism risk were compared with respect to amount of alcohol consumption, presence of personality pathology, and the relationship between personality pathology and alcohol consumption. Method: Research subjects were young adult men recruited from local colleges, a trade school and the community. The risk groups included (1) a group with a biological alcoholic father and significant additional familial alcoholism (n = 106); (2) subjects with an alcoholic father, but without significant additional familial alcoholism (n = 100); and (3) a group with no paternal alcoholism and at most only one second/third-degree alcoholic relative (n = 190). Absolute daily ounces of alcohol was determined using a standard quantity-frequency scale. Prevalence of DSM-III-R personality disorders (PDs) was evaluated using the Personality Disorder Questionnaire-Revised both with and without application of an impairment and distress scale. Familial risk determination was based on agree ment between four separate self-report assessments. Results: The first group consumed significantly more alcohol than the other two groups, which did not differ in alcohol consumption. The first group's subjects were more likely to meet criteria for virtually all of the PD diagnoses than were the other two groups. A greater proportion of the second group's subjects qualified for various PDs than did the third group's subjects. Personality pathology was consistently or usually associated with more drinking in the first and third groups, respectively, but associated with less consumption in the second group. Conclusions: Young men with high-density familial alcoholism are at greater risk for the development of alcoholism than those with alcoholic fathers and little additional familial alcoholism. Relationships between personality pathology and alcohol consumption, and possibly the development of alcoholism, differ for the three risk groups. C1 Univ Penn, Hlth Syst, Dept Psychiat, Treatment Res Ctr,Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Alterman, AI (reprint author), Univ Penn, Hlth Syst, Dept Psychiat, Treatment Res Ctr,Sch Med, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIAAA NIH HHS [AA07361]; NIDA NIH HHS [DA05186] NR 29 TC 20 Z9 20 U1 2 U2 4 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD SEP PY 1998 VL 59 IS 5 BP 495 EP 502 PG 8 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 107NN UT WOS:000075215500002 PM 9718101 ER PT J AU Baer, JS Barr, HM Bookstein, FL Sampson, PD Streissguth, AP AF Baer, JS Barr, HM Bookstein, FL Sampson, PD Streissguth, AP TI Prenatal alcohol exposure and family history of alcoholism in the etiology of adolescent alcohol problems SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID CROSS-FOSTERING ANALYSIS; INHERITANCE; CHILDREN; ETHANOL; AGE; DRINKING; PARENTS; ABUSE AB Objective: To examine the relative importance of prenatal alcohol exposure and family history of alcoholism fcr the prediction of adolescent alcohol problems. Method: In 1974-75, a population-based, longitudinal prospective study of alcohol and pregnancy began with self-report of alcohol use by pregnant women. In a 14-year follow-up, 439 parents provided information on the family history of alcohol problems for these adolescent offspring. The 14-year-old adolescents provided information on the frequency and quantity of their own alcohol consumption within the past month, on the consequences of their drinking over the past 3 years, and on their age at first intoxication. Additional covariates were assessed prenatally and at follow-up. Results: Prenatal alcohol exposure was more predictive of adolescent alcohol use and its negative consequences than was family history of alcohol problems. Prenatal exposure retained a significant predictive effect even after adjustment for family history and other prenatal and environmental covariates. By contrast, the nominally significant correlation of family history with adolescent drinking is weaker after adjustment for prenatal alcohol exposure and disappears entirely after adjustment for other relevant covariates. We observed no evidence for an interactive effect of fetal exposure and family history in predicting adolescent alcohol use. Conclusions: Fetal alcohol exposure is a risk factor for adolescent alcohol involvement and alcohol-related problems and may account for variance in prediction of problems otherwise attributed to family history of alcoholism. Studies of alcoholism etiology and family history need to include consideration of even modest levels of fetal alcohol exposure. C1 Univ Washington, Sch Arts & Sci, Dept Psychiat, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Streissguth, AP (reprint author), Fetal Alcohol & Drug Unit, 180 Nickerson St,Suite 309, Seattle, WA 98109 USA. RI Rohlf, F/A-8710-2008 FU NIAAA NIH HHS [AA 01455-01-22] NR 46 TC 94 Z9 95 U1 3 U2 11 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD SEP PY 1998 VL 59 IS 5 BP 533 EP 543 PG 11 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 107NN UT WOS:000075215500006 PM 9718105 ER PT J AU Ehrman, RN Robbins, SJ Childress, AR Goehl, L Hole, AV O'Brien, CP AF Ehrman, RN Robbins, SJ Childress, AR Goehl, L Hole, AV O'Brien, CP TI Laboratory exposure to cocaine cues does not increase cocaine use by outpatient subjects SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE addiction; cocaine; relapse; conditioning; cue exposure ID ABUSE PATIENTS; RESPONSES; URINE AB Sixty-nine cocaine-dependent outpatients were exposed to cocaine-related stimuli and to nondrug events on separate days. Cocaine cue sessions were always followed by a meeting with a trained clinician designed to eliminate any craving that remained following cue presentations. Urine samples were collected before each laboratory session and 1 to 3 days later. Neither rates of cocaine use nor average urine metabolite values differed following the two sessions. Nearly 90% of subjects had the same urine test result both before and after the cocaine cue session. Thus, laboratory presentation of cocaine cues to outpatient subjects did not increase their risk of subsequent drug-faking. These results suggest that with proper clinical protections, cue exposure Can be used as a treatment outcome measure and a behavioral intervention in outpatient settings without increasing the risk of drug use. (C) 1998 Elsevier Science Inc. C1 Univ Penn, Dept Psychiat, Treatment Res Ctr, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Beaver Coll, Dept Psychol, Glenside, PA USA. RP Ehrman, RN (reprint author), Univ Penn, Dept Psychiat, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [P50-DA09252-02, DA03008] NR 15 TC 16 Z9 17 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD SEP-OCT PY 1998 VL 15 IS 5 BP 431 EP 435 DI 10.1016/S0740-5472(97)00290-0 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 116AU UT WOS:000075699800005 PM 9751000 ER PT J AU Menaker, GM Moy, RL Lamb, P AF Menaker, GM Moy, RL Lamb, P TI Surgical pearl: Dermal advancement flaps for filling deep dorsal nasal defects under grafts SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article C1 Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Moy, RL (reprint author), 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. NR 2 TC 8 Z9 8 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 SEP PY 1998 VL 39 IS 3 BP 478 EP 480 PG 3 WC Dermatology SC Dermatology GA 117HA UT WOS:000075774800015 PM 9738784 ER PT J AU Duke, D Urioste, SS Dover, JS Anderson, RR AF Duke, D Urioste, SS Dover, JS Anderson, RR TI A reaction to a red lip cosmetic tattoo SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CARBON-DIOXIDE LASER; Q-SWITCHED RUBY; DOSE-RESPONSE; PIGMENT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. Eastern Connecticut Dermatol PC, Groton, CT 06340 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Duke, D (reprint author), Eastern Connecticut Dermatol PC, 491 Goldstar Highway,Suite 310, Groton, CT 06340 USA. NR 29 TC 30 Z9 30 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 SEP PY 1998 VL 39 IS 3 BP 488 EP 490 DI 10.1016/S0190-9622(98)70330-5 PG 3 WC Dermatology SC Dermatology GA 117HA UT WOS:000075774800018 PM 9738787 ER PT J AU Hunt, MK Stoddard, AM Peterson, K Sorensen, G Hebert, JR Cohen, N AF Hunt, MK Stoddard, AM Peterson, K Sorensen, G Hebert, JR Cohen, N TI Comparison of dietary assessment measures in the Treatwell 5 A Day worksite study SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID PATTERNS; VALIDITY; HEALTH; FRUIT; FAT C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. Univ Massachusetts, Dept Nutr, Amherst, MA 01003 USA. Harvard Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Univ Massachusetts, Med Ctr, Div Prevent & Behav Med, Worcester, MA 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 15 TC 24 Z9 24 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 1998 VL 98 IS 9 BP 1021 EP 1023 DI 10.1016/S0002-8223(98)00233-8 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 116ZX UT WOS:000075756200015 PM 9739803 ER PT J AU Chiodo, LK Royall, DR Jaramillo, CJ Polk, MJ AF Chiodo, LK Royall, DR Jaramillo, CJ Polk, MJ TI Olfactory function and cognition in independent elders. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 MA P217 BP S71 EP S71 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400283 ER PT J AU Guerrero, ET Perell, K Fang, MA AF Guerrero, ET Perell, K Fang, MA TI Comparison of kinematic gait parameters in knee osteoarthritis on disease severity, pain and quality of life SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 MA P123 BP S47 EP S47 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400189 ER PT J AU Steele, B Holt, L Belza, B Buchner, D AF Steele, B Holt, L Belza, B Buchner, D TI Objective measurement of physical activity in the chronically ill elderly SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Univ Washington, Sch Med, Seattle, WA 98108 USA. Univ Washington, Sch Nursing, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1998 VL 46 IS 9 MA P306 BP S93 EP S93 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 116TR UT WOS:000075741400372 ER PT J AU Curhan, GC Willett, WC Rimm, EB Speizer, FE Stampfer, MJ AF Curhan, GC Willett, WC Rimm, EB Speizer, FE Stampfer, MJ TI Body size and risk of kidney stones SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CALCIUM-OXALATE NEPHROLITHIASIS; FOOD FREQUENCY QUESTIONNAIRE; DIETARY CALCIUM; URIC-ACID; EXCRETION; REPRODUCIBILITY; TRANSPORT; NUTRIENTS; VALIDITY; WEIGHT AB A variety of factors influence the formation of calcium oxalate kidney stones, including gender, diet, and urinary excretion of calcium, oxalate, and uric acid. Several of these factors may be related to body size. Because men on average have a larger body size and a threefold higher lifetime risk of stone formation than women, body size may be an important risk factor for calcium oxalate stone formation. The association between body size (height, weight, and body mass index) and the risk of kidney stone formation was studied in two large cohorts: the Nurses' Health Study (NHS; n = 89,376 women) and the Health Professionals Follow-up Study (HPFS; n = 51,529 men). Information on body size, kidney stone formation, and other exposures of interest was obtained by mailed questionnaires. A total of 1078 incident cases of kidney stones in NHS during 14 yr of follow-up and a total of 956 cases in HPFS during 8 yr of follow-up were confirmed. In both cohorts, the prevalence of a stone disease history and the incidence of stone disease were directly associated with weight and body mass index. However, the magnitude of the associations was consistently greater among women. Specifically, the age-adjusted prevalence odds ratio for women with body mass index greater than or equal to 32 kg/m(2) compared with 21 to 22.9 kg/m(2) was 1.76 (95% confidence interval, 1.50 to 2.07), but 1.38 (95% confidence interval, 1.16 to 1.65) for the same comparison in men. For incident stone formation, the multivariate relative risks for the similar comparisons were 1.89 (1.51 to 2.36) for women and 1.19 (0.83 to 1.70) in men. Height was inversely associated with the prevalence of stone disease but was not associated with incident stone formation. These results suggest that body size is associated with the risk of stone formation and that the magnitude of risk varies by gender. Additional studies are necessary to determine whether a reduction in body weight decreases the risk of stone formation, particularly in women. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Curhan, GC (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA55075]; NHLBI NIH HHS [HL35464]; NIDDK NIH HHS [DK45362] NR 27 TC 135 Z9 138 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1998 VL 9 IS 9 BP 1645 EP 1652 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 112KZ UT WOS:000075495000013 PM 9727373 ER PT J AU Spiess, BD Ley, C Body, SC Siegel, LC Stover, EP Maddi, R D'Ambra, M Jain, U Liu, F Herskowitz, A Mangano, DT Levin, J AF Spiess, BD Ley, C Body, SC Siegel, LC Stover, EP Maddi, R D'Ambra, M Jain, U Liu, F Herskowitz, A Mangano, DT Levin, J CA Inst Multicenter Study Perioperative Ischemia R TI Hematocrit value on intensive care unit entry influences the frequency of Q-wave myocardial infarction after coronary artery bypass grafting SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Cardiovascular-Anesthesiologists CY MAY 07-10, 1995 CL PHILADELPHIA, PA SP Soc Cardiovasc Anesthesiologists ID SURGERY; TRANSFUSION; BLOOD; REVASCULARIZATION; HEMODILUTION; OPERATIONS; MORBIDITY; RISK; HEMODYNAMICS; METABOLISM AB Objectives: No data exist regarding "the best" hematocrit value after coronary artery bypass graft surgery. Transfusion practice varies, because neither an optimal hematocrit value nor a uniform transfusion trigger criterion has been determined. Methods: To investigate the optimal hematocrit value, we studied 2202 patients undergoing coronary bypass. The hematocrit value on entry into the intensive care unit (IHCT) was categorized into three groups: high (greater than or equal to 34%), medium (25% to 33%), and low (less than or equal to 24%). Characteristics and adverse events (outcomes) were compared, and the effect of IHCT on the risk of myocardial infarction was determined by logistic regression. Results: High IHCT (greater than or equal to 34%) was associated with an increased rate of myocardial infarction (8.3% vs 5.5% vs 3.6%; p less than or equal to 0.03, high, medium vs low) and with more severe left ventricular dysfunction (11.7% vs 7.4% and 5.7%; p = 0.006, high, medium vs low). Mortality rate increased with higher IHCT when all the high-risk subgroups were combined (8.6% vs 4.5% vs 3.2%; p < 0.001, high, medium vs low). By multivariate analysis, IHCT remained the most significant predictor of adverse outcomes (relative risk high vs low 2.22, 95% confidence interval: 1.04 to 4.76). No characteristic, event, medication, or transfusion therapy confounded the relationship between IHCT and outcome. Conclusion: High IHCT is associated with a higher rate of myocardial infarction and is an independent predictor of infarction, On the basis of the risk of myocardial infarction, there is no rationale for transfusion to an arbitrary level after coronary artery by-pass grafting. C1 Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Ischemia Res & Educ Fdn, San Francisco, CA USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Dept Anesthesiol, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. Vet Adm Med Ctr, Dept Anesthesiol, San Francisco, CA 94121 USA. Vet Adm Med Ctr, Dept Lab Med, San Francisco, CA 94121 USA. RP Spiess, BD (reprint author), Univ Washington, Dept Anesthesiol, Box 35640, Seattle, WA 98195 USA. OI Siegel, Lawrence/0000-0002-8456-7551 NR 30 TC 117 Z9 121 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD SEP PY 1998 VL 116 IS 3 BP 460 EP 467 DI 10.1016/S0022-5223(98)70012-1 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 115MA UT WOS:000075667700012 PM 9731788 ER PT J AU Boeve, TJ Reed, GL de Oliveira, NC Titus, J Janssens, S Giugliano, RP Torchiana, D Daggett, W Schwarz, R Jang, IK AF Boeve, TJ Reed, GL de Oliveira, NC Titus, J Janssens, S Giugliano, RP Torchiana, D Daggett, W Schwarz, R Jang, IK TI Comparison of argatroban and hirudin for the reperfusion of thrombotic arterial occlusion by tissue plasminogen activator SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE plasminogen activator; reperfusion; thrombin inhibitor ID ACUTE MYOCARDIAL-INFARCTION; RECOMBINANT HIRUDIN; ADJUNCTIVE THERAPY; HEPARIN; THROMBOLYSIS; INHIBITION; PATENCY; TRIAL; FIBRINOPEPTIDE; STREPTOKINASE AB Despite theoretical advantages of direct thrombin inhibitors, recent clinical studies failed to show the superiority of hirudin over heparin in patients with acute coronary syndromes. However, these inhibitors have important in vitro differences for the inhibition of clot-bound thrombin that may translate into different in vivo relative efficacy. The effects of two direct thrombin inhibitors, argatroban and hirudin, on the reperfusion of thrombotic arterial occlusion by t-PA were compared. In anesthetized rabbits thrombotic occlusion was induced in the femoral artery t-PA, aspirin, and various doses of argatroban (1.25, 2.5, and 5.0 mg/kg/h) or hirudin (2.5 and 5.0 mg/kg/h) were administered (six animals in each group). Blood flow was measured for 4 hours, Animals treated with 2.5 mg argatroban more rapidly achieved full reperfusion than those treated with high-dose argatroban or hirudin (P < 0.05). At the doses that induced comparable prolongation of bleeding time, argatroban showed a significantly faster and higher level of reperfusion than hirudin. In animals treated with hirudin, there was a positive correlation between the aPTT and the mean reperfusion blood flow (r = 0.70, P < 0.05). In animals treated with argatroban, this correlation did not exist and the high-dose argatroban was paradoxically less effective in promoting thrombolysis despite greater anticoagulation effects. In this animal model of arterial thrombosis, argatroban was more effective than hirudin in inducing rapid, full reperfusion with t-PA. Although they are both direct thrombin inhibitors, these two agents showed important dose-related differences in efficacy and anticoagulant effects. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. EM jang.ik@mgh.har-vard.edu NR 27 TC 6 Z9 7 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD SEP PY 1998 VL 6 IS 2 BP 103 EP 108 DI 10.1023/A:1008889202725 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 138GX UT WOS:000076964700004 ER PT J AU Encke, J Putlitz, JZ Heintges, T Wands, JR AF Encke, J Putlitz, JZ Heintges, T Wands, JR TI Total chemical synthesis of the 3 ' untranslated region of the hepatitis C virus with long oligodeoxynucleotides SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article; Proceedings Paper CT Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY MAY 19-22, 1996 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Study Liver Dis DE hepatitis C virus; oligodeoxynucleotides; chemical synthesis ID ESCHERICHIA-COLI; GENOME RNA; CDNA CLONE; 3'-TERMINUS; EXPRESSION; GENE; IDENTIFICATION; TRANSMISSION; SEQUENCE AB Hepatitis C Virus (HCV) is the major causative agent of chronic hepatitis. Since it has been difficult to obtain full-length cDNA clones of HCV including the 3' untranslated region (UTR) that give rise to replication competent virus, we generated the 3'UTR by a modified protocol of total chemical synthesis (TCS) with overlap-extension-PCR using four long oligodeoxynucleotides. A synthetic cDNA fragment of about 340 nucleotides (nt) in length was generated, subcloned and sequenced. This approach represents a rapid and easy alternative to RT-PCR from infectious serum and may be a highly valuable method to generate partial cDNA clones of HCV and other viruses including defined variants. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Mol Hepatol Lab, Charlestown, MA 02129 USA. RP Wands, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Mol Hepatol Lab, 149 13th St, Charlestown, MA 02129 USA. FU NIAAA NIH HHS [AA02169]; PHS HHS [35711] NR 16 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD SEP PY 1998 VL 74 IS 1 BP 117 EP 121 DI 10.1016/S0166-0934(98)00077-9 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 120YU UT WOS:000075986100014 PM 9763135 ER PT J AU Farzan, M Choe, H Desjardins, E Sun, Y Kuhn, J Cao, J Archambault, D Kolchinsky, P Koch, M Wyatt, R Sodroski, J AF Farzan, M Choe, H Desjardins, E Sun, Y Kuhn, J Cao, J Archambault, D Kolchinsky, P Koch, M Wyatt, R Sodroski, J TI Stabilization of human immunodeficiency virus type 1 envelope glycoprotein trimers by disulfide bonds introduced into the gp41 glycoprotein ectodomain SO JOURNAL OF VIROLOGY LA English DT Article ID GCN4 LEUCINE-ZIPPER; OLIGOMERIC STRUCTURE; INFLUENZA HEMAGGLUTININ; MONOCLONAL-ANTIBODIES; HIV-1 ENTRY; COILED-COIL; RECEPTOR; GP120; PROTEIN; FUSION AB Biochemical and structural studies of fragments of the ectodomain of the human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane envelope glycoprotein have demonstrated that the molecular contacts between alpha helices allow the formation of a trimeric coiled coil. By introducing cysteine residues into specific locations along these alpha helices, the normally labile HIV-1 gp160 envelope glycoprotein was converted into a stable disulfide-linked oligomer. Although proteolytic cleavage into gp120 and gp41 glycoproteins was largely blocked, the disulfide-linked oligomer was efficiently transported to Be cell surface and was recognized by a series of conformationally dependent antibodies. The pattern of hetero oligomer formation between this construct and an analogous construct lacking portions of the gp120 variable loops and of Be gp41 cytoplasmic tail demonstrates that these oligomers are trimers. These results support the relevance of the proposed gp41 structure and intersubunit contacts to the native, complete HIV-1 envelope glycoprotein. Disulfide-mediated stabilization of the labile HIV-1 envelope glycoprotein oligomer, which has been suggested to possess advantages as an immunogen, may assist attempts to develop vaccines. C1 Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. RP Farzan, M (reprint author), Dana Farber Canc Inst, Div Human Retrovirol, JFB824,44 Binney St, Boston, MA 02115 USA. RI Kuhn, Jens H./B-7615-2011 OI Kuhn, Jens H./0000-0002-7800-6045 FU NCI NIH HHS [P30 CA006516]; NIAID NIH HHS [AI 24755, AI 28691, AI 39420, P30 AI028691, R01 AI039420, R37 AI024755] NR 41 TC 75 Z9 76 U1 0 U2 4 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 SEP PY 1998 VL 72 IS 9 BP 7620 EP 7625 PG 6 WC Virology SC Virology GA 109NK UT WOS:000075328600077 PM 9696864 ER PT J AU Verdolini, K Druker, DG Palmer, PM Samawi, H AF Verdolini, K Druker, DG Palmer, PM Samawi, H TI Laryngeal adduction in resonant voice SO JOURNAL OF VOICE LA English DT Article DE resonant voice; laryngeal adduction; voice therapy; electroglottography; closed quotient ID CONTACT AREA AB The primary question in this study was whether subjects with nodules and subjects with healthy larynges would produce "resonant voice" with a similar laryngeal configuration. A second question regarded whether the electroglottographic closed quotient (EGG CQ) could be used to noninvasively distinguish resonant from other voice types. Twelve adult singers and actors served as subjects, including 6 persons with healthy larynges and 6 persons with nodules. Performers were used as an attempt to maximize token validity and stability. Subjects produced repeated tokens of resonant, pressed, normal, and breathy voice during sustained vowels. Laryngeal adduction was directly estimated using blinded, ordinal, visual-perceptual ratings based on videoscopic views of the larynx. EGG CQs were further calculated based on separate trials. The perceptual ratings indicated that subjects in both groups produced resonant voice with a barely adducted or barely abducted laryngeal configuration that was distinct from configurations for pressed and breathy (but not normal) voice. Previous literature suggests that this configuration may be relevant in many cases of voice therapy (1). Average CQs distinguished resonant from pressed voice, but inconsistently distinguished resonant from breathy voice. Further CQs were reliably different across healthy subjects and subjects with nodules. Thus, the utility of this measure to noninvasively estimate resonant voice may be limited, particularly without ongoing subject-specific calibration procedures. C1 Harvard Univ, Sch Med, Div Otol & Laryngol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. MGH Inst Hlth Profess, Boston, MA USA. Beth Israel Deaconess Med Ctr, Voice Speech Swallowing Div, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Iowa, Dept Speech Pathol & Audiol, Iowa City, IA 52242 USA. Univ Iowa, Dept Prevent Med & Environm Hlth, Div Biostat, Iowa City, IA 52242 USA. Natl Ctr Voice & Speech, Iowa City, IA USA. Univ Utah, Hosp & Clin, Off Informat Resources, Salt Lake City, UT USA. RP Verdolini, K (reprint author), 101 Merrimac St, Boston, MA 02114 USA. RI Palmer, Phyllis/C-5921-2009 FU NIDCD NIH HHS [K08 DC00139, P60 DC00976] NR 15 TC 78 Z9 80 U1 2 U2 8 PU SINGULAR PUBLISHING GROUP INC PI SAN DIEGO PA 401 WEST A ST, STE 325, SAN DIEGO, CA 92101-7904 USA SN 0892-1997 J9 J VOICE JI J. Voice PD SEP PY 1998 VL 12 IS 3 BP 315 EP 327 DI 10.1016/S0892-1997(98)80021-0 PG 13 WC Otorhinolaryngology SC Otorhinolaryngology GA 122RL UT WOS:000076085200005 PM 9763181 ER PT J AU Jette, AM Assmann, SF Rooks, D Harris, BA Crawford, S AF Jette, AM Assmann, SF Rooks, D Harris, BA Crawford, S TI Interrelationships among disablement concepts SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PHYSICAL PERFORMANCE; FUNCTIONAL LIMITATIONS; INSTRUMENTAL ACTIVITIES; MEDICAL CONDITIONS; DISABILITY; STRENGTH; IMPAIRMENTS; MOBILITY; HEALTH; ELDERS AB Background. Understanding interrelationships among disablement concepts is critical to the design of future disability treatment and prevention interventions. Methods. This study uses cross-sectional data to examine the relationships among physiologic impairments, functional limitations, and disability in a moderately disabled sample of 207 community-dwelling older adults. Results. As hypothesized, the data revealed statistically significant curvilinear relationships of upper and lower extremity strength and balance with mobility in this older sample. Multivariate analyses further clarified the hypothesized causal mechanism among the disablement concepts by demonstrating that most of the association of muscle strength and balance with disability was through the intermediary role of mobility limitations. Conclusions. The findings from this study highlight the value of clinical trials that focus on prevention or treatment of mobility limitations as a means of preventing disability; our findings underscore the need for future research that examines the effects of other variables believed to influence disablement in late life. C1 Boston Univ, Sargent Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. New England Res Inst, Watertown, MA 02172 USA. Beth Israel Hosp, Boston, MA 02215 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Jette, AM (reprint author), Boston Univ, Sargent Coll Hlth & Rehabil Sci, 635 Commonwealth Ave, Boston, MA 02215 USA. EM ajette@bu.edu FU NIA NIH HHS [P50 AG11669] NR 38 TC 66 Z9 66 U1 3 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 1998 VL 53 IS 5 BP M395 EP M404 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120JK UT WOS:000075953100021 PM 9754147 ER PT J AU Lichtenstein, MJ Dhanda, R Cornell, JE Escalante, A Hazuda, HP AF Lichtenstein, MJ Dhanda, R Cornell, JE Escalante, A Hazuda, HP TI Disaggregating pain and its effect on physical functional limitations SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID CHRONIC MUSCULOSKELETAL PAIN; DEPRESSIVE SYMPTOMS; JOINT IMPAIRMENT; NUTRITION EXAMINATION; DISABLEMENT PROCESS; MEXICAN-AMERICANS; NATIONAL-HEALTH; OLDER ADULTS; KNEE PAIN; DISABILITY AB Background. Pain is a common impairment that limits the abilities of older persons. The purposes of this article are to: (i) describe the distribution of pain location using the McGill Pain Map (MPM) in a community-based cohort of aged subjects; (ii) investigate whether individual areas of pain could be sensibly grouped into regions of pain; (iii) determine whether intensity, frequency, and location constitute independent dimensions of pain; and (iv) determine whether these three pain dimensions make differential contributions to the presence of self-reported physical functional limitations. Methods, A total of 833 Mexican American;and European American subjects, aged 65-79 years, were enrolled in the San Antonio Longitudinal Study of Aging and were interviewed in their homes between 1992 and 1996. A total of 373 (46%) of the subjects reported having pain in the past week. Physical functional limitations were ascertained using the nine items from the Nagi scale. Three composite scales were created: upper extremity, lower extremity, and total. Pain intensity and frequency were ascertained using the McGill Pain Questionnaire. Pain location was ascertained by using the MPM. Results. Pain was reported in every area of the MPM. Using multiple groups confirmatory factor analysis, the 36 areas were grouped into 7 regions of pain: head, arms, hands and wrists, trunk, back, upper leg, and lower leg. Among persons with pain, pain frequency, intensity, and location were weakly associated with each other. Pain regions were primarily independent of each other, yet weak associations existed between 6 of the 21 pair-wise correlations between regions. Pain regions were differentially associated with individual physical functional limitations. Pain in the upper leg was associated with 8 of the 9 physical tasks. In multivariate analyses, age, gender, and ethnic group accounted for only 2-3% of the variance in physical functional limitations. Pain intensity accounted for 5-6% of the variance in the composite scores of functional limitation. Pain frequency accounted for 4-5% of the variance in upper extremity limitations but did not contribute to the modeling of lower extremity limitations. In contrast, pain location accounted for 9-14% of the variance in physical functional limitations. Conclusions. We tested a method for ascertaining pain location and clearly demonstrated that pain location is an important determinant of sell-reported physical functional limitations. The MPM methodology may be used in population-based studies or in clinical samples that focus on specific impairments and seek to control for pain frequency and intensity. Future studies can link specific diseases with the common impairment of pain and tease out the pathways that lead to other impairments (e.g., weakness), functional limitations, and disability. C1 Univ Texas, Hlth Sci Ctr, Div Geriatr & Gerontol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Div Clin Epidemiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Rheumatol Sect, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Ctr Agr Res & Educ, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Lichtenstein, MJ (reprint author), Univ Texas, Hlth Sci Ctr, Div Geriatr & Gerontol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU AHRQ HHS [1-UO1-HS07397]; NCRR NIH HHS [MO1-RR-01346]; NIA NIH HHS [1-RO1-AG-10444] NR 40 TC 39 Z9 39 U1 2 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 1998 VL 53 IS 5 BP M361 EP M371 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 120JK UT WOS:000075953100016 PM 9754142 ER PT J AU Salusky, IB Kuizon, BD Belin, TR Ramirez, JA Gales, B Segre, GV Goodman, WG AF Salusky, IB Kuizon, BD Belin, TR Ramirez, JA Gales, B Segre, GV Goodman, WG TI Intermittent calcitriol therapy in secondary hyperparathyroidism: A comparison between oral and intraperitoneal administration SO KIDNEY INTERNATIONAL LA English DT Article DE dialyzed children; bone histology; peritoneal dialysis; parathyroid hormone; skeletal lesion; end-stage renal disease; mineral metabolism ID PARATHYROID-HORMONE; INTRAVENOUS CALCITRIOL; RENAL OSTEODYSTROPHY; PERITONEAL-DIALYSIS; PEDIATRIC-PATIENTS; UREMIC PATIENTS; BONE; CHILDREN; CALCIUM; INSUFFICIENCY AB Background. Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat secondary hyperparathyroidism (2 degrees HPT). This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal (i.p.) versus oral doses of calcitriol in children with 2 degrees HPT undergoing peritoneal dialysis (CCPD). Methods. Forty-six patients aged 12.5 +/- 4.8 years on CCPD for 22 +/- 25 months were randomly assigned to treatment with oral (p.o.) or i.p. calcitriol for 12 months; 17 subjects given p.o. calcitriol and 16 subjects given i.p. calcitriol completed the study. Bone biopsies were performed at the beginning and at the end of the study, while determinations of serum and total ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and calcitriol levels were done monthly. Results. Serum total and ionized calcium levels were higher in subjects treated with i.p. calcitriol, P < 0.0001, whereas serum phosphorus levels were higher in those given p.o. calcitriol, P < 0.0001. For the i.p. group, serum PTH levels decreased from pre-treatment values of 648 +/- 325 pg/ml to a nadir of 169 +/- 57 pg/ml after nine months. In contrast, serum PTH levels did not change from baseline values of 670 +/- 97 pg.ml in subjects given p.o. calcitriol, P < 0.0001 by multiple regression analysis. Serum alkaline phosphatase levels were also lower in patients treated with i.p, calcitriol, P < 0.0001, but there was no difference between groups in the average dose of calcitriol given thrice weekly. The skeletal lesions of 2 degrees HPT improved in both groups, 33% of patients developed adynamic bone lesion. Conclusion. Differences in the bioavailability of calcitriol and/or in phosphorus metabolism may account for the divergent biochemical response to p.o. and i.p. calcitriol. C1 Univ Calif Los Angeles, Med Ctr, Sch Med, Dept Pediat,Div Pediat Nephrol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biomath, 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 Salusky, IB (reprint author), Univ Calif Los Angeles, Med Ctr, Sch Med, Dept Pediat,Div Pediat Nephrol, A2-383 MDCC,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM salusky@crc.medsch.ucla.edu FU NCRR NIH HHS [RR-00865]; NIDDK NIH HHS [DK-35423] NR 32 TC 80 Z9 81 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1998 VL 54 IS 3 BP 907 EP 914 DI 10.1046/j.1523-1755.1998.00045.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 113MC UT WOS:000075553900023 PM 9734615 ER PT J AU Piza, J Northrop, C Eavey, RD AF Piza, J Northrop, C Eavey, RD TI Embryonic middle ear mesenchyme disappears by redistribution SO LARYNGOSCOPE LA English DT Article ID OLIGOHYDRAMNIOS AB Objective: The fate of embryonic middle ear mesenchyme from a postgestational infant ear has been speculative. Recently a volume analysis of human neonatal temporal bones demonstrated that embryonic mesenchyme disappeared by redistribution and thinning to surface a growing middle ear space.(1) If this model is accurate, interaction with amniotic fluid and the gestational environment should not influence mesenchymal behavior. Therefore an opossum marsupial model was compared with human data. Methods: The temporal bones of opossum pups (20 to 36 days of age) were sectioned for histologic analysis. Computations were made for the volume of the middle ear air cavity (VAC), volume of the bone cavity (VBC), volume of mesenchyme (VM), and percentage of the middle ear occupied by mesenchyme (%M), which were plotted against height using regression statistics. These data were compared with human neonatal (0 to 30 days of age) temporal bones. Results: In both the opossum and the human the VAC and the VBC increased in parallel with growth of the body. In the opossum the VAC and VBC both grew at 0.148 mm(3)/mm of body length. In humans, both the VAC and VBC grew 6.1 mm(3)/cm of body length. The VM in the opossum remained constant at 0.98 mm(3), regardless of body length. In humans the VM remained constant at 71.7 mm(3), regardless of body length. Therefore the %M proportionately decreased inversely with increasing ear size in both the opossum and the human neonate. Conclusion: This study supports a simple and credible explanation for the illusion of mesenchymal disappearance in the neonatal middle ear. The mesenchymal connective tissue redistributes to cover a larger surface area in a persistently enlarging cavity, These findings occur in different species, whether gestation is completed in an intrauterine or an extrauterine environment. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Hosp Nacl Ninos, Dept Pathol, San Jose, Costa Rica. Univ Costa Rica, San Jose, Costa Rica. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 1998 VL 108 IS 9 BP 1378 EP 1381 DI 10.1097/00005537-199809000-00023 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 116YU UT WOS:000075753300023 PM 9738761 ER PT J AU Graziano, SL Kern, JA Herndon, JE Tatum, A Brisson, ML Memoli, V Sugarbaker, D Skarin, AT Kreisman, H Green, MR AF Graziano, SL Kern, JA Herndon, JE Tatum, A Brisson, ML Memoli, V Sugarbaker, D Skarin, AT Kreisman, H Green, MR TI Analysis of neuroendocrine markers, HER2 and CEA before and after chemotherapy in patients with stage IIIA non-small cell lung cancer: A Cancer and Leukemia Group B study SO LUNG CANCER LA English DT Article DE molecular markers; neuroendocrine; tyrosine kinase activity; leukemia group B ID NEURON-SPECIFIC ENOLASE; GROWTH-FACTOR RECEPTOR; RANDOMIZED TRIAL; ENDOCRINE-CELLS; PULMONARY ADENOCARCINOMA; PROGNOSTIC FACTOR; CHROMOGRANIN-A; TUMORS; CARCINOMA; DIFFERENTIATION AB Several studies have suggested that biochemical or molecular markers examined in non-small cell lung cancer carry prognostic or treatment response information. Non-small cell lung cancer patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of HER2 (c-erbB-2), a membrane-bound receptor with tyrosine kinase activity, has been associated with shortened survival. The Cancer and Leukemia Group B (CALGB) performed a study of patients with stage IIIA (N2 nodes positive) non-small cell lung cancer in which patients received initial chemotherapy followed by surgery, then post-operative therapy consisting of sequential chemotherapy and radiation therapy. Since all patients underwent mediastinoscopy, this provided an opportunity to compare pre- and post-chemotherapy tumor specimens to test the hypothesis that these proteins would predict treatment response. In particular, we hypothesized that the post-chemotherapy specimens would be enriched for NE marker negative cells because of the increased sensitivity of NE positive cells to chemotherapy. We performed immunohistochemical analysis for a panel of NE markers [neuron-specific enolase (NSE), Leu-7, chromogranin A (ChrA), synaptophysin (Syn)], HER2 and CEA to determine if there was an effect of therapy on the percentage of cells expressing these markers. Secondary endpoints were a correlation with chemotherapy response and survival. Slides were scored for intensity (0-4) and percentage of cells positive (0-4). Of 61 eligible patients, there were 38 with both pre- and post-chemotherapy specimens. When both;intensity of staining and percentage of positive cells were considered, post-chemotherapy specimens had a higher percentage of positive NE markers compared with prechemotherapy. In addition, there was no correlation between NE marker, HER2 or CEA expression (prior to or post treatment) and response to chemotherapy or survival. These data do not support the hypothesis that NE positive tumor cells are preferentially killed by chemotherapy in patients with stage IIIA non-small cell lung cancer. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 SUNY Hlth Sci Ctr, Dept Med, Div Hematol Oncol, Syracuse, NY 13210 USA. Vet Affairs Med Ctr, Syracuse, NY 13210 USA. Univ Iowa, Dept Med, Iowa City, IA 52242 USA. Duke Univ, Med Ctr, Dept Community & Family Med, CALGB Stat Off, Durham, NC 27705 USA. SUNY Hlth Sci Ctr, Dept Pathol, Syracuse, NY 13210 USA. Jewish Gen Hosp, Dept Pathol, Montreal, PQ H3T 1E2, Canada. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Dartmouth 03756, NH, Lebanon. Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Jewish Gen Hosp, Dept Med, Montreal, PQ H3T 1E2, Canada. Med Univ S Carolina, Hollings Canc Ctr, Dept Med, Charleston, SC USA. RP Graziano, SL (reprint author), SUNY Hlth Sci Ctr, Dept Med, Div Hematol Oncol, 750 E Adams St, Syracuse, NY 13210 USA. FU NCI NIH HHS [CA21060, CA33601, CA47642] NR 54 TC 29 Z9 31 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 SEP PY 1998 VL 21 IS 3 BP 203 EP 211 DI 10.1016/S0169-5002(98)00063-4 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 142NF UT WOS:000077206000006 PM 9857998 ER PT J AU Szpirer, C Szpirer, J Van Vooren, P Tissir, F Simon, JS Koike, G Jacob, HJ Lander, ES Helou, K Klinga-Levan, K Levan, G AF Szpirer, C Szpirer, J Van Vooren, P Tissir, F Simon, JS Koike, G Jacob, HJ Lander, ES Helou, K Klinga-Levan, K Levan, G TI Gene-based anchoring of the rat genetic linkage and cytogenetic mans: new regional localizations, orientation of the linkage groups, and insights into mammalian chromosome evolution SO MAMMALIAN GENOME LA English DT Review ID SPONTANEOUSLY HYPERTENSIVE RAT; NITRIC-OXIDE SYNTHASE; DEPENDENT DIABETES-MELLITUS; 7 POLYMORPHIC MARKERS; MESSENGER-RNA; RECEPTOR GENE; 6-PHOSPHOFRUCTO-2-KINASE FRUCTOSE-2,6-BISPHOSPHATASE; NUCLEOTIDE-SEQUENCE; TISSUE DISTRIBUTION; MOLECULAR-CLONING AB In order to generate anchor points connecting the rat cytogenetic and genetic maps, the cytogenetic position of 62 rat markers (including 55 genes) already localized genetically was determined by fluorescence in situ hybridization. Whenever possible, markers located near one end of the linkage groups were included. These new localizations allowed us to unambiguously orient the 20 autosomal and the X chromosome linkage groups. The position of the centromere in the linkage map could also be determined in the case of several metacentric chromosomes. In addition, the regional localization of 15 other rat genes was determined. These new data bring useful information with respect to comparative mapping with the mouse and the human and to mammalian evolution. They illustrate, for instance, that groups of genes can remain syntenic during mammalian evolution while being subjected to intrachromosomal rearrangements in some lineages (synteny is conserved while gene order is not:). This analysis also disclosed cases of synteny conservation in one the two rodent species and the human, while the synteny is split in the other rodent species: such configurations are likely examples of lineage-specific interchromosomal rearrangements associated with speciation. C1 Free Univ Brussels, Dept Biol Mol, B-1640 Rhode St Genese, Belgium. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. Univ Goteborg, CMB Genet, S-40530 Gothenburg, Sweden. RP Szpirer, C (reprint author), Free Univ Brussels, Dept Biol Mol, Rue Chevaux 67, B-1640 Rhode St Genese, Belgium. FU NHLBI NIH HHS [5RO1 HL55726, HL08968] NR 133 TC 52 Z9 53 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD SEP PY 1998 VL 9 IS 9 BP 721 EP 734 DI 10.1007/s003359900853 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 115FY UT WOS:000075653900006 PM 9716657 ER PT J AU Mylonakis, E Hohmann, EL Caderwood, SB AF Mylonakis, E Hohmann, EL Caderwood, SB TI Central nervous system infection with Listeria monocytogenes - 33 years' experience at a general hospital and review of 776 episodes from the literature SO MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE BACTERIAL-MENINGITIS; CHRONIC LYMPHOCYTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; PREVIOUSLY HEALTHY-ADULTS; SPINAL-CORD ABSCESS; LOS-ANGELES-COUNTY; TRIMETHOPRIM-SULFAMETHOXAZOLE; BRAIN-ABSCESS; UNITED-STATES C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Caderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM calderwood.stephen@mgh.harvard.edu NR 319 TC 182 Z9 200 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD SEP PY 1998 VL 77 IS 5 BP 313 EP 336 DI 10.1097/00005792-199809000-00002 PG 24 WC Medicine, General & Internal SC General & Internal Medicine GA 124EH UT WOS:000076168100002 PM 9772921 ER PT J AU Dey, B Sykes, M Spitzer, TR AF Dey, B Sykes, M Spitzer, TR TI Outcomes of recipients of both bone marrow and solid organ transplants - A review SO MEDICINE LA English DT Review ID VERSUS-HOST DISEASE; ORTHOTOPIC LIVER-TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; SEVERE APLASTIC-ANEMIA; NON-B-HEPATITIS; POLYMERASE CHAIN-REACTION; COLONY-STIMULATING FACTOR; NON-A; MIXED CHIMERISM; CELL-MIGRATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplantat Unit, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplantat Unit, FND 626, Boston, MA 02114 USA. NR 107 TC 75 Z9 75 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD SEP PY 1998 VL 77 IS 5 BP 355 EP 369 DI 10.1097/00005792-199809000-00005 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 124EH UT WOS:000076168100005 PM 9772924 ER PT J AU Stafford, RS Saglam, D Causino, N Blumenthal, D AF Stafford, RS Saglam, D Causino, N Blumenthal, D TI The declining impact of race and insurance status on hormone replacement therapy SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE hormone replacement therapy; race; insurance status; medical practice variations ID ESTROGEN REPLACEMENT; WOMEN; MENOPAUSE; TRENDS; CARE AB Objective Socioeconomic barriers may limit the adoption of hormone replacement therapy, but little is known about recent trends in their influence. We evaluated trends in the impact of race and insurance status on national rates of hormone replacement therapy. Design: We analyzed 32,608 physician office visits by nonpregnant women 40 years of age and older available from the 1989 through 1996 National Ambulatory Medical Care Surveys. The proportion of visits with new or continuing use of noncontraceptive estrogens reported was the main outcome measured. Multiple logistic regression was used to evaluate the independent. effects of year, race, and expected payment source on hormone replacement therapy. Results: Overall, the report of hormone replacement therapy increased from 5.7% of visits in 1989-1990 to 10.9% in 1995-1996. In 1989-1990, hormone replacement therapy was less likely in nonwhite women (3.6% vs. 6.3% for whites) and in women with Medicaid coverage (1.3% vs. 8.4% for privately insured women). These differences diminished over time, particularly for women without menopausal symptoms. In 1989-1990. the adjusted odds ratio of hormone replacement in women without menopausal symptoms was 0.31 (95% confidence interval 0.2-0.5) in nonwhites compared with whites, but increased to 0.57 (0.4-0.8) 1995-1996. In 1989-1990, the adjusted odds ratio far hormone replacement among women with Medicaid was 0.31 (0.09-1.0) compared with those with private insurance. This ratio increased to 0.86 (0.5-1.4) by 1995-1996. Conclusions: Racial and payment source influences on hormone replacement therapy appeared to have lessened over time. Despite these changes substantial socioeconomic differences in treatment patterns remain to be addressed. ((Menopause 1998,5.140-144. (C) 1998, The North American Menopause Society.) C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hlth Policy Res & Dev Unit, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Stafford, RS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU AHRQ HHS [R01-HS07892]; NHLBI NIH HHS [K08-HL03548] NR 23 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD FAL PY 1998 VL 5 IS 3 BP 140 EP 144 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 120QF UT WOS:000075966600002 PM 9774758 ER PT J AU Milstone, DS Fukumura, D Padgett, RC O'Donnell, PE Davis, VM Benavidez, OJ Monsky, WL Melder, RJ Jain, RK Gimbrone, MA AF Milstone, DS Fukumura, D Padgett, RC O'Donnell, PE Davis, VM Benavidez, OJ Monsky, WL Melder, RJ Jain, RK Gimbrone, MA TI Mice lacking E-selectin show normal numbers of rolling leukocytes but reduced leukocyte stable arrest on cytokine-activated microvascular endothelium SO MICROCIRCULATION-LONDON LA English DT Article DE E-selectin; inflammation; endothelium; leukocyte adhesion; tumor-necrosis factor alpha; intravital microscopy ID TUMOR-NECROSIS-FACTOR; P-SELECTIN; DEFICIENT MICE; ADHESION MOLECULE-1; VASCULAR ENDOTHELIUM; CELL-ADHESION; FACTOR-ALPHA; IN-VIVO; MYELOID CELLS; NEUTROPHILS AB Objective: Previous work indicated that E-selectin mediates transient interactions between leukocytes and cytokine-activated endothelium in vitro. Here we examine the role of E-selectin in blood leukocyte interactions with microvascular endothelium in vivo. Methods: E-selectin-deficient (E-/-) mice were produced by gene targeting. The effect of this null mutation on leukocyte-endothelial interactions was determined by intravital microscopy before and 4 to 5 hours after local administration of the proinflammatory cytokine tumor necrosis factor alpha (TNF alpha) in dermal microvessels with low blood flow (dorsal skin-fold chambers, intact ear skin), and after endotoxin activation in exteriorized mesenteric microvessels ai-ah higher blood flow. Results: E-/- mice were viable, fertile with normal circulating leukocyte and platelet profiles. Approximately 60% of circulating leukocytes rolled in dermal microvessels of both normal (E+/+) and E-/- mice without inflammatory stimulation. After local administration of TNF alpha, rolling increased modestly and equivalently in both genotypes. The main effect of TNF alpha was a dramatic increase in leukocyte stable adhesion and, unlike rolling, this manifestation of endothelial activation was significantly reduced in E-/- animals. This reflected fewer dermal microvessels supporting higher adhesion densities ill E-/- mice, and a similar trend was observed in mesenteric microvessels. Conclusions: E-selectin plays a previously unappreciated role in facilitating and/or mediating stable adhesion of leukocytes to inflamed microvascular endothelium. C1 Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA. Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. RP Milstone, DS (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, LMRC 421,221 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R35-CA-56591]; NHLBI NIH HHS [P0I-HL30628] NR 62 TC 72 Z9 73 U1 1 U2 2 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON SE1 8HN, ENGLAND SN 1073-9688 J9 MICROCIRCULATION-LON JI Microcirculation-London PD SEP PY 1998 VL 5 IS 2-3 BP 153 EP 171 DI 10.1080/713773857 PG 19 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 144HW UT WOS:000077309300010 PM 9789256 ER PT J AU Hartwell, DW Butterfield, CE Frenette, PS Kenyon, BM Hynes, RO Folkman, J Wagner, DD AF Hartwell, DW Butterfield, CE Frenette, PS Kenyon, BM Hynes, RO Folkman, J Wagner, DD TI Angiogenesis in P- and E-selectin-deficient mice SO MICROCIRCULATION-LONDON LA English DT Article DE angiogenesis; selectins; bFGF; TNF alpha ID NECROSIS-FACTOR-ALPHA; DOUBLE MUTANT MICE; ENDOTHELIAL SELECTINS; SUSCEPTIBILITY; RECRUITMENT; DEFECTS; CELLS AB Objectives: Several observations reported earlier indicated that the selectins, in particular E-selectin, might be involved in angiogenesis; however, mice deficient in the endothelial selectins develop normally. To clarify the role of endothelial selectins in angiogenesis, we have studied experimentally induced angiogenesis in selectin-deficient mice. Methods: Hydron pellets containing either basic fibroblast growth factor or the inflammatory cytokine tumor necrosis factor alpha were implanted into the corneas of wild-type and P- and/or E-selectin-deficient mice. Results: The lengths and circumferential range of the newly formed blood vessels in the corneas of the endothelial selectin-deficient mice were similar to those of wild-type mice. Conclusion: The endothelial selectins are not essential in experimentally induced angiogenesis in vivo. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. MIT, Ctr Canc Res, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Frenette, Paul/J-8272-2012 FU NCI NIH HHS [P01-CA 45548]; NHLBI NIH HHS [HL-09264, HL-53756] NR 23 TC 19 Z9 19 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON SE1 8HN, ENGLAND SN 1073-9688 J9 MICROCIRCULATION-LON JI Microcirculation-London PD SEP PY 1998 VL 5 IS 2-3 BP 173 EP 178 DI 10.1038/sj.mn.7300010 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 144HW UT WOS:000077309300011 PM 9789257 ER PT J AU Chang, JH Pratt, JC Sawasdikosol, S Kapeller, R Burakoff, SJ AF Chang, JH Pratt, JC Sawasdikosol, S Kapeller, R Burakoff, SJ TI The small GTP-binding protein rho potentiates AP-1 transcription in T cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; ACTIN STRESS FIBERS; NF-KAPPA-B; KINASE-C; CDC42 GTPASES; SIGNAL-TRANSDUCTION; ACTIVATING PROTEIN; RAS TRANSFORMATION; GENE-EXPRESSION; STIMULATION AB The Rho family of small GTP-binding proteins is invoiced in the regulation of cytoskeletal structure, gene transcription, specific cell fate development, and transformation. We demonstrate in this report that overexpression of an activated form of Rho enhances AP-1 activity in Jurkat T cells in the presence of phorbol myristate acetate (PMA), but activated Rho (V14Rho) has little or no effect on NFAT, Oct-1, and NF-kappa B enhancer element activities under similar conditions. Overexpression of a V14Rho construct incapable of membrane localization (CAAX deleted) abolishes PMA-induced AP-1 transcriptional activation. The effect of Rho on AP-1 is independent of the mitogen-activated protein kinase pathway, as a dominant-negative MEK and a MEK inhibitor (PD98059) did not affect Rho-induced AP-1 activity. V14Rho binds strongly to protein kinase C alpha (PKC alpha) in vivo; however, deletion of the CAAX site on V14Rho severely diminished this association. Evidence for a role for PKC alpha as an effector of Rho was obtained by the observation that coexpression of the N-terminal domain of PKC alpha blocked the effects of activated Rho plus PMA on AP-1 transcriptional activity. These data suggest that Rho potentiates AP-1 transcription during T-cell activation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Burakoff, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM steven_burakoff@dfci.harvard.edu FU NIAID NIH HHS [AI-17258] NR 54 TC 80 Z9 83 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 SEP PY 1998 VL 18 IS 9 BP 4986 EP 4993 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300005 PM 9710582 ER PT J AU Jiang, H Chou, HS Zhu, LA AF Jiang, H Chou, HS Zhu, LA TI Requirement of cyclin E-Cdk2 inhibition in p16(INK4a)-mediated growth suppression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FUNCTIONAL RETINOBLASTOMA PROTEIN; DEPENDENT KINASE INHIBITOR; D-CDK COMPLEXES; CELL-CYCLE; GENE-EXPRESSION; MAMMALIAN-CELLS; G(1); P21; FIBROBLASTS; CANCER AB Loss-of-function mutations of p16(INK4a) have been identified in a large number of human tumors. An established biochemical function of p16 is its ability to specifically inhibit cyclin D-dependent kinases in vitro, and this inhibition is believed to be the cause of the p16-mediated G(1) cell cycle arrest after reintroduction of p16 into p16-deficient tumor cells. However, a mutant of Cdk4, Cdk4(N158), designed to specifically inhibit cyclin D-dependent kinases through dominant negative interference, was unable to arrest the cell cycle of the same cells (S. van den Heuvel and E. Harlow, Science 262:2050-2054, 1993). In this study, we determined functional differences between p16 and Cdk4(N158). We show that p16 and Cdk4(N158) inhibit the kinase activity of cellular cyclin D1 complexes through different mechanisms. p16 dissociated cyclin D1-Cdk4 complexes with the release of bound p27(KIP1), while Cdk4(N158) formed complexes with cyclin D1 and p27. In cells induced to overexpress p16, a higher portion of cellular p27 formed complexes with cyclin E-Cdk2, and Cdk2-associated kinase activities were correspondingly inhibited. Cells engineered to express moderately elevated levels of cyclin E became resistant to p16-mediated growth suppression. These results demonstrate that inhibition of cyclin D-dependent kinase activity may not be sufficient to cause G(1) arrest in actively proliferating tumor cells. Inhibition of cyclin E-dependent kinases is required in p16-mediated growth suppression. C1 Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Zhu, LA (reprint author), Albert Einstein Coll Med, Dept Dev & Mol Biol, 1300 Morris Pk Ave,Room U-519, Bronx, NY 10461 USA. EM lizhu@accom.yu.edu NR 47 TC 97 Z9 100 U1 0 U2 3 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 SEP PY 1998 VL 18 IS 9 BP 5284 EP 5290 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300036 PM 9710613 ER PT J AU Kivens, WJ Hunt, SW Mobley, JL Zell, T Dell, CL Bierer, BE Shimizu, Y AF Kivens, WJ Hunt, SW Mobley, JL Zell, T Dell, CL Bierer, BE Shimizu, Y TI Identification of a proline-rich sequence in the CD2 cytoplasmic domain critical for regulation of integrin-mediated adhesion and activation of phosphoinositide 3-kinase SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID T-CELL ACTIVATION; ERYTHROCYTE BINDING-PROTEIN; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; KINASE-ACTIVITY; TYROSINE PHOSPHORYLATION; LYMPHOCYTES-T; PROTOONCOGENE PRODUCT; ALTERNATIVE PATHWAY; LIGAND INTERACTIONS AB The CD2 molecule is one of several lymphocyte receptors that rapidly initiates signaling events regulating integrin-mediated cell adhesion. CD2 stimulation of resting human T cells results within minutes in an increase in beta 1-integrin-mediated adhesion to fibronectin. We have utilized the HL60 cell line to map critical residues within the CD2 cytoplasmic domain involved in CD2 regulation of integrin function. A panel of CD2 cytoplasmic domain mutants was constructed and analyzed for their ability to upregulate integrin-mediated adhesion to fibronectin. Mutations in the CD2 cytoplasmic domain implicated in CD2-mediated interleukin-2 production or CD2 avidity do not affect CD2 regulation of integrin activity. A proline-rich sequence, K-G-PP-L-P (amino acids 299 to 305), is essential for CD2-mediated regulation of pi integrin activity. CD2-induced increases in beta 1 integrin activity could be blocked by two phosphoinositide 3-kinase (PI 3-K) inhibitors or by overexpression of a dominant negative form of the p85 subunit of PI 3-K. In addition, CD2 cytoplasmic domain mutations that abrogate CD2-induced increases in integrin-mediated adhesion also ablate CD2-induced increases in PI 3-K enzymatic activity. Surprisingly, CD2 cytoplasmic domain mutations that inhibit CD2 regulation of adhesion do not affect the constitutive association of the p85 subunit of PI 3-K association with CD2. Mutation of the proline residues in the K-G-P-P-L-P motif to alanines prevented CD2-mediated activation of integrin function and PI 3-K activity but not mitogen-activated protein (MAP) kinase activity. Furthermore, the MEK inhibitor PD 098059 blocked CD2-mediated activation of MAP kinase but had no effect on CD2-induced adhesion. These studies identify a proline-rich sequence in CD2 critical for PI 3-K-dependent regulation of (beta 1 integrin adhesion by CD2. In addition, these studies suggest that CD2-mediated activation of MAP kinase is not involved in CD2 regulation of integrin adhesion. C1 Univ Minnesota, Sch Med, Ctr Immunol, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Ctr Canc, Minneapolis, MN 55455 USA. Parke Davis Pharmaceut Res, Dept Immunopathol, Ann Arbor, MI 48105 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shimizu, Y (reprint author), Univ Minnesota, Sch Med, Ctr Immunol, Dept Lab Med & Pathol, Box 609 UMHC,420 Delaware St SE, Minneapolis, MN 55455 USA. EM shimi002@tc.umn.edu OI Shimizu, Yoji/0000-0001-9760-0288 FU NIAID NIH HHS [AI38474, R01 AI031126, R01 AI038474, R56 AI038474, AI31126]; NIAMS NIH HHS [F32-AR09438] NR 91 TC 35 Z9 35 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1998 VL 18 IS 9 BP 5291 EP 5307 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 112FW UT WOS:000075484300037 PM 9710614 ER PT J AU Kaldis, P Russo, AA Chou, HS Pavletich, NP Solomon, MJ AF Kaldis, P Russo, AA Chou, HS Pavletich, NP Solomon, MJ TI Human and yeast Cdk-activating kinases (CAKs) display distinct substrate specificities SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CYCLIN-DEPENDENT KINASES; TRANSCRIPTION FACTOR TFIIH; RING FINGER PROTEIN; CELL-CYCLE; CATALYTIC SUBUNIT; INHIBITOR P27(KIP1); CRYSTAL-STRUCTURE; BUDDING YEAST; SACCHAROMYCES-CEREVISIAE; DUAL PHOSPHORYLATION AB Cell cycle progression is controlled by the sequential functions of cyclin-dependent kinases (cdks). Cdk activation requires phosphorylation of a key residue (on sites equivalent to Thr-160 in human cdk2) carried out by the cdk-activating kinase (CAK). Human CAK has been identified as a p40(MO15)/cyclin H/MAT1 complex that also functions as part of transcription factor III-I (TFIIH) where it phosphorylates multiple transcriptional components including the C-terminal domain (CTD) of the large subunit of RNA polymerase II. In contrast, CAK from budding yeast consists of a single polypeptide (Cak1p), is not a component of TFIIH, and lacks CTD kinase activity. Here we report that Cak1p and p40(MO15) have strikingly different substrate specificities. Cak1p preferentially phosphorylated monomeric cdks, whereas p40(MO15) preferentially phosphorylated cdk/cyclin complexes. Furthermore, p40(MO15) only phosphorylated cdk6 bound to cyclin D3, whereas Cak1p recognized monomeric cdk6 and cdk6 bound to cyclin D1, D2, or D3. We also found that cdk inhibitors, including p21(CIPI) p27(KIP1), P57(KIP2), p16(INK4a), and p18(INK4c), could block phosphorylation by p40(MO15) but not phosphorylation by Cak1p. Our results demonstrate that although both Cak1p and p40(MO15) activate cdks by phosphorylating the same residue, the structural mechanisms underlying the enzyme-substrate recognition differ greatly. Structural and physiological implications of these findings will be discussed. C1 Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10021 USA. Massachusetts Gen Hosp, Ctr Canc, Oncol Mol Lab, Charlestown, MA 02129 USA. RP Yale Univ, Sch Med, Dept Mol Biophys & Biochem, 333 Cedar St, New Haven, CT 06520 USA. EM Mark.Solomon@Yale.edu RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU NIGMS NIH HHS [R01 GM047830, GM-47830] NR 79 TC 83 Z9 85 U1 3 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1998 VL 9 IS 9 BP 2545 EP 2560 PG 16 WC Cell Biology SC Cell Biology GA 119AW UT WOS:000075874000015 PM 9725911 ER PT J AU Pan, HC Yin, CY Dyson, NJ Harlow, E Yamasaki, L Van Dyke, T AF Pan, HC Yin, CY Dyson, NJ Harlow, E Yamasaki, L Van Dyke, T TI Key roles for E2F1 in signaling p53-dependent apoptosis and in cell division within developing tumors SO MOLECULAR CELL LA English DT Article ID S-PHASE ENTRY; RETINOBLASTOMA PROTEIN; IN-VIVO; SUPPRESSOR GENES; CYCLE REGULATION; TRANSGENIC MICE; DNA-SYNTHESIS; DEREGULATED EXPRESSION; ECTOPIC EXPRESSION; MOUSE LENS AB Apoptosis induced by the p53 tumor suppressor can attenuate cancer growth in preclinical animal models. Inactivation of the pRb proteins in mouse brain epithelium by the T-121 oncogene induces aberrant proliferation and p53-dependent apoptosis. p53 inactivation causes aggressive tumor growth due to an 85% reduction in apoptosis. Here, we show that E2F1 signals p53-dependent apoptosis since E2F1 deficiency causes an 80% apoptosis reduction. E2F1 acts upstream of p53 since transcriptional activation of p53 target genes is also impaired. Yet, E2F1 deficiency does not accelerate tumor growth. Unlike normal cells, tumor cell proliferation is impaired without E2F1, counterbalancing the effect of apoptosis reduction. These studies may explain the apparent paradox that E2F1 can act as both an oncogene and a tumor suppressor in experimental systems. C1 Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Chung Shan Med & Dent Coll, Dept Life Sci, Taichung 402, Taiwan. Columbia Univ, Dept Biol, New York, NY 10027 USA. RP Van Dyke, T (reprint author), Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA65773, CA46283] NR 56 TC 161 Z9 162 U1 0 U2 2 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 SEP PY 1998 VL 2 IS 3 BP 283 EP 292 DI 10.1016/S1097-2765(00)80273-7 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124NY UT WOS:000076189700001 PM 9774967 ER PT J AU Chen, JJ Silver, DP Walpita, D Cantor, SB Gazdar, AF Tomlinson, G Couch, FJ Weber, BL Ashley, T Livingston, DM Scully, R AF Chen, JJ Silver, DP Walpita, D Cantor, SB Gazdar, AF Tomlinson, G Couch, FJ Weber, BL Ashley, T Livingston, DM Scully, R TI Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells SO MOLECULAR CELL LA English DT Article ID CANCER SUSCEPTIBILITY GENE; EMBRYONIC CELLULAR PROLIFERATION; BREAST-CANCER; STRAND EXCHANGE; RAD51 PROTEIN; DNA-REPAIR; TRANSCRIPTIONAL ACTIVATION; EPITHELIAL-CELLS; MUTATIONS; HETEROZYGOSITY AB BRCA1 and BRCA2 account for most cases of familial, early onset breast and/or ovarian cancer and encode products that each interact with hRAD51. Results presented here show that BRCA1 and BRCA2 coexist in a biochemical complex and colocalize in subnuclear foci in somatic cells and on the axial elements of developing synaptonemal complexes. Like BRCA1 and RAD51, BRCA2 relocates to PCNA(+) replication sites following exposure of S phase cells to hydroxyurea or UV irradiation. Thus, BRCA1 and BRCA2 participate, together, in a pathway(s) associated with the activation of double-strand break repair and/or homologous recombination. Dysfunction of this pathway may be a general phenomenon in the majority of cases of hereditary breast and/or ovarian cancer. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75235 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Scully, Ralph/F-5008-2013 NR 65 TC 426 Z9 432 U1 2 U2 10 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 SEP PY 1998 VL 2 IS 3 BP 317 EP 328 DI 10.1016/S1097-2765(00)80276-2 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124NY UT WOS:000076189700004 PM 9774970 ER PT J AU Parker, D Jhala, US Radhakrishnan, I Yaffe, MB Reyes, C Shulman, AI Cantley, LC Wright, PE Montminy, M AF Parker, D Jhala, US Radhakrishnan, I Yaffe, MB Reyes, C Shulman, AI Cantley, LC Wright, PE Montminy, M TI Analysis of an activator : coactivator complex reveals an essential role for secondary structure in transcriptional activation SO MOLECULAR CELL LA English DT Article ID DEPENDENT PROTEIN-KINASE; CREB-BINDING-PROTEIN; FACTOR-I; CAMP; CBP; PHOSPHORYLATION; INDUCTION; MECHANISM; MULTIPLE; EVENTS AB Ser-133 phosphorylation of CREB within the kinase-inducible domain (KID) promotes target gene activation via complex formation with the KIX domain of the coactivator CBP. Concurrent phosphorylation of CREB at Ser-142 inhibits transcriptional induction via an unknown mechanism. Unstructured in the free state, KID folds into a helical structure upon binding to KIX. Using site-directed mutagenesis based on the NMR structure of the KID:KIX complex, we have examined the mechanisms by which Ser-133 and Ser-142 phosphorylation regulate CREB activity. Our results indicate that phospho-Ser-133 stablizes whereas phospho-Ser-142 disrupts secondary structure-mediated interactions between CREB and CBP. Thus, differential phosphorylation of CREB may form the basis by which upstream signals regulate the specificity of target gene activation. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Surg, Boston, MA 02215 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92038 USA. RP Montminy, M (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Wright, Peter/0000-0002-1368-0223 FU PHS HHS [R01-37828] NR 27 TC 130 Z9 131 U1 1 U2 5 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 SEP PY 1998 VL 2 IS 3 BP 353 EP 359 DI 10.1016/S1097-2765(00)80279-8 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124NY UT WOS:000076189700007 PM 9774973 ER PT J AU Schwartz, PT Vallejo, M AF Schwartz, PT Vallejo, M TI Differential regulation of basal and cyclic adenosine 3 ',5 '-monophosphate-induced somatostatin gene transcription in neural cells by DNA control elements that bind homeodomain proteins SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PANCREATIC-ISLET CELLS; RESTRICTIVE SILENCER ELEMENT; HOMEOBOX-CONTAINING GENE; CAMP RESPONSE ELEMENT; SODIUM-CHANNEL GENE; N-TERMINAL-ARM; ENDOCRINE-CELLS; RECEPTOR GENE; EXPRESSION; RAT AB A number of genes encoding neuropeptides are expressed in the peripheral and central nervous systems, in different endocrine organs, and in specialized cells distributed along the gastrointestinal tract. Whether expression of the same neuropeptide gene in different tissues is regulated by similar transcriptional mechanisms or by mechanisms that differ in a cell-specific manner remains unclear. We report on promoter studies on the regulation of the somatostatin gene in immortalized neural precursor cells derived from developing rat forebrain. Expression of the somatostatin gene in these cells was determined by RT-PCR/Southern blot analysis, by immunocytochemistry, and by RIA. We show that in cerebrocortical and hippocampal cells, expression of the somatostatin gene is regulated by several negative and positive DNA cis-regulatory elements located throughout the promoter region. The somatostatin cAMP-response element appears to play a prominent role in neural somatostatin gene expression by acting as a strong enhancer even in the absence of cAMP stimulation. Site-directed mutagenesis followed by transient transfection assays indicated that SMS-TAAT1,SMS-TAATP, and SMS-UE, three previously identified homeodomain protein-binding regulatory elements that enhance transcription in pancreatic cells, act as repressors of transcription in neural cells. Electrophoretic mobility shifts assays indicate that those elements bind protein complexes that differ between neural and pancreatic cells. Our results support the notion that expression of the somatostatin gene in neural cells ocours via transcriptional mechanisms that are different from those regulating expression of the same gene in pancreatic cells. C1 Harvard Univ, Reprod Endocrine Unit, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vallejo, M (reprint author), Harvard Univ, Reprod Endocrine Unit, Sch Med, Massachusetts Gen Hosp, BHX-516,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-49670] NR 65 TC 8 Z9 8 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1998 VL 12 IS 9 BP 1280 EP 1293 DI 10.1210/me.12.9.1280 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 114GR UT WOS:000075601200002 PM 9731698 ER PT J AU Buggs, C Nasrin, N Mode, A Tollet, P Zhao, HF Gustafsson, JA Alexander-Bridges, M AF Buggs, C Nasrin, N Mode, A Tollet, P Zhao, HF Gustafsson, JA Alexander-Bridges, M TI IRE-ABP (insulin response element-A binding protein), an SRY-like protein, inhibits C/EBP alpha (CCAAT/enhancer-binding protein alpha)-stimulated expression of the sex-specific cytochrome P450 2C12 gene SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE-SECRETION; PHOSPHOENOLPYRUVATE CARBOXYKINASE GTP; RAT-LIVER; TRANSCRIPTION FACTORS; NUCLEAR-PROTEIN; DETERMINING REGION; PROMOTER; HEPATOCYTES; CYP2C12; TRANSACTIVATION AB In primary hepatocytes, overexpression of an insulin response element-a binding protein (IRE-ABP), a member of the SRY family of high-mobility group (HMG) proteins, inhibits CCAAT/enhancer-binding protein alpha (C/EBP alpha)-mediated activation of the female-specific cytochrome P450 2C12 (CYP2C12) gene, but not the male-specific cytochrome P450 2C11 (CYP2C11) gene. IRE-ABP and C/EBP alpha have overlapping specificity for the C/EBP alpha target site in the CYP2C12 promoter and compete for binding to CYP2C12 DNA in vitro. In contrast, IRE-ABP and C/EBP alpha bind distinct sequences in the CYP2C11 promoter. A single amino acid substitution in the HMG domain of IRE-ABP impairs its ability to bind DNA and to inhibit the effect of C/EBP alpha on CYP2C12 gene expression. Therefore, the ability of IRE-ABP to inhibit C/EBP alpha-stimulated CYP2C12 gene expression requires a functional DNA-binding domain. Taken together, our findings suggest that SRY-like proteins can bind to a subset of sequences recognized by the C/EBP family of DNA-binding proteins and modulate gene transcription in a context-specific manner. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Karolinska Inst, Dept Med Nutr, S-14186 Huddinge, Sweden. Natl Res Council Canada, Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada. RP Alexander-Bridges, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Diabet Unit, 50 Blossom St,Wellman 306, Boston, MA 02114 USA. FU NIDDK NIH HHS [F31 DK008719-05, F31-DK-08729] NR 50 TC 14 Z9 14 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1998 VL 12 IS 9 BP 1294 EP 1309 DI 10.1210/me.12.9.1294 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 114GR UT WOS:000075601200003 PM 9731699 ER PT J AU Chaidarun, SS Alexander, JM AF Chaidarun, SS Alexander, JM TI A tumor-specific truncated estrogen receptor splice variant enhances estrogen-stimulated gene expression SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN BREAST-CANCER; EXON-5 DELETION VARIANT; OSTEOSARCOMA CELL-LINE; HORMONE-BINDING DOMAIN; MESSENGER-RNA; WILD-TYPE; TRANSCRIPTIONAL ACTIVITY; ACTIVATION FUNCTION; IDENTIFICATION; YEAST AB This study examines the cooperative effects of a human estrogen receptor-alpha (ER alpha) isoform on estrogen (E-2)-mediated gene activation in U2-OS osteosarcoma cells. Delta 5ER alpha, an alternatively spliced ER alpha variant lacking exon 5, is coexpressed with normal ER alpha in several E-2-responsive neoplastic tissues. However, the potential interactions of Delta 5ER alpha with normal ER alpha have not been functionally characterized. Delta 5ER alpha encodes the hormone-independent trans-activating function (AF-1), as well as the constitutive receptor dimerization and DNA-binding domains. It is generated by an alternate splice event that omits exon 5 and alters the reading frame of the resulting mRNA. The Delta 5ER alpha protein is prematurely truncated and lacks the majority of the hormone-binding and activating function-2 (AF-2) domains. When Delta 5ER alpha mammalian expression vector was transfected alone in human ER alpha/ER beta-negative osteosarcoma U2-OS cells, it had no effect on either basal or E-2-mediated EREtk81Luc reporter transcriptional activity, while transfected cells expressing control normal ER alpha increased EREtk81Luc activity up to 20-fold in response to 10 nM E-2. However, when Delta 5ER alpha was cotransfected with normal ER alpha, both basal and E-2-stimulated EREtk81Luc reporter activation were increased approximately 500% over levels observed when cells were transfected with ER alpha alone. Similar effects of Delta 5ER alpha and normal ER alpha coexpression were observed using an E-2-responsive human C3 promoter/luciferase reporter construct. The effects of Delta 5ER alpha on normal ER alpha were further assessed in U2-OS cells stably transfected with normal ER alpha. Transfection of increasing amounts of Delta 5ER alpha expression vector into [ER alpha+]OS cells resulted in potentiation of E-2-stimulated ERELuc activity in a synergistic, dose-dependent manner. Moreover, coexpression of Delta 5ER alpha in [ER alpha+]OS cells improved E-2 sensitivity 100-fold over cells expressing ER alpha alone. Proliferation rates of stable U2-OS cell lines expressing Delta 5ER alpha were significantly increased (P < 0.05), with cell doubling times reduced from 35 h in control parental U2-OS cells to 28 h in [Delta 5ER alpha]OS cells. However, growth rates were not affected by either E-2 or tamoxifen treatment. Electromobility shift/supershift assays using nuclear extracts of U2-OS cells stably transfected with ER alpha and Delta 5ER alpha confirmed the constitutive binding of Delta 5ER alpha and ER alpha protein to estrogen-response element (ERE) sequence independent of E-2 and also showed an increase in Delta 5ER alpha/ER alpha-ERE complexes with E-2 treatment. These data are consistent with interactive effects of normal ER alpha and Delta 5ER alpha on transcription from classic ERE gene promoters. Delta 5ER alpha appears to therefore act as a dominant positive receptor that increases both basal and E-2-stimulated gene transactivation of normal ER alpha. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Alexander, JM (reprint author), Beth Israel Deaconess Med Ctr, Harvard Inst Med, Div Bone & Mineral Metab, Room 944,330 Brookline Ave, Boston, MA 02215 USA. NR 45 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 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1998 VL 12 IS 9 BP 1355 EP 1366 DI 10.1210/me.12.9.1355 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 114GR UT WOS:000075601200008 PM 9731704 ER PT J AU Martin, KJ Kwan, CP Nagasaki, K Zhang, XH O'Hare, MJ Kaelin, CM Burgeson, RE Pardee, AB Sager, R AF Martin, KJ Kwan, CP Nagasaki, K Zhang, XH O'Hare, MJ Kaelin, CM Burgeson, RE Pardee, AB Sager, R TI Down-regulation of laminin-5 in breast carcinoma cells SO MOLECULAR MEDICINE LA English DT Article ID MAMMARY EPITHELIAL-CELLS; JUNCTIONAL EPIDERMOLYSIS-BULLOSA; DIFFERENTIAL DISPLAY; CHAIN GENE; MYOEPITHELIAL CELLS; GASTRIC-CARCINOMA; ADHESIVE LIGAND; SCATTER FACTOR; GROWTH-FACTORS; CANCER-CELLS AB Background: Laminin-5 (ln-5), a large heterotrimeric glycoprotein consisting of an alpha 3, beta 3, and gamma 2 chain, is a component of epithelial cell basement membranes that functions as a ligand of the alpha 3 beta 1 and alpha 6 beta 4 integrins to regulate cell adhesion, migration, and morphogenesis. The ln-5 chains show tissue-specific patterns of regulation in tumors derived from different tissues. For example, ln-5 is often up-regulated in gliomas, gastric carcinomas, and squamous carcinomas and down-regulated in prostate and basal cell carcinomas. Ln-5 expression patterns may represent useful tumor markers and help to elucidate the role of ln-5 in tumor progression in different tissue types. Materials and Methods: Mie have studied ln-5 expression patterns in the breast. mRNA levels were examined in tumor and normal breast epithelial cell lines, tissue samples, and immunomagnetically sorted primary cultures using differential display, Northern blotting, and hybridization arrays. Protein levels were examined by immunoprecipitation. Gene integrity was assessed by Southern blotting of representative cell types. Results: Ln-5 alpha 3, beta 3, and gamma 2 mRNA expression was found to be markedly down-regulated in a panel of breast tumor cell lines when compared with normal breast epithelial cells. Ln-5 mRNA was expressed at relatively high levels in MCF-10A immortal normal breast epithelial cells, long-term cultures of normal breast cells, and sorted primary cultures of normal breast luminal epithelial and myoepithelial cells. Reduced, but detectable, levels of ln-5 tended to be expressed in cell lines derived from early-stage breast tumors, whereas expression was generally not detected in cell lines derived from later-stage tumors. Zn breast tumor tissue specimens, expression of in alpha 3 and beta 3 mRNAs tended to be reduced relative to levels observed in adjacent nontumor tissue, whereas in gamma 2 levels were elevated in specimens with increased amounts of myoepithelial cells. These ln-5 expression changes could not be attributed to large-scale mutations or gene rearrangements. Ln-5 protein levels were found to reflect mRNA levels in representative cell lines. At senescence, a growth slate believed to suppress tumorigenesis, expression of all three ln-5 mRNAs was up-regulated. Conclusion: The down-regulation of ln-5 mRNA expression in breast tumors cells provides a new molecular marker and suggests that ln-5 functions to control tumor progression in the breast. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. UCL, Sch Med, Dept Surg, LICR UCL Breast Canc Lab, London, England. Brigham & Womens Hosp, Dept Surg, Comprehens Breast Hlth Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Anat & Cellular Biol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Dana Farber Canc Inst, Div Canc Genet, Boston, MA 02115 USA. RP Martin, KJ (reprint author), Dana Farber Canc Inst, Div Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM kmartin@mbcrr.harvard.edu NR 60 TC 61 Z9 62 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD SEP PY 1998 VL 4 IS 9 BP 602 EP 613 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 125FM UT WOS:000076226800003 PM 9848077 ER PT J AU Molineaux, CJ Sluss, PM Bree, MP Gefter, ML Sullivan, LM Garnick, MB AF Molineaux, CJ Sluss, PM Bree, MP Gefter, ML Sullivan, LM Garnick, MB TI Suppression of plasma gonadotropins by abarelix: A potent new LHRH antagonist SO MOLECULAR UROLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; PROSTATE-CANCER; TESTOSTERONE; PITUITARY; ANALOGS; MEN AB Abarelix (PPI-149) is the decapeptide N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-NM-Tyr-Asn-Leu-ILys-Pro-Gly-NH2. This compound is a novel, potent competitive luteinizing hormone-releasing hormone (LHRH) antagonist with a high water solubility and low induction of histamine release, Abarelix administered via continuous infusion induces a rapid decrease in the plasma concentration of testosterone that is maintained throughout the course of administration of the antagonist. The drop in plasma testosterone is accompanied by a corresponding decrease in the plasma levels of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), The LHRH agonists currently used in the treatment of prostate cancer induce a large increase in plasma levels of gonadotropins and gonadal steroids prior to downregulating pituitary gonadotropin secretion. This study compares the initial stimulatory effects of the LHRH agonist leuprolide in rats with the rapid suppression of plasma testosterone, LH, and FSH induced by abarelix. C1 PRAECIS Pharmaceut Inc, Cambridge, MA 02146 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. RP Molineaux, CJ (reprint author), PRAECIS Pharmaceut Inc, 1 Hampshire St,5th Floor, Cambridge, MA 02146 USA. NR 23 TC 17 Z9 17 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1091-5362 J9 MOL UROL JI Mol. Urol. PD FAL PY 1998 VL 2 IS 3 BP 265 EP 268 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 154NV UT WOS:000077895900042 ER PT J AU Child, J Bierer, M Eagle, K AF Child, J Bierer, M Eagle, K TI Unexpected factors predict control of hypertension in a hospital-based homeless clinic SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE hypertension; control; compliance; homeless persons; psychiatric ID POPULATION AB Background: Boston Health Care for the Homeless Program (BHCHP) physicians conduct a primary care clinic twice a week at Massachusetts General Hospital (MGH). The MGH clinic is part of a citywide network of BHCHP clinics providing primary care services to indigent patients. Despite this network long term control of chronic illnesses such as hypertension (HTN) continues to challenge the clinic staff. Methods: In an effort to better understand the factors obstructing long term treatment of chronic illnesses, we conducted a chart review of hypertensive patients seen over a three-year period (January 1991 to March 1994) at the MGH clinic. Frequency of visits, total number of visits and physicians' notes on concomitant diagnoses were analyzed for their correlation to control of hypertension. Results: Overall control of hypertension was poor (42%). A greater proportion of patients with a diagnosis of psychiatric illness responded to treatment intended to lower their blood pressure below 140/90 mm Hg than those without such a diagnosis (odds ratio: 10.2). While there was no difference in the total number of clinic visits during the study period, those with a diagnosis of psychiatric illness had a lower average number of days between their first and third visits (52 days vs 108 p=0.002). Conclusions: A greater proportion of patients with concomitant psychiatric diagnoses exhibited blood pressures less than or equal to 140/90 mm Hg than patients without mental illness. The increased frequency of visits at the onset of treatment may confer a positive effect on long term control of HTN among homeless patients attending outpatient hospital-based clinics. C1 Mt Sinai Sch Med, New York, NY USA. Massachusetts Gen Hosp, Boston Hlth Care Homeless Program, Gen Internal Med Unit, Boston, MA 02114 USA. Univ Michigan, Michigan Heart Care Program, Ann Arbor, MI 48109 USA. RP Child, J (reprint author), 230 Everet St, New Haven, CT 06511 USA. NR 12 TC 6 Z9 6 U1 0 U2 0 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD SEP PY 1998 VL 65 IS 4 BP 304 EP 307 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 116YJ UT WOS:000075752400013 PM 9757754 ER PT J AU Mendez, MF Mirea, A AF Mendez, MF Mirea, A TI Adult head-banging and stereotypic movement disorders SO MOVEMENT DISORDERS LA English DT Article DE stereotypic movement disorder; self-injury; head-banging; naltrexone ID SELF-INJURIOUS-BEHAVIOR; MENTAL-RETARDATION; MUTILATION; DOPAMINE AB Stereotypic movement disorders (SMD) such as head-banging, which are common among children with mental retardation or pervasive developmental disorders, may also occur in intellectually normal adults. We report a 27-year history of daily head-banging with self-injury in a 49-year-old man with normal cognition. The patient had no personal or family history of Tourette's syndrome, tic disorder, obsessive-compulsive disorder (OCD), or mental retardation. The frequency of his stereotypical head-banging increased with anxiety, loud noises with startle, and boredom. He reported a sense of pleasure from his head-banging, and the frequency of this behavior decreased when he was treated with the opioid antagonist naltrexone. Although not diagnostic, the self-stimulatory or pleasurable component of head-banging, body-rocking, thumb-sucking, and other SMD may help distinguish them from ties, Tourette's syndrome, OCD, and deliberate self-harming behavior. This report reviews the disorders associated with SMD and discusses the potential mechanisms for these behaviors. The treatment of SMD includes drugs that work through opioid, serotonergic, or dopaminergic systems. C1 W Los Angeles Vet Affairs Med Ctr, Neurobehav Unit 691 116AF, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. RP Mendez, MF (reprint author), W Los Angeles Vet Affairs Med Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 23 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 1998 VL 13 IS 5 BP 825 EP 828 DI 10.1002/mds.870130512 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 119LX UT WOS:000075898900010 PM 9756153 ER PT J AU Seed, B AF Seed, B TI PPAR gamma and colorectal carcinoma: Conflicts in a nuclear family SO NATURE MEDICINE LA English DT Editorial Material ID ACTIVATED RECEPTOR-GAMMA; DIFFERENTIATION; LIGAND; J(2) AB Two new mouse studies suggest that PPAR gamma agonists may promote tumorigenesis in colon epithelium whereas a third study in humans indicates a possible protective role for these drugs (pages 1046-1061). C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 12 TC 33 Z9 33 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 SEP PY 1998 VL 4 IS 9 BP 1004 EP 1005 DI 10.1038/1990 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 117VV UT WOS:000075804100026 PM 9734386 ER PT J AU Sarraf, P Mueller, E Jones, D King, FJ DeAngelo, DJ Partridge, JB Holden, SA Chen, LB Singer, S Fletcher, C Spiegelman, BM AF Sarraf, P Mueller, E Jones, D King, FJ DeAngelo, DJ Partridge, JB Holden, SA Chen, LB Singer, S Fletcher, C Spiegelman, BM TI Differentiation and reversal of malignant changes in colon cancer through PPAR gamma SO NATURE MEDICINE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ACTIVATED RECEPTOR-GAMMA; LAMININ-BINDING PROTEIN; GENE-EXPRESSION; MESSENGER-RNAS; X-RECEPTOR; CELLS; ALPHA; MICE; ADIPOGENESIS AB PPAR gamma is a nuclear receptor that has a dominant regulatory role in differentiation of cells of the adipose lineage, and has recently been shown to be expressed in the colon. We show here that PPAR gamma is expressed at high levels in both well- and poorly-differentiated adenocarcinomas, in normal colonic mucosa and in human colon cancer cell lines. Ligand activation of this receptor in colon cancer cells causes a considerable reduction in linear and clonogenic growth, increased expression of carcinoembryonic antigen and the reversal of many gene expression events specifically associated with colon cancer. Transplantable tumors derived from human colon cancer cells show a significant reduction of growth when mice are treated with troglitazone, a PPAR gamma ligand. These results indicate that the growth and differentiation of colon cancer cells can be modulated through PPAR gamma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Shionogi BioRes Corp, Lexington, MA 02421 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Jones, Daniel/I-7399-2015 FU NIDDK NIH HHS [R37 DK-31405] NR 31 TC 804 Z9 819 U1 3 U2 15 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 SEP PY 1998 VL 4 IS 9 BP 1046 EP 1052 DI 10.1038/2030 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 117VV UT WOS:000075804100038 PM 9734398 ER PT J AU Soares, MP Lin, Y Anrather, J Csizmadia, E Takigami, K Sato, K Grey, ST Colvin, RB Choi, AM Poss, KD Bach, FH AF Soares, MP Lin, Y Anrather, J Csizmadia, E Takigami, K Sato, K Grey, ST Colvin, RB Choi, AM Poss, KD Bach, FH TI Expression of heme oxygenase-1 can determine cardiac xenograft survival SO NATURE MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL-CELLS; REJECTION; STRESS; ACCOMMODATION; ANTIOXIDANT; RESISTANCE; APOPTOSIS; FERRITIN; PROTEIN AB The rejection of concordant xenografts, such as mouse-to-rat cardiac xenografts, is very similar to the delayed rejection of porcine-to-primate discordant xenografts(1,2-6). In concordant models, this type of rejection is prevented by brief complement inhibition by cobra venom factor (CVF) and sustained T-cell immunosuppression by cyclosporin A (CyA) (refs. 7-10). Mouse hearts that survive indefinitely in rats treated with CVF plus CyA express the anti-inflammatory gene heme oxygenase-l (HO-1) in their endothelial cells and smooth muscle cells(9,11-14). The anti-inflammatory properties of HO-1 are thought to rely on the ability of this enzyme to degrade heme and generate bilirubin, free iron and carbon monoxide(15) Bilirubin is a potent anti-oxidant(13), free iron upregulates the transcription of the cytoprotective gene, ferritin(16), and carbon monoxide is thought to be essential in regulating vascular relaxation in a manner similar to nitric oxide(15). We show here that the expression of the HO-1 gene is functionally associated with xenograft survival, and that rapid expression of HO-1 in cardiac xenografts can be essential to ensure long-term xenograft survival. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Internal Med, Pulm & Crit Care Sect, New Haven, CT 06513 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RP Soares, MP (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr, Boston, MA 02215 USA. RI Grey, Shane/B-3020-2008; OI Grey, Shane/0000-0003-2160-1625; Soares, Miguel/0000-0002-9314-4833 NR 30 TC 502 Z9 528 U1 0 U2 10 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 SEP PY 1998 VL 4 IS 9 BP 1073 EP 1077 DI 10.1038/2063 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 117VV UT WOS:000075804100044 PM 9734404 ER PT J AU Anderson, B Heilman, KM AF Anderson, B Heilman, KM TI Touching and timing consciousness SO NEUROLOGY LA English DT Editorial Material ID LATERALIZATION; SPECIALIZATION; HEMISPHERE; LANGUAGE; SPEECH; PAIN C1 Birmingham VAMC, Serv Neurol, Birmingham, AL 35233 USA. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Gainesville VA Med Ctr, Neurol Serv, Gainesville, FL USA. Univ Florida, Dept Neurol, Gainesville, FL USA. RP Anderson, B (reprint author), Birmingham VAMC, Serv Neurol, 700 S 19th St, Birmingham, AL 35233 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1998 VL 51 IS 3 BP 666 EP 668 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 119LR UT WOS:000075898300006 PM 9748006 ER PT J AU Greenberg, SM AF Greenberg, SM TI Cerebral amyloid angiopathy - Prospects for clinical diagnosis and treatment SO NEUROLOGY LA English DT Review ID ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; BETA-PROTEIN; INTRACEREBRAL HEMORRHAGE; LOBAR HEMORRHAGE; IN-VIVO; TRANSGENIC MICE; SENILE PLAQUES; DUTCH TYPE; MUTATION AB This article reviews diagnosis of cerebral amyloid angiopathy (CAA) during life and possible approaches to prevention. A clinical diagnosis of "probable CAA" can be made in patients aged 60 years or older with multiple hemorrhages confined to lobar brain regions and no other cause of hemorrhage. Gradient-echo MRI facilitates diagnosis by showing previous hemorrhages with high sensitivity. This technique can also mark the progression of CAA, as 50% of studied patients developed new petechial hemorrhages during 1.5 years of follow-up. The apolipoprotein E epsilon 2 and epsilon 4 alleles are associated with increased risk. and earlier age of first hemorrhage, but are neither sensitive nor specific for CAA. The major remaining challenges are to develop new markers for the presence of CAA and treatments to block vascular amyloid deposition and vessel breakdown. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 836, Boston, MA 02114 USA. FU NIA NIH HHS [AG00725] NR 50 TC 154 Z9 160 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1998 VL 51 IS 3 BP 690 EP 694 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 119LR UT WOS:000075898300011 PM 9748011 ER PT J AU Ay, H Furie, KL Yamada, K Koroshetz, WJ AF Ay, H Furie, KL Yamada, K Koroshetz, WJ TI Diffusion-weighted MRI characterizes the ischemic lesion in transient global amnesia SO NEUROLOGY LA English DT Article AB We present a patient with transient global amnesia (TGA) whose diffusion-weighted MRI (DWI) showed increased signal in the splenium of the corpus callosum and in the left parahippocampal gyrus. The absence of high signal on the corresponding apparent diffusion coefficient (ADC) images supports the diagnosis of an acute infarction. This finding provides a temporal relation between cerebral ischemia and infarction in the territory of posterior cerebral artery and in certain cases of TGA. An early means of detecting ischemia in TGA by DWI may influence clinical decisions made in patient evaluation and management. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. RP Furie, KL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke Serv, VBK-802,32 Fruit St, Boston, MA 02114 USA. NR 10 TC 52 Z9 53 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1998 VL 51 IS 3 BP 901 EP 903 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 119LR UT WOS:000075898300056 PM 9748056 ER PT J AU Jackson, GR Salecker, I Dong, XZ Yao, X Arnheim, N Faber, PW MacDonald, ME Zipursky, SL AF Jackson, GR Salecker, I Dong, XZ Yao, X Arnheim, N Faber, PW MacDonald, ME Zipursky, SL TI Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons SO NEURON LA English DT Article ID MACHADO-JOSEPH DISEASE; SPINOCEREBELLAR ATAXIA TYPE-2; PROGRAMMED CELL-DEATH; CAG REPEAT EXPANSION; INTRANUCLEAR INCLUSIONS; NEUROLOGICAL PHENOTYPE; PALLIDOLUYSIAN ATROPHY; TRINUCLEOTIDE REPEAT; EMBRYONIC LETHALITY; GENE HOMOLOG AB Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Disease alleles contain a trinucleotide repeat expansion of variable length, which encodes polyglutamine tracts near the amino terminus of the HD protein, huntingtin. Polyglutamine-expanded huntingtin, but not normal huntingtin, forms nuclear inclusions. We describe a Drosophila model for HD. Amino-terminal fragments of human huntingtin containing tracts of 2, 75, and 120 glutamine residues were expressed in photoreceptor neurons in the compound eye. As in human neurons, polyglutamine-expanded huntingtin induced neuronal degeneration. The age of onset and severity of neuronal degeneration correlated with repeat length, and nuclear localization of huntingtin presaged neuronal degeneration. In contrast to other cell death paradigms in Drosophila, coexpression of the Viral antiapoptotic protein, P35, did not rescue the cell death phenotype induced by polyglutamine-expanded huntingtin. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. Univ So Calif, Sch Med, Program Mol Biol, Los Angeles, CA 90089 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Zipursky, SL (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. FU NINDS NIH HHS [NS16367, NS32765] NR 79 TC 339 Z9 346 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP PY 1998 VL 21 IS 3 BP 633 EP 642 DI 10.1016/S0896-6273(00)80573-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 124RV UT WOS:000076196400019 PM 9768849 ER PT J AU Power, WJ Rodriguez, A Pedroza-Seres, M Foster, CS AF Power, WJ Rodriguez, A Pedroza-Seres, M Foster, CS TI Outcomes in anterior uveitis associated with the HLA-B27 haplotype SO OPHTHALMOLOGY LA English DT Article ID HL-A 27; CLINICAL-FEATURES; CLASSIFICATION; PATTERNS AB Objective: This study aimed to test the hypothesis that patients presenting with anterior uveitis who are HLA-B27 positive, either with or without associated systemic disease, have a less-favorable outcome than do patients with idiopathic anterior uveitis who are HLA-B27 negative. Design: Retrospective case-controlled series. Participants: Ninety-seven patients who were HLA-B27 positive with no systemic disease, 94 patients who were HLA-B27 positive with systemic disease, and 72 patients who were HLA-B27 negative who presented with anterior uveitis were studied. Main Outcome Measures: Ocular complications (e.g., secondary glaucoma, cataract formation, pupillary synechiae, vitritis, cystoid macular edema, and optic disc edema), medical and surgical treatment, number of recurrent attacks, and final visual acuity were recorded for all patients. Results: The patients who were HLA-B27 positive, either with or without systemic disease, experienced a greater number of complications than did the patients who were HLA-B27 negative. Periocular corticosteroids, systemic corticosteroids, and systemic immunosuppressive chemotherapy were required in a far greater number of HLA-B27-positive patients than in HLA-B27-negative patients (60% vs. 11%, 53% vs. 7%, and 18% vs. 1%, respectively; P < 0.001). The percentage of legally blind eyes was significantly greater in the HLA-B27-positive group, both with and without systemic disease, when compared with the HLA-B27-negative group (11% vs. 2%; P < 0.005). Conclusions The prognosis of anterior uveitis associated with the HLA-B27 haplotype, either with or without associated systemic disease, is less favorable when compared with that of HLA-B27-negative patients with idiopathic anterior uveitis. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, Boston, MA USA. RP Power, WJ (reprint author), Royal Victorian Eye & Ear Hosp, Adelaide Rd, Dublin 2, Ireland. OI Rodriguez-Garcia, Alejandro/0000-0002-1419-2109 NR 20 TC 64 Z9 67 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1998 VL 105 IS 9 BP 1646 EP 1651 DI 10.1016/S0161-6420(98)99033-9 PG 6 WC Ophthalmology SC Ophthalmology GA 121NE UT WOS:000076019400034 PM 9754172 ER PT J AU El-Shabrawi, Y Livir-Rallatos, C Christen, W Baltatzis, S Foster, CS AF El-Shabrawi, Y Livir-Rallatos, C Christen, W Baltatzis, S Foster, CS TI High levels of interleukin-12 in the aqueous humor and vitreous of patients with uveitis SO OPHTHALMOLOGY LA English DT Article ID INFLAMMATORY AUTOIMMUNE-DISEASE; IMMUNE-RESPONSES; CD40 LIGAND; T-CELLS; MICE; CYTOKINES; IL-12; PATHOGENESIS; ANTIBODIES; DEVIATION AB Objective: This study aimed to investigate the role of interleukin-12 (IL-12) and interleukin-10 (IL-10) in initiation and maintenance of intraocular inflammation. Design: Case series. Participants: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured in 22 patients with uveitis undergoing cataract surgery, paracentesis of the anterior chamber, and/or vitrectomy for diagnostic reasons, and in 4 patients with cataract only. Intervention: Aqueous humor and vitreous levels of IL-12 and IL-10 were measured with specific enzyme-linked immunosorbent assays. Main Outcome Measures: Disease activity was correlated to IL-12 levels in the aqueous humor and the vitreous of patients with uveitis. Results: Cytokine levels found in the anterior chamber and the vitreous are presented in picogram/milliliter (medium; range). The highest IL-12 levels were found in patients with active uveitis (108.5 pg/ml; 72-293 pg/ml). Interleukin-12 in patients with moderate uveitis or with their disease in remission was lower (32 pg/ml; 15-94 pg/ml) than in patients with active disease (P > 0.001) but higher than in the control group (10.5 pg/ml; 9-14 pg/ml). Interleukin-10 was detectable in only 3 of 22 patients with uveitis (12 pg/ml; 9-23 pg/ml). Conclusion: The authors found statistically significant differences of IL-12 levels in the various patient groups (active vs, inactive vs. control), These results support the idea that these uveitis cases represent type 1 (Th1)-T lymphocyte-mediated diseases in which IL-12 plays a pivotal role in the initiation and maintenance of the intraocular inflammation. The high levels of IL-12 in the vitreous and/or aqueous humor of the patients with uveitis suggest that susceptibility or resistance to ocular autoimmunity may be connected to a genetic predisposition to an elevated Th1 response. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Uveitis & Immunol Serv, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Uveitis & Immunol Serv, Boston, MA 02114 USA. NR 24 TC 37 Z9 37 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1998 VL 105 IS 9 BP 1659 EP 1663 DI 10.1016/S0161-6420(98)99035-2 PG 5 WC Ophthalmology SC Ophthalmology GA 121NE UT WOS:000076019400036 PM 9754174 ER PT J AU Rubash, HE AF Rubash, HE TI Osteolysis: Dealing with the consequences SO ORTHOPEDICS LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Rubash, HE (reprint author), Massachusetts Gen Hosp, Gray Bldg,Rm 624,55 Fruit St, Boston, MA 02115 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD SEP PY 1998 VL 21 IS 9 BP 949 EP 950 PG 2 WC Orthopedics SC Orthopedics GA 124HU UT WOS:000076177000005 PM 9769033 ER PT J AU Harris, WH AF Harris, WH TI Reconstruction at a high hip center in acetabular revision surgery using a cementless acetabular component SO ORTHOPEDICS LA English DT Article C1 Massachusetts Gen Hosp, Orthoped Biomech Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthoped Biomech Lab, GR J 1126, Boston, MA 02114 USA. NR 0 TC 24 Z9 27 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD SEP PY 1998 VL 21 IS 9 BP 991 EP 992 PG 2 WC Orthopedics SC Orthopedics GA 124HU UT WOS:000076177000015 PM 9769043 ER PT J AU Fraenkel, L Zhang, YQ Trippel, SB McAlindon, TE LaValley, MP Assif, A Adams, KE Evans, SR Felson, DT AF Fraenkel, L Zhang, YQ Trippel, SB McAlindon, TE LaValley, MP Assif, A Adams, KE Evans, SR Felson, DT TI Longitudinal analysis of the relationship between serum insulin-like growth factor-I and radiographic knee osteoarthritis SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE IGF-I; osteoarthritis; knee; radiograph ID CARTILAGE; PROTEOGLYCAN; CYTOKINES AB Objective: To examine the relation between serum insulin-like growth factor I (IGF-I) levels and both incident and progressive radiographic knee osteoarthritis (OA) in the Framingham Osteoarthritis Study. Design: Subjects had bilateral weight-bearing, anterior-posterior knee radiographs performed in 1983-1985 and again in 1992-1993. IGF-I levels were measured from blood specimens obtained in 1988-1989 by a competitive binding radio-immunoassay (RIA) after separation with octadecasilyl-silica cartridges of serum IGF-I from binding proteins. Participants without baseline radiographic OA [Kellgren and Lawrence grades (K&L)= 0-1] were classified as having incident disease if they had K&L greater than or equal to 2 grades at follow-up. Progressive OA was defined as an increase in K&L score of greater than or equal to 1 in knees with baseline OA (K&L greater than or equal to 2). All analyses were knee-based and sex-specific. We examined IGF-I tertiles in relation to the risk of incident and progressive radiographic OA separately, adjusting. for age, body mass index (BMI), and baseline K&L score, and used generalized estimating equations to adjust for the correlation between fellow knees. Results: Four hundred and forty-one participants had knee radiographs and serum IGF-I levels measured. No associations were found for serum IGF-I levels and incident [women: OR = 0.9 (0.6-1.7), men OR = 1.2 (0.6-2.6)] or progressive [women OR = 0.9 (0.6-1.6) men OR = 0.9 (0.3-3.0)] radiographic knee OA in either sex. Neither did we observe any association between IGF-I and worsening of individual radiographic features of OA (i.e., osteophyte growth and joint space loss). Conclusion: In summary, this longitudinal study did not demonstrate arty association of serum IGF-I and incident or progressive radiographic knee OA. Further studies are needed to clarify the role of IGF-I in OA. C1 Boston Univ, Ctr Arthritis, Med Ctr, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Heart Lung & Blood Inst Heart Study, Framingham, MA USA. RP Fraenkel, L (reprint author), Boston Univ, Ctr Arthritis, Med Ctr, 715 Albany St,A203, Boston, MA 02118 USA. FU NIA NIH HHS [AG09300]; NIAMS NIH HHS [AR20613, AR31068] NR 21 TC 9 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 1998 VL 6 IS 5 BP 362 EP 367 DI 10.1053/joca.1998.0135 PG 6 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 114WV UT WOS:000075632900008 PM 10197171 ER PT J AU Campo, S AF Campo, S TI Paediatric patients: SIDS, safety and positioning SO PAEDIATRIC ANAESTHESIA LA English DT Editorial Material ID INFANT-DEATH-SYNDROME; SLEEPING POSITION; SUDDEN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Campo, S (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1155-5645 J9 PAEDIATR ANAESTH JI Paediatr. Anaesth. PD SEP PY 1998 VL 8 IS 5 BP 371 EP 372 DI 10.1046/j.1460-9592.1998.00273.x PG 2 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 114JF UT WOS:000075604800001 PM 9742530 ER PT J AU Woolf, CJ Bennett, GJ Doherty, M Dubner, R Kidd, B Koltzenburg, M Lipton, R Loeser, JD Payne, R Torebjork, E AF Woolf, CJ Bennett, GJ Doherty, M Dubner, R Kidd, B Koltzenburg, M Lipton, R Loeser, JD Payne, R Torebjork, E TI Towards a mechanism-based classification of pain? SO PAIN LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4903, Charlestown, MA 02129 USA. RI Koltzenburg, Martin/C-1349-2008 OI Koltzenburg, Martin/0000-0001-9181-5966 NR 0 TC 302 Z9 303 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 1998 VL 77 IS 3 BP 227 EP 229 PG 3 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 130UZ UT WOS:000076539900001 PM 9808347 ER PT J AU Kuhlthau, K Perrin, JM Ettner, SL McLaughlin, TJ Gortmaker, SL AF Kuhlthau, K Perrin, JM Ettner, SL McLaughlin, TJ Gortmaker, SL TI High-expenditure children with supplemental security income SO PEDIATRICS LA English DT Article DE children; chronic illness; expenditures; high expenditure; Medicaid; Supplemental Security Income ID CARE AB Objective. To examine the clinical characteristics and health service use of children with high Medicaid expenditures. Methodology. We examined 1992 Medicaid claims and eligibility files from four states (California, Georgia, Michigan, Tennessee) for children with at least $10 000 billed to Medicaid who obtained Medicaid through the Supplemental Security Income (SSI) Program and a comparison group (matched by age group and gender) of children receiving Medicaid for other reasons. We compared mean expenditures, examined expenses by category, and examined diagnoses associated with at least $10 000 in expenses. Results. In 1992, Medicaid paid on average similar to$1000 for children with non-SSI Medicaid enrollment. Expenditures for children with SSI were 2.9 to 9.4 times higher, but once the similar to 10% of children with high expenditures were excluded, SSI average expenditures were only 1.5 to 2.7 times higher than the non-SSI average. Children with high expenditures are likely to use hospitals and longterm care, and these services account for more than half of the average expenditures. Children with high expenditures and SSI are more likely to have chronic medical conditions than are their peers enrolled in Medicaid but not through SSI. Conclusions. A small proportion of children, even on SSI, account for very large proportions of Medicaid expenditures. Most children with SSI, despite having relatively severe mental health, physical, or developmental disabilities, have relatively modest Medicaid expenditures. C1 Massachusetts Gen Hosp, WACC, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. RP Kuhlthau, K (reprint author), Massachusetts Gen Hosp, WACC, 715 Fruit St, Boston, MA 02114 USA. FU PHS HHS [MCJ-250634] NR 18 TC 30 Z9 30 U1 0 U2 3 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 SEP PY 1998 VL 102 IS 3 BP 610 EP 615 DI 10.1542/peds.102.3.610 PG 6 WC Pediatrics SC Pediatrics GA 117EB UT WOS:000075766800024 PM 9738184 ER PT J AU Walker, WA AF Walker, WA TI Subspecialist's view of training and pediatric practice in the next millennium SO PEDIATRICS LA English DT Editorial Material ID ACADEMIC MEDICAL-CENTERS; US PHYSICIAN WORKFORCE; BIOMEDICAL-RESEARCH; CLINICAL RESEARCH; SHATTUCK-LECTURE; MANAGED CARE; WORK-FORCE; HEALTH; DIVERTICULITIS; INVESTIGATOR C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. RP Walker, WA (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. NR 32 TC 9 Z9 9 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 SEP PY 1998 VL 102 IS 3 BP 636 EP 644 DI 10.1542/peds.102.3.636 PG 9 WC Pediatrics SC Pediatrics GA 117EB UT WOS:000075766800028 PM 9738188 ER PT J AU Ferris, TG Crain, EF Oken, E Woodruff, PG Camargo, CA AF Ferris, TG Crain, EF Oken, E Woodruff, PG Camargo, CA TI A prospective multicenter study of primary care provider status among children presenting to the emergency department with acute asthma. SO PEDIATRICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Jacobi Hosp, Dept Pediat, Bronx, NY USA. Jacobi Hosp, Dept Emergency Med, Bronx, NY USA. NR 0 TC 0 Z9 0 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 SEP PY 1998 VL 102 IS 3 SU 1 BP 717 EP 717 PG 1 WC Pediatrics SC Pediatrics GA 117YM UT WOS:000075810500104 ER PT J AU Islam, S Masiakos, PT Schnitzer, JJ Doody, DP Ryan, DP AF Islam, S Masiakos, PT Schnitzer, JJ Doody, DP Ryan, DP TI Diltiazem reduces pulmonary arterial pressures in recurrent pulmonary hypertension SO PEDIATRICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 SEP PY 1998 VL 102 IS 3 SU 1 BP 791 EP 791 PG 1 WC Pediatrics SC Pediatrics GA 117YM UT WOS:000075810500273 ER PT J AU Goldstein, AM Chen, JN Van Praagh, R Ticho, BS Fishman, MC AF Goldstein, AM Chen, JN Van Praagh, R Ticho, BS Fishman, MC TI Disorders of left-right development: Causes and consequences. SO PEDIATRICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 SEP PY 1998 VL 102 IS 3 SU 1 BP 804 EP 804 PG 1 WC Pediatrics SC Pediatrics GA 117YM UT WOS:000075810500311 ER PT J AU Banerjee, S Raghavan, S Wasserman, EJ Linder, BL Saenger, P DiMartino-Nardi, J AF Banerjee, S Raghavan, S Wasserman, EJ Linder, BL Saenger, P DiMartino-Nardi, J TI Hormonal findings in African-American and Caribbean Hispanic girls with premature adrenarche: Implications for polycystic ovarian syndrome SO PEDIATRICS LA English DT Article DE premature adrenarche; 17 hydroxypregnenolene; polycystic ovarian disease; African-American; Caribbean Hispanic ID DEPENDENT DIABETES-MELLITUS; INSULIN ACTION; PUBARCHE; WOMEN; HIRSUTISM; ADRENOCORTICOTROPIN; HYPERANDROGENISM; STEROIDOGENESIS; POPULATION; DEFICIENCY AB Background. Premature adrenarche refers to the early maturation of the adrenal zona reticularis such that the resultant modest hyperandrogenism causes the early appearance of pubic hair before the age of 8 years in girls and 9 years in boys. The precise etiology of premature adrenarche is not known. However, recent studies indicate that certain girls with premature adrenarche are at risk of developing functional ovarian hyperandrogenism, polycystic ovarian syndrome, and hyperinsulinism. Caribbean Hispanic women in general are at increased risk of developing polycystic ovarian syndrome, and African-Americans are at increased risk of developing the complications of hyperinsulinism. Previously, girls with premature adrenarche were reported to have androgens in the range found in normal children in the early stages of puberty. We noted that many of our African-American and Caribbean Hispanic patients with premature adrenarche had androgens that were much higher than what has been reported previously. Objective. This retrospective study was performed to characterize the adrenocorticotropin-stimulated androgen response in an African-American and Caribbean Hispanic population of girls with premature adrenarche. Methodology. The androgen response to adrenocorticotropin stimulation in 72 African-American and Caribbean Hispanic girls with premature adrenarche was compared with those reported for normal girls in early puberty (Tanner stages II and III). The mean age was 6.8 +/- 0.8 years, bone age was 8 +/- 1.5 years, pubic hair was Tanner stages II and III, and body mass index was 18.6 +/- 4. Results. Of the girls, 28% were found to have elevated stimulated 17OHPregnenolone (17OHPreg) levels that were >2 SD units above the mean for normal early pubertal children. The stimulated ratio of 17OHPreg/17OHProgesterone also was elevated in 18% of the girls and showed a modest correlation with body mass index. Conclusion. In contrast to previous studies of girls of mixed ethnic backgrounds with premature adrenarche, 28% of the 72 African-American and Caribbean Hispanic girls with premature adrenarche had adrenocorticotropin-stimulated 17OHPreg levels that were significantly higher than those seen in early pubertal girls. Because 17OHPreg hyperresponsiveness has been described previously in women with hirsutism or polycystic ovarian syndrome, the similar finding in many African-American and Caribbean Hispanic girls with premature adrenarche suggests that the two conditions may share a common mechanism for their hyperandrogenism. Therefore, the hyperandrogenism in certain African-American and Caribbean Hispanic girls with premature adrenarche may not be benign and may be the first presentation of polycystic ovarian syndrome. C1 Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Div Pediat Endocrinol, Bronx, NY 10467 USA. Floyd Mem Hosp, Joslin Diabet Ctr, New Albany, IN USA. RP DiMartino-Nardi, J (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, Div Pediat Endocrinol, 111 E 210th St, Bronx, NY 10467 USA. NR 29 TC 17 Z9 18 U1 1 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1998 VL 102 IS 3 AR e36 DI 10.1542/peds.102.3.e36 PG 4 WC Pediatrics SC Pediatrics GA 117EB UT WOS:000075766800013 PM 9724684 ER PT J AU Wolden-Hanson, T Gidal, BE Atkinson, RL AF Wolden-Hanson, T Gidal, BE Atkinson, RL TI Evaluation of a rat model of valproate-induced obesity SO PHARMACOTHERAPY LA English DT Article ID ACID HEPATIC FATALITIES; BETA-OXIDATION; WEIGHT-GAIN; FOOD-INTAKE; ENERGY-BALANCE; METABOLISM; GLUCOSE; INHIBITION; EPILEPSY; INVITRO AB Long-term treatment with the anticonvulsant valproate (VPA) leads to well-documented weight gain and obesity in humans. In an attempt to develop an animal model of this condition, adult rats were given VPA 20 g/kg (high-dose) or 2 g/kg (low-dose) in their daily feeding or orally 120 mg/kg body weight/day in two divided doses, and food intake and body weight were assessed. Valproate resulted in lower body weights in all protocols. Food intake was lower (p<0.001) for rats receiving high-dose VPA than for controls. Feed efficiency (change in weight divided by cumulative food intake for that period) was lower than that of controls for both high (p<0.0001) and low doses (NS). Metabolic rate and physical activity were not different between control and VPA animals, although decreased food intake would be expected to decrease metabolic rate. Valproate failed to produce obesity in rats in any treatment period. For reasons that are unclear, rats do not appear to be suitable as a model to study this adverse side effect of VPA in humans with epilepsy. C1 Univ Wisconsin, Beers Murphy Clin Nutr Ctr, Madison, WI 53706 USA. Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA. RP Wolden-Hanson, T (reprint author), VA Puget Sound Hlth Care Syst, GRECC 182B, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 23 TC 9 Z9 9 U1 0 U2 1 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 SEP-OCT PY 1998 VL 18 IS 5 BP 1075 EP 1081 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 122JH UT WOS:000076068100015 PM 9758318 ER PT J AU Aveline, BM Redmond, RW AF Aveline, BM Redmond, RW TI Exclusive free radical mechanisms of cellular photosensitization SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; LIPID-PEROXIDATION; HYDROXYL RADICALS; PHOTOPHYSICAL PROPERTIES; AQUEOUS-SOLUTION; RATE CONSTANTS; OXYGEN; PHOTOCHEMISTRY; N-HYDROXYPYRIDINE-2(1H)-THIONE; APOPTOSIS AB In order to determine the specific effects of radical-induced reactions in the absence of complicating excited-state pathways, four different thiohydroxamic esters and their parent molecule, N-hydroxypyridine-2(1H)-thione, have been studied in murine L1210 leukemia cells for their ability to produce photobiological damage. Irradiation (lambda(exc) = 355 mm) of cells in the presence of thiopyridone esters, specific photolytic precursors of sulfur-, carbon- and oxygen-centered radicals, caused toxicity that was unambiguously demonstrated to result from radical photosensitization mechanisms, Cellular morphological changes were observed following irradiation but apoptosis was not found to take place. A good correlation was evident between lipid peroxidation, measured by the thiobarbituric acid method, and phototoxicity, assessed by the trypan blue exclusion assay, indicating that the ester derivatives exert their effects mainly in plasma and/or subcellular membranes. Irradiation performed under deaerated conditions also induced significant phototoxicity but the effects of deaeration were dependent on the ester used and are discussed in terms of the nature of the primary radical species generated in each case. Irradiation of L1210 cells in the presence of N-hydroxypyridine-2(1H)-thione, a nonspecific, photochemical source of hydroxyl radical, was also found to trigger phototoxicity and Lipid peroxidation. However in this case, photodamage cannot yet be definitely attributed to a radical or type II mechanism although the apparent oxygen independence of phototoxicity would indicate that type II contribution is not significant. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, W-224, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA68524 A] NR 44 TC 15 Z9 15 U1 0 U2 3 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 SEP PY 1998 VL 68 IS 3 BP 266 EP 275 DI 10.1111/j.1751-1097.1998.tb09680.x PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 120YY UT WOS:000075986500009 PM 9747582 ER PT J AU Lilge, L Molpus, K Hasan, T Wilson, BC AF Lilge, L Molpus, K Hasan, T Wilson, BC TI Light dosimetry for intraperitoneal photodynamic therapy in a murine xenograft model of human epithelial ovarian carcinoma SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID OPTICAL-PROPERTIES; PHASE-I; TUMOR; PHOTOIMMUNOTHERAPY; TISSUES; ASCITES; CELLS; MICE AB Few studies have been published to date measuring spatially resolved fluence rates in complex tissue geometries. Here the light distributions of three different intraperitoneal light delivery geometries in a murine ovarian cancer model were investigated to assess their influence on the tumorcidal efficacy of photodynamic therapy (PDT). IIE vivo fluence rate measurements in the peritoneal cavities of mice, with the light intensity being mapped in three transverse planes, were performed using fiber-optic detectors. Three different source fiber designs and placements were tested for their ability to pro,ide uniform irradiation of the peritoneal cavity, The biological response to a PDT protocol comprising three separate treatments administered at 72 h intervals, each consisting of a 0.25 mg kg(-1) intraperitoneal injection of benzoporphyrin derivative-mono acid ring A followed 90 min later by delivery of 15 J of 690 nm light, was measured. The tissue response was evaluated by measuring the number of remaining visible lesions and the total residual tumor mass. Fluence rate measurements showed large variations in the fluence rate distribution for similar intended treatments. The most uniform and reproducible illumination was achieved using two 18 mm long cylindrical emitting optical fibers. The biological response was comparable to that produced when a flat-cleaved end optical fiber is used to illuminate the four quadrants of the abdomen sequentially. While a good reproducibility in tumor induction in this animal model exists, no correlation was found between the flueuce rate distribution measured in one group of animals and the biological response in a separate group of similarly treated animals. Due to the large intra-animal variability in fluence rate distribution, representative flueuce rate mapping in complex tissue geometries is of limited value when applied to an individual PDT treatment. Thus, surveillance of the fluence rate during individual treatments will be required for acceptable PDT dosimetry, To improve the versatility of this particular animal model for PDT research, a large number of extended sources are required to increase uniformity of the illumination in order to reduce unwanted cytotoxic side effects resulting from foci of high fluence rates. In this way, subsequent increase of the total energy delivered to the tumor may be possible. C1 Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada. Photon Res Ontario, Toronto, ON, Canada. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA USA. RP Lilge, L (reprint author), Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Princess Margaret Hosp, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. RI Lilge, lothar/J-6434-2013 FU NIAMS NIH HHS [R01-AR40352] NR 28 TC 24 Z9 24 U1 1 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 SEP PY 1998 VL 68 IS 3 BP 281 EP 288 DI 10.1111/j.1751-1097.1998.tb09682.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 120YY UT WOS:000075986500011 PM 9747583 ER PT J AU Sage, DR Chillemi, AC Fingeroth, JD AF Sage, DR Chillemi, AC Fingeroth, JD TI A versatile prokaryotic cloning vector with six dual restriction enzyme sites in the polylinker facilitates efficient subcloning into vectors with unique cloning sites SO PLASMID LA English DT Article DE multifunctional vector; dual restriction enzyme sites; complex vectors; virus ID EPSTEIN-BARR VIRUS; COLI LAC REPRESSOR; MAMMALIAN-CELLS; GENE-EXPRESSION; DNA-SEQUENCE; CLONES; MAP; TETRACYCLINE; CONSTRUCTION; CHROMOSOME AB In large and complex vectors a single restriction enzyme recognition site may be available for introduction of additional DNA requiring the development of linker fragments to create compatible insertion sites. This technology can he time consuming and costly. We describe the construction of a simple phagemid, pSFI, with a polylinker that contains six pairs of dual, rare-cutting, restriction enzyme recognition sites (NotI, SpeI, EcoRV, PstI, SacII. EagI) with multiple unique sites between each pair. This has permitted rapid subcloning of DNA with creation of single flanking restriction enzyme sites. pSFI was used to expedite transfer of viral genes to a LacZ-inducible expression vector and to an adenovirus expression cassette for production of replication-defective virus. The use of this phagemid has facilitated complex vector manipulations and is a valuable adjunct to the family of multifunctional cloning vectors. (C) 1998 Academic Press. C1 Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fingeroth, JD (reprint author), Dana Farber Canc Inst, Div Infect Dis, 44 Binney St, Boston, MA 02115 USA. FU NIDCR NIH HHS [R01 DE12186] NR 21 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0147-619X J9 PLASMID JI Plasmid PD SEP PY 1998 VL 40 IS 2 BP 164 EP 168 DI 10.1006/plas.1998.1357 PG 5 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 123WD UT WOS:000076147800008 PM 9735318 ER PT J AU Pousti, TJ Upton, J Loh, M Grier, H AF Pousti, TJ Upton, J Loh, M Grier, H TI Congenital fibrosarcoma of the upper extremity SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID INFANTILE FIBROSARCOMA; FIBRO-SARCOMA; CHEMOTHERAPY C1 Childrens Hosp, Dept Surg, Boston, MA USA. Childrens Hosp, Dept Pediat, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Hosp, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Beth Israel Hosp, Dept Surg, Cambridge, MA 02138 USA. RP Upton, J (reprint author), 830 Boylston St, Chestnut Hill, MA 02167 USA. NR 21 TC 21 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP PY 1998 VL 102 IS 4 BP 1158 EP 1162 DI 10.1097/00006534-199809040-00037 PG 5 WC Surgery SC Surgery GA 116ET UT WOS:000075711300037 PM 9734437 ER PT J AU Lanza, H Eavey, R AF Lanza, H Eavey, R TI Jack Davis, MD, 1918-1997 SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Biographical-Item C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP PY 1998 VL 102 IS 4 BP 1306 EP 1306 DI 10.1097/00006534-199809040-00077 PG 1 WC Surgery SC Surgery GA 116ET UT WOS:000075711300074 ER PT J AU Schulman, BA Lindstrom, DL Harlow, E AF Schulman, BA Lindstrom, DL Harlow, E TI Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN CELL-CYCLE; S-PHASE; RETINOBLASTOMA PROTEIN; DNA-REPLICATION; CDC2 KINASE; SACCHAROMYCES-CEREVISIAE; NUCLEAR-LOCALIZATION; CRYSTAL-STRUCTURE; CDK COMPLEXES; E2F AB An important question in the cell cycle field is how cyclin-dependent kinases (cdks) target their substrates. We have studied the role of a conserved hydrophobic patch on the surface of cyclin A in substrate recognition by cyclin A-cdk2. This hydrophobic patch is approximate to 35 Angstrom away from the active site of cdk2 and contains the MRAIL sequence conserved among a number of mammalian cyclins. In the x-ray structure of cyclin A-cdk2-p27, this hydrophobic patch contacts the RNLFG sequence in p27 that is common to a number of substrates and inhibitors of mammalian cdks. We find that mutation of this hydrophobic patch on cyclin A eliminates binding to proteins containing RXL motifs without affecting binding to cdk2. This docking site is critical for cyclin A-cdk2 phosphorylation of substrates containing RXL motifs, but not for phosphorylation of histone I-Il. Impaired substrate binding by the cyclin is the cause of the defect in RXL substrate phosphorylation, because phosphorylation can be rescued by restoring a cyclin A-substrate interaction in a heterologous manner. In addition, the conserved hydrophobic patch is important for cyclin A function in cells, contributing to cyclin A's ability to drive cells out of the Gr phase of the cell cycle. Thus, we define a mechanism by which cyclins can recruit substrates to cdks, and our results support the notion that a high local concentration of substrate provided by a protein-protein interaction distant from the active site is critical for phosphorylation by cdks. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. RP Schulman, BA (reprint author), Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, 1275 York Ave,Box 576, New York, NY 10021 USA. NR 64 TC 251 Z9 257 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10453 EP 10458 DI 10.1073/pnas.95.18.10453 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500022 PM 9724724 ER PT J AU Berrueta, L Kraeft, SK Tirnauer, JS Schuyler, SC Chen, LB Hill, DE Pellman, D Bierer, BE AF Berrueta, L Kraeft, SK Tirnauer, JS Schuyler, SC Chen, LB Hill, DE Pellman, D Bierer, BE TI The adenomatous polyposis coli-binding protein EB1 is associated with cytoplasmic and spindle microtubules SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DETYROSINATED TUBULIN; MITOTIC SPINDLE; YEAST; MOTORS AB The evolutionarily conserved protein EB1 originally was identified by its physical association with the carboxyl-terminal portion of the adenomatous polyposis coli (APC) tumor suppressor protein, an APC domain commonly mutated in familial and sporadic forms of colorectal neoplasia, The subcellular localization of EB1 in epithelial cells was studied by using immunofluorescence and biochemical techniques. EB1 colocalized both to cytoplasmic microtubules in interphase cells and to spindle microtubules during mitosis, with pronounced centrosome staining. The cytoskeletal array detected by anti-EB1 antibody was abolished by incubation of the cells with nocodazole, an agent that disrupts microtubules; upon drug removal, EB1 localized to the microtubule-organizing center. Immunofluorescence analysis of SW480, a colon cancer cell line that expresses only carboxyl-terminal-deleted APC unable to interact with EB1, demonstrated that EB1 remained localized to the microtubule cytoskeleton, suggesting that this pattern of subcellular distribution is not mediated by its interaction with APC, rn vitro cosedimentation with taxol-stabilized microtubules demonstrated that a significant fraction of EB1 associated with microtubules, Recent studies of the yeast EB1 homologues Mal3 and Bim1p have demonstrated that both proteins localize to microtubules and are important in vivo for microtubule function. Our results demonstrate that EB1 is a novel component of the microtubule cytoskeleton in mammalian cells. Associating with the mitotic apparatus, EB1 may play a physiologic role connecting APC to cellular division, coordinating the control of normal growth and differentiation processes in the colonic epithelium. C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Los Andes, Inst Clin Immunol, Merida 5101, Venezuela. Oncogene Res Prod, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP NHLBI, Bldg 10,Room 5D49,10 Ctr Dr, Bethesda, MD 20892 USA. EM biererb@nih.gov RI Hill, David/B-6617-2011; OI Berrueta, Lisbeth/0000-0002-5674-6448 NR 16 TC 141 Z9 142 U1 1 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10596 EP 10601 DI 10.1073/pnas.95.18.10596 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500047 PM 9724749 ER PT J AU Jain, RK Safabakhsh, N Sckell, A Chen, Y Jiang, P Benjamin, L Yuan, F Keshet, E AF Jain, RK Safabakhsh, N Sckell, A Chen, Y Jiang, P Benjamin, L Yuan, F Keshet, E TI Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: Role of vascular endothelial growth factor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE vascular regression; permeability; vascular density ID REGRESSION; ARCHITECTURE; LETHALITY; VESSELS AB The sequence of events that leads to tumor vessel regression and the functional characteristics of these vessels during hormone-ablation therapy are not known. This is because of the lack of an appropriate animal model and monitoring technology. By using in vivo microscopy and in situ molecular analysis of the androgen-dependent Shionogi carcinoma grown in severe combined immunodeficient mice, we show that castration of these mice leads to tumor regression and a concomitant decrease in vascular endothelial growth factor (VEGF) expression, Androgen withdrawal is known to induce apoptosis in Shionogi tumor cells. Surprisingly, tumor endothelial cells begin to undergo apoptosis before neoplastic cells, and rarefaction of tumor vessels precedes the decrease in tumor size. The regressing vessels begin to exhibit normal phenotype, i.e., lower diameter, tortuosity, vascular permeability, and leukocyte adhesion. Two weeks after castration, a second wave of angiogenesis and tumor growth begins with a concomitant increase in VEGF expression. Because human tumors often relapse following hormone-ablation therapy, our data suggest that these patients may benefit from combined anti-VEGF therapy. C1 Harvard Univ, Sch Med, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biol Mol, IL-91120 Jerusalem, Israel. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. RI Yuan, Fan/A-1287-2011; OI Sckell, Axel/0000-0002-9992-0784 FU NCI NIH HHS [R35-CA56591] NR 25 TC 263 Z9 269 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 1998 VL 95 IS 18 BP 10820 EP 10825 DI 10.1073/pnas.95.18.10820 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116NB UT WOS:000075730500086 PM 9724788 ER PT J AU Barsky, AJ Ahern, DK Brener, J Surman, OS Ring, C Dec, GW AF Barsky, AJ Ahern, DK Brener, J Surman, OS Ring, C Dec, GW TI Palpitations and cardiac awareness after heart transplantation SO PSYCHOSOMATIC MEDICINE LA English DT Article DE heart disease; heart transplantation; palpitations; heartbeat detection ID MEDICAL OUTPATIENTS; SOMATOSENSORY AMPLIFICATION; CONSTANT STIMULI; DEPRESSION SCALE; FOLLOW-UP; ARRHYTHMIAS; HYPOCHONDRIASIS; PERCEPTION; SYMPTOMS; REINNERVATION AB Objective: The aim of this study was to examine the awareness of resting heartbeat in heart transplantation recipients, compare it with that found in other medical populations, and determine whether clinical characteristics are associated with accurate heartbeat awareness. Methods: Eligible patients underwent a research battery consisting of a heartbeat detection task and self-report questionnaires assessing cardiac symptoms, psychosocial variables, and cognitive function. The accurate awareness of resting heartbeat was determined by presenting the patients with auditory stimuli at each of six different delays following the R wave on the EGG. Patients then selected the tones that they thought coincided with the sensation they had of their heart beating. The patients' physicians rated their cardiac morbidity. The results were contrasted with comparable data obtained in previous work with other ambulatory medical populations. Results: Forty-one consecutive heart transplantation recipients who survived for at least 3 months after surgery were eligible. Thirty-four (82.9%) of them were studied and complete data were obtained on 26 (63.4%). Nine patients (34.6%) were reliably able to detect their resting heartbeat. When compared with the 17 patients who were not accurately aware of their heartbeat, the two groups did not differ significantly in cardiac morbidity, cognitive brain dysfunction, generalized psychiatric distress, depression, somatization, or hypochondriacal attitudes. A significantly higher proportion of heart transplantation recipients were accurately aware of their heartbeat than was found in a sample of general medical outpatients and in asymptomatic, nonpatient volunteers. Conclusions: One-third of heart transplant recipients are accurately aware of resting heartbeat, despite the absence of cardiac innervation. C1 Brigham & Womens Hosp, Div Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat Serv, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med Serv, Cardiac Unit, Boston, MA 02114 USA. SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. Univ Birmingham, Sch Sport & Exercise Sci, Birmingham, W Midlands, England. RP Barsky, AJ (reprint author), Brigham & Womens Hosp, Div Psychiat, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL43216] NR 53 TC 18 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP-OCT PY 1998 VL 60 IS 5 BP 557 EP 562 PG 6 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 123ER UT WOS:000076113300005 PM 9773758 ER PT J AU Hamner, MB AF Hamner, MB TI Recurrent psychotic depression associated with GM2 gangliosidosis SO PSYCHOSOMATICS LA English DT Article ID HEXOSAMINIDASE-A DEFICIENCY; DEGENERATION; DISEASE C1 Ralph H Johnson VA Med Ctr, Psychiat Serv 116A, Charleston, SC 29401 USA. RP Hamner, MB (reprint author), Ralph H Johnson VA Med Ctr, Psychiat Serv 116A, 109 Bee St, Charleston, SC 29401 USA. NR 9 TC 3 Z9 5 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 1998 VL 39 IS 5 BP 446 EP 448 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 121ZZ UT WOS:000076047100007 PM 9775702 ER PT J AU Mendez, MF AF Mendez, MF TI Postictal violence and epilepsy SO PSYCHOSOMATICS LA English DT Article ID AGGRESSION; SEIZURES C1 W Los Angeles Vet Affairs Med Ctr, Neurobehav Unit 691116AF, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol & Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), W Los Angeles Vet Affairs Med Ctr, Neurobehav Unit 691116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 20 TC 9 Z9 9 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 1998 VL 39 IS 5 BP 478 EP 480 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 121ZZ UT WOS:000076047100015 PM 9775710 ER PT J AU Siqueland, L Chittams, J Frank, A Thase, ME Gastfriend, DR Mercer, D Muenz, L Crits-Christoph, P Blaine, J AF Siqueland, L Chittams, J Frank, A Thase, ME Gastfriend, DR Mercer, D Muenz, L Crits-Christoph, P Blaine, J TI The protocol deviation patient: Characterization and implications for clinical trials research SO PSYCHOTHERAPY RESEARCH LA English DT Article ID ADDICTION SEVERITY INDEX; COGNITIVE THERAPY; COCAINE ABUSERS; DEPRESSION; PHARMACOTHERAPY; PREDICTORS; ALCOHOL AB This paper addresses those patients who neither complete treatment nor drop out from clinical trials but who deviate from the protocol treatment by seeking or receiving additional treatment. Psychotherapy researchers may be missing important information by withdrawing these: patients from analyses or combining them with dropouts from treatment. In a multisite psychotherapy outcome study for patients with cocaine dependence, patients who deviated from protocol could be distinguished from completers and dropouts on pretreatment patient characteristics. Patients who deviated from protocol were more likely to be African American, to have higher psychiatric severity, and to have had more previous drug treatment attempts. Data indicate that there is a value in obtaining follow-up assessment after the protocol deviation and including these patients in data analysis to avoid bias in findings. Differential outcome for protocol deviation patients compared to dropouts and completers is discussed. C1 Univ Penn, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Brookside Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. Natl Inst Drug Abuse, Treatment Res Branch, Rockville, MD 20857 USA. RP Siqueland, L (reprint author), Room 705,3600 Market St, Philadelphia, PA USA. NR 31 TC 1 Z9 1 U1 1 U2 2 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1050-3307 J9 PSYCHOTHER RES JI Psychother. Res. PD FAL PY 1998 VL 8 IS 3 BP 287 EP 306 PG 20 WC Psychology, Clinical SC Psychology GA 120CM UT WOS:000075937100004 ER PT J AU Oliver, LC Shackleton, BW AF Oliver, LC Shackleton, BW TI The indoor air we breathe SO PUBLIC HEALTH REPORTS LA English DT Article ID SICK BUILDING SYNDROME; OFFICE WORKERS; SYMPTOMS; DISEASE AB INCREASINGLY RECOGNIZED as a potential public health problem since the outbreak of Legionnaire's disease in Philadelphia in 1976, polluted indoor air has been associated with health problems that include asthma, sick building syndrome, multiple chemical sensitivity, and hypersensitivity pneumonitis. Symptoms are often nonspecific and include headache, eye and throat irritation, chest tightness and shortness of breath, and fatigue. Airborne contaminants include commonly used chemicals, vehicular exhaust, microbial organisms, fibrous glass particles, and dust. Identified causes include defective building design and construction, aging of buildings and their ventilation systems, poor climate control, inattention to building maintenance. A major contributory factor is the explosion in the use of chemicals in building construction and furnishing materials over the past four decades. Organizational issues and psychological variables often contribute to the problem and hinder its resolution. This article describes the health problems related to poor indoor air quality and offers solutions. C1 Occupat Hlth Initiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Oliver, LC (reprint author), Occupat Hlth Initiat, 98 N Washington St,Suite 207, Boston, MA 02114 USA. NR 23 TC 17 Z9 17 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 1998 VL 113 IS 5 BP 398 EP 409 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 161RV UT WOS:000078303600014 PM 9769764 ER PT J AU Boiselle, PM Patz, EF Vining, DJ Weissleder, R Shepard, JO McLoud, TC AF Boiselle, PM Patz, EF Vining, DJ Weissleder, R Shepard, JO McLoud, TC TI Imaging of mediastinal lymph nodes: CT, MR, and FDG PET SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the Radiological-Society-of-North-America CY NOV 30-DEC 05, 1997 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE lung neoplasms, metastases; lung neoplasms, staging; lymphatic system, neoplasms; mediastinum, neoplasms ID CELL LUNG-CANCER; BRONCHOGENIC-CARCINOMA AB The evaluation of mediastinal lymph nodes is an important aspect of staging in patients with non-small cell lung cancer. Anatomic imaging of lymph nodes with computed tomography (CT) and magnetic resonance (MR) imaging has been limited by the relatively low sensitivity and specificity of these techniques. Advances in physiologic imaging of mediastinal lymph nodes with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) have resulted in improved diagnostic accuracy in the determination of nodal status, Despite the limitations of CT, this technique still plays an important role by aiding in the selection of the most appropriate procedure for staging, by guiding biopsy, and by providing anatomic information for visual correlation with FDG PET images, At present, anatomic MR imaging of lymph nodes is primarily a problem-solving tool for cases with inconclusive CT results, Physiologic MR imaging with iron oxide is an exciting area of investigation, and the accuracy of this technique is being assessed in clinical trials. Anatomic and physiologic imaging techniques should be considered complementary rather than competitive imaging strategies. C1 Temple Univ Hosp, Dept Diagnost Imaging, Philadelphia, PA 19140 USA. Wake Forest Univ, Sch Med, Dept Radiol, Winston Salem, NC 27109 USA. Duke Univ Hosp, Dept Radiol, Durham, NC USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Boiselle, PM (reprint author), Temple Univ Hosp, Dept Diagnost Imaging, 3401 N Broad St, Philadelphia, PA 19140 USA. NR 17 TC 64 Z9 64 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 1998 VL 18 IS 5 BP 1061 EP 1069 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 117BJ UT WOS:000075759800003 PM 9747607 ER PT J AU Curtin, HD Chavali, R AF Curtin, HD Chavali, R TI Imaging of the skull base SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PERINEURAL TUMOR EXTENSION; TEMPORAL BONE; CHONDROID CHORDOMA; MR; CT; DIAGNOSIS; FORAMEN; FOSSA; NECK AB Skull-base imaging has been a key factor in the advancement of skull-base surgery. The analysis of MR imaging or CT of the skull base emphasizes important landmarks, which are key to surgical planning. Although the definitive diagnosis usually is done by biopsy, the radiologist can limit the list of possibilities of the identity of a skull base lesion. The apparent site of origin is a key factor. Separation of cystic abnormalities from more solid enhancing abnormalities also is critical. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neuroradiol, Boston, MA 02115 USA. RP Curtin, HD (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. NR 28 TC 19 Z9 19 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 1998 VL 36 IS 5 BP 801 EP + DI 10.1016/S0033-8389(05)70065-8 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 120UN UT WOS:000075975900004 PM 9747190 ER PT J AU Stone, ME AF Stone, ME TI Completely queer: The gay and lesbian encyclopedia. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Ref Serv, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Ref Serv, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD FAL PY 1998 VL 38 IS 1 BP 90 EP 90 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 160WY UT WOS:000078255800021 ER PT J AU Metlay, JP Atlas, SJ Borowsky, LH Singer, DE AF Metlay, JP Atlas, SJ Borowsky, LH Singer, DE TI Time course of symptom resolution in patients with community-acquired pneumonia SO RESPIRATORY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02, 1998 CL WASHINGTON, D.C. SP Soc Gen Internal Med ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND AB The majority of patients with community-acquired pneumonia are at low risk for short-term mortality or serious morbidity and are increasingly managed in the outpatient setting. Efforts to improve the quality of care for these patients will need to measure patient outcomes such as disease-specific symptom resolution. The aims of this study were to (1) develop a self-administered daily version of a symptom questionnaire for patients with pneumonia, (2) measure the reliability of this instrument, and (3) provide estimates for recovery rates based on symptom resolution in a cohort of low-risk patients with community-acquired pneumonia. This study was conducted as part of a prospective study of a new emergency department protocol for pneumonia at the Massachusetts General Hospital. Eligible study subjects included all adult patients with pneumonia presenting to the emergency department with a predicted low risk of short-term mortality. The main outcome measures were based on a new five item symptom questionnaire which rates the severity of cough, fatigue, dyspnea, myalgia, and fever. The questionnaires were self-administered on days 0-7, 14, 21 and 28 from the time of diagnosis of pneumonia. The symptom questions were also administered during patient interviews on days 0, 7, 14 and 28 in order to assess the questionnaire's reliability. Of the 166 eligible patients, 134 (81%) consented to participate in this study. The mean intra-class reliability coefficient of the symptom questionnaire was 0.75. The median times to resolution of individual symptoms ranged from 3 days for fever to 14 days for cough and fatigue. Thirty-five percent of patients had at least one symptom still present at the end of the 28-day study period. We found that a daily self-report questionnaire is a reliable measure of symptom resolution for patients with pneumonia. Full resolution of symptoms takes more than 28 days for a significant proportion of patients with pneumonia. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Div Gen Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Metlay, JP (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Div Gen Internal Med, 712 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. FU BHP HRSA HHS [5T32PE11001-08] NR 15 TC 24 Z9 26 U1 1 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD SEP PY 1998 VL 92 IS 9 BP 1137 EP 1142 DI 10.1016/S0954-6111(98)90408-5 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 126JE UT WOS:000076289500009 PM 9926169 ER PT J AU Meissner, HH Robinson, L Dubinett, SM Santiago, SM AF Meissner, HH Robinson, L Dubinett, SM Santiago, SM TI Pulmonary edema as a result of chronic upper airway obstruction SO RESPIRATORY MEDICINE LA English DT Article ID RHEUMATOID-ARTHRITIS; SLEEP-APNEA; PRESSURE AB This is the first case of an adult who developed recurrent pulmonary edema as a result of unrecognized chronic upper airway obstruction due to polyarticular juvenile rheumatoid arthritis. The case highlights the importance of considering upper airway involvement in the differential diagnosis of sedentary patients with arthritic joint disease and breathing difficulties. C1 W Los Angeles Vet Affairs Med Ctr, Pulm & Crit Care Med Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. RP Santiago, SM (reprint author), W Los Angeles Vet Affairs Med Ctr, Pulm & Crit Care Med Sect, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD SEP PY 1998 VL 92 IS 9 BP 1174 EP 1176 DI 10.1016/S0954-6111(98)90416-4 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 126JE UT WOS:000076289500017 PM 9926177 ER PT J AU Fan, CM AF Fan, CM TI Tunneled catheters SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Review DE catheters and catheterization; central venous access ID VENOUS ACCESS DEVICES; SUBCLAVIAN VEIN STENOSIS; PEDIATRIC ONCOLOGY PATIENTS; LONG-TERM HEMODIALYSIS; HICKMAN CATHETER; DUAL-LUMEN; VASCULAR ACCESS; SILICONE CATHETERS; CANCER-PATIENTS; PERCUTANEOUS PLACEMENT AB In the past 10 years, intervention radiologists have become increasingly involved in the placement of long-term venous access devices. The intent of this article is to familiarize the reader with tunneled cathethers, a subgroup of venous access devices that are widely used in the hemodialysis and oncologic patients. This article provides a brief discussion of the different types of commercially available tunneled catheters; an illustrated, step-by-step presentation of the radiological techniques of catheter insertion commonly used, including discussion about patient selection and preparation; and a review of the radiological and surgical experience with tunneled catheters, focusing on the early and late complications associated with the devices. C1 Univ Maryland, Sch Med, Dept Radiol, Baltimore, MD 21201 USA. RP Fan, CM (reprint author), Massachusetts Gen Hosp, Gray 2, Boston, MA 02114 USA. NR 58 TC 5 Z9 5 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD SEP PY 1998 VL 15 IS 3 BP 273 EP 286 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 172RV UT WOS:000078938800007 ER PT J AU Noh, HM Kaufman, JA Fan, CM Geller, SC Waltman, AC AF Noh, HM Kaufman, JA Fan, CM Geller, SC Waltman, AC TI Radiological approach to central venous catheters: Cost analysis SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Review DE cost analysis; central venous catheterization; interventional radiology ID SUBCUTANEOUS INFUSION PORTS; RIGHT ATRIAL CATHETERS; HICKMAN CATHETERS; INFECTIOUS COMPLICATIONS; ACCESS CATHETERS; PLACEMENT; SYSTEM; INSERTION; EXPERIENCE; CHEMOTHERAPY AB In recent years, use of central venous access catheters has dramatically increased. In the past, placement of these catheters has been within the domain of the surgeon. However, the recent trend is for the radiologist to become the primary role player in placement and management of these catheters. To justify this current trend, it is important to analyze the potential differences in cost of catheter placement, efficacy, and complications of radiological approach to central venous access in comparison with the surgical approach. This article summarizes various studies on these issues including two studies at the author's institution that compared the initial cost of radiological placement of long-term tunneled hemodialysis catheters and chest ports with the costs associated with surgical placement. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kaufman, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 36 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD SEP PY 1998 VL 15 IS 3 BP 335 EP 340 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 172RV UT WOS:000078938800013 ER PT J AU Solomon, R AF Solomon, R TI Radiocontrast-induced nephropathy SO SEMINARS IN NEPHROLOGY LA English DT Review ID ACUTE-RENAL-FAILURE; RADIOGRAPHIC CONTRAST AGENT; ATRIAL-NATRIURETIC-PEPTIDE; RANDOMIZED CLINICAL-TRIAL; PROXIMAL TUBULE CELLS; HIGH-OSMOLALITY; NITRIC-OXIDE; BLOOD-FLOW; CARDIAC-CATHETERIZATION; INDUCED NEPHROTOXICITY C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Solomon, R (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 78 TC 28 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD SEP PY 1998 VL 18 IS 5 BP 551 EP 557 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 119DZ UT WOS:000075881700010 PM 9754608 ER PT J AU Ronningstam, EF Maltsberger, JT AF Ronningstam, EF Maltsberger, JT TI Pathological narcissism and sudden suicide-related collapse SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID PERSONALITY-DISORDER; DEATH AB Psychiatric inpatient admission of three nondepressed young men who escaped deadly self-injury provided an opportunity to study their character organization. Defects in affect-regulatory functions and evidences of pathological narcissism were identified and explored. Each patient had a specific suicide-risk consultation and a psychotherapy evaluation. Each denied intent to kill himself, and none acknowledged experience of depression or the wish to die. Each also denied his suicidal behavior involved significant risks, and each discounted the importance of obvious, identifiable stressors as triggers for it. The interrelation between pathological narcissism and this particular suicidal behavior is discussed. These observations can assist in the assessment of suicide risk in nondepressed patients. C1 McLean Hosp, Psychosocial Ctr, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ronningstam, EF (reprint author), McLean Hosp, Psychosocial Ctr, 115 Mill St, Belmont, MA 02178 USA. NR 55 TC 15 Z9 15 U1 1 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD FAL PY 1998 VL 28 IS 3 BP 261 EP 271 PG 11 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 134XF UT WOS:000076768500004 PM 9807772 ER PT J AU Ojemann, RG AF Ojemann, RG TI Proposal concerning neurosurgical residency financing SO SURGICAL NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Ojemann, RG (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 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 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD SEP PY 1998 VL 50 IS 3 BP 287 EP 287 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 117AK UT WOS:000075757400042 ER PT J AU Cooper, DS Specker, B Ho, M Sperling, M Ladenson, PW Ross, DS Ain, KB Bigos, ST Brierley, JD Haugen, BR Klein, I Robbins, J Sherman, SI Taylor, T Maxon, HR AF Cooper, DS Specker, B Ho, M Sperling, M Ladenson, PW Ross, DS Ain, KB Bigos, ST Brierley, JD Haugen, BR Klein, I Robbins, J Sherman, SI Taylor, T Maxon, HR TI Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: Results from the National Thyroid Cancer Treatment Cooperative Registry SO THYROID LA English DT Article ID MEDICAL THERAPY; LEVOTHYROXINE AB The ideal therapy for differentiated thyroid cancer is uncertain. Although thyroid hormone treatment is pivotal, the degree of thyrotropin (TSH) suppression that is required to prevent recurrences has not been studied in detail. We have examined the relation of TSH suppression to baseline disease characteristics and to the likelihood of disease progression in a cohort of thyroid cancer patients who have been followed in a multicenter thyroid cancer registry that was established in 1986. The present study describes 617 patients with papillary and 66 patients with follicular thyroid cancer followed annually for a median of 4.5 years (range 1-8.6 years). Cancer staging was assessed using a staging scheme developed and validated by the registry. Cancer status was defined as no residual disease; progressive disease at any follow-up time; or death from thyroid cancer. A mean TSH score was calculated for each patient by averaging all available TSH determinations, where 1 = undetectable TSH; 2 = subnormal TSH; 3 = normal TSH; and 4 = elevated TSH. Patients were also grouped by their TSH scores: group 1: mean TSH score 1.0-1.99; group 2: mean TSH score 2.0-2.99; group 3: mean TSH score 3.0-4.0. The degree of TSH suppression did not differ between papillary and follicular thyroid cancer patients. However, TSH suppression was greater in papillary cancer patients who were initially classified as being at higher risk for recurrence. This was not the case for follicular cancer patients, where TSH suppression was similar for ail patients. For all stages of papillary cancer, a Cox proportional hazards model showed that disease stage, patient age, and radioiodine therapy all predicted disease progression, but TSH score category did not. However, TSH score category was an independent predictor of disease progression in high risk patients (p = 0.03), but was no longer significant when radioiodine therapy was included in the model (p = 0.09). There were too few patients with follicular cancer for multivariate analysis. These data suggest that physicians use greater degrees of TSH suppression in higher risk papillary cancer patients. Our data do not support the concept that greater degrees of TSH suppression are required to prevent disease progression in low-risk patients, but this possibility remains in high-risk patients. Additional studies with more patients and longer follow-up may provide the answer to this important question. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. S Dakota State Univ, Ethel Austin Program Nutr, Brookings, SD 57007 USA. Univ Cincinnati, Med Ctr, Dept Pediat, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Dept Radiol, Cincinnati, OH 45267 USA. Johns Hopkins Univ, Sch Med, Div Endocrinol, Baltimore, MD USA. Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. Univ Kentucky, Med Ctr, Div Endocrinol, Lexington, KY USA. Maine Med Ctr, Div Endocrinol, Portland, ME 04102 USA. Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. Univ Colorado, Hlth Sci Ctr, Div Endocrinol, Denver, CO USA. N Shore Univ Hosp, Div Endocrinol, Manhasset, NY USA. Cornell Univ, Coll Med, New York, NY 10021 USA. NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Cancer Ctr, Div Endocrinol, Houston, TX 77030 USA. Bayer Corp, W Haven, CT USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Sinai Hosp, Div Endocrinol, Baltimore, MD 21215 USA. RP Cooper, DS (reprint author), Sinai Hosp, Div Endocrinol, 2401 W Belvedere Ave, Baltimore, MD 21215 USA. RI Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; Sherman, Steven/0000-0002-3079-5153 NR 12 TC 140 Z9 153 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD SEP PY 1998 VL 8 IS 9 BP 737 EP 744 DI 10.1089/thy.1998.8.737 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 124UC UT WOS:000076199600001 PM 9777742 ER PT J AU Yu, N Ohashi, M Alosco, S Salazar, M Cao, K Vina, MF Yunis, EJ AF Yu, N Ohashi, M Alosco, S Salazar, M Cao, K Vina, MF Yunis, EJ TI Typing of HLA-B*15 alleles using sequence-specific primers SO TISSUE ANTIGENS LA English DT Article DE allele; antigen; HLA-B15; PCR-SSP; serology; transplantation ID HLA-B; PCR-SSP; DNA; TRANSPLANTATION; AMPLIFICATION; SEROLOGY; HLA-B15; SYSTEM AB We have developed a DNA based typing method to detect 38 known B*15 alleles using sequence-specific primers (PCR-SSP). This method involves 38 primers and 39 PCR-SSP reactions with results that can be obtained in 3 hours The method is easy, fast and suitable fur clinical typing for bone marrow and organ transplantation. We have typed 106 HLA-B15 samples using this method. For homozygous HLA-B15 samples, some B*15 allele combinations need to be resolved by additional PCR reactions not included in this article. The method allows the detection of potential new alleles requiring sequencing for confirmation, and it is useful to resolve unusual serological reaction patterns for different HLA-B15 serological specificities. In addition, it could be used to resolve ambiguous PCR-SSOP typing results and for recognition of mismatches in serologically matched unrelated individuals. C1 Amer Red Cross, Blood Serv, HLA Lab, Dedham, MA 02026 USA. Amer Red Cross, Natl Histocompatibil Lab, Bethesda, MD 20814 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Immunol Canc & AIDS, Boston, MA 02115 USA. RP Yu, N (reprint author), Amer Red Cross, Blood Serv, HLA Lab, 180 Rustcraft Rd,Suite 150, Dedham, MA 02026 USA. NR 20 TC 10 Z9 10 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD SEP PY 1998 VL 52 IS 3 BP 260 EP 269 DI 10.1111/j.1399-0039.1998.tb03041.x PG 10 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 124AJ UT WOS:000076157900009 PM 9802606 ER PT J AU Clavijo, OP Delgado, JC Awdeh, ZL Fici, D Turbay, D Alper, CA Truedsson, L Yunis, EJ AF Clavijo, OP Delgado, JC Awdeh, ZL Fici, D Turbay, D Alper, CA Truedsson, L Yunis, EJ TI HLA-Cw alleles associated with HLA extended haplotypes and C2 deficiency SO TISSUE ANTIGENS LA English DT Article DE c2 deficiency; extended haplotypes; HLA-Cw alleles; MHC ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLOZAPINE-INDUCED AGRANULOCYTOSIS; DIFFERENT ETHNIC-GROUPS; MHC HAPLOTYPES; B-REGION; COMPLOTYPES; VARIANTS; GENES; DNA; POLYMORPHISMS AB There are four NMC-linked complement genes, BE C2, C4A and C4B, that are inherited as single DNA units, known as complotypes. Extended haplotypes were initially defined by studying the distribution of complotypes in relation to HLA-B and HLA-DR loci in Caucasian families. In order to analyze the distribution of HLA-Cw alleles in relation to extended haplotypes, we studied a large panel of MHC homozygous and hetero zygous cell lines representing previously described Caucasian derived extended haplotypes and 14 patients with complete C2 deficiency. HLA alleles were assigned using sequence-specific oligonucleotide probe hybridization (SSOP). Family analysis served to assign haplotypes for heterozygous samples. We found distinctive HLA-Cw alleles for each independent extended haplotype. Their association in each instance was statistically significant. All patients with C2 deficiency carrying the haplotype [HLA-B18, S042, DR2] were associated with HLA-Cw*1203. These conserved allelic combinations may become an important tool for the study of human evolution and may contribute to the expeditious selection of prospective donors in clinical transplantation. 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, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Lund, Dept Med Microbiol, Clin Immunol Sect, Lund, Sweden. RP Yunis, EJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 1 Jimmy Fund Way, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-29583]; NIAID NIH HHS [AI14157]; NIMH NIH HHS [MH47029] NR 29 TC 10 Z9 10 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD SEP PY 1998 VL 52 IS 3 BP 282 EP 285 DI 10.1111/j.1399-0039.1998.tb03045.x PG 4 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 124AJ UT WOS:000076157900013 PM 9802610 ER PT J AU Rubin, RH Fishman, JA AF Rubin, RH Fishman, JA TI A consideration of potential donors with active infection - is this a way to expand the donor pool? SO TRANSPLANT INTERNATIONAL LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rubin, RH (reprint author), Massachusetts Gen Hosp, 32 Fruit St, Boston, MA 02114 USA. NR 13 TC 18 Z9 19 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0934-0874 J9 TRANSPLANT INT JI Transpl. Int. PD SEP PY 1998 VL 11 IS 5 BP 333 EP 335 DI 10.1111/j.1432-2277.1998.tb00814.x PG 3 WC Surgery; Transplantation SC Surgery; Transplantation GA 123NG UT WOS:000076130800001 PM 9787408 ER PT J AU Wekerle, T Sachs, DH Sykes, M AF Wekerle, T Sachs, DH Sykes, M TI Mixed chimerism for the induction of tolerance: Potential applicability in clinical composite tissue grafting SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT International Symposium on Composite Tissue Allotransplantation CY NOV 19-20, 1997 CL LOUISVILLE, KENTUCKY ID BONE-MARROW TRANSPLANTATION; ANTIBODY MAB INJECTIONS; WHOLE-BODY IRRADIATION; T CELL MABS; ALLOGENEIC CHIMERISM; ALLOGRAFT TOLERANCE; THYMIC IRRADIATION; STEM-CELLS; MICE; ENGRAFTMENT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Surg Serv,Bone Marrow Transportat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Surg Serv,Bone Marrow Transportat Sect, MGH E,Bldg 149-5102, Boston, MA 02129 USA. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [R01 HL49915] NR 19 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD SEP PY 1998 VL 30 IS 6 BP 2708 EP 2710 DI 10.1016/S0041-1345(98)00793-3 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 119FK UT WOS:000075885200091 PM 9745551 ER PT J AU Lee, WPA Rubin, JP Cober, S Ierino, F Randolph, MA Sachs, DH AF Lee, WPA Rubin, JP Cober, S Ierino, F Randolph, MA Sachs, DH TI Use of swine model in transplantation of vascularized skeletal tissue allografts SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT International Symposium on Composite Tissue Allotransplantation CY NOV 19-20, 1997 CL LOUISVILLE, KENTUCKY ID MINIATURE SWINE; RENAL-ALLOGRAFTS; SURVIVAL; LOCALIZATION; ANTIGENS; ACCEPTANCE; KIDNEY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Biol Res Ctr, Boston, MA 02114 USA. RP Lee, WPA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab, WAC-453, Boston, MA 02114 USA. NR 15 TC 34 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD SEP PY 1998 VL 30 IS 6 BP 2743 EP 2745 DI 10.1016/S0041-1345(98)00801-X PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 119FK UT WOS:000075885200101 PM 9745559 ER PT J AU Schmahmann, JD AF Schmahmann, JD TI Dysmetria of thought: clinical consequences of cerebellar dysfunction on cognition and affect SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID OLIVOPONTOCEREBELLAR ATROPHY; MENTAL SKILLS; RHESUS-MONKEY; DEGENERATION; PATHOLOGY; CHILDREN; MOVEMENT; DAMAGE; ATAXIA; MUTISM AB Cognitive and emotional changes might be prominent or even principal manifestations I of cerebellar lesions. This realization supports evidence suggesting that the cerebellum is an important part of a set of distributed neural circuits that subserve higher-order processing. Early anecdotal clinical accounts described aberrant: mental or intellectual functions in the setting of cerebellar atrophy. Later systematic analyses showed that the cerebellum is able to influence autonomic, vasomotor, and emotional behaviors, and further studies revealed neuropsychological deficits in patients with degenerative diseases. Current descriptions of behavioral changes in adults and children with acquired cerebellar lesions bring the debate about the cerebellar role in neural function within the realm of clinically relevant cognitive neuroscience. The activationof focal cerebellar regions by cognitive tasks on functional neuroimaging studies, and morphologic abnormalities of cerebellum in psychiatric diseases such as autism and schizophrenia further support this view. Anatomical substrates have been elucidated that could support a cerebellar role in cognition and emotion. Our concept of 'dysmetria of thought' draws an analogy with the motor system to describe and explain the impairments of higher-order behavior that result when the distributed neural circuits subserving cognitive operations are deprived of cerebellar modulation. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM schmahmann@helix.mgh.harvard.edu NR 82 TC 108 Z9 110 U1 4 U2 12 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD SEP PY 1998 VL 2 IS 9 BP 362 EP 371 DI 10.1016/S1364-6613(98)01218-2 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 171PJ UT WOS:000078872200009 PM 21227233 ER PT J AU Collins, MM O'Leary, MP Barry, MJ AF Collins, MM O'Leary, MP Barry, MJ TI Prevalence of bothersome genitourinary symptoms and diagnoses in younger men on routine primary care visits SO UROLOGY LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; SEEKING BEHAVIOR; NONBACTERIAL PROSTATITIS; URINARY SYMPTOMS; QUESTIONNAIRE; PROSTATODYNIA; CONTRACTION; INDEXES; SCORE AB Objectives. To assess the prevalence of bothersome genitourinary (GU) symptoms in younger men an routine primary care physician visits. Methods. One hundred six men aged 18 to 50 years were approached to complete a brief, self-administered survey that included the American Urological Association Symptom Index, a benign prostatic hyperplasia (BPH) Impact Index, and additional questions about GU pain and sexual dysfunction and about a history of GU diseases. Men with GU symptoms had their outpatient records reviewed. Results. Of the 101 respondents (mean age 36 years), 50% reported GU symptoms. Of these men, 25% were bothered by their symptoms and 17% wanted to talk about them with their physicians; 22% were worried that their GU symptoms might be due to prostate cancer; 27% of all men reported a history of at least one GU disease and 17% had more than one; 16% of all men had been to a urologist. Chart review for the 51 men with symptoms revealed physician documentation of GU symptoms in only 24% of cases and an abnormal GU examination in 8%. One third of reviewed charts documented a GU problem that visit. A broad spectrum of GU diagnoses was documented; no one cause predominated. Ninety percent of all men reported that primary care physicians should routinely ask younger men GU questions as part of their general healthcare. Conclusions. The high prevalence of bothersome GU symptoms and diagnoses in younger men suggests that information about the clinical, functional, and quality of life implications of these symptoms needs to be collected in this population. UROLOGY 52: 422-427, 1998. (C) 1998, Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Med Serv, Div Gen Med, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. RP Collins, MM (reprint author), Massachusetts Gen Hosp, Med Serv, Div Gen Med, Med Practices Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU AHRQ HHS [HS 08397]; BHP HRSA HHS [5T32 PE11001-08] NR 24 TC 13 Z9 13 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 1998 VL 52 IS 3 BP 422 EP 427 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 114KV UT WOS:000075609200014 PM 9730454 ER PT J AU Hinze, R Holzhausen, HJ Gimm, O Dralle, H Rath, FW AF Hinze, R Holzhausen, HJ Gimm, O Dralle, H Rath, FW TI Primary hereditary medullary thyroid carcinoma - C-cell morphology and correlation with preoperative calcitonin levels SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY LA English DT Article DE multiple endocrine neoplasia type 2a; medullary thyroid carcinoma; calcitonin; prophylactic thyroidectomy ID MULTIPLE ENDOCRINE NEOPLASIA; RET PROTOONCOGENE; MEN 2A; HYPERPLASIA; MUTATIONS; FAMILIES; DISEASE AB Early thyroidectomy offers an opportunity of preventing the development of medullary thyroid carcinoma (MTC) in patients at risk for hereditary MTC. We investigated the thyroid glands of 32 patients with hereditary MTC to identify the changes in C-cell morphology,and to correlate these with plasma calcitonin (CT) levels and with clinical data. The entire thyroid gland was processed for histological examination including immunostaining for CT. All glands revealed C-cell hyperplasia (CCH), and MTC was found in 21 patients (66% of 32, youngest patient 6 years, youngest with lymph node metastases [LNM] 17 years). The transition from CCH to MTC was characterized by destruction of the follicular basement membrane and by diminished intensity of CT immunostaining. Normal plasma CT levels after provocation with pentagastrin were found only in patients with CCH. Basally elevated plasma CT levels were restricted to MTC. LNM were only found in multifocal tumours at least 4 mm in diameter. It is::riot yet clear whether or nob CCH in patients at risk for hereditary MTC is a neoplastic change, but in these patients the term 'C-cell hyperplasia' is of doubtful value. All MEN gene carriers reveal CCH, and almost all of them will develop multifocal MTC, so that CCH is probably a precursor lesion of an indubitably malignant tumour. Prophylactic thyroidectomy is justified at the age of 6 to anticipate development of a MTC. Lymphadenectomy is necessary in children if they are older than 10 years or have elevated plasma CT levels. C1 Univ Halle Wittenberg, Inst Pathol, Fac Med, D-06097 Halle, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Halle Wittenberg, Dept Gen Surg, D-06097 Halle, Germany. RP Hinze, R (reprint author), Univ Halle Wittenberg, Inst Pathol, Fac Med, Magdeburgerstr 14, D-06097 Halle, Germany. EM raoul.hinze@medizin.uni-halle.de NR 29 TC 51 Z9 52 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. Int. J. Pathol. PD SEP PY 1998 VL 433 IS 3 BP 203 EP 208 PG 6 WC Pathology SC Pathology GA 123QR UT WOS:000076136300002 PM 9769122 ER PT J AU Mondor, I Moulard, M Ugolini, S Klasse, PJ Hoxie, J Amara, A Delaunay, T Wyatt, R Sodroski, J Sattentau, QJ AF Mondor, I Moulard, M Ugolini, S Klasse, PJ Hoxie, J Amara, A Delaunay, T Wyatt, R Sodroski, J Sattentau, QJ TI Interactions among HIV gp120, CD4, and CXCR4: Dependence on CD4 expression level, gp120 viral origin, conservation of the gp120 COOH- and NH(2)-termini and V1/V2 and V3 loops, and sensitivity to neutralizing antibodies SO VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; LINE-ADAPTED HIV-1; CHEMOKINE RECEPTORS; ENVELOPE GLYCOPROTEINS; INFECTION; ENTRY; BINDING; CORECEPTOR; EPITOPE AB The binding of HIV-derived recombinant soluble (s)gp120 to the CD(4+)/CXCR(4+) A3.01 T cell line inhibits the binding of the CXCR4-specific monoclonal antibodies 12G5, which interacts with the second extracellular loop, and 6H8, which binds the NH(2) terminus. We have used this as an assay to analyse the interaction of recombinant sgp120 from diverse viral origins with CXCR4. The strength of the interaction between sgp120 and CXCR4 correlated with sgp120 affinity for the CD4-CXCR4 complex, and the interaction of sgp120(MN) and sgp120(IIIB) with CXCR4 was highly dependent on the level of CD4 expressed on a variety of different T cell lines. sgp120 from X4, R5X4, and R5 viruses interacted with CXCR4, although the R5 sgp120-CXCR4 interactions were weaker than those of the other gp120s. The interaction of sgp120(IIIB) or sgp120(MN) with CXCR4 was inhibited by neutralizing monoclonal antibodies that prevent the sgp120-CD4 interaction but also by antibodies specific for the gp120 V2 and V3 loops, the CD4-induced epitope and the 2G12 epitope, which interfere weakly or not at all with CD4-sgp120 binding. The binding to A3.01 cells of wild-type sgp120(HxB2), but not of sgp120 deleted in the COOH and NH(2) termini, interfered with 12G5 binding in a dose-dependent manner. Further deletion of the V1 and V2 loops restored CXCR4 binding activity, but additional removal of the V3 loop eliminated the gp120-CXCR4 interaction, without decreasing the affinity between mutated sgp120 and CD4. Taken together these results demonstrate that the interactions between sgp120 and CXCR4 are globally similar to those previously observed between sgp120 and CCR5, with some apparent differences in the strength of the sgp120-CXCR4 interactions and their dependence on CD4. (C) 1998 Academic Press. C1 Ctr Immunol Marseille Luminy, F-13288 Marseille 9, France. UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England. Univ Penn, Philadelphia, PA 19104 USA. Inst Pasteur, Unite Immunol Virale, F-75724 Paris 15, France. INRA, Pathol Vegetale Stn, Villenave Dornon, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Sattentau, QJ (reprint author), Ctr Immunol Marseille Luminy, Case 906, F-13288 Marseille 9, France. EM sattenta@ciml.univ-mrs.fr NR 70 TC 65 Z9 67 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 1998 VL 248 IS 2 BP 394 EP 405 DI 10.1006/viro.1998.9282 PG 12 WC Virology SC Virology GA 117CC UT WOS:000075761800022 PM 9721247 ER PT J AU Goldsmith, KT Dion, LD Curiel, DT Garver, RI AF Goldsmith, KT Dion, LD Curiel, DT Garver, RI TI trans E1 component requirements for maximal replication of E1-defective recombinant adenovirus SO VIROLOGY LA English DT Article ID PROTEINS INDUCE APOPTOSIS; E1B-58KD TUMOR-ANTIGEN; THYMIDINE KINASE GENE; CELL LUNG-CARCINOMA; RAT EMBRYO CELLS; EARLY REGION-1B; MESSENGER-RNAS; BCL-2 PROTEIN; 19-KILODALTON PROTEIN; TRANSFORMED-CELLS AB Strategies that enable EI-defective recombinant adenoviruses to selectively undergo replication in neoplastic tissue may be useful for future investigations or therapies of malignancies. A growing body of evidence suggests that some molecular alterations commonly associated with malignancies, such as p53 mutations, can modify the specific EI requirements for replication of human serotype adenoviruses, In the studies reported here, a panel of human non-small cell lung cancer cell lines with previously defined p53 status were characterized for basal interleukin-6 (IL-6) and bcl-2 content because previous studies have indicated both proteins can functionally substitute for the replication requirements provided by native EI viral proteins. Cell lines were infected with El-defective adenovirus 5 and simultaneously transfected with different combinations of El plasmids, or a bcl-2 expression plasmid, and adenovirus present in the cells was quantified 6 days later. These assays demonstrated that E1A with both 19- and 55-kDa E1B-encoding plasmids were required for maximal adenoviral replication, independent of the varying p53/IL-6/basal bcl-2 phenotypes of the host cell lines. EIA was required for maximal replication enablement, independent of the basal IL-6 content of these cell lines, and exogenous IL-6 also did not obviate the E1A requirement Interestingly, the bcl-2 expression plasmid did not consistently substitute for the 19-kDa expression plasmid in the context of this replication complementation assay. These results suggest that (1) basal levels of IL-6 greater than that present in these cell lines are necessary for functional replacement of the EIA replication function and (2) bcl-2 does not predictably substitute for the 19-kDa E1B replication function in the context of trans complementation. (C) 1998 Academic Press. C1 Univ Alabama, Sch Med, Birmingham, AL 35294 USA. Birmingham VAMC, Dept Med, Gene Therapy Program, Div Pulm & Crit Care Med, Birmingham, AL 35294 USA. RP Garver, RI (reprint author), Univ Alabama, Sch Med, 701 S 19th St, Birmingham, AL 35294 USA. EM robgarver@sprintmail.com NR 70 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 1998 VL 248 IS 2 BP 406 EP 419 DI 10.1006/viro.1998.9293 PG 14 WC Virology SC Virology GA 117CC UT WOS:000075761800023 PM 9721248 ER PT J AU Meissner, HH Santiago, SM Stein, M Goldman, MD Williams, AJ AF Meissner, HH Santiago, SM Stein, M Goldman, MD Williams, AJ TI Failure of physician documentation of sleep complaints in hospitalized patients SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID MULTIPLE-SCLEROSIS; DISTURBANCE; SYMPTOMS; INSOMNIA; FATIGUE AB Sleep disorders are acknowledged to be common but remain underrecognized by the medical community, often attributed to the failure to question patients about their sleep quality. We examined the prevalence of sleep complaints (insomnia or excessive daytime sleepiness) in a group of general medical patients by administering a questionnaire to hospitalized patients in a Veterans Affairs tertiary care medical center. A total of 222 consecutive adults (215 men, 60 +/- 14 years; body mass index, 24.8 +/- 5.6) completed the questionnaire. Of these, 105 patients (47%) had either insomnia, excessive daytime somnolence, or both; 63 (28%) had excessive daytime somnolence, which was severe in 27 (12%). Of 75 patients (34%) who had insomnia, a third were taking hypnotic medication. Forty patients (18%) had snoring, which was associated with excessive daytime somnolence in 36, whereas 46 patients (21%) had either restless legs or a combination of leg jerks and leg kicking or twitching during sleep, associated with a sleep complaint (insomnia in 32). The medical records were subsequently reviewed to assess the admitting physicians' recognition of these symptoms. No record included mention of any patient symptom related to sleep. We conclude that symptoms related to sleep, some of which may be clinically important, are common, and that none of these complaints appear to be recognized by the physicians of record. C1 W Los Angeles Vet Affairs Med Ctr, Med Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. St Thomas Hosp, Lane Fox Resp Unit, London, England. RP Meissner, HH (reprint author), W Los Angeles Vet Affairs Med Ctr, Med Serv, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 17 TC 53 Z9 53 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD SEP PY 1998 VL 169 IS 3 BP 146 EP 149 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 119NK UT WOS:000075902400002 PM 9771152 ER PT J AU McNamara, MJ Ruff, CT Wasco, W Tanzi, RE Thinakaran, G Hyman, BT AF McNamara, MJ Ruff, CT Wasco, W Tanzi, RE Thinakaran, G Hyman, BT TI Immunohistochemical and in situ analysis of amyloid precursor-like protein-1 and amyloid precursor-like protein-2 expression in Alzheimer disease and aged control brains SO BRAIN RESEARCH LA English DT Article DE amyloid precursor-like proteins; amyloid precursor protein; Alzheimer's disease; immunohistochemistry; in situ hybridization ID RAT-BRAIN; HOMOLOG; GENE; IMMUNOREACTIVITY; IDENTIFICATION; APLP2; CDNA; APP AB Amyloid precursor protein (APP) is a ubiquitously expressed membrane spanning glycoprotein which is endoproteolytically processed to AP, a 39-43 amino acid peptide that is the main component of senile plaques in Alzheimer Disease (AD). APP is a member of a highly conserved gene family, including Amyloid Precursor-Like Proteins (APLPs) APLP1 and APLP2. We now characterize APLP1 and APLP2 mRNA and protein expression in AD and aged control brains. Using in situ hybridization in hippocampal tissue from control and AD brain, we show that APLP1 and APLP2 mRNA are expressed primarily in the granule cells of the dentate gyrus, in areas CA1-CA3, and subiculum. Immunohistochemistry reveals staining for both APLP1 and APLP2 in neurons and blood vessels in AD and control cases. In addition, in AD brain, large dystrophic neurites in a subset of senile plaques are conspicuously labeled with APLP1 and APLP2 antibodies. The aged control brains have significantly fewer immunoreactive plaques and dystrophic neurites. The regional, cellular, and subcellular distribution of APLP1 and APLP2 overlap with each other and with APP. These observations support the hypothesis that the members of this family of proteins may perform similar functions. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimer Res Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurogenet Unit, Boston, MA USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Unit, 149 13th St,CNY 6405, Charlestown, MA 02129 USA. EM b_hyman@helix.mgh.harvard.edu FU NIA NIH HHS [AG11337, AG11899] NR 21 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 31 PY 1998 VL 804 IS 1 BP 45 EP 51 DI 10.1016/S0006-8993(98)00653-2 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 115XV UT WOS:000075692400005 PM 9729270 ER PT J AU Peterfy, M Gyuris, T Antonio, L Takacs, L AF Peterfy, M Gyuris, T Antonio, L Takacs, L TI Characterization and chromosomal mapping of two pseudogenes of the mouse Pafaha/Lis1 gene: retrointegration hotspots in the mouse genome SO GENE LA English DT Article DE platelet-activating factor acetylhydrolase; lissencephaly; Miller-Dieker syndrome; retrotransposition ID RNA-POLYMERASE-III; PLATELET-ACTIVATING-FACTOR; DIEKER LISSENCEPHALY GENE; PROCESSED PSEUDOGENES; NEURONAL MIGRATION; CLOSE PROXIMITY; LIS1; TRANSCRIPTION; ACETYLHYDROLASE; INTEGRATION AB Isolated lissencephaly sequence and Miller-Dieker syndrome are related neurodevelopmental disorders caused by defects of the LIS1 gene encoding the alpha subunit of intracellular platelet-activating factor acetylhydrolase. In addition to the ortholog of the human LIS1 gene (Pafaha/Lis1), the mouse genome contains two more homologs. In order to characterize the new members of this gene family, we isolated both Pafaha/Lis1-related genes (Pafaha-ps1 and Pafaha-ps2) from a mouse genomic library. Pafaha-ps1 and Pafaha-ps2 are processed pseudogenes formed by the retroinsertion of 5'-truncated Pafaha/Lis1 cDNAs. Sequence analysis revealed a striking accumulation of retroelements at both loci, identifying two retroinsertion hotspots in the mouse genome. The recognition of tRNA genes flanking Pafaha-ps1 provides an example for the potential association of RNA polymerase III transcription and retroinsertion in mammals. Linkage mapping placed Pafaha-ps1 and Pafaha-ps2 to distal chromosome (Chr) 3 and proximal Chr 7, respectively. Our results indicate that only one of the three LIS1-related mouse loci (Pafaha/Lis1) is functional, in contrast with two closely related functional genes (LIS1 and LIS2) reported in humans. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Amgen Inc, Dept Biomed Sci, Thousand Oaks, CA 91320 USA. Amgen Inc, Dept Computat Biol, Thousand Oaks, CA 91320 USA. RP Peterfy, M (reprint author), W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, 11301 Wilshire Blvd,Bldg 113,Room 312, Los Angeles, CA 90073 USA. NR 28 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD AUG 31 PY 1998 VL 216 IS 2 BP 225 EP 231 DI 10.1016/S0378-1119(98)00321-7 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 117RX UT WOS:000075796500001 PM 9729401 ER PT J AU Fink, D Nebel, S Norris, PS Baergen, RN Wilczynski, SP Costa, MJ Haas, M Cannistra, SA Howell, SB AF Fink, D Nebel, S Norris, PS Baergen, RN Wilczynski, SP Costa, MJ Haas, M Cannistra, SA Howell, SB TI Enrichment for DNA mismatch repair-deficient cells during treatment with cisplatin SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID RESISTANT TUMOR-CELLS; MICROSATELLITE INSTABILITY; CANCER; RETROVIRUS; LINES AB In addition to playing a role in tumorigenesis, loss of DNA mismatch repair results in low-level intrinsic resistance to cisplatin and carboplatin. We used a mismatch repair-deficient (clone B) and -proficient (clone B/rev) pair of Chinese hamster ovary sublines to determine the ability of cisplatin to enrich for repair-deficient cells during growth in vitro and in vivo. Clone B cells were 1.8-fold resistant to cisplatin as measured by a clonogenic assay. These cells were molecularly engineered to express constitutively the green fluorescent protein, and changes in the fraction of these repair-deficient cells were monitored by flow cytometric analysis. A single 1-hr exposure to cisplatin at an IC50 concentration enriched populations initially containing either 5 or 10% clone B cells by 81 and 75%, respectively, when measured at 5 days. Enrichment increased as a function of drug concentration to 158 and 169%, respectively, following an IC90 exposure. When grown as a xenograft, a single LD10 dose of cisplatin enriched the tumors by 48% from 4.6 to 6.8% repair-deficient cells (p = 0.04), To determine whether similar enrichment occurs during the treatment of human ovarian cancer patients, paired tumor samples were obtained from 38 patients before and after treatment with a minimum of 3 cycles of platinum drug-based primary chemotherapy and analyzed immunohistochemically for changes in the fraction of tumor cells expressing hMHL1. Following treatment there was a reduction in hMLH1 staining in 66% of the cases (p = 0.0005), Our results demonstrate that, despite the fact that loss of mismatch repair yields only modest levels of cisplatin resistance, even a single exposure to cisplatin produces quite a marked enrichment for repair-deficient cells in vitro and in vivo. Our results are consistent with the concept that treatment with cisplatin or carboplatin selects for preexisting mismatch repair-deficient cells, and that this contributes to the frequent development of clinical resistance. (C) 1998 Wiley-Liss, Inc. C1 Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. Dept Anat Pathol, Duarte, CA USA. Univ Calif Davis, Dept Pathol, Sacramento, CA 95817 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fink, D (reprint author), Univ Zurich, Dept Obstet & Gynecol, CH-8091 Zurich, Switzerland. NR 23 TC 64 Z9 68 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 31 PY 1998 VL 77 IS 5 BP 741 EP 746 DI 10.1002/(SICI)1097-0215(19980831)77:5<741::AID-IJC13>3.0.CO;2-4 PG 6 WC Oncology SC Oncology GA 104CE UT WOS:000074994100013 PM 9688308 ER PT J AU Adebanjo, OA Moonga, BS Haddad, JG Huang, CLH Zaidi, M AF Adebanjo, OA Moonga, BS Haddad, JG Huang, CLH Zaidi, M TI A possible new role for vitamin D-Binding protein in osteoclast control: Inhibition of extracellular Ca2+ sensing at low physiological concentrations SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ACTIVATION; COMPONENT; CELLS; ACTIN; GC AB Upon removal of its sialic acid or galactose residue, vitamin D-binding protein (DBP) becomes a potent macrophage-activating factor, DBP-MAF. Here we document a new function of DBP-MAF and its parent molecule, DBP, in osteoclast control. We show that all DBPs potently inhibit extracellular Ca2+ (cation) sensing at low nanomolar concentrations with the following rank order of potency: native DBP = sialidase-treated DBP > beta-galactosidase-treated DBP. This attenuation remains unaffected despite co-incubation either with the native DBP ligand, 1,25-dihydroxyvitamin D-3, Or with an asialoglycoprotein receptor modulator, asialoorosomucoid. Taken together, the results suggest that circulating DBP may play a role in the systemic control of osteoclastic bone resorption, a hitherto unrecognized action of the protein, (C) 1998 Academic Press. C1 Vet Affairs Med Ctr, Ctr Osteoporosis & Skeletal Abing, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Med Coll Penn & Hahnemann Univ, Sch Med, Philadelphia, PA 19104 USA. Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England. RP Adebanjo, OA (reprint author), Vet Affairs Med Ctr, Ctr Osteoporosis & Skeletal Abing, Philadelphia, PA 19104 USA. RI Huang, Christopher/A-6248-2008 FU NIA NIH HHS [R01 AG 14971-02] NR 15 TC 13 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 28 PY 1998 VL 249 IS 3 BP 668 EP 671 DI 10.1006/bbrc.1998.9037 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 116XV UT WOS:000075751100018 PM 9731194 ER PT J AU Ierino, FL Yamada, K Lorf, T Arn, JS Sachs, DH AF Ierino, FL Yamada, K Lorf, T Arn, JS Sachs, DH TI Mechanism of tolerance to class I mismatched renal allografts in miniature swine - Regulation of interleukin-2 receptor alpha-chain expression on CD8 peripheral blood lymphocytes of tolerant animals SO TRANSPLANTATION LA English DT Article ID REACTIVE T-CELLS; MONOCLONAL-ANTIBODY; KIDNEY ALLOGRAFTS; DOWN-REGULATION; INDUCTION; COSTIMULATION; CYCLOSPORINE; RESPONSES; SURVIVAL; ANERGY AB Background. Donor-specific tolerance to renal allografts in miniature swine is uniformly induced across a two-haplotype class I plus minor histocompatibility antigen disparity by a la-day course of cyclosporine. Recent studies have demonstrated that the thymus is essential for rapid and stable tolerance induction, because either prior thymectomy or a series of thymic biopsies induce a spontaneously reversible rejection crisis after the la-day course of cyclosporine. The present study examined the peripheral cellular mechanisms of tolerance by analyzing cytotoxic effector pathways in peripheral blood lymphocytes (PBL) of tolerant animals. Methods. The phenotype and cytotoxic T lymphocyte response of alloantigen-activated PBL cultures using cells from a series of tolerant animals with stable renal function (no thymic manipulation), or during a rejection crisis (induced by thymic biopsies), were studied. The in vitro findings were correlated with the in vivo clinical course of experimental animals. Results. The data demonstrated that in vivo and in vitro tolerance was associated with a specific deficiency of interleukin-alpha receptor (IL-SR) alpha-chain upregulation on CD8 single-positive (SP) T cells expressing high levels of CD8 (CD8(high)) when PBL from tolerant animals are stimulated with donor class I alloantigen. Stimulation by third party class I alloantigen, or by donor antigen during a rejection crisis, produced efficient cytotoxic T lymphocyte responses and expression of IL-2R alpha on CD8(high) SP cells. Conclusion. Antigen-specific regulation of the IL-2R alpha expression on CD8(high) SP PBL is a principal event associated with and potentially involved in the mechanism of tolerance in this preclinical large animal model. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,MGH E, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,MGH E, Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [P01 HL18646]; NIAID NIH HHS [2RO1 AI31046] NR 39 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 1998 VL 66 IS 4 BP 454 EP 460 DI 10.1097/00007890-199808270-00007 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 116HM UT WOS:000075718800007 PM 9734487 ER PT J AU Ehmann, UK Stevenson, MA Calderwood, SK DeVries, JT AF Ehmann, UK Stevenson, MA Calderwood, SK DeVries, JT TI Physical connections between feeder cells and recipient normal mammary epithelial cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID CADHERIN; ADHESION; GROWTH; PHENOTYPE; CATENIN AB Cells of the LA7 rat mammary tumor line stimulate proliferation of normal mouse mammary epithelial cells in culture when in direct physical contact with them. We examined junctional connections between these LA7 feeders and the recipient mouse mammary epithelial cells in order to study the role these junctions may play in growth signaling. Tight junctions and desmosomes between LA7 feeders and mouse mammary cells were detected by immunocytochemistry. These junctions connected every cell of either type with each of its neighbors. Adherens junctions, although evident between mouse mammary cells, could not be detected between LA7 and mouse mammary cells or between LA7 cells themselves. However, E-cadherin, the transmembrane protein of adherens junctions, was present in LA7 cell lysates. beta-catenin, which normally binds cadherins, was detected at the borders of LA7 cells. Presence of gap junctions between LA7 and mouse mammary cells was determined by traverse of lucifer yellow from an injected LA7 cell to surrounding mouse mammary epithelial cells. The experiments thus indicate that three types of intercellular junctions occur between cells active in direct cell-cell-stimulated proliferation signaling. (C) 1998 Academic Press. C1 Vet Affairs Palo Alto Hlth Care Syst, Dept Pathol & Lab Serv, Palo Alto, CA 94304 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 Ehmann, UK (reprint author), Vet Affairs Palo Alto Hlth Care Syst, Dept Pathol & Lab Serv, 3801 Miranda Ave, Palo Alto, CA 94304 USA. NR 27 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 25 PY 1998 VL 243 IS 1 BP 76 EP 86 DI 10.1006/excr.1998.4054 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 116YT UT WOS:000075753200009 PM 9716451 ER PT J AU Walker, WH Daniel, PB Habener, JF AF Walker, WH Daniel, PB Habener, JF TI Inducible cAMP early repressor ICER down-regulation of CREB gene expression in Sertoli cells SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE CREB; ICER; Sertoli cell; follicle stimulating hormone; spermatogenesis; testis; gene expression ID RESPONSE ELEMENT-BINDING; FOLLICLE-STIMULATING-HORMONE; TRANSCRIPTION FACTOR CREB; PROTEIN CREB; CYCLIC-AMP; C-FOS; SPERMATOGENESIS; FSH; ACTIVATOR; PROMOTER AB The cAMP response element binding protein (CREB) and the cAMP-responsive element modulator (CREM) are cyclically expressed in the seminiferous tubules during spermatogenesis. In the somatic Sertoli cells, which are the major supporters of germ cell development in the seminiferous tubules, the expression of CREB is cyclical and appears to be regulated by the levels of cAMP produced in response to the pituitary derived follicle-stimulating hormone FSH. Cyclic AMP response elements (CREs) located in the promoter of the CREB gene were shown earlier to be implicated in an autopositive feedback loop that up-regulates the expression of CREB. Here we show that in Sertoli cells FSH-mediated induction of the CREM repressor isoform, ICER (inducible cAMP early repressor) is correlated with the inhibition and delay of CREB gene expression in the seminiferous tubules. ICER binds to the two CREs located in the promoter of the CREB gene and in transient transfection assays of Sertoli cells, ICER expression vectors down-regulate transcription of a reporter gene driven by the CREB gene promoter. In addition, analyses of ICER and CREB gene expression in isolated segments of rat seminiferous tubules reveals stage-specific and cycle-dependent expression of ICER. The periods of enhanced expression of ICER correspond to the stages of spermatogenesis with the lowest levels of CREB expression. We suggest that the expression of ICER in Sertoli cells may contribute to the periodic repression of CREB gene expression during the repeated 12-day cycles of spermatogenesis, and may be required to reset the levels of activator CREB prior to the initiation of each new cycle of spermatogenesis. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp,Lab Mol Endocrinol, Wellman 320, Boston, MA 02114 USA. EM habenerj@al.mgh.harvard.edu FU NIDDK NIH HHS [DK25532] NR 40 TC 35 Z9 37 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD AUG 25 PY 1998 VL 143 IS 1-2 BP 167 EP 178 DI 10.1016/S0303-7207(98)00082-3 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 127JB UT WOS:000076346400017 PM 9806361 ER PT J AU Pellacani, A Wiesel, P Sharma, A Foster, LC Huggins, GS Yet, SF Perrella, MA AF Pellacani, A Wiesel, P Sharma, A Foster, LC Huggins, GS Yet, SF Perrella, MA TI Induction of heme oxygenase-1 during endotoxemia is downregulated by transforming growth factor-beta 1 SO CIRCULATION RESEARCH LA English DT Article DE vascular smooth muscle cell; endotoxic shock; gene expression; enzyme activity ID NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE CELLS; OLFACTORY RECEPTOR NEURONS; TUMOR-NECROSIS-FACTOR; FACTOR-BETA; CARBON-MONOXIDE; INFLAMMATORY RESPONSE; ZINC-PROTOPORPHYRIN; CYTOKINE PRODUCTION; MESSENGER-RNA AB Heme oxygenase (HO)-1 generates CO, a gas with vasodilatory properties, during heme metabolism. HO-1 is expressed highly in vascular tissue after endotoxin stimulation: and generation of CO through the HO-1 pathway contributes to the hemodynamic compromise of endotoxic shock. Shock related to endotoxemia is an immune-mediated process that involves the generation of proinflammatory cytokines such as interleukin (IL)-1 beta. Because transforming growth factor (TGF)-beta 1 is a modulator of immune-mediated inflammatory responses and it blocks the hypotension of endotoxic shock, we determined whether TGF-beta 1 could be used to reduce expression of HO-1 in vascular tissue and smooth muscle cells. In a rat model of endotoxic shock, lipopolysaccharide-induced HO-1 mRNA and protein expression was reduced by TGF-beta 1 in highly vascularized tissue, such as heart and lung, by Northern and Western analysis. Furthermore, TGF-beta 1 dovynregulated HO-1 mRNA after its induction by IL-1 beta in vascular smooth muscle cells in culture. TGF-beta 1 also decreased HO-1 but not HO-2 protein expression in these cells. TGF-beta 1 decreased HO enzyme activity induced in IL-1 beta-treated vascular smooth muscle cells to a level not different from that in vehicle-treated cells. These studies suggest that this downregulation of HO-1 mRNA and protein expression and decrease in IL-1 beta-induced HO enzyme activity may contribute to the beneficial effect of TGF-beta 1 on endotoxic shock. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. RP Perrella, MA (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Bldg 2,677 Huntington Ave, Boston, MA 02115 USA. RI Yet, Shaw-Fang/B-1067-2010; OI Yet, Shaw-Fang/0000-0001-9097-3962 FU NHLBI NIH HHS [HL-03194] NR 45 TC 53 Z9 54 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG 24 PY 1998 VL 83 IS 4 BP 396 EP 403 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 112ZH UT WOS:000075524400006 PM 9721696 ER PT J AU Bhatia, SN Balis, U Yarmush, ML Toner, M AF Bhatia, SN Balis, U Yarmush, ML Toner, M TI Development of microfabricated hepatocyte co-cultures. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Shriners Burns 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 AUG 23 PY 1998 VL 216 MA 137-BIOT BP U289 EP U289 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900787 ER PT J AU Choi, SW Hu, ZY Hanson, RN Elmaleh, DR Fischman, AJ AF Choi, SW Hu, ZY Hanson, RN Elmaleh, DR Fischman, AJ TI 4-amino- and 3-aminomethyl-piperidine analogs of GBR 12909 as inhibitors of the dopamine transporter. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, 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 AUG 23 PY 1998 VL 216 MA 128-MEDI BP U239 EP U239 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000778 ER PT J AU Lazarou, E Lee, N Wei, K Szostak, JW Suga, H AF Lazarou, E Lee, N Wei, K Szostak, JW Suga, H TI Structural characterization of an acyl-transferase ribozyme. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA. Massachusetts Gen Hosp, Dept Mol Biol, 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 AUG 23 PY 1998 VL 216 MA 042-BIOL BP U217 EP U218 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900599 ER PT J AU Lee, N Cowan, JA Szostak, JW Suga, H AF Lee, N Cowan, JA Szostak, JW Suga, H TI Unusual metal ion catalysis in an acyl-transferase ribozyme. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA. Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Dept Mol Biol, 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 AUG 23 PY 1998 VL 216 MA 044-BIOL BP U218 EP U218 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900601 ER PT J AU Muratoglu, OK Bragdon, CR O'Connor, DO Jasty, M Gul, R Harris, WH AF Muratoglu, OK Bragdon, CR O'Connor, DO Jasty, M Gul, R Harris, WH TI The effect of molecular weight between crosslinks (M-c) on the wear behavior of crosslinked UHMWPE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. GIK Inst Engn Sci & Technol, Topi, Pakistan. 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 AUG 23 PY 1998 VL 216 MA 251-PMSE BP U891 EP U891 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235002677 ER PT J AU Rajur, SB Roth, CM Morgan, JR Yannush, ML AF Rajur, SB Roth, CM Morgan, JR Yannush, ML TI Synthetic conjugates of N-acetylgalactoside and oligonucleotides for use as molecular therapeutics. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Ctr Engn Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Surg Serv, 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 AUG 23 PY 1998 VL 216 MA 190-MEDI BP U258 EP U258 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000840 ER PT J AU Roy, P Margolies, MN Yarmush, ML Roth, CM AF Roy, P Margolies, MN Yarmush, ML Roth, CM TI Antigen-antibody interactions under high hydrostatic pressures: The effect of ionic strength and temperature perturbations. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Shriners Hosp Crippled Children, 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 AUG 23 PY 1998 VL 216 MA 189-BIOT BP U303 EP U304 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234900839 ER PT J AU Seth, AK AF Seth, AK TI Laboratory renovation issues. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Massachusetts Gen 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 AUG 23 PY 1998 VL 216 MA 006-CHAS BP U361 EP U361 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WX UT WOS:000075234901014 ER PT J AU Torchilin, VP AF Torchilin, VP TI Polychelating polymers as key components of macroparticulate diagnostic agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 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 AUG 23 PY 1998 VL 216 MA 193-POLY BP U57 EP U57 PN 3 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WZ UT WOS:000075235100192 ER PT J AU Whittington, DA Rosenzweig, AC Frederick, CA Lippard, SJ AF Whittington, DA Rosenzweig, AC Frederick, CA Lippard, SJ TI Crystallographic characterization of xenon and halogenated alkyl substrate binding in the methane monooxygenase hydroxylase. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MIT, Dept Chem, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 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 AUG 23 PY 1998 VL 216 MA 391-INOR BP U116 EP U116 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 107WY UT WOS:000075235000391 ER PT J AU Song, CS Jung, MH Kim, SC Hassan, T Roy, AK Chatterjee, B AF Song, CS Jung, MH Kim, SC Hassan, T Roy, AK Chatterjee, B TI Tissue-specific and androgen-repressible regulation of the rat dehydroepiandrosterone sulfotransferase gene promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENRICHED TRANSCRIPTION FACTOR; NF-KAPPA-B; DNA-BINDING; HYDROXYSTEROID SULFOTRANSFERASE; MOLECULAR-CLONING; MESSENGER-RNA; RECEPTOR GENE; LIVER; PROTEIN; HORMONE AB Dehydroepiandrosterone sulfotransferase (Std) catalyzes sulfonation of androgenic steroids and certain aromatic procarcinogens, In rats, this enzyme is selectively expressed in the fiver, and its expression is strongly repressed by androgens, DNase I footprinting and electrophoretic mobility shift analyses revealed two hepatocyte nuclear factor-1 (HNF1), three CCAAT/enhancer-binding protein (C/EBP), and one consensus palindromic thyroid hormone response elements within the first 215 base pairs (bp) of the promoter sequence of sat Std. This promoter is normally inactive in fibroblast-derived NIH 3T3 cells. However, overexpression of HNF1 and C/EBP resulted in synergistic activation of the Std promoter in this cell type, indicating essential roles of these two trans-regulators in liver-selective expression of the rat Std gene. On the other hand, point mutations at any one of five cis elements proximal to the -215 bp region markedly reduced reporter gene expression, suggesting that all of these sites are important for overall promoter function. Androgenic repression of the Std gene in rat liver can be recapitulated in androgen receptor (AR)-negative HepG2 hepatoma cells after co-transfection with an AR expression plasmid. Functional assay of a nested set of 5'-deleted promoters mapped the negative androgen response region between positions -235 and -310, Antibody supershift and oligonucleotide competition identified three OCT-1 and two C/EBP elements between bp -231 and -292, An additional OCT-1 site was found to overlap with a C/EBP element at the -262/-252 position. Mutational inactivation of any one of five cis elements within the -231/-292 region abolished negative androgen response, However, none of these cis elements showed DNase I protection by recombinant AR in footprinting assay, suggesting the absence of a direct AR-DNA interaction. Thus, these studies on rat Std promoter function indicate that (i) HNF1 and C/EBP are responsible for Liver specificity of the rat Std gene; (ii) androgenic repression of the gene requires the presence of all of the OCT-1 and C/EBP elements between positions -231 and -292; and (iii) AR may exert its negative regulatory effect indirectly through transcriptional interference of OCT-1 and C/EBP rather than through a direct DNA-AR interaction. C1 Univ Texas, Hlth Sci Ctr, Dept Struct & Cellular Biol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Chatterjee, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Struct & Cellular Biol, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG-03527] NR 49 TC 56 Z9 57 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 AUG 21 PY 1998 VL 273 IS 34 BP 21856 EP 21866 DI 10.1074/jbc.273.34.21856 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 112JY UT WOS:000075492600058 PM 9705324 ER PT J AU Tabor, DE Kim, JB Spiegelman, BM Edwards, PA AF Tabor, DE Kim, JB Spiegelman, BM Edwards, PA TI Transcriptional activation of the stearoyl-CoA desaturase 2 gene by sterol regulatory element-binding protein/adipocyte determination and differentiation factor 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FARNESYL DIPHOSPHATE SYNTHASE; MUTANT HAMSTER-CELLS; 3T3-L1 PREADIPOCYTES; FATTY-ACIDS; EXPRESSION; CHOLESTEROL; PROMOTER; PROTEIN; METABOLISM; MYC AB To identify genes that are transcriptionally activated by sterol regulatory element-binding proteins (SREBPs), we utilized mRNA differential display and mutant cells that express either high car low levels of transcriptionally active SREBP. This approach identified stearoyl-CoA desaturase 2 (SCD2) as a new SREBP-regulated gene. Cells were transiently transfected with reporter genes blinder the control of different fragments of the mouse SCD2 promoter. Constructs containing >199 base pairs of the SCD2 proximal promoter were activated following incubation of cells in sterol-depleted medium or as a result of co-expression of SREBP-1a, SREBP-2, or rat adipocyte determination and differentiation factor 1 (ADD1). Electromobility shift assays and DNase I footprint analysis demonstrated that recombinant SREBP-1a hound to a novel cis element (5'-AGCAGATTGTG-3') in the proximal promoter of the SCD2 gene. The finding that the endogenous SCD2 mRNA Bevels were induced when wild-type Chinese hamster ovary fibroblasts were incubated in sterol-deficient medium is consistent with a role for SREBP in regulating transcription of the gene. These studies identify SCD2 as a new member of the family of genes that are transcriptionally regulated in response to changing levels of nuclear SREBP/ADD1. In addition, the sterol regulatory element in the SCD2 promoter is distinct from all previously characterized motifs that confer SREBP- and ADD1-dependent transcriptional activation. C1 Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Edwards, PA (reprint author), Univ Calif Los Angeles, Dept Biol Chem, CHS 33-257, Los Angeles, CA 90095 USA. EM pedwards@medicine.medsch.ucla.edu FU NHLBI NIH HHS [HL 30568] NR 32 TC 84 Z9 85 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 1998 VL 273 IS 34 BP 22052 EP 22058 DI 10.1074/jbc.273.34.22052 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 112JY UT WOS:000075492600082 PM 9705348 ER PT J AU Wagner, AD Schacter, DL Rotte, M Koutstaal, W Maril, A Dale, AM Rosen, BR Buckner, RL AF Wagner, AD Schacter, DL Rotte, M Koutstaal, W Maril, A Dale, AM Rosen, BR Buckner, RL TI Building memories: Remembering and forgetting of verbal experiences as predicted by brain activity SO SCIENCE LA English DT Article ID EPISODIC MEMORY; FUNCTIONAL MRI; RETRIEVAL; HUMANS; SYSTEMS; MODEL; FMRI; PET AB A fundamental question about human memory is why some experiences are remembered whereas others are forgotten. Brain activation during word encoding was measured using blocked and event-related functional magnetic resonance imaging to examine how neural activation differs for subsequently remembered and subsequently forgotten experiences. Results revealed that the ability to later remember a verbal experience is predicted by the magnitude of activation in left prefrontal and temporal cortices during that experience. These findings provide direct evidence that left prefrontal and temporal regions jointly promote memory formation for verbalizable events. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Otto Von Guericke Univ, D-39120 Magdeburg, Germany. RP Wagner, AD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010; Frank, David/E-8213-2012; Li, Chong/F-4265-2015; OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG08441, AG05778]; NIDCD NIH HHS [DC03245-02] NR 32 TC 1031 Z9 1047 U1 17 U2 75 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 AUG 21 PY 1998 VL 281 IS 5380 BP 1188 EP 1191 DI 10.1126/science.281.5380.1188 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 113CE UT WOS:000075531200052 PM 9712582 ER PT J AU Chow, T Galvin, J McGovern, B AF Chow, T Galvin, J McGovern, B TI Antiarrhythmic drug therapy in pregnancy and lactation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC-ARRHYTHMIAS; BREAST-MILK; PROPRANOLOL; CONTRACTIONS; EXCRETION; SOTALOL; FETUS; FETAL AB Antiarrhythmic agents commonly used in clinical practice are reviewed with respect to their potential for teratogenic or other adverse fetal effects. Although most experience with antiarrhythmic drug therapy during pregnancy has accrued with digoxin, quinidine, and propranolol, other antiarrhythmic agents may also be used in the pregnant patient if indicated, The choice of antiarrhythmic drug depends on the specific arrhythmia being treated, the cardiac condition of the patient or fetus, and the known or anticipated actions of the antiarrhythmic drug being considered. The management of specific arrhythmias encountered in pregnant women are also discussed. For benign arrhythmias, a conservative approach starting first with preventive measures is appropriate. For more severe or symptomatic arrhythmias, pharmacologic therapy should be instituted using drugs with proven safety to the fetus, if possible. Electrical cardioversion of the patient may be performed with relative safety in more emergent situations. (C)1998 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP McGovern, B (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Fruit St, Boston, MA 02114 USA. NR 46 TC 7 Z9 10 U1 0 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 20 PY 1998 VL 82 IS 4A SI SI BP 58I EP 62I DI 10.1016/S0002-9149(98)00473-1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 116BE UT WOS:000075701000009 PM 9737655 ER PT J AU Ligos, JM Gerwin, N Fernandez, P Gutierrez-Ramos, JC Bernad, A AF Ligos, JM Gerwin, N Fernandez, P Gutierrez-Ramos, JC Bernad, A TI Cloning, expression analysis, and functional characterization of PKL12, a member of a new subfamily of ser/thr kinases SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-KINASE; CONSERVED FEATURES; IDENTIFICATION; SUBUNIT; DOMAIN; FAMILY; CELLS; BETA AB We report the cloning of the full-length cDNA of a new murine protein kinase, mPKL12. The sequence reveals a 305-amino-acid protein that contains the characteristic subdomains of the kinase superfamily and particular homology indicating a ser/thr specificity. We have also identified its human homologue gene (94% identical) and the putative homologue proteins from Saccharomyces cerevisiae and Arabidoposis thaliana. These four sequences appear to form a new subfamily of protein kinases, close in size to the theoretical minimal catalytic domain, therefore suggesting that they could be the catalytic unit of a more complex holoenzyme. Using Escherichia coli-purified protein, we have demonstrated that the mPKL12 enzyme possesses an intrinsic kinase activity, capable of phosphorylating enolase and also of promoting autophosphorylation, with a ser/thr specificity. Tissue expression analysis of mPKL12 showed that it is ubiquitously expressed, although at very low levels. RT-PCR analysis of several cell lines also supports this view, therefore suggesting that PKL12 may play a role in a very general cellular function, probably related with the secretory pathway. (C) 1998 Academic Press. C1 CSIC, Ctr Nacl Biotecnol, Dept Inmunol & Oncol, E-28049 Madrid, Spain. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Ctr Blood Res Inc, Boston, MA 02115 USA. RP CSIC, Ctr Nacl Biotecnol, Dept Inmunol & Oncol, Campus Univ Autonoma Madrid, E-28049 Madrid, Spain. EM abernad@cnb.uam.es NR 15 TC 17 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 19 PY 1998 VL 249 IS 2 BP 380 EP 384 DI 10.1006/bbrc.1998.9163 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 112VT UT WOS:000075515900016 PM 9712705 ER PT J AU Budman, DR Berry, DA Cirrincione, CT Henderson, IC Wood, WC Weiss, RB Ferree, CR Muss, HB Green, MR Norton, L Frei, E AF Budman, DR Berry, DA Cirrincione, CT Henderson, IC Wood, WC Weiss, RB Ferree, CR Muss, HB Green, MR Norton, L Frei, E TI Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID STAGE-II; C-ERBB-2 EXPRESSION; FOLLOW-UP; CHEMOTHERAPY; THERAPY; REGRESSION; TRIALS; MODELS; WOMEN; TIME AB Background: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer. Methods: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity. The patients received cyclophosphamide, doxorubicin, and 5-fluorouracil on day 1 of each chemotherapy cycle, with 5-fluorouracil administration repeated on day 8, The high-dose arm had twice the dose intensity and twice the drug dose as the low-dose arm. The moderate-dose arm had two thirds the dose intensity as the high-dose arm but the same total drug dose. Disease-free survival and overall survival were primary end points of the study. Results: At a median follow-up of 9 years, disease-free survival and overall survival for patients on the moderate- and high-dose arms are superior to the corresponding survival measures for patients on the low-dose arm (two-sided P<.0001 and two-sided P =.004, respectively), with no difference in disease-free or overall survival between the moderate- and the high-dose arms. At 5 years, overall survival (average +/- standard error) is 79% +/- 2% for patients on the high-dose arm, 77% +/- 2% for the patients on the moderate-dose arm, and 72% +/- 2% for patients on the low-dose arm; disease-free survival is 66% +/- 2%, 61% +/- 2%, and 56% +/- 2%, respectively. Conclusion: Within the conventional dose range for this chemotherapy regimen, a higher dose is associated with better disease-free survival and overall survival. C1 New York Univ, Sch Med, Div Oncol, Don Monti Div Oncol,N Shore Univ Hosp, Manhasset, NY 11030 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Canc Leukemia Grp B CALGB Stat Ctr, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. CALGB Cent Off, Chicago, IL USA. NYU, Sch Med, New York, NY 10003 USA. Univ Vermont, Coll Med, Burlington, VT 05405 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Budman, DR (reprint author), New York Univ, Sch Med, Div Oncol, Don Monti Div Oncol,N Shore Univ Hosp, 300 Community Dr, Manhasset, NY 11030 USA. EM budman@nshs.edu FU NCI NIH HHS [CA59518, CA31946, CA33601] NR 30 TC 343 Z9 351 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 19 PY 1998 VL 90 IS 16 BP 1205 EP 1211 DI 10.1093/jnci/90.16.1205 PG 7 WC Oncology SC Oncology GA 112CN UT WOS:000075476700010 PM 9719081 ER PT J AU Ghendler, Y Teng, MK Liu, JH Witte, T Liu, J Kim, KS Kern, P Chang, HC Wang, JH Reinherz, EL AF Ghendler, Y Teng, MK Liu, JH Witte, T Liu, J Kim, KS Kern, P Chang, HC Wang, JH Reinherz, EL TI Differential thymic selection outcomes stimulated by focal structural alteration in peptide/major histocompatibility complex ligands SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-CELL-RECEPTOR; CLASS-I H-2K(B); POSITIVE SELECTION; CRYSTAL-STRUCTURE; NEGATIVE SELECTION; VIRAL PEPTIDES; DEFICIENT MICE; ANTIGEN; RECOGNITION; THYMOCYTES AB The T lineage repertoire is shaped by T cell receptor (TCR)-dependent positive and negative thymic selection processes. Using TCR-transgenic (N15tg) beta(2)-microglobulin-deficient (beta(2)m(-/-)) RAG-2(-/-) H-2(b) mice specific for the VSV8 (RGYVYQGL) octapeptide bound to Kb, We identified a single weak agonist peptide variant V4L (L4) inducing phenotypic and functional T cell maturation. The cognate VSV8 peptide, in contrast, triggers negative selection. The crystal structure of L4/K-b was determined and refined to 2.1 Angstrom for comparison with the VSV8/K-b structure at similar resolution, Aside from changes on the p4 side chain of L4 and the resulting alteration of the exposed K-b Lys-66 side chain, these two structures are essentially identical. Hence, a given TCR recognizes subtle distinctions between highly related ligands, resulting in dramatically different selection outcomes. Based on these finding and the recent structural elucidation of the N15-VSV8/K-b complex, moreover, it appears that the germ-line V alpha repertoire contributes in a significant way to positive selection. C1 Harvard Univ, Sch Med, Immunobiol Lab, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Immunobiol Lab, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NIAID NIH HHS [AI19807, AI39098, R01 AI019807, R37 AI019807, R56 AI019807]; NIGMS NIH HHS [GM56008] NR 55 TC 48 Z9 48 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 1998 VL 95 IS 17 BP 10061 EP 10066 DI 10.1073/pnas.95.17.10061 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 112BX UT WOS:000075475200063 PM 9707600 ER PT J AU Tanaka, S Akiyoshi, T Mori, M Wands, JR Sugimachi, K AF Tanaka, S Akiyoshi, T Mori, M Wands, JR Sugimachi, K TI A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BETA-CATENIN; COLORECTAL-CANCER; PROTEIN; RECEPTOR; MEMBER; FAMILY; EXPRESSION; MUTATIONS; HOMOLOG; COMPLEX AB A novel member of the human frizzled (Fz) gene family was cloned and found to be specifically expressed in 3 of 13 well differentiated (23%), 13 of 20 moderately differentiated (62%), and 12 of 14 poorly differentiated (86%) squamous cell esophageal carcinomas compared with the adjacent uninvolved normal mucosa. The FzE3 cDNA encodes a protein of 574 amino acids and shares high sequence homology with the human FzD2 gene particularly in the putative ligand binding region of the cysteine-rich extracellular domain, Functional analysis revealed that transfection and expression of the FzE3 cDNA in esophageal carcinoma cells stimulates complex formation between adenomatous polyposis coli (APC) and beta-catenin followed by nuclear translocation of beta-catenin, Furthermore, cotransfection of a mutant construct encoding a FzE3 protein with a C-terminal truncation completely inhibited the interaction of APC with beta-catenin in cells. Finally, coexpression of FzE3 with Lef-1 transcription factor enhanced beta-catenin translocation to the nucleus. These observations suggest that FzE3 gene expression may down-regulate APC function and enhance beta-catenin mediated signals in poorly differentiated human esophageal carcinomas. C1 Kyushu Univ, Med Inst Bioregulat, Dept Surg, Beppu, Oita 8740838, Japan. Kyushu Univ, Fac Med, Dept Surg 2, Beppu, Oita 8740838, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Tanaka, S (reprint author), Kyushu Univ, Med Inst Bioregulat, Dept Surg, 4546 Tsurumibaru, Beppu, Oita 8740838, Japan. RI Mori, Masaki/A-4501-2011; U-ID, Kyushu/C-5291-2016 FU NCI NIH HHS [R01 CA035711, CA-35711, R37 CA035711] NR 30 TC 105 Z9 113 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 AUG 18 PY 1998 VL 95 IS 17 BP 10164 EP 10169 DI 10.1073/pnas.95.17.10164 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 112BX UT WOS:000075475200081 PM 9707618 ER PT J AU Zhou, L Jang, JC Jones, TL Sheen, J AF Zhou, L Jang, JC Jones, TL Sheen, J TI Glucose and ethylene signal transduction crosstalk revealed by an Arabidopsis glucose-insensitive mutant SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-EXPRESSION; HIGHER-PLANTS; THALIANA; PATHWAY; SUCROSE; METABOLISM; ACCUMULATION; BIOSYNTHESIS; REPRESSION; SEEDLINGS AB Glucose is an essential signaling molecule that controls plant development and gene expression through largely unknown mechanisms. To initiate the dissection of the glucose signal transduction pathway in plants by using a genetic approach, we have identified an Arabidopsis mutant, gin1 (glucose-insensitive), in which glucose repression of cotyledon greening and expansion, shoot development, floral transition, and gene expression is impaired. Genetic analysis indicates that GINI acts downstream of the sensor hexokinase in the glucose signaling pathway. Surprisingly, gin1 insensitivity to glucose repression of cotyledon and shoot development is phenocopied by ethylene precursor treatment of wild-type plants or by constitutive ethylene biosynthesis and constitutive ethylene signaling mutants. In contrast, the ethylene insensitive mutant etr1-1 exhibits glucose hypersensitivity. Epistasis analysis places GIN1 downstream of the ethylene receptor, ETR1, and defines a new branch of ethylene signaling pathway that is uncoupled from the triple response induced by ethylene. The isolation and characterization of gin1 reveal an unexpected convergence between the glucose and the ethylene signal transduction pathways. GINI may function to balance the control of plant development in response to metabolic and hormonal stimuli that act antagonistically. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM sheen@frodo.mgh.harvard.edu NR 47 TC 278 Z9 300 U1 3 U2 34 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 AUG 18 PY 1998 VL 95 IS 17 BP 10294 EP 10299 DI 10.1073/pnas.95.17.10294 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 112BX UT WOS:000075475200104 PM 9707641 ER PT J AU Rajan, P Gearan, T Fink, JS AF Rajan, P Gearan, T Fink, JS TI Leukemia inhibitory factor and NGF regulate signal transducers and activators of transcription activation in sympathetic ganglia: convergence of cytokine- and neurotrophin-signaling pathways SO BRAIN RESEARCH LA English DT Article DE sympathetic ganglion; axotomy; intracellular signaling; LIF; STAT; NGF ID NERVE GROWTH-FACTOR; VASOACTIVE-INTESTINAL-PEPTIDE; ADULT SENSORY NEURONS; SUPERIOR CERVICAL-GANGLION; STAT PROTEINS; NEUROPEPTIDE EXPRESSION; PHENOTYPIC PLASTICITY; SUBSTANCE-P; IN-VIVO; CULTURE AB We have used the response of the superior cervical ganglia (SCG) to axotomy to investigate interactions between neuropoietic cytokines and neurotrophins. Postganglionic sympathetic axotomy leads to a prolonged leukemia inhibitory factor (LIF)-dependent activation of signal transducers and activators of transcription (STAT) factors. To study regulation of LIF-dependent activation of STAT proteins and to mimic the loss of target-derived NGF resulting from postganglionic axotomy in vivo, SCG were explanted into media lacking NGF and activation of STAT proteins was assessed by electrophoretic mobility shift assay. Like postganglionic axotomy in vivo, STAT proteins were activated for up to 8 days after explantation of SCG in vitro. SCG cultured in the presence of NGF showed decreased STAT binding when compared to ganglia cultured in NGF-free media. This inhibition of STAT activation by NGF was only present in ganglia cultured for more than 5 days and was mimicked by brain-derived neurotrophic factor (BDNF). The serine kinase inhibitor H7 augmented the increase of STAT binding produced by explantation, suggesting the presence of a labile repressor of STAT activation in the SCG. These data indicated that the neuropoietic cytokine-signaling pathway interacts with neurotrophin and H7-sensitive-signaling pathways to regulate activation of STAT proteins in sympathetic neurons. Moreover, these data suggest that one of the mechanisms leading to prolonged activation of STAT proteins after postganglionic axotomy in vivo is loss of target-derived neurotrophins. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Mol Neurobiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Rajan, P (reprint author), NINDS, Mol Biol Lab, NIH, Bldg 36,Room 3C09, Bethesda, MD 20892 USA. EM rajan@codon.nih.gov FU NIMH NIH HHS [MH-11205]; NINDS NIH HHS [NS-27514] NR 41 TC 28 Z9 28 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 AUG 17 PY 1998 VL 802 IS 1-2 BP 198 EP 204 DI 10.1016/S0006-8993(98)00611-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 115BY UT WOS:000075644700022 PM 9748576 ER PT J AU De Tulleo, L Kirchhausen, T AF De Tulleo, L Kirchhausen, T TI The clathrin endocytic pathway in viral infection SO EMBO JOURNAL LA English DT Article DE clathrin adaptors; coated vesicles; endocytosis; viral entry ID SEMLIKI FOREST VIRUS; COATED VESICLE FORMATION; RECEPTOR-MEDIATED ENDOCYTOSIS; VESICULAR STOMATITIS-VIRUS; LYSOSOMOTROPIC WEAK BASES; LOW-DENSITY-LIPOPROTEIN; SINDBIS VIRUS; HELA-CELLS; LOW-PH; RHINOVIRUS RECEPTOR AB How important is the clathrin-dependent endocytic pathway for entry of viruses into host cells' While it is widely accepted that Semliki Forest virus (SFV), an enveloped virus, requires this pathway there are conflicting data concerning the closely related Sindbis virus, as well as varying results with picornaviruses such as human rhinovirus 14 (HRV 14) and poliovirus. We have examined the entry mode of SFV, Sindbis virus, HRV 14 and poliovirus using a method that identifies single infected cells. This assay takes advantage of the observation that the clathrin-dependent endocytic pathway is specifically and potently arrested by overexpression of dynamin mutants that prevent clathrin-coated pit budding. Using HeLa cells and conditions of low multiplicity of infection to favor use of the most avid pathway of cell entry, it was found that SFV, Sindbis virus and HRV 14 require an active clathrin-dependent endocytic pathway for successful infection. In marked contrast, infection of HeLa cells by poliovirus did not appear to require the clathrin pathway. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Grad Program Virol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu FU NIGMS NIH HHS [GM 36548] NR 32 TC 167 Z9 171 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 17 PY 1998 VL 17 IS 16 BP 4585 EP 4593 DI 10.1093/emboj/17.16.4585 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 114ML UT WOS:000075613200004 PM 9707418 ER PT J AU Takekawa, M Maeda, T Saito, H AF Takekawa, M Maeda, T Saito, H TI Protein phosphatase 2C alpha inhibits the human stress-responsive p38 and JNK MAPK pathways SO EMBO JOURNAL LA English DT Article DE MAP kinase; protein kinase; protein phosphatase; signal transduction; stress response ID SIGNAL-TRANSDUCTION PATHWAY; DUAL-SPECIFICITY PHOSPHATASE; TYROSINE-PHOSPHATASE; KINASE CASCADE; FISSION YEAST; MAMMALIAN-CELLS; IN-VIVO; MITOGEN; ACTIVATION; 2C AB MAPK (mitogen-activated protein kinase) cascades are common eukaryotic signaling modules that consist of a MAPK, a MAPK kinase (MAPKK) and a MAPKK kinase (MAPKKK). Because phosphorylation is essential for the activation of both MAPKKs and MAPKs, protein phosphatases are likely to be important regulators of signaling through MAPK cascades. To identify protein phosphatases that negatively regulate the stress-responsive p38 and JNK MAPK cascades, we screened human cDNA libraries for genes that downregulated the yeast HOG1 MAPK pathway, which shares similarities with the p38 and JNK pathways, using a hyperactivating yeast mutant. In this screen, the human protein phosphatase type 2C alpha (PP2C alpha) was found to negatively regulate the HOG1 pathway in yeast. Moreover, when expressed in mammalian cells, PP2C alpha inhibited the activation of the p38 and JNK cascades induced by environmental stresses. Both in vivo and in vitro observations indicated that PP2C alpha dephosphorylated and inactivated MAPKKs (MKK6 and SEK1) and a MAPK (p38) in the stress-responsive MAPK cascades. Furthermore, a direct interaction of PP2C alpha and p38 was demonstrated by a co-immunoprecipitation assay. This interaction was observed only when cells were stimulated with stresses or when a catalytically inactive PP2C alpha mutant was used, suggesting that only the phosphorylated form of p38 interacts with PP2C alpha. 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 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM haruo_saito@dfci.harvard.edu FU NIGMS NIH HHS [GM56699, GM50909] NR 47 TC 203 Z9 208 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD AUG 17 PY 1998 VL 17 IS 16 BP 4744 EP 4752 DI 10.1093/emboj/17.16.4744 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 114ML UT WOS:000075613200019 PM 9707433 ER PT J AU Kirch, SA Rathbun, GA Oettinger, MA AF Kirch, SA Rathbun, GA Oettinger, MA TI Dual role of RAG2 in V(D)J recombination: catalysis and regulation of ordered Ig gene assembly SO EMBO JOURNAL LA English DT Article DE B-cell development; immunoglobulin; RAG2; V(D)J recombination ID B-CELL-DEVELOPMENT; MURINE LEUKEMIA-VIRUS; LIGHT CHAIN GENES; IMMUNOGLOBULIN HEAVY; STRUCTURE REQUIREMENTS; TARGETED DELETION; DNA-SEQUENCE; 2 STEPS; REARRANGEMENT; REGIONS AB Immunoglobulin genes are assembled during lymphoid development by a series of site-specific rearrangements that are tightly regulated to ensure that functional antibodies are generated in B (but not T) cells and that a unique receptor is present on each cell. Because a common V(D)J recombinase comprising RAG1 and RAG2 proteins is used for both B- and T-cell antigen receptor assembly, lineage-specific rearrangement must be modulated through differential access to sites of recombination, We show here that the C-terminus of the RAG2 protein, although dispensable for the basic recombination reaction and for Ig heavy chain Du to JH joining, is essential for efficient V-H to DJ(H) rearrangement at the IgH locus, Thus, the RAG2 protein plays a dual role in V(D)J recombination, acting both in catalysis of the reaction and in governing access to particular loci. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Dept Biochem & Mol Biol, Cambridge, MA 02138 USA. Harvard Univ, Beth Israel Hosp, Inst Med, Dept Med, Boston, MA 02115 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM oettinger@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM48026] NR 44 TC 70 Z9 72 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 17 PY 1998 VL 17 IS 16 BP 4881 EP 4886 DI 10.1093/emboj/17.16.4881 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 114ML UT WOS:000075613200033 PM 9707447 ER PT J AU Yu, GS Lu, YC Gulick, T AF Yu, GS Lu, YC Gulick, T TI Expression of novel isoforms of carnitine palmitoyltransferase I (CPT-1) generated by alternative splicing of the CPT-I beta gene SO BIOCHEMICAL JOURNAL LA English DT Article ID MALONYL-COA SENSITIVITY; RAT-LIVER; CHROMOSOMAL LOCALIZATION; SINGLE POLYPEPTIDE; CARDIAC MYOCYTES; ENZYME-SYSTEM; CDNA; HEART; CLONING; ACETYLTRANSFERASE AB Carnitine palmitoyltransferase I (CPT-I) catalyses the rate-determining step in mitochondrial fatty acid beta-oxidation. The enzyme has two cognate structural genes that are preferentially expressed in liver (alpha) or fat and muscle (beta). We hypothesized the existence of additional isoforms in heart to account for unique kinetic characteristics of enzyme activity in this tissue. Hybridization and PCR screening of a human cardiac cDNA library revealed the expression of two novel CPT-I isoforms generated by alternative splicing of the CPT-I beta transcript, in addition to the beta and alpha cDNA species previously described. Ribonuclease protection and reverse transcriptase-mediated PCR assays confirmed the presence of mRNA species of each splicing variant in heart, skeletal muscle and liver, with differing relative concentrations in the tissues. The novel splicing variants omit exons or utilize a cryptic splice donor site within an exon. Deduced polypeptide sequences of the novel enzymes include omissions in the region of putative membrane-spanning and malonyl-CoA regulatory domains compared with the previously described CPT-Is, implying that the encoded enzymes will exhibit unique features with respect to outer mitochondrial membrane topology and response to physiological and pharmacological inhibitors. C1 Massachusetts Gen Hosp, Diabet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gulick, T (reprint author), Massachusetts Gen Hosp, Diabet Unit, MGH E,CNY 149 3610,149 13th St, Charlestown, MA 02129 USA. EM gulick@helix.mgh.harvard.edu FU NIDDK NIH HHS [P30-DK40561, K02-DK02461] NR 37 TC 23 Z9 23 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 15 PY 1998 VL 334 BP 225 EP 231 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 113NM UT WOS:000075558200031 PM 9693124 ER PT J AU Seidman, LJ Biederman, J Weber, W Hatch, M Faraone, SV AF Seidman, LJ Biederman, J Weber, W Hatch, M Faraone, SV TI Neuropsychological function in adults with attention-deficit hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; neuropsychology; adults; frontal lobe; memory; learning ID OSTERRIETH COMPLEX FIGURE; QUANTITATIVE MORPHOLOGY; CAUDATE-NUCLEUS; CORPUS-CALLOSUM; CHILDREN; COMORBIDITY; PERFORMANCE; PSYCHOPATHOLOGY; DYSFUNCTION; SAMPLE AB Background: Recent studies indicate that attention-deficit hyperactivity disorder (ADHD) persists into adulthood, but little is known about the neuropsychological features of adult ADHD, Our objective was to assess neuropsychological functioning in adults with ADHD with a battery of executive function tests. Methods: Subjects were 64 unmedicated adults, 19-59 years of age, with DSM-III-R ADHD of childhood onset who met criteria for ADHD when referred in adulthood and 73 non-ADHD controls of similar age and gender Information on neuropsychological performance was obtained irt a standardized manner blind to clinical status. Results: Compared with controls, adults with ADHD were significantly impaired on measures of vigilance, semantic encoding for verbal memory, and written arithmetic, irrespective of age, gender, psychiatric comorbidity, or presence of learning disability. Despite comparable educational level and IQ, ADHD adults had a trend to lower occupational attainment and had significantly? more academic problems in school. Conclusions: These executive, attention, and achievement dysfunctions demonstrated in adults with ADHD provide additional support for the validity of the syndrome in adults. Biol Psychiatry 1998;44:260-268 (C) 1998 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725, Boston, MA 02114 USA. Massachusetts Mental Hlth Ctr, Neuropsychol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA 02401 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Brockton, MA 02401 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725, Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01MH-41314] NR 49 TC 178 Z9 182 U1 3 U2 17 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 AUG 15 PY 1998 VL 44 IS 4 BP 260 EP 268 DI 10.1016/S0006-3223(97)00392-2 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 110CP UT WOS:000075362800004 PM 9715357 ER PT J AU Biederman, J Wilens, TE Mick, E Faraone, SV Spencer, T AF Biederman, J Wilens, TE Mick, E Faraone, SV Spencer, T TI Does attention-deficit hyperactivity disorder impact the developmental course of drug and alcohol abuse and dependence? SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; drug; alcohol; PSUD; attention; development ID YOUNG ADULTHOOD; PSYCHIATRIC COMORBIDITY; RISK-FACTORS; ADOLESCENCE; CHILDHOOD; PATTERNS; PROGRESSION; PRECURSORS; BOYS AB Background: The co-occurrence of attention-deficit hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD) in adults has been the focus of much clinical and scientific inquiry. In this study we examine the effects of ADHD on the transitions from substance abuse to dependence and between different classes of agents of abuse. Methods: An ADHD sample of 239 consecutively referred adults of both genders with a clinical diagnosis of childhood-onset and persistent DSM-III-R ADHD confirmed by structured interview were compared with 268 non-ADHD healthy adults. Results: ADHD was associated with a twofold increased risk for PSUD, ADHD subjects were significantly more likely than comparisons to make the transition from an alcohol use disorder to a drug use disorder (hazard ratio = 3.8) and were significantly more likely to continue to abuse substances following a period of dependence (hazard ratio = 4.9). Conclusions: ADHD is associated with a sequence of PSUD in which early alcohol use disorder increases the risk for subsequent drug use disorder and early substance dependence increases the risk for subsequent substance abuse. If confirmed such developmental pathways might lead to preventive and early intervention strategies aimed at reducing the risk for PSUD in ADHD subjects. Biol Psychiatry 1998;44:269-273 (C) 1998 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, ACC 725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brockton W Roxbury Vet Affairs Med Ctr, Dept Psychiat,Inst Psychiat Epidemiol & Genet, Brockton, MA 02401 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, ACC 725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K20MHO1175, R01MH41314] NR 34 TC 178 Z9 181 U1 1 U2 9 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 AUG 15 PY 1998 VL 44 IS 4 BP 269 EP 273 DI 10.1016/S0006-3223(97)00406-X PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 110CP UT WOS:000075362800005 PM 9715358 ER PT J AU Harris, KW Hu, XJ Schultz, S Arcasoy, MO Forget, BG Clare, N AF Harris, KW Hu, XJ Schultz, S Arcasoy, MO Forget, BG Clare, N TI The distal cytoplasmic domain of the erythropoietin receptor induces granulocytic differentiation in 32D cells SO BLOOD LA English DT Article ID STIMULATING-FACTOR-RECEPTOR; GROWTH; PROLIFERATION; SUPPRESSION; APOPTOSIS; LEUKEMIA; SIGNALS; LINES AB The role of hematopoietic growth factors in lineage commitment and differentiation is unclear, We present evidence that heterologous expression of an erythroid specific receptor allows granulocytic differentiation of a myeloid cell line. We have previously characterized a truncation mutant of the erythropoietin receptor (EpoR), which is associated with familiar erythrocytosis (Blood 89:4628, 1997), This truncated EpoR lacks the distal 70 amino acids of the cytoplasmic domain. To study the functional role of this distal receptor domain, 32D cells, a murine interleukin-3 (IL-3)-dependent myeloid line, were transfected with the wild-type EpoR (32D/EpoR Wi) or the truncated EpoR (32D/EpoR FE). 32D cells expressing either the full-length or truncated EpoR display equivalent proliferative rates in saturating concentrations of Epo. There is a dramatic difference in maturational phenotype between the two cell lines, however. The 32D/EpoR FE cells and mock transfected 32D cells have an immature, monoblastic morphology and do not express the primary granule protein myeloperoxidase, The 32D/EpoR WT cells, on the other hand, demonstrate granulocytic differentiation with profuse granulation, mature, clumped chromatin, and myeloperoxidase expression. There is no evidence of erythroid differentiation in 32D cells transfected with either the full-length or truncated EpoR. Treatment of the cells with the specific Jak2 inhibitor tyrphostin AG 490 inhibits myeloid differentiation driven by the distal EpoR. We conclude that: (1) the distal cytoplasmic domain of the EpoR is able to induce a specific myeloid differentiation signal distinct from mitogenic signaling, and (2) these data extend to myelopoiesis the growing body of evidence that the cellular milieu, not the specific cytokine receptor, determines the specificity of differentiation after cytokine receptor activation, (C) 1998 by The American Society of Hematology. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Yale Univ, Sch Med, Dept Med, Hematol Sect, New Haven, CT USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Harris, KW (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDDK NIH HHS [DK 44058] NR 24 TC 12 Z9 12 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1998 VL 92 IS 4 BP 1219 EP 1224 PG 6 WC Hematology SC Hematology GA 109MR UT WOS:000075326800017 PM 9694710 ER PT J AU Renshaw, AA Richie, JP Loughlin, KR Jiroutek, M Chung, A D'Amico, AV AF Renshaw, AA Richie, JP Loughlin, KR Jiroutek, M Chung, A D'Amico, AV TI The greatest dimension of prostate carcinoma is a simple, inexpensive predictor of prostate specific antigen failure in radical prostatectomy specimens SO CANCER LA English DT Article DE prostatic neoplasms; pathology; volume; methods; prognosis ID PATHOLOGICAL FEATURES; MULTIVARIATE-ANALYSIS; TUMOR VOLUME; FOLLOW-UP; CANCER; PROGNOSIS; STAGE AB BACKGROUND. Tumor volume in radical prostatectomies can be determined by several different techniques and appears to predict clinical progression. Greatest tumor dimension and area are easily obtained measures that are both correlated with tumor volume. The authors sought to determine whether greatest tumor dimension and/or area were predictors of prostate specific antigen (PSA) failure in men who underwent radical prostatectomy for adenocarcinoma of the prostate. METHODS. Fifty-seven men with prostate carcinoma who underwent surgical resection were followed for a median of 27.2 months (range, 1-112 months); 24 (42%) of these men had PSA failure. Preoperative PSA, Gleason grade, pathologic stage, margin status, and greatest tumor dimension and area were determined, and both univariate and multivariate analyses of the outcomes of PSA failure were performed. RESULTS. In the univariate analysis, larger values of greatest tumor dimension and area were strongly associated with increased incidence of PSA failure (P = 0.0001 and 0.0011, respectively). The forward stepwise multivariate analysis indicated that greatest tumor dimension had marginal statistical significance as a risk factor for PSA failure (P = 0.0577; risk ratio, 1.117). However, in this series, men with a greatest tumor dimension of less than 1 cm did not experience failure, whereas all patients with a greatest tumor dimension of more than 2 cm did. CONCLUSIONS. Measuring greatest tumor dimension is a simple, inexpensive predictor of PSA failure in men who have undergone radical prostatectomy. Cancer 1998;83:748-52. (C) 1998 American Cancer Society. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. RP Renshaw, AA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 18 TC 38 Z9 39 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1998 VL 83 IS 4 BP 748 EP 752 DI 10.1002/(SICI)1097-0142(19980815)83:4<748::AID-CNCR17>3.0.CO;2-S PG 5 WC Oncology SC Oncology GA 107QV UT WOS:000075221500017 PM 9708940 ER PT J AU Chung, DC Brown, SB Graeme-Cook, F Tillotson, LG Warshaw, AL Jensen, RT Arnold, A AF Chung, DC Brown, SB Graeme-Cook, F Tillotson, LG Warshaw, AL Jensen, RT Arnold, A TI Localization of putative tumor suppressor loci by genome-wide allelotyping in human pancreatic endocrine tumors SO CANCER RESEARCH LA English DT Article ID PARATHYROID ADENOMAS; SOMATIC MUTATIONS; TRANSGENIC MICE; P53 MUTATIONS; FREQUENT LOSS; RAS ONCOGENE; GENE; DNA; ADENOCARCINOMA; TUMORIGENESIS AB Only two tumor suppressor gene loci, one on 3p25 and the MEN1 gene on 11q13, have thus far been implicated in the pathogenesis of sporadic human pancreatic endocrine tumors (PETs), A genome-wide allelotyping study of 28 human PETs was undertaken to identify other potential tumor suppressor gene loci. In addition to those on chromosomes 3p and 11q, frequent allelic deletions were identified on 3q (32%), 11p (36%), 16p (36%), and 22q (29%). Finer deletion mapping studies localized the smallest regions of common deletion to 3q27, 11p13, and 16p12.3-13.11. Potential candidate genes at these loci include WT1 (11p13), TSC2 (16p13), and NF2 (22q12), but no known tumor suppressor gene localizes to 3q27, The mean fractional allelic loss among these human PETs is 0.126, and no correlation was observed between allelic loss and clinical parameters, including age, sea, hormonal subtype, and disease stage. These findings highlight novel locations of tumor suppressor gene Loci that contribute to the pathogenesis of human PETs, and several of these on 3p, 3q, and 22q are syntenic with loci on mouse chromosomes 9 and 16 that are implicated in a murine transgenic model of PETs. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Endocrine Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Univ N Carolina, Div Digest Dis, Chapel Hill, NC 27599 USA. NIH, Digest Dis Branch, Bethesda, MD 20892 USA. RP Chung, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, GRJ 823,32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK01410-11] NR 35 TC 70 Z9 72 U1 0 U2 0 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 AUG 15 PY 1998 VL 58 IS 16 BP 3706 EP 3711 PG 6 WC Oncology SC Oncology GA 112EU UT WOS:000075481800038 PM 9721882 ER PT J AU Robles, AI Rodriguez-Puebla, ML Glick, AB Trempus, C Hansen, L Sicinski, P Tennant, RW Weinberg, RA Yuspa, SH Conti, CJ AF Robles, AI Rodriguez-Puebla, ML Glick, AB Trempus, C Hansen, L Sicinski, P Tennant, RW Weinberg, RA Yuspa, SH Conti, CJ TI Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo SO GENES & DEVELOPMENT LA English DT Article DE knockout; Tg.AC; cell cycle; keratinocyte; two-stage carcinogenesis ID EPIDERMAL-KERATINOCYTES; D1 OVEREXPRESSION; LUNG-CANCER; CELL-LINES; MOUSE SKIN; EXPRESSION; P16(INK4); GROWTH; CARCINOGENESIS; TRANSFORMATION AB Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as eel growth in culture. Here, rye provide evidence that ras-mediated tumorigenesis depends on signaling pathways that act preferentially through cyclin D1. Cyclin D1 expression and the activity of its associated kinase are up-regulated in keratinocytes in response to oncogenic ras. Furthermore, cyclin D1 deficiency results in up to an 80% decrease in the development of squamous tumors generated through either grafting of retroviral ras-transduced keratinocytes, phorbol ester treatment of ras transgenic mice, or two-stage carcinogenesis. C1 Univ Texas, MD Anderson Cancer Ctr, Sci Pk Res Div, Smithville, TX 78957 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. RP Conti, CJ (reprint author), Univ Texas, MD Anderson Cancer Ctr, Sci Pk Res Div, Smithville, TX 78957 USA. EM SA83125@odin.mdacc.tmc.edu FU NCI NIH HHS [CA42157, R01 CA042157] NR 35 TC 181 Z9 184 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 15 PY 1998 VL 12 IS 16 BP 2469 EP 2474 DI 10.1101/gad.12.16.2469 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 114JG UT WOS:000075604900003 PM 9716400 ER PT J AU Paradis, S Ruvkun, G AF Paradis, S Ruvkun, G TI Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor SO GENES & DEVELOPMENT LA English DT Article DE insulin signaling; dauer; fork head transcription factor; life span ID PROTEIN-KINASE; C-ELEGANS; PHOSPHATIDYLINOSITOL 3-KINASE; CHEMOSENSORY NEURONS; LARVAL DEVELOPMENT; AKT PROTOONCOGENE; FAMILY MEMBER; LIFE-SPAN; LONGEVITY; GENE AB A neurosecretory pathway regulates a reversible developmental arrest and metabolic shift at the Caenorhabditis elegans dauer larval stage, Defects in an insulin-like signaling pathway cause arrest at the dauer stage. We show here that two C. elegans Akt/PKB homologs, akr-l and akt-2, transduce insulin receptor-like signals that inhibit dauer arrest and that AKT-1 and AKT-2 signaling are indispensable for insulin receptor-like signaling in C. elegans, A loss-of-function mutation in the Pork head transcription factor DAF-16 relieves the requirement far Akt/PKB signaling, which indicates that AKT-1 and AKT-2 function primarily to antagonize DAF-16. This is the first evidence that the major target of Akt/PKB signaling is a transcription factor. An activating mutation in akt-1, revealed by a genetic screen, as well as increased dosage of wild-type akt-1 relieves the requirement for signaling from AGE-1 PI3K, which acts downstream of the DAF-2 insulin/IGF-1 receptor homolog. This demonstrates that Akt/PKB activity is not necessarily dependent on AGE-1 PI3K activity. akt-1 and akt-2 are expressed in overlapping patterns In the nervous system and in tissues that are remodeled during dauer formation. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM Ruvkun@frodo.mgh.harvard.edu FU NIA NIH HHS [R01 AG014161, R01AG14161] NR 44 TC 442 Z9 457 U1 3 U2 30 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 15 PY 1998 VL 12 IS 16 BP 2488 EP 2498 DI 10.1101/gad.12.16.2488 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 114JG UT WOS:000075604900005 PM 9716402 ER PT J AU Biswas, DK Mhashilkar, AM Ewaniuk, DS Pezza, JA Oh, LM Kannangara, GSK Tius, MA Pardee, AB AF Biswas, DK Mhashilkar, AM Ewaniuk, DS Pezza, JA Oh, LM Kannangara, GSK Tius, MA Pardee, AB TI Inhibition of HIV-1 replication by combination of a novel inhibitor of TNF-alpha with AZT SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE combination therapy; cellular; viral; factors; TNF-alpha inhibitor ID HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; LONG TERMINAL REPEAT; TAT; TYPE-1; EXPRESSION; INFECTION; MECHANISM; ACTIVATION AB The small molecule S9a was derived from an established tumor necrosis factor-alpha (TNF-alpha) inhibitor (Canventol) by replacement of the isopropylidine group with a phenyl ring. S9a at 10 to 100 nM inhibited HIV production as potently as 3'-azido-3'-deoxythymidine (AZT), an inhibitor of viral reverse transcriptase. Further more, S9a and AZT in combination, at noncytoxic concentrations strongly inhibited HIV-1 replication that was more than additive and substantially prolonged the appearance of virus both in acutely infected CD4(+) lymphocytes (SupT) in culture and in peripheral blood mononuclear cells (PBMCs) infected with a primary HIV-I isolate. S9a inhibited TNF-alpha promoter-driven reporter gene activity. It was proposed that the mechanism of antiviral action of S9a war; on the host cell, by blocking TNF-alpha transcription via a Tat-induced tar-independent loop, which decreases downstream NF-kappa B activation of HIV-1 long terminal repeat (LTR), S9a was superior to the first generation compound Canventol, which was superior to the natural compound sarcophytol A, demonstrating that further structure-based enhancement of potency of these compounds is feasible. This study suggests a therapeutic approach against AIDS by application of tyro drugs, one against a cellular and the other a viral target, which may provide an approach to the problem of frequent emergence of resistant variants to combinations of drugs that target only HIV-genes. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cell Growth & Regulat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Human Retrovirol, Boston, MA 02115 USA. Univ Hawaii, Dept Chem, Honolulu, HI 96822 USA. RP Biswas, DK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cell Growth & Regulat, 44 Binney St, Boston, MA 02115 USA. EM biswas@mbcrr.harvard.edu NR 32 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD AUG 15 PY 1998 VL 18 IS 5 BP 426 EP 434 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 113VX UT WOS:000075575500003 PM 9715838 ER PT J AU Tanaka, S Mori, M Akiyoshi, T Tanaka, Y Mafune, K Wands, JR Sugimachi, K AF Tanaka, S Mori, M Akiyoshi, T Tanaka, Y Mafune, K Wands, JR Sugimachi, K TI A novel variant of human Grb7 is associated with invasive esophageal carcinoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE Grb7; Mig-10; splice variant; esophageal carcinoma; metastasis ID GROWTH-FACTOR RECEPTOR; PLECKSTRIN HOMOLOGY DOMAINS; CANCER METASTASIS; C-ABL; PROTEIN; CLONING; INSULIN; BINDING; FAMILY; EXPRESSION AB The cDNAs of a putative growth factor-bound (Grb) 7 signal transduction molecule and Grb7V novel splice variant were isolated from an invasive human esophageal carcinoma. Although both Grb7 isoforms share homology with the Mig-10 cell migration gene, the Grb7V isoform lacks 88 base pairs in the C terminus; the resultant frame shift leads to substitution of an SH2 domain with a short hydrophobic sequence. The wild-type Grb7 protein, but not the Grb7V isoform, is rapidly tyrosyl phosphorylated in response to EGF stimulation in esophageal carcinoma cells. Analysis of human esophageal tumor tissues and regional lymph nodes with metastases revealed that Grb7V was expressed in 40% of Grb7-positive esophageal carcinomas. More importantly, Grb7V expression was enhanced after metastatic spread to lymph nodes as compared to the original tumor tissues. Finally, transfection of an antisense Grb7 RNA expression construct lowered endogenous Grb7 protein levels and suppressed the invasive phenotype exhibited by esophageal carcinoma cells. These findings suggest that Grb7 isoforms are involved in cell invasion and metastatic progression of human esophageal carcinomas. C1 Kyushu Univ, Med Inst Bioregulat, Dept Surg, Beppu, Oita 8740838, Japan. Kyushu Univ, Fac Med, Dept Surg 2, Fukuoka 812, Japan. Saitama Canc Ctr, Dept Surg, Ina, Saitama, Japan. Univ Tokyo, Fac Med, Dept Surg, Tokyo 113, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. RP Tanaka, S (reprint author), Kyushu Univ, Med Inst Bioregulat, Dept Surg, 4546 Tsurumibaru, Beppu, Oita 8740838, Japan. RI Mori, Masaki/A-4501-2011; U-ID, Kyushu/C-5291-2016 FU NCI NIH HHS [CA35711] NR 23 TC 62 Z9 64 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 15 PY 1998 VL 102 IS 4 BP 821 EP 827 DI 10.1172/JCI2921 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 113MX UT WOS:000075556500021 PM 9710451 ER PT J AU Jin, YJ Friedman, J Burakoff, SJ AF Jin, YJ Friedman, J Burakoff, SJ TI Regulation of tyrosine phosphorylation in isolated T cell membrane by inhibition of protein tyrosine phosphatases SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; ZETA-CHAIN; KINASE; ACTIVATION; ZAP-70; CD45; STIMULATION; INVOLVEMENT; PATHWAY AB Jurkat T cells activated by the phosphotyrosine phosphatase inhibitors H2O2 or vanadate were found to have a similar pattern of tyrosine phosphorylation when compared with T cells stimulated by anti-CD3 Ab cross-linking, suggesting that protein tyrosine phosphatase (PTP) inhibitors affect the early steps of TCR signaling. To study the role of PTPs in the most proximal membrane events of tyrosine phosphorylation, subcellular fractions of T cells were treated with the PTP inhibitors in the presence of ATP, In the membrane fraction, tyrosine phosphorylation of Lck, Fyn, and CD3 zeta can be induced by PTP inhibitors, but not by anti-CD3, Detailed characterization of this cell-free system showed that the pattern and the order of induced tyrosine phosphorylation is similar to that induced in intact cells, Upon removal of the PTP inhibitor, the tyrosine-phosphorylated proteins, including Lck, Fyn, Syk, Zap70, and CD3 zeta, are rapidly dephosphorylated. Preliminary characterizations indicate that a PTP distinct from CD45, SHP1, and SHP2 is present in T cell membranes and the inhibition of this get unidentified PTP is most likely responsible for the Lck-dependent tyrosine phosphorylation triggered by PTP inhibitors. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Jin, YJ (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Room M654,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA 70758] NR 40 TC 51 Z9 51 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 AUG 15 PY 1998 VL 161 IS 4 BP 1743 EP 1750 PG 8 WC Immunology SC Immunology GA 109VV UT WOS:000075345400022 PM 9712039 ER PT J AU Kline, DD Yang, TN Huang, PL Prabhakar, NR AF Kline, DD Yang, TN Huang, PL Prabhakar, NR TI Altered respiratory responses to hypoxia in mutant mice deficient in neuronal nitric oxide synthase SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID NUCLEUS-TRACTUS-SOLITARII; CAT CAROTID-BODY; VENTILATORY RESPONSE; RAT; OXYGEN; INHIBITION; LOCALIZATION; CEREBELLUM; MESSENGER; ISOFORMS AB 1. The role of endogenous nitric oxide (NO) generated by neuronal nitric oxide synthase (NOS-l) in the control of respiration during hypoxia and hypercapnia was assessed using mutant mice deficient in NOS-1. 2. Experiments were performed on awake and anaesthetized mutant and ir wild-type control mice. Respiratory responses to varying levels of inspired oxygen (100, 21 and 12% O-2) and carbon dioxide (3 and 5% CO2 balanced oxygen) were analysed. In a awake animals, respiration was monitored by body plethysmograph along with oxygen consumption ((V) over dot(O2)), CO2 production ((V) over dot(CO2)) and body temperature. In anaesthetized, spontaneously breathing mice, integrated efferent phrenic nerve activity was monitored as an index of neural respiration along with arterial blood pressure and blood gases. Cyclic 3',5'-guanosine monophosphate (cGMP) levels in the brainstem were analysed by radioimmunoassay as an index of nitric oxide generation. 3. Unanaesthetized mutant mice exhibited greater respiratory responses during 21 and 12% O-2 than the wild-type controls. Respiratory responses were associated with significant decreases in oxygen consumption in both groups of mice, and the magnitude of change was greater in mutant than wild-type mice. Changes in CO2 production and body temperature, however, were comparable between both groups of mice. 4. Similar augmentation of respiratory responses during hypoxia was also observed in anaesthetized mutant mice. In addition, five of the fourteen mutant mice displayed periodic oscillations in respiration (brief episodes of increases in respiratory rate and tidal phrenic nerve activity) while breathing 21 and 12% O-2, but not during 100% O-2. The time interval between the episodes decreased by reducing inspired oxygen from 21 to 12% O-2. 5. Changes in arterial blood pressure and arterial blood gases were comparable at any given level of inspired oxygen between both groups of mice, indicating that changes in these variables do not account for the differences in the response to hypoxia. 6. Respiratory responses to brief hyperoxia (Dejours test) and to cyanide, a potent chemoreceptor stimulant, were more pronounced in mutant mice, suggesting augmented peripheral chemoreceptor sensitivity. 7. cGMP levels were elevated in the brainstem during 21 and 12% O-2 in wild-type but not in mutant mice, indicating decreased formation of nitric oxide in mutant mice. 8. The magnitude of respiratory responses to hypercapnia (3 and 5% CO2 balanced oxygen) was comparable in both groups of mice in the awake and anaesthetized conditions. 9. These observations suggest that the hypoxic responses were selectively augmented in mutant mice deficient in NOS-1. Peripheral as well as central mechanisms contributed to the altered responses to hypoxia. These results support the idea that nitric oxide generated by NOS-1 is an important physiological modulator of respiration during hypoxia. C1 Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. RP Prabhakar, NR (reprint author), Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, 10900 Euclid Ave, Cleveland, OH 44106 USA. OI Kline, David/0000-0003-3269-0184 FU NHLBI NIH HHS [HL-07714-05, HL-2580, T32 HL007714] NR 40 TC 97 Z9 98 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD AUG 15 PY 1998 VL 511 IS 1 BP 273 EP 287 DI 10.1111/j.1469-7793.1998.273bi.x PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 121XD UT WOS:000076040400026 PM 9679181 ER PT J AU Bosch, RJ Ryan, LM AF Bosch, RJ Ryan, LM TI Generalized Poisson models arising from Markov processes SO STATISTICS & PROBABILITY LETTERS LA English DT Article DE birth process; overdispersion; underdispersion; differential equations ID BIRTH PROCESSES; LIKELIHOOD AB We develop a family of distributions which allow for over- and underdispersion relative to the Poisson. This latter feature is particularly appealing since many existing methods only allow for overdispersion. These distributions arise from underlying continuous-time Markov processes in which event rates depend on how many events have already occurred. The results are illustrated with underdispersed count data from a polyspermy study and overdispersed data from the Canadian Sickness Survey. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 22 TC 5 Z9 5 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7152 J9 STAT PROBABIL LETT JI Stat. Probab. Lett. PD AUG 15 PY 1998 VL 39 IS 3 BP 205 EP 212 DI 10.1016/S0167-7152(98)00028-5 PG 8 WC Statistics & Probability SC Mathematics GA 111TX UT WOS:000075455000003 ER PT J AU Simon, AR Warrens, AN Yazzie, NP Seebach, JD Sachs, DH Sykes, M AF Simon, AR Warrens, AN Yazzie, NP Seebach, JD Sachs, DH Sykes, M TI Cross-species interaction of porcine and human integrins with their respective ligands - Implications for xenogeneic tolerance induction SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; CELL-ADHESION MOLECULE-1; HEMATOPOIETIC PROGENITORS; STEM-CELLS; T-CELLS; NONMYELOABLATIVE REGIMEN; DENDRITIC CELLS; XENOGRAFT DONOR; CLONAL DELETION; SPLICED DOMAIN AB Background, Organ transplantation is limited by the number of available donors. One possible solution would be the use of pigs as organ donors. However, current immunosuppressive protocols cannot prevent rejection of these organs. If donor-specific tolerance toward porcine antigens could be induced in recipients, subsequent implantation of porcine organs would be possible without further immunosuppression. Induction of tolerance can be achieved with a bone marrow transplant if donor antigen presenting cells successfully differentiate in the recipient thymus to induce deletion of donor-reactive host cells. Migration of porcine progenitor cells to the host marrow and thymus and differentiation into tolerance-inducing antigen-presenting cells is likely to require successful interaction of porcine adhesion molecules with human ligands. In this study, we investigated whether very late antigen (VLA)-4 and VLA-6 integrins, which play important roles in homing and differentiation of hematopoietic progenitor cells, function across the pig-to-human species barrier. Methods. Static cell-to-cell and cell-to-extracellular matrix protein adhesion assays were used to examine the cross-species interaction of porcine adhesion molecules with human ligands. Results. Our studies show that porcine cells adhere to various human endothelial cell monolayers and extracellular matrix proteins and demonstrate that porcine VLA-4 and VLA-6 appear to be fully cross-reactive to the human ligands vascular cell adhesion molecule-1 and laminin, respectively. Conclusions. It is likely that porcine hematopoietic progenitor cells will be able to successfully employ pVLA-4- and pVLA-6-human ligand interactions in a pig-to-human bone marrow transplantation model in order to induce donor-specific tolerance. C1 Harvard Univ, Sch Med,Massachusetts Gen Hosp, Surg Serv,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Surg Serv,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL46532, HL254038] NR 48 TC 35 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 15 PY 1998 VL 66 IS 3 BP 385 EP 394 DI 10.1097/00007890-199808150-00017 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 112QZ UT WOS:000075506800017 PM 9721809 ER PT J AU Kleinschmidt-DeMasters, BK Mahalingam, R Shimek, C Marcoux, HL Wellish, M Tyler, KL Gilden, DH AF Kleinschmidt-DeMasters, BK Mahalingam, R Shimek, C Marcoux, HL Wellish, M Tyler, KL Gilden, DH TI Profound cerebrospinal fluid pleocytosis and Froin's syndrome secondary to widespread necrotizing vasculitis in an HIV-positive patient with varicella zoster virus encephalomyelitis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE varicella zoster virus; encephalomyelitis; pleocytosis; vasculitis; Froin's syndrome; cerebrospinal fluid; polymerase chain reaction; HIV ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; POLYMERASE CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; HERPES-ZOSTER; IMMUNOSUPPRESSED PATIENTS; CEREBRAL VASCULOPATHY; ENCEPHALITIS; DNA; SIMPLEX; COMPLICATIONS AB Demonstration of the direct involvement of cranial blood Vessels by varicella tester virus (VZV) is facilitated by immunohistochemistry (IHC), in situ hybridization (ISH) and polymerase chain reaction (PCR) techniques. The extent to which an inflammatory vasculitis serves as the pathogenic mechanism for VZV encephalomyelitis (VZVE) is still, however, debated. Most VZVE patients are immuno-compromised and show little inflammation, either pre-mortem in cerebrospinal fluid (CSF) or at autopsy. We describe an HIV-positive patient with a moderately depressed CD4 count (304) who presented with massively elevated CSF protein (1800 mg/dl), bloody CSF and pleocytosis (1300 white blood cells (WBC)/mm(3)). His CSF was positive for VZV DNA by PCR. He was treated with acyclovir and foscarnet, but died. At autopsy, an unusually widespread, inflammatory, transmural vasculitis caused by VZV affected meningeal vessels at virtually all brain stem and spinal cord levels, causing multiple subpial hemorrhages and necrosis. Virus DNA in multiple areas of brain, brainstem and spinal cord was readily revealed by PCR, but not by the presence of viral inclusions, IHC or ISH. This case, with a clinically confusing presentation for VZVE, illustrates the extensive, albeit infrequent, degree of necrotizing vasculitis and CSF abnormalities that VZV is capable of producing. Antiviral therapy may have inhibited VZV genome replication and subsequent antigen production, resulting in negative ISH and IHC studies, but generated increased VZV genomic fragments that were detectable by the more sensitive PCR technique. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Denver VA Med Ctr, Dept Neurol, Denver, CO 80262 USA. RP Kleinschmidt-DeMasters, BK (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pathol, 4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 NR 28 TC 14 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD AUG 14 PY 1998 VL 159 IS 2 BP 213 EP 218 DI 10.1016/S0022-510X(98)00171-3 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 115DB UT WOS:000075647300017 PM 9741410 ER PT J AU Wu, MX Ao, ZH Prasad, KVS Wu, RL Schlossman, SF AF Wu, MX Ao, ZH Prasad, KVS Wu, RL Schlossman, SF TI IEX-1L, an apoptosis inhibitor involved in NF-kappa B-mediated cell survival SO SCIENCE LA English DT Article ID EARLY-RESPONSE GENE; MICE LACKING; DEATH; EXPRESSION; PROTEIN AB Transcription factors of the nuclear factor-kappa B/rel (NF-kappa B) family may be important in cell survival by regulating unidentified, anti-apoptotic genes. One such gene that protects cells from apoptosis induced by pas or tumor necrosis factor type or (TNF), IEX-1L, is described here. Its transcription induced by TNF was decreased in cells with defective NF-kappa B activation, rendering them sensitive to TNF-induced apoptosis, which was abolished by transfection with IEX-1L. In support, overexpression of antisense IEX-1L partially blocked TNF-induced expression of IEX-1L and sensitized normal cells to killing. This study demonstrates a key role of IEX-1L in cellular resistance to TNF-induced apoptosis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wu, MX (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI12069, P30AI28691] NR 17 TC 363 Z9 373 U1 0 U2 1 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 AUG 14 PY 1998 VL 281 IS 5379 BP 998 EP 1001 DI 10.1126/science.281.5379.998 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 110ZK UT WOS:000075412700050 PM 9703517 ER PT J AU Jones, D Ballestas, ME Kaye, KM Gulizia, JM Winters, GL Fletcher, J Scadden, DT Aster, JC AF Jones, D Ballestas, ME Kaye, KM Gulizia, JM Winters, GL Fletcher, J Scadden, DT Aster, JC TI Primary-effusion lymphoma and Kaposi's sarcoma in a cardiac-transplant recipient SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN HERPESVIRUS-8 DNA; AIDS-RELATED LYMPHOMAS; CASTLEMANS DISEASE; SEQUENCES; VIRUS; KSHV; ESTABLISHMENT; TISSUE; TUMORS; CELLS C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Ctr AIDS Res, Boston, MA 02114 USA. RP Aster, JC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RI Jones, Daniel/I-7399-2015 FU NCI NIH HHS [CA66849, CA67380, CA73580] NR 48 TC 119 Z9 122 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 13 PY 1998 VL 339 IS 7 BP 444 EP 449 DI 10.1056/NEJM199808133390705 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 109UP UT WOS:000075342500005 PM 9700178 ER PT J AU O'Gara, PT Weyman, AE Narula, N Madsen, JC Mark, EJ AF O'Gara, PT Weyman, AE Narula, N Madsen, JC Mark, EJ TI A 34-year-old man with new mitral regurgitation after aortic-valve replacement for bacterial endocarditis - Necrosis of the anterolateral papillary muscle of the left ventricle, with mitral regurgitation (after aortic-valve replacement because of acute bacterial endocarditis) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; INFECTIVE ENDOCARDITIS; CLINICAL CORRELATIONS; ADDICTS; NECROPSY; PROLAPSE; RISK; ERA C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP O'Gara, PT (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. NR 44 TC 0 Z9 0 U1 1 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 13 PY 1998 VL 339 IS 7 BP 459 EP 466 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 109UP UT WOS:000075342500008 ER PT J AU FitzGerald, MG Marsh, DJ Wahrer, D Bell, D Caron, S Shannon, KE Ishioka, C Isselbacher, KJ Garber, JE Eng, C Haber, DA AF FitzGerald, MG Marsh, DJ Wahrer, D Bell, D Caron, S Shannon, KE Ishioka, C Isselbacher, KJ Garber, JE Eng, C Haber, DA TI Germline mutations in PTEN are an infrequent cause of genetic predisposition to breast cancer SO ONCOGENE LA English DT Article DE PTEN/MMAC1; Cowden syndrome; breast cancer; genetic predisposition; yeast truncation assay AB Heterozygous germline mutations in PTEN are responsible for most cases of Cowden Syndrome, a rare familial trait characterized by hamartomas and by predisposition to cancer of the breast and thyroid. The variable and often subtle clinical findings that characterize Cowden Syndrome are frequently unrecognized, raising the possibility that germline PTEN mutations may confer susceptibility to breast cancer in women who have not been diagnosed with this syndrome. To determine whether such mutations contribute to genetic predisposition to breast cancer within the general population, we analysed a cohort of women with early-onset breast cancer ( 600 nM). Upon addition of 1 mM Mn2+, or activating antibody 9EG7, binding affinity for both laminin-5 and invasin increased by about 10-fold, whereas the affinity decreased upon addition of 2 mM Ca2+. Thus, functional regulation of the purified soluble integrin alpha(3)beta(1) ectodomain heterodimer resembles that of wild-type membrane-anchored beta(1) integrins. The integrin alpha(3) subunit was entirely cleaved into disulfide-linked heavy and light chains, at a newly defined cleavage site located C-terminal of a tetrabasic RRRR motif. Within the alpha(3) light chain, all potential N-glycosylation sites bear N-linked mannose-rich carbohydrate chains, suggesting an important structural role of these sugar residues in the stalk-like region of the integrin heterodimer. In conclusion, studies of our recombinant alpha(3)beta(1) integrin have provided new insights into alpha(3)beta(1) structure, ligand binding function, specificity, and regulation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Tufts Univ, Sch Med, Howard Hughes Med Inst, Dept Microbiol & Mol Biol, Boston, MA 02111 USA. RP Eble, JA (reprint author), Univ Munster, Inst Physiol Chem & Pathobiochem, Waldeyerstr 15, D-48149 Munster, Germany. EM eble@uni-muenster.de FU NCI NIH HHS [CA42368] NR 70 TC 92 Z9 92 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 4 PY 1998 VL 37 IS 31 BP 10945 EP 10955 DI 10.1021/bi980175+ PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 110TT UT WOS:000075397000010 PM 9692987 ER PT J AU Gaubatz, S Wood, JG Livingston, DM AF Gaubatz, S Wood, JG Livingston, DM TI Unusual proliferation arrest and transcriptional control properties of a newly discovered E2F family member, E2F-6 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; CELL-CYCLE PROGRESSION; GROWTH SUPPRESSION; PROTEIN; PROMOTER; DP-1; DNA; SWITCHES; BINDING; TARGET AB E2F transcription factors play an important role in the regulation of cell cycle progression. We report here the cloning and characterization of an additional member of this family, E2F-6. E2F-6 lacks pocket protein binding and transactivation domains, and it is a potent transcriptional repressor that contains a modular repression domain at its carboxyl terminus. Overproduction of E2F-6 had no specific effect on cell cycle progression in asynchronously growing Saos2 and NIH 3T3 cells, but it inhibited emery into S phase of NIH 3T3 cells stimulated to exit G(0). Taken together, these data suggest that E2F-6 can regulate a subset of E2F-dependent genes whose products are required for entry into the cell cycle but not for normal cell cycle progression. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 32 TC 134 Z9 139 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 4 PY 1998 VL 95 IS 16 BP 9190 EP 9195 DI 10.1073/pnas.95.16.9190 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 108BR UT WOS:000075246600026 PM 9689056 ER PT J AU Park, M Lewis, C Turbay, D Chung, A Chen, JN Evans, S Breitbart, RE Fishman, MC Izumo, S Bodmer, R AF Park, M Lewis, C Turbay, D Chung, A Chen, JN Evans, S Breitbart, RE Fishman, MC Izumo, S Bodmer, R TI Differential rescue of visceral and cardiac defects in Drosophila by vertebrate tinman-related genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HOMEOBOX-CONTAINING GENE; HEART DEVELOPMENT; OVEREXPRESSION; SPECIFICATION; XNKX-2.3 AB tinman, a mesodermal NK2-type homeobox gene, is absolutely required for the subdivision of the early Drosophila mesoderm and for the formation of the heart as well as the visceral muscle primordia, Several vertebrate relatives of tinman, many of which are predominately expressed in the very early cardiac progenitors (and pharyngeal endoderm), also seem to promote heart development, Here, we show that most of these vertebrate tinman-related genes can readily substitute for Drosophila tinman function in promoting visceral mesoderm-specific marker gene expression, but much less in promoting cardiac-specific gene expression indicative of heart development, In addition, another mesodermal NK2-type gene from Drosophila, bagpipe, which is normally only needed for visceral mesoderm but not heart development, cannot substitute for tinman at all. These data indicate that the Functional equivalence of the tinman-related subclass of NK2-type genes (in activating markers of visceral mesoderm development in Drosophila) is specific to this subclass and distinct from other homeobox genes, Despite the apparent overall conservation of heart development between vertebrates and invertebrates, the differential rescue of visceral mesoderm versus heart development suggests that some of the molecular mechanisms of organ formation may have diverged during evolution. C1 Univ Michigan, Dept Biol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. RP Bodmer, R (reprint author), Univ Michigan, Dept Biol, 830 N Univ, Ann Arbor, MI 48109 USA. EM rolf@umich.edu RI Evans, Sylvia/G-1980-2015; OI Chen, Jau-Nian/0000-0001-8807-3607 NR 20 TC 38 Z9 41 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 AUG 4 PY 1998 VL 95 IS 16 BP 9366 EP 9371 DI 10.1073/pnas.95.16.9366 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 108BR UT WOS:000075246600056 PM 9689086 ER PT J AU Ma, Q Jones, D Borghesani, PR Segal, RA Nagasawa, T Kishimoto, T Bronson, RT Springer, TA AF Ma, Q Jones, D Borghesani, PR Segal, RA Nagasawa, T Kishimoto, T Bronson, RT Springer, TA TI Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LYMPHOCYTE CHEMOATTRACTANT; CHROMOSOMAL LOCALIZATION; CELL LYMPHOPOIESIS; MOLECULAR-CLONING; HIV-1 ENTRY; STEM-CELLS; SDF-1; GENE; 7-TRANSMEMBRANE; LESTR/FUSIN AB The chemokime stromal cell-depived factor 1, SDF-1, is an important regulates of leukocyte and hematopoietic precursor migration and pre-B cell proliferation. The receptor for SDF-1, CXCR4, also functions as a coreceptor For T-tropic HIV-1 entry. We find that mice deficient for CXCR4 die perinatally and display profound defects in the hematopoietic and nervous systems. CXCR4-deficient mice have severely reduced B-lymphopoiesis, reduced myelopoiesis in fetal liver, and a virtual absence of myelopoiesis in bone marrow. However, T-lymphopoiesis is unaffected. Furthermore, the cerebellum develops abnormally with an irregular external granule cell layer, ectopically located Purkinje cells, and numerous chromophilic cell clumps of abnormally migrated granule cells within the cerebellar anlage, Identical defects are observed in mice lacking SDF-1, suggesting a monogamous relationship between CXCR4 and SDF-1. This receptor-ligand selectivity is unusual among chemokines and their receptors, as is the function in migration of nonhematopoietic cells. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Osaka Med Ctr Maternal & Child Hlth, Res Inst, Dept Immunol, Osaka 59002, Japan. Osaka Univ, Sch Med, Dept Med 3, Suita, Osaka 565, Japan. Tufts Univ, Sch Med & Vet Med, Boston, MA 02111 USA. RP Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. EM springer@sprsgi.med.harvard.edu RI Kishimoto, Tadamitsu/C-8470-2009; Jones, Daniel/I-7399-2015 FU NHLBI NIH HHS [HL-48675, P01 HL048675] NR 41 TC 1154 Z9 1191 U1 3 U2 17 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 AUG 4 PY 1998 VL 95 IS 16 BP 9448 EP 9453 DI 10.1073/pnas.95.16.9448 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 108BR UT WOS:000075246600070 PM 9689100 ER PT J AU Denis, C Methia, N Frenette, PS Rayburn, H Ullman-Cullere, M Hynes, RO Wagner, DD AF Denis, C Methia, N Frenette, PS Rayburn, H Ullman-Cullere, M Hynes, RO Wagner, DD TI A mouse model of severe von Willebrand disease: Defects in hemostasis and thrombosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SELECTIN-DEFICIENT MICE; FACTOR-VIII; VONWILLEBRAND DISEASE; BLOOD; GENE; FIBRONECTIN; LACKING; CELLS AB von Willebrand factor (vWf) deficiency causes severe von Willebrand disease in humans. We generated a mouse model for this disease by using gene targeting. vWf-deficient mice appeared normal at birth; they were viable and fertile. Neither vWf nor vWf propolypeptide (von Willebrand antigen II) were detectable in plasma, platelets, or endothelial cells of the homozygous mutant mice. The mutant mice exhibited defects in hemostasis with a highly prolonged bleeding time and spontaneous bleeding events in approximate to 10% of neonates, As in the human disease, the factor VIII level in these mice was reduced strongly as a result of the lack of protection provided by vWf. Defective thrombosis in mutant mice was also evident in an in vivo model of vascular injury, In this model, the exteriorized mesentery was superfused with ferric chloride and the accumulation of fluorescently labeled platelets was observed by intravital microscopy, We conclude that these mice very closely mimic severe human von Willebrand disease and will be very useful for investigating the role of vWf in normal physiology and in disease models. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. MIT, Ctr Canc Res, Dept Biol, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntingdon Ave, Boston, MA 02115 USA. RI Frenette, Paul/J-8272-2012; Denis , Cecile/A-7649-2011 OI Denis , Cecile/0000-0001-5152-9156 FU NHLBI NIH HHS [HL41484, R01 HL041002, R01 HL41002] NR 26 TC 325 Z9 328 U1 0 U2 5 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 AUG 4 PY 1998 VL 95 IS 16 BP 9524 EP 9529 DI 10.1073/pnas.95.16.9524 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 108BR UT WOS:000075246600083 PM 9689113 ER PT J AU Mazo, IB Gutierrez-Ramos, JC Frenette, PS Hynes, RO Wagner, DD von Andrian, UH AF Mazo, IB Gutierrez-Ramos, JC Frenette, PS Hynes, RO Wagner, DD von Andrian, UH TI Hematopoietic progenitor cell rolling in bone marrow microvessels: Parallel contributions by endothelial selectins and vascular cell adhesion molecule 1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE bone marrow; selectins; alpha 4 integrin; intravital microscopy; homing ID STEM-CELLS; P-SELECTIN; IN-VIVO; STROMAL CELLS; ALPHA-4 INTEGRINS; LEUKOCYTE; EXPRESSION; FLOW; MICE; DIFFERENTIATION AB We have used intravital microscopy to study physiologically perfused microvessels in murine bone mallow (BM). BM sinusoids and venules, but not adjacent bone vessels, supported rolling interactions of hematopoietic progenitor cells. Rolling did not involve L-selectin, but was partially reduced in wild-type mice treated with antibodies to P- or E-selectin and in mice that were deficient in these two selectins. Selectin-independent rolling was mediated by alpha 4 integrins, which interacted with endothelial vascular cell adhesion molecule (VCAM)-1. Parallel contribution of the endothelial selectins and VCAM-1 is not known to direct blood cell trafficking to other noninflamed tissues. This combination of constitutively expressed adhesion molecules may thus constitute a BM-specific recruitment pathway for progenitor cells analogous to the vascular addressins that direct selective lymphocyte homing to lymphoid organs. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Millenium Pharmaceut Inc, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP von Andrian, UH (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008; Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [HL-54936, HL-56949, P01 HL056949, R01 HL054936] NR 49 TC 286 Z9 296 U1 0 U2 10 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 AUG 3 PY 1998 VL 188 IS 3 BP 465 EP 474 DI 10.1084/jem.188.3.465 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 109BA UT WOS:000075300300005 PM 9687524 ER PT J AU Schust, DJ Tortorella, D Seebach, J Phan, C Ploegh, HL AF Schust, DJ Tortorella, D Seebach, J Phan, C Ploegh, HL TI Trophoblast class I major histocompatibility complex (MHC) products are resistant to rapid degradation imposed by the human cytomegalovirus (HCMV) gene products US2 and US11 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE trophoblast; cytomegalovirus; human; MHC class I; HLA-G ID HLA-G GENE; CHORIOCARCINOMA CELL-LINE; G MESSENGER-RNA; HEAVY-CHAINS; MONOCLONAL-ANTIBODIES; ANTIGEN PRESENTATION; C LOCUS; EXPRESSION; POLYMORPHISM; VIRUS AB US11 and US2 encode gene products expressed early in the replicative cycle of human cytomegalovirus (HCMV), which cause dislocation of human and murine major histocompatibility complex (MHC) class I molecules from the lumen of the endoplasmic reticulum to the cytosol, where the class I heavy chains are rapidly degraded. Human histocompatibility leukocyte antigens (HLA)-C and HLA-G are uniquely resistant to the effects of both US11 and US2 in a human trophoblast cell line as well as in porcine endothelial cells stably transfected with human class I genes. Dislocation and degradation of MHC class I heavy chains do not appear to involve cell type-specific factors, as US11 and US2 are fully active in this xenogeneic model. Importantly, trophoblasts HLA-G and HLA-C possess unique characteristics that allow their escape from HCMV-associated MHC class I degradation. Trophoblast class I molecules could serve not only to block recognition by natural killer cells, but also to guide virus-specific HLA-C- and possibly HLA-G-restricted cytotoxic T-lymphocytes to their targets. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02119 USA. RP Ploegh, HL (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave,Bldg D2,Rm 137, Boston, MA 02115 USA. EM ploegh@hms.harvard.edu OI Tortorella, Domenico/0000-0003-0961-3535 FU NIAID NIH HHS [R01AI38577-01]; NICHD NIH HHS [K12HD00840] NR 54 TC 94 Z9 95 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 3 PY 1998 VL 188 IS 3 BP 497 EP 503 DI 10.1084/jem.188.3.497 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 109BA UT WOS:000075300300008 PM 9687527 ER PT J AU Itzhak, Y Martin, JL Black, MD Huang, PL AF Itzhak, Y Martin, JL Black, MD Huang, PL TI The role of neuronal nitric oxide synthase in cocaine-induced conditioned place preference SO NEUROREPORT LA English DT Article DE cocaine; conditioned place preference; knockout mice; nitric oxide; 7-nitroindazole; reward ID BEHAVIORAL SENSITIZATION; MICE AB PREVIOUS studies suggested the involvement of the neuronal nitric oxide synthase (nNOS) in the development of sensitization to psychostimulants. In the present study we investigated the role of nNOS in the rewarding properties of cocaine. Swiss Webster mice treated with cocaine (20 mg/kg) and saline every other day for 8 days (four drug and four saline sessions) developed conditioned place preference (CPP) for the drug-paired compartment of the cage. Pretreatment with the nNOS inhibitor, 7-nitroindazole (7-NI; 25mg/kg), completely blocked cocaine-induced CPP. Mice deficient for the nNOS gene (homozygote nNOS(-/-) mice) were resistant to cocaine-induced CPP, while wild-type nNOS(+/+) mice developed a marked CPP following cocaine administration. Both, the pharmacological and genetic manipulations of nNOS suggest that nitric oxide (NO) is involved in the rewarding properties of cocaine. NeuroReport 9: 2485-2488 (C) 1998 Rapid Science Ltd. C1 Univ Miami, Sch Med, Dept Biochem & Mol Biol R629, Miami, FL 33101 USA. Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Biochem & Mol Biol R629, POB 016129, Miami, FL 33101 USA. FU NIDA NIH HHS [DA08584] NR 16 TC 60 Z9 62 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG 3 PY 1998 VL 9 IS 11 BP 2485 EP 2488 DI 10.1097/00001756-199808030-00011 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 110YE UT WOS:000075408500012 PM 9721919 ER PT J AU Liu, W Staecker, H Stupak, H Malgrange, B Lefebvre, P Van de Water, TR AF Liu, W Staecker, H Stupak, H Malgrange, B Lefebvre, P Van de Water, TR TI Caspase inhibitors prevent cisplatin-induced apoptosis of auditory sensory cells SO NEUROREPORT LA English DT Article DE apoptosis; auditory sensory cells; caspases; caspase inhibitors; cisplatin damage; protection ID CELLULAR SUICIDE; DEATH; PROTEASE; FAMILY AB IN VITRO studies tested the efficacy of three caspase inhibitors, Ac-VAD-cmk (caspase-1 inhibitor), z-DEVD-fmk (caspase -3 inhibitor) and B-D-fmk (BOCDFK, a general inhibitor), for protecting auditory sensory cells from cisplatin-damage induced loss. Treatment of 3-day-old rat organ of Corti explants with these caspase inhibitors protected > 80% of the auditory hair cells from cisplatin-damage initiated apoptosis. Dissociated cell cultures of 3-day-old rat spinal ganglia treated with any of these three caspase inhibitors in addition to exogenous neurotrophin have highly significant increases in neuronal survival following cisplatin exposure. These results indicate that loss of auditory sensory cells as a result of cisplatin-induced damage involves apoptosis and that blocking of this cell death pathway at the caspase level effectively rescues both hair cells and neurons. (C) 1998 Rapid Science Ltd. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Otolaryngol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Liege, Dept Human Physiol & Pathophysiol, Liege, Belgium. RP Van de Water, TR (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Otolaryngol, Room 302,1410 Pelham Pkwy S, Bronx, NY 10461 USA. OI Staecker, Hinrich/0000-0002-0348-3015; Malgrange, Brigitte/0000-0002-8957-2528 NR 23 TC 107 Z9 116 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG 3 PY 1998 VL 9 IS 11 BP 2609 EP 2614 DI 10.1097/00001756-199808030-00034 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 110YE UT WOS:000075408500035 PM 9721942 ER PT J AU Saouaf, R Arora, S Smakowski, P Caballero, AE Veves, A AF Saouaf, R Arora, S Smakowski, P Caballero, AE Veves, A TI Reactive hyperemic response of the brachial artery: Comparison of proximal and distal occlusion SO ACADEMIC RADIOLOGY LA English DT Article DE arteries, US ID DEPENDENT DIABETES-MELLITUS; ENDOTHELIAL DYSFUNCTION; NITRIC-OXIDE; CORONARY; DISEASE; ATHEROSCLEROSIS; VASODILATION; DILATATION; ADULTS; WOMEN AB Rationale and Objectives. The authors compared the postocclusion hyperemic responses of the brachial artery after occluding blood flow proximal to and distal to the studied area. Materials and Methods. Response of the brachial artery to hypoxia was evaluated with duplex Doppler ultrasound in 13 healthy subjects. A pneumatic tourniquet was first positioned 2-5 cm superior to the left elbow, proximal to the area of artery studied. Two hours later the response was remeasured with the tourniquet positioned 2-5 cm inferior to the elbow, distal to the artery studied. Arterial diameter, mean and peak flow velocities, and heart rate were assessed. Results. No significant differences were observed between measurements of baseline and postischemic arterial diameter, percentage diameter change, baseline mean arterial blood flow velocity, baseline peak arterial blood flow velocity, or postischemic heart rate obtained with proximal occlusion of the artery and those obtained with distal occlusion. In contrast, mean and peak postischemic arterial blood flow velocity and preocclusion heart rate were higher in measurements made during proximal artery occlusion. Significant correlation was found between measurements of percentage change in artery diameter obtained with proximal artery occlusion and those obtained with distal occlusion (r = 0.611, P < .05). Conclusion. There are no major differences in postischemic changes in brachial artery diameter related to reactive hyperemia between blood flow occlusion applied proximal and distal to the studied area. However, there are significant differences in the mean and peak systolic velocities. Either occlusion site can be used for clinical studies if arterial diameter change is monitored, but if velocity measurements are being compared, a single occlusion site should be chosen. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Vasc Surg, Boston, MA USA. Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Saouaf, R (reprint author), Columbia Presbyterian Med Ctr, Dept Radiol, MHB-2-121,177 Ft Washington Ave, New York, NY 10032 USA. NR 17 TC 5 Z9 5 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1998 VL 5 IS 8 BP 556 EP 560 DI 10.1016/S1076-6332(98)80207-9 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 104UH UT WOS:000075033500006 PM 9702266 ER PT J AU Li, G Berven, S Simpson, H Triffitt, JT AF Li, G Berven, S Simpson, H Triffitt, JT TI Expression of BMP-4 mRNA during distraction osteogenesis in rabbits SO ACTA ORTHOPAEDICA SCANDINAVICA LA English DT Article ID MESSENGER-RNA; BONE; PROTEINS; LOCALIZATION AB We characterized the presence and localization of bone morphogenetic protein 4 (BMP-4) mRNA in the regenerating tissues produced by distraction osteogenesis following tibial osteotomy in the rabbit. The findings are consistent with previous reports on the localization of BMP-4 mRNA expression during fracture repair. The BMP-4 gene is expressed by less differentiated osteoprogenitor cells (fibroblastic mesenchymal cells and preosteoblasts), and not by fully differentiated osteoblasts. BMP-4 gene expression is localized in callus-forming tissue (muscle, periosteum) during callus formation. Our observations suggest that the BMP-4 gene product is one of the local contributing factors in regulating bone and cartilage formation in distraction osteogenesis. C1 Univ Oxford, Nuffield Orthopaed Ctr, Nuffield Dept Orthopaed Surg, Oxford OX3 7LD, England. Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Nuffield Orthopaed Ctr, MRC, Bone Res Lab, Oxford OX3 7LD, England. RP Li, G (reprint author), Univ Oxford, Nuffield Orthopaed Ctr, Nuffield Dept Orthopaed Surg, Oxford OX3 7LD, England. RI Simpson, Alasdair/F-1887-2013 OI Simpson, Alasdair/0000-0001-7793-642X NR 24 TC 36 Z9 38 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6470 J9 ACTA ORTHOP SCAND JI Acta Orthop. Scand. PD AUG PY 1998 VL 69 IS 4 BP 420 EP 425 DI 10.3109/17453679808999060 PG 6 WC Orthopedics SC Orthopedics GA 126VB UT WOS:000076314300020 PM 9798455 ER PT J AU Dan, L Cluette-Brown, JE Kabakibi, A Laposata, M AF Dan, L Cluette-Brown, JE Kabakibi, A Laposata, M TI Quantitation of the mass of fatty acid ethyl esters synthesized by Hep G2 cells incubated with ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE fatty acid ethyl ester; ethanol; fatty acid; Hep H2 cells ID METABOLISM; RAT; PURIFICATION; ARACHIDONATE; DEFICIENCY; ALCOHOL; PLASMA; LIPASE; LINE AB Fatty acid ethyl esters (FAEE), esterification products of fatty acids and ethanol, have been increasingly implicated as mediators of ethanol-induced organ damage, The first goal of this study was to determine the mass of FAEE synthesized by Hep G2 cells exposed to a given dose of ethanol, The second goal was to determine whether all fatty acids in cells are equally available for FAEE synthesis, Hep Ca cells and essential fatty acid deficient Hep Ca cells (Hep G2-EFD) were used to study the synthesis of FAEE upon exposure to ethanol, A two-pool fatty acid model was created: (1) a "previously incorporated pool" formed by incubating the cells with C-14-labeled fatty acids for 24 hr; and (2) a "newly incorporated pool" formed by incubating cells with H-3-labeled fatty acids for 0.5 hr, The FAEE production from each pool was then determined. The total production of FAEE within 3 hr by Hep G2 cells in culture was 150 to 250 pmol/mg cell protein. The fatty acids most recently incorporated into the cells were preferred as substrates for FAEE synthesis because a higher percentage of fatty acids from the newly incorporated pool was used for FAEE synthesis than from the previously incorporated pool. Furthermore, a dose-response relationship was observed between the amount of fatty acid in the newly incorporated pool and FAEE production, but not between the amount of fatty acid in the previously incorporated pool and FAEE synthesis, Taken together, the results indicate that a relatively small amount of endogenously synthesized FAEE is generated from specific intracellular pools of fatty acid since not all fatty acids are equally available for FAEE synthesis. This indicates that a endogenous FAEE are toxic, they exert their toxic effect at very low intracellular FAEE concentrations. C1 Massachusetts Gen Hosp, Div Clin Labs, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Div Clin Labs, Dept Pathol, Room 235 Gray Bldg, Boston, MA 02114 USA. NR 24 TC 17 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 1998 VL 22 IS 5 BP 1125 EP 1131 DI 10.1097/00000374-199808000-00022 PG 7 WC Substance Abuse SC Substance Abuse GA 112BW UT WOS:000075475100022 PM 9726285 ER PT J AU Wu, YS Salmela, KS Lieber, CS AF Wu, YS Salmela, KS Lieber, CS TI Microsomal acetaldehyde oxidation is negligible in the presence of ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE acetaldehyde oxidation; microsomal ethanol oxidizing system (MEOS); CYP2E1; ethanol ID ALDEHYDE DEHYDROGENASE; SUBCELLULAR-DISTRIBUTION; AFFINITY-CHROMATOGRAPHY; OXIDIZING SYSTEM; HUMAN LIVER; RAT-LIVER; CYTOCHROME-P-450; METABOLISM; MUTANT; CYP2E1 AB The microsomal ethanol oxidizing system (MEOS), inducible by ethanol and acetone, oxidizes ethanol to acetaldehyde, which causes many toxic effects associated with excess ethanol. Recent studies reported that rat liver microsomes also oxidize acetaldehyde, thereby challenging the validity of the assessment of MEOS activity by measuring acetaldehyde production and suggesting that MEOS activity results in the accumulation not of acetaldehyde but, rather, of its less toxic metabolite, acetate. To address these issues, we compared both metabolic rates of ethanol and acetaldehyde and the effect of ethanol on the acetaldehyde metabolism. Liver microsomes were prepared from Sprague-Dawley rats induced either with acetone for 3 days or ethanol for 3 weeks. NADPH-dependent acetaldehyde (300 mu M) metabolism was measured in two ways: (1) by detection of acetaldehyde disappearance by headspace gas chromatography, and (2) by assessment of acetaldehyde oxidation by liquid scintillation counting of acetate formed from 1:1,2-C-14]acetaldehyde. Ethanol (50 mM) oxidation was measured by gas chromatography. In acetone- and ethanol-induced rat liver microsomes, the acetaldehyde disappearance (p < 0.0001) and oxidation (p < 0.0001) rates were both significantly increased. The rates of acetaldehyde oxidation paralleled those of p-nitrophenol hydroxylation (r = 0.974, p < 0.0001), with a K-m of 82 +/- 14 mu M and a V-max of 4.8 +/- 0.5 nmol/min/mg protein in acetone-induced microsomes. Acetaldehyde disappearance in acetone-induced microsomes and acetaldehyde oxidation in acetone-induced and ethanol-induced microsomes were significantly lower than the corresponding ethanol oxidation, with rates (nmol/min/mg protein) of 4.6 +/- 0.6 versus 9.0 +/- 0.8 Go < 0.005), 4.4 +/- 0.3 versus 9.1 +/- 0.5 Go < 0.0005), and 14.0 +/- 0.9 versus 19.5 +/- 1.8 Ip < 0.05), respectively. The presence of 50 mM ethanol decreased this metabolism to 0.9 +/- 0.3 (p < 0.005), 0.5 +/- 0.1 Go < 0.001), and 1.8 rt 0.3 Go < 0.001), resulting in rates of acetaldehyde metabolism of only 9.8 +/- 3.2%, 6.0 +/- 0.5%, and 9.5 +/- 1.2% (respectively) of those of ethanol oxidation. In conclusion, rat liver microsomes oxidize acetaldehyde at much lower rates than ethanol, and this acetaldehyde metabolism is strikingly inhibited by ethanol. Accordingly, acetaldehyde formation provides an accurate assessment of MEOS activity. Furthermore, because acetaldehyde production vastly exceeds its oxidation, the net result of MEOS activity is the accumulation of this toxic metabolite. C1 Bronx Vet Affairs Med Ctr, Alcohol Res & Treatment 151 2, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY USA. RP Lieber, CS (reprint author), Bronx Vet Affairs Med Ctr, Alcohol Res & Treatment 151 2, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIAAA NIH HHS [AA07275, AA05934] NR 20 TC 11 Z9 13 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 1998 VL 22 IS 5 BP 1165 EP 1169 DI 10.1097/00000374-199808000-00028 PG 5 WC Substance Abuse SC Substance Abuse GA 112BW UT WOS:000075475100028 PM 9726291 ER PT J AU Fukagawa, NK Yu, YM Young, VR AF Fukagawa, NK Yu, YM Young, VR TI Methionine and cysteine kinetics at different intakes of methionine and cystine in elderly men and women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE balance study; amino acid requirements; kinetics; oxidation; protein turnover; methionine; leucine; cystine; elderly ID AMINO-ACID-REQUIREMENTS; PROTEIN-SYNTHESIS; LEUCINE KINETICS; ADULT HUMANS; YOUNG MEN; TRACER; METABOLISM; PHENYLALANINE; PATTERN; L-<1-C-13>LEUCINE AB Earlier nitrogen balance studies led to the conclusion that requirements for methionine in older individuals are much higher than those in younger adults. Hence, we examined the kinetics of whole-body methionine, cysteine, and leucine metabolism postabsorptively using a continuous intravenous infusion of L-[(CH3)-H-2, 1-C-13]methionine, L-[H-2(3)]leucine, and [3,3-H-2(2)]cysteine in 12 elderly men (n = 5) and women (n = 7) given as a 3-h infusion after a 12-h fast (study 1) and in 8 elderly men (n = 4) and women (12 = 4) as an 8-h Infusion according to a 3-h fasted, 5-h fed protocol (study 2) for 6 d. Before tracer infusion, each of 3 L-amino acid diets supplying the following nominal, but known, amounts (mg.kg(-1).d(-1)) of methionine and cystine, respectively, were used in study 2: diet 1: 13 and 0: diet 3: 6.5 and 5.2: and diet 5: 6.5 and 21. Studies I and 2 gave values for plasma methionine flux that agreed with the leucine flux data, which, in turn, also appeared to be comparable with findings in healthy younger adults. In study 2, methionine oxidation rates were the same across all diets in the fasted state and the same with diets 1 and 3 in the fed state but lower with diet 5, suggesting;1 modest sparing effect of dietary cystine on methionine oxidation, Estimated daily methionine balance was at equilibrium for diet I and negative (significantly different from zero, P < 0.05) with diets 3 and 5, The results were evaluated against our previous findings in younger adults. C1 Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. Univ Vermont, Clin Res Ctr, Burlington, VT 05405 USA. MIT, Sch Sci, Human Nutr Lab, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. RP Fukagawa, NK (reprint author), Univ Vermont, Coll Med, Dept Med, Given Bldg,Room C-207, Burlington, VT 05405 USA. FU NIA NIH HHS [AG 00599]; NIDDK NIH HHS [DK15856, DK42101] NR 54 TC 53 Z9 54 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 1998 VL 68 IS 2 BP 380 EP 388 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 105XX UT WOS:000075101600027 PM 9701197 ER PT J AU Nguyen, PL Olszak, I Harris, NL Preffer, FI AF Nguyen, PL Olszak, I Harris, NL Preffer, FI TI Myeloperoxidase detection by three-color flow cytometry and by enzyme cytochemistry in the classification of acute leukemia SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE acute leukemia; myeloperoxidase; cytochemistry; flow cytometry ID ANTIGENS AB In the classification of acute leukemia, the presence of myeloperoxidase (MPO) within the leukemic blasts indicates myeloid leukemia. Previous studies compared enzyme cytochemistry (EC) or flow cytometry (FC) with immunocytochemistry in detecting MPO. Our study is the first direct comparison of EC with 3-color FC in a large group of acute leukemias. We studied 26 cases of acute myeloid leukemia (AML) and 4 cases of B-precursor acute lymphoblastic leukemia (B-ALL). Classification was according to the French-American-British criteria. The cells were analyzed for MPO expression by 3-color FC after cell permeabilization followed by staining with anti-MPO antibody. For FC, the blasts were defined by a combination of light scatter characteristics and dim CD45 expression. Concordance between EC and FC was seen in 27 of 30 cases (23/26 AML and all B-ALL), including all AML cases of M1, M2, M3, and M4 subtypes. In 1 of 4 AML-M0 and 2 of 5 AML-M5a cases, FC demonstrated the presence of MPO in 8%, 86%, and 94% blasts; EC detected none. Three-color FC may be more sensitive than routine EC in demonstrating the presence of MPO in AML cases and may offer the advantages of multiparametric analysis. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. RP Nguyen, PL (reprint author), Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Div Hematopathol, Mayo D219-7,Box 609,420 Delaware St SE, Minneapolis, MN 55455 USA. NR 14 TC 10 Z9 11 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 1998 VL 110 IS 2 BP 163 EP 169 PG 7 WC Pathology SC Pathology GA 110VZ UT WOS:000075403400006 PM 9704614 ER PT J AU Lester, N Johnson, C Fogaren, C Godfrey, L Steinberg, S Simmons, B Prentice, R Hackett, MJ Schwartz, P Ambrose, JW Blanter, M Schwartz, PD Splaine, EA Washington, D AF Lester, N Johnson, C Fogaren, C Godfrey, L Steinberg, S Simmons, B Prentice, R Hackett, MJ Schwartz, P Ambrose, JW Blanter, M Schwartz, PD Splaine, EA Washington, D TI Cultural competence - A nursing dialogue SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 Childrens Hosp, Boston, MA 02115 USA. Off Staff Builders Home Hlth Care, Allston, MA USA. Good Samaritan Med Ctr, Community Outreach Serv, Brockton, MA USA. Good Samaritan Med Ctr, Interpreter Serv, Brockton, MA USA. Massachusetts Gen Hosp, ICU Acute Dialysis Unit, Boston, MA 02114 USA. Spectrum Hlth Syst Inc, Marlboro, MA USA. S Cove Community Hlth Ctr, Ob Gyn Unit, Boston, MA USA. S Cove Community Hlth Ctr, Ob Gyn Unit, Quincy, MA USA. St Elizabeths Med Ctr, Emergency Treatment Ctr, Brighton, MA USA. Massachusetts Gen Hosp, Preadmiss Testing Clin, Boston, MA 02114 USA. Boston Med Ctr, Latino Pediat Clin, Boston, MA USA. Boston Home Infus, Boston, MA USA. Charlestown High Sch, Charlestown, MA USA. Harvard Vanguard Med Associates, Ctr Fertil & Reprod Hlth, Boston, MA USA. Harvard Univ, Sch Med, Nursing Teaching Program, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Mental Hlth Fellowship, Dept Ambulatory Care & Prevent, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. Queens Med Ctr, Oahu, HI USA. NR 10 TC 10 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD AUG PY 1998 VL 98 IS 8 BP 26 EP 33 DI 10.2307/3471906 PG 8 WC Nursing SC Nursing GA 107NX UT WOS:000075216300012 PM 9711146 ER PT J AU Chung, PY Schuman, JS Netland, PA Lloyd-Muhammad, RA Jacobs, DS AF Chung, PY Schuman, JS Netland, PA Lloyd-Muhammad, RA Jacobs, DS TI Five-year results of a randomized, prospective, clinical trial of diode vs argon laser trabeculoplasty for open-angle glaucoma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OCULAR HYPERTENSION; THERAPY AB PURPOSE: To evaluate the safety and efficacy of laser trabeculoplasty (LTP) with a semiconductor diode laser (810 nm, [DLT]) vs an argon blue-green laser (488 to 514 nm, [ALT]). METHODS: In a prospective, randomized clinical trial, 50 eyes of 46 patients with uncontrolled open angle glaucoma on maximally tolerated medical therapy were treated and followed at regular intervals for 5 years. Fifty laser spots were applied over 180 degrees using either maximal laser power or sufficient power to produce blanching or a small bubble (570 to 850 mW, DLT; 400 to 1,100 mW, ALT). We performed DLT using a 100-mu m spot size, a 0.5-second exposure, and a Ritch lens; we conducted ALT with a 50-mu m spot, a 0.1-second exposure, and a Goldmann lens. Patients in the study were followed until trabeculectomy was required. RESULTS: The mean follow-up times +/- SD for all eyes were 38.6 +/- 5.4 months, DLT (n = 22; range, 1 to 68 months) and 35.5 +/- 4.8 months, ALT (n = 28; range, 1 to 66 months). Those in the diode laser group (n = 16) who had more than 1 year of follow-up were tracked for 49.4 months, and those in the argon laser group (n = 21) were tracked for 45.8 months. There were no significant differences in the mean pretreatment intraocular pressures (IOPs): 21.2 mm Hg, DLT (n = 22) and 21.5, ALT 21.5 mm Hg (n = 28); P = .81] or in mean final IOPs (15.7 mm Hg, DLT and 17.1 mm Hg, ALT; P = .19). Time to surgical failure showed no significant differences, with 50% of the DLT eyes and 58% of the ALT eyes surviving at 5 years (P = .59). CONCLUSION: In eyes with open-angle glaucoma and unsatisfactory IOP control on maximally tolerated medical therapy, DLT and ALT are equally effective in lowering IOP over a 5-year period. (Am J Ophthalmol 1998;126:185-190, (C) 1998 by Elsevier Science Inc. All rights reserved.). C1 Loma Linda Univ, Sch Med, Inland Eye Inst, Loma Linda, CA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Harvard Univ, Beth Israel Med Ctr, Sch Med, Brookline, MA USA. Tufts Univ, Sch Med, New England Eye Ctr, Boston, MA 02111 USA. RP Schuman, JS (reprint author), Tufts Univ, Sch Med, New England Eye Ctr, 750 Washington St,Box 450, Boston, MA 02111 USA. EM jss@mediaone.net RI Schuman, Joel/K-7304-2012 OI Schuman, Joel/0000-0002-8885-3766 NR 23 TC 27 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 1998 VL 126 IS 2 BP 185 EP 190 DI 10.1016/S0002-9394(98)00151-2 PG 6 WC Ophthalmology SC Ophthalmology GA 111CJ UT WOS:000075419500003 PM 9727511 ER PT J AU Ng, EWM Samiy, N Ruoff, KL Cousins, FV Hooper, DC Von Gunten, S D'Amico, DJ Baker, AS AF Ng, EWM Samiy, N Ruoff, KL Cousins, FV Hooper, DC Von Gunten, S D'Amico, DJ Baker, AS TI Treatment of experimental Staphylococcus epidermidis endophthalmitis with oral trovafloxacin SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID AQUEOUS-HUMOR; VITREOUS CAVITY; INTRAVITREAL PENETRATION; QUINOLONE RESISTANCE; CIPROFLOXACIN; PHARMACOKINETICS; OFLOXACIN; RABBITS; CP-99,219; HUMANS AB PURPOSE: To investigate the ocular pharmacokinetics and efficacy of oral trovafloxacin, a novel fluoroquinolone antibiotic, in Staphylococcus epidermidis endophthalmitis. METHODS: Albino rabbits (n = 20) were infected with an intravitreal inoculum of S epidermidis (1.0 x 10(8) colony-forming units [CFU]/0.1 ml) and 24 hours later received a single oral dose of trovafloxacin (250 mg/kg), Serum and intraocular samples from infected and control (noninfected) eyes were obtained up to 24 hours after antibiotic administration for measurement of trovafloxacin levels. A second group of rabbits (n = 72) was infected intraocularly and randomized 24 hours later to oral trovafloxacin (250 mg/kg twice a day) for 6 days or no treatment (control). Treatment efficacy was assessed by vitreous culture, clinical examination, and histopathology. RESULTS: Following a single dose of trovafloxacin, maximal vitreous levels were achieved at 8 hours in infected eyes, with a penetration ratio of 36%. Vitreous levels were greater than 15 times the minimum inhibitory concentration of the strain employed. In animals with established endophthalmitis, treated eyes were sterilized after 5 days (P = .0495) compared with control eyes, which autosterilized at 14 days. Clinical and histologic examination revealed significant amelioration of anterior segment inflammation in treated eyes, although severe destruction of posterior segment structures occurred in both groups after 6 days of therapy. CONCLUSIONS: These data support trovafloxacin as a potential oral agent for treatment or prophylaxis of S epidermidis endophthalmitis, although retinal alterations that occur over the period required for vitreous sterilization suggest that it will not replace intravitreal therapy in established endophthalmitis. (Am J Ophthalmol 1998;126: 278-287. (C) 1998 by Elsevier Science Inc. All rights reserved.). C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Microbiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Laser Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Serv, Boston, MA 02114 USA. Hop Cantonal Univ Geneva, Clin Ophtalmol, CH-1211 Geneva, Switzerland. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP D'Amico, DJ (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 33 TC 12 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 1998 VL 126 IS 2 BP 278 EP 287 DI 10.1016/S0002-9394(98)00157-3 PG 10 WC Ophthalmology SC Ophthalmology GA 111CJ UT WOS:000075419500014 PM 9727522 ER PT J AU Aronson, D Wojtaszewski, JFP Thorell, A Nygren, J Zangen, D Richter, EA Ljungqvist, O Fielding, RA Goodyear, LJ AF Aronson, D Wojtaszewski, JFP Thorell, A Nygren, J Zangen, D Richter, EA Ljungqvist, O Fielding, RA Goodyear, LJ TI Extracellular-regulated protein kinase cascades are activated in response to injury in human skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE mitogen-activated protein kinase; signal transduction; stress enzymology ID SIGNAL-TRANSDUCTION PATHWAYS; MAP KINASE; C-JUN; GROWTH-FACTOR; HEAT-SHOCK; MAMMALIAN-CELLS; WOUND FLUID; STRESS; PHOSPHORYLATION; EXPRESSION AB The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. However, it is not known whether these signaling cascades also participate in the response to injury in human tissues. To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing. C1 Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Boston Univ, Sargent Coll Allied Hlth Profess, Dept Hlth Sci, Boston, MA 02215 USA. Univ Copenhagen, August Krogh Inst, Copenhagen Muscle Res Ctr, DK-2100 Copenhagen, Denmark. Karolinska Hosp & Inst, Dept Surg, S-10401 Stockholm, Sweden. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. RI Aronson, Doron/F-3390-2010; Wojtaszewski, Jorgen /P-6583-2014 OI Wojtaszewski, Jorgen /0000-0001-9785-6830 FU NIAMS NIH HHS [AR-42238] NR 38 TC 44 Z9 46 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 AUG PY 1998 VL 275 IS 2 BP C555 EP C561 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 106WQ UT WOS:000075174400025 PM 9688610 ER PT J AU Gilbert, RJ Reese, TG Daftary, SJ Smith, RN Weisskoff, RM Wedeen, VJ AF Gilbert, RJ Reese, TG Daftary, SJ Smith, RN Weisskoff, RM Wedeen, VJ TI Determination of lingual myoarchitecture in whole tissue by NMR imaging of anisotropic water diffusion SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE tongue; deformation; diffusion tensor; magnetic resonance; imaging ID NUCLEAR MAGNETIC-RESONANCE; IN-VIVO; MUSCLE; MRI; COEFFICIENT; TENSOR; STROKE AB The muscular anatomy of the tongue consists of a complex three-dimensional array of fibers, which together produce the variations of shape and position necessary for deglutition. To define the myoarchitecture of the intact mammalian tongue, we have utilized NMR techniques to assess the location and orientation of muscle fiber bundles through measurement of the direction-specific diffusional properties of water molecules. Whole sheep tongues were excised and imaged with a slice-selective stimulated-echo diffusion sequence in the midline sagittal plane, and three-dimensional diffusion tensors were determined for each voxel. The derived diffusion tensors were depicted graphically as octahedra whose long axes indicate local muscle fiber orientation. Two distinct groups of midline fibers were identified: I) in-plane sagittal fibers originating in the posteroinferior region of the tongue, radiating with a fanlike projection anteriorly and superiorly and merging with vertically oriented fibers, and 2) cross-plane (transverse) fibers, oriented at right angles to the vertically aligned fibers, predominantly in the anterior and superior regions of the tongue. Regional comparison of diffusion anisotropy revealed uniform and parallel alignment thigh anisotropy) in the posteroinferior region of the tongue, corresponding to the base of the genioglossus, and less uniform, orthogonally aligned fibers (low anisotropy) in the anterosuperior region of the tongue, corresponding to the core intrinsic muscles. These data indicate that lingual myoarchitecture, determined through direction-dependent mobility of water molecules, can be depicted as discrete regions of muscle fibers, whose orientation and extent of diffusion anisotropy predict local contractility. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Boston Univ, Sch Engn, Dept Biomed Engn, Boston, MA 02215 USA. RP Gilbert, RJ (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 28 TC 18 Z9 18 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 AUG PY 1998 VL 275 IS 2 BP G363 EP G369 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 108WT UT WOS:000075289300023 PM 9688664 ER PT J AU Liberman, RP Wallace, CJ Blackwell, G Kopelowicz, A Vaccaro, JV Mintz, J AF Liberman, RP Wallace, CJ Blackwell, G Kopelowicz, A Vaccaro, JV Mintz, J TI Skills training versus psychosocial occupational therapy for persons with persistent schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID OUTPATIENTS AB Objective: The authors compared the community functioning of outpatients with persistent forms of schizophrenia after treatment with psychosocial occupational therapy or social skills training, with the latter conducted by paraprofessionals. Method: Eighty outpatients with persistent forms of schizophrenia were randomly assigned to receive either psychosocial occupational therapy or skills training for 12 hours weekly for 6 months, followed by 18 months of follow-up with case management in the community. Antipsychotic medication was prescribed through "doctor's choice" by psychiatrists who were blind to the psychosocial treatment assignments. Results: Patients who received skills training showed significantly greater independent living skills during a 2-year follow-up of everyday community functioning. Conclusions: Skills training can be effectively conducted by paraprofessionals, with durability and generalization of the skills greater than that achieved by occupational therapists who provide their patients with psychosocial occupational therapy. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Liberman, RP (reprint author), 528 Lake Sherwood Dr, Thousand Oaks, CA 91361 USA. EM rpl@ucla.edu OI kopelowicz, alex/0000-0002-1728-4105 FU NIMH NIH HHS [MH-30911] NR 20 TC 159 Z9 165 U1 3 U2 10 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1998 VL 155 IS 8 BP 1087 EP 1091 PG 5 WC Psychiatry SC Psychiatry GA 106JG UT WOS:000075125700016 PM 9699698 ER PT J AU Goldstein, G Allen, DN van Kammen, DP AF Goldstein, G Allen, DN van Kammen, DP TI Individual differences in cognitive decline in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB The authors' goal was to determine whether cognitively impaired patients with schizophrenia exhibit age-related cognitive declines similar to those of patients with schizophrenia who do not have substantial cognitive impairment. Method: Correlation coefficients were computed between age and the Average impairment Rating, a summary index of cognitive ability, in a group of 77 patients with schizophrenia. These patients were clustered into two groups: one with near-normal cognitive function (N=51) and one with severely impaired cognitive function (N=26). A group of patients with senile dementia (N=21) and another comparison group of nonschizophrenic patients (N=299) were used as reference groups. Results: There were significant correlations between age and the Average Impairment Rating in all groups except the cognitively impaired patients with schizophrenia, in which a zero-order correlation was obtained. Conclusions: Patients with schizophrenia who have substantial cognitive impairment do not have the significant correlation between age and cognitive function found in patients with schizophrenia who have mildly impaired or normal cognitive abilities, suggesting earlier onset of cognitive deficit in the cognitively impaired patients with schizophrenia. C1 VA Pittsburgh Healthcare Syst, Highland Dr Div 151R, Pittsburgh, PA 15206 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, Highland Dr Div 151R, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 7 TC 15 Z9 15 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1998 VL 155 IS 8 BP 1117 EP 1118 PG 2 WC Psychiatry SC Psychiatry GA 106JG UT WOS:000075125700024 PM 9699706 ER PT J AU Carlson, MJ Baker, LH AF Carlson, MJ Baker, LH TI Difficult, dangerous, and drug seeking: The 3D way to better patient care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Bayer Inst Hlth Care Commun, Portland, OR USA. RP Carlson, MJ (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 AUG PY 1998 VL 88 IS 8 BP 1250 EP 1252 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 106XJ UT WOS:000075176300026 PM 9702164 ER PT J AU Kubaska, SM Shepard, JAO Chew, FS Keel, SB AF Kubaska, SM Shepard, JAO Chew, FS Keel, SB TI Whipple's disease involving the mediastinum SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Chew, FS (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 5 TC 3 Z9 3 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 AUG PY 1998 VL 171 IS 2 BP 364 EP 364 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 104AU UT WOS:000074990700015 PM 9694452 ER PT J AU Rao, PM AF Rao, PM TI Technical and interpretative pitfalls of appendiceal CT imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 8 TC 24 Z9 24 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 1998 VL 171 IS 2 BP 419 EP 425 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 104AU UT WOS:000074990700030 PM 9694467 ER PT J AU Reiber, GE Lipsky, BA Gibbons, GW AF Reiber, GE Lipsky, BA Gibbons, GW TI The burden of diabetic foot ulcers SO AMERICAN JOURNAL OF SURGERY LA English DT Article ID QUALITY-OF-LIFE; AMPUTATION; INFECTIONS; MELLITUS; CARE; ULCERATION; MANAGEMENT; PREVENTION; DISEASE; COSTS AB Lower extremity ulcers represent a major concern for patients with diabetes and for those who treat them, from both a quality of life and an economic standpoint. Studies to evaluate quality of life have shown that patients with foot ulcers have decreased physical, emotional, and social function. Analyses of economic impact have shown (1) the majority of costs occur in the inpatient setting, (2) a lack of financial benefit when comparing primary amputation with an aggressive approach to limb salvaging including vascular reconstruction, and (3) private insurance provides greater reimbursement for inpatient care than does Medicare. Results of etiologic studies suggest that hyperglycemia induces diabetes-related complications through sorbitol accumulation and protein glycation, and the resultant nerve damage manifests as peripheral neuropathy, which predisposes to ulcer development. Patients with diabetes also have an increased incidence of peripheral vascular disease, impaired wound healing, and decreased ability to fight infection. In light of these factors, it is sometimes difficult to determine the optimal course for patient management. This review is aimed at helping healthcare providers make better decisions about treatment, resource use, and strategies for future foot ulcer prevention. Am J Suug. 1998;176(Suppl 2A):5S-10S. (C) 1998 by Excerpta Medica, Inc. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98109 USA. Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. RP Reiber, GE (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way 152, Seattle, WA 98109 USA. NR 40 TC 104 Z9 105 U1 0 U2 8 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD AUG PY 1998 VL 176 IS 2A SU S BP 5S EP 10S DI 10.1016/S0002-9610(98)00181-0 PG 6 WC Surgery SC Surgery GA 128NC UT WOS:000076412000003 PM 9777967 ER PT J AU Oliva, E Clement, PB Young, RH Scully, RE AF Oliva, E Clement, PB Young, RH Scully, RE TI Mixed endometrial stromal and smooth muscle tumors of the uterus - A clinicopathologic study of 15 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE uterus; endometrial stromal tumors; smooth muscle tumor; stromomyoma ID SEX-CORD TUMORS; MESENCHYMAL TUMORS; IMMUNOHISTOCHEMICAL ANALYSIS; DIFFERENTIATION; SARCOMA; STROMOMYOMA; NEOPLASMS; NODULES AB Uterine tumors composed of a prominent component of smooth muscle (SM) and endometrial stroma (ES) (so-called stromomyomas) have received little attention in the Literature. The features of 15 of these tumors, defined as those containing more than 30% of each component, were evaluated. Many of the tumors were referred because of problems in the differential diagnosis. Patient age ranged from 29 to 68 years (mean, 46 years). The tumors ranged from 3 to 27 cm (average 9.6 cm) in diameter, and most were grossly well circumscribed. The sectioned surfaces often had soft, tan-yellow areas admired with firm, whorled areas. Microscopic evaluation disclosed that nine tumors were well circumscribed, and six had infiltrating tongues typical of endometrial stromal sarcoma (ESS). The endometrial stromal component, which predominated in five cases, typically was characterized by a diffuse growth of closely packed, minimally atypical small cells accompanied by numerous arterioles and was desmin-negative in all cases tested, except for rare desmin-positive cells in three tumors. Five tumors showed sex-cord-like differentiation in these areas. The smooth muscle component, which predominated ir. seven cases, was composed predominantly of spindle cells in disorganized short fascicles, longer fascicles, or nodules with prominent central hyalinization. This component appeared benign, except in one case with moderate cytologic atypia, focal tumor cell necrosis, and 4 mitotic figures/10 high-power fields. The smooth muscle component was strongly desmin-positive in all the tumors tested. Follow-up of more than 1 year was available for seven patients. Six patients were alive and well, bur one tumor with infiltrative borders recurred at 48 months as a pure endometrial stromal sarcoma. Mixed endometrial stromal and smooth muscle tumors should be distinguished from highly cellular leiomyomas, pure endometrial stromal tumors, and "uterine tumors resembling ovarian sex cord tumors," at least until knowledge of their clinicopathologic features is more complete. For treatment purposes, these tumors should be reported as endometrial stromal nodules or as endometrial stromal sarcomas with smooth muscle differentiation and any un usual features of either component recorded in a notation. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ British Columbia, Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Young, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 32 Fruit St, Boston, MA 02114 USA. NR 30 TC 83 Z9 93 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 1998 VL 22 IS 8 BP 997 EP 1005 DI 10.1097/00000478-199808000-00010 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 108CK UT WOS:000075248300010 PM 9706980 ER PT J AU Asch, S Leake, B Knowles, L Gelberg, L AF Asch, S Leake, B Knowles, L Gelberg, L TI Tuberculosis in homeless patients: Potential for case finding in public emergency departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID MANAGEMENT; HEALTH AB Study objectives: Previous studies have had difficulty evaluating the optimal clinical site for screening homeless patients for active tuberculosis (TB). We hypothesized that homeless patients with TB would not frequently reside in shelters at the time of their diagnosis and would be more likely than other patients with TB to seek care in public hospitals, thus presenting an opportunity for screening radiography. Methods: This registry-based survey included 743 consecutive patients with confirmed active TB in Los Angeles County. No therapeutic intervention was involved. Results: When compared with patients with TB who were not homeless, homeless patients with TB were more likely to be male (93% versus 63%, P < .001), black (44% versus 15%, P < .001), living in the inner city (55% versus 7%, P < .001), and born in the United States (67% versus 32%, P < .001). They were more infectious than other patients with TB as evidenced by a trend toward more cavitary radiographic lesions (24% versus 16%, P = .11) and significantly more positive sputum smears (56% versus 41%, P = .009). Less than a third lived in congregate facilities such as shelters at the time of their diagnosis. Instead, their disease was diagnosed more often at county hospitals (54% versus 23%, P < .001) than patients with TB who were not homeless. Conclusion: Widespread screening for TB in shelters may miss most homeless patients with TB. Because most county-hospital homeless patients with TB initially present to emergency departments and many do not live in shelters, future cost-effectiveness studies should evaluate chest radiograph screening for all homeless ED patients. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Asch, S (reprint author), W Los Angeles Vet Affairs Med Ctr, Mail Code 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 10 TC 10 Z9 10 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 1998 VL 32 IS 2 BP 144 EP 147 DI 10.1016/S0196-0644(98)70128-3 PG 4 WC Emergency Medicine SC Emergency Medicine GA 106JL UT WOS:000075126100003 PM 9701295 ER PT J AU Barach, P Rivkind, A Israeli, A Berdugo, M Richter, ED AF Barach, P Rivkind, A Israeli, A Berdugo, M Richter, ED TI Emergency preparedness and response in Israel during the Gulf War (vol 30, pg 513, 1997) SO ANNALS OF EMERGENCY MEDICINE LA English DT Correction ID INDUSTRIAL RESPIRATORS AB We examined the effect of the emergency response on medical and public health problems during the 1991 Gulf War in Israel. On the first day of the conflict, the number of deaths from suffocation, asphyxiation, aspiration, myocardial infarction, cardiac arrest, and cerebrovascular accident increased abruptly, as did the number of sudden deaths associated with the use of tight-fitting masks with filters in sealed rooms. Much of the excess risk for death from cardiorespiratory complications during the first alert may have been a consequence of its duration (140 minutes). Mass evacuation and concrete buildings are believed to have kept the death toll from trauma down, and mask use may have protected against facial and upper-airway injuries. Falls and hip fractures, airway irritation from exposure to bleach, carbon monoxide intoxication from open kerosene heaters in sealed rooms, and self-injection with atropine syringes were also noted. A measles epidemic and increased death rates from automobile crashes were other preventable causes of death. Protection against biological warfare was limited to surveillance of trends for pneumonia and gastroenteritis. Emergency planners failed to anticipate the need for better mask fit, hands-on training in the use of masks, and special guidelines for older persons to prevent deaths from suffocation and other cardiovascular-respiratory problems in the first minutes of use. If masks are to be distributed as a protection against chemi cal warfare, a simpler model including the use of shrouds for whole-body skin protection might help avoid cardiorespiratory complications. Public health problems not adequately dealt with in the predisaster period are apt to emerge with greater severity during a crisis. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Barach, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, 32 Fruit St, Boston, MA 02114 USA. RI Barach, paul/B-9915-2016 OI Barach, paul/0000-0002-7906-698X NR 40 TC 17 Z9 17 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 1998 VL 32 IS 2 BP 224 EP 233 DI 10.1016/S0196-0644(98)70140-4 PG 10 WC Emergency Medicine SC Emergency Medicine GA 106JL UT WOS:000075126100015 PM 9701306 ER PT J AU Roila, F Del Favero, A Gralla, RJ Tonato, M Aapro, MS Andrews, PLR Ballatori, E De Mulder, PHM Dicato, MA du Bois, A Feyer, PC Gandara, DR Gralla, RJ Gralla, RJ Groshen, S Grunberg, SM Herrstedt, J Hesketh, PJ Joss, RA Kris, MG Marty, MM Morrow, GR Naylor, RJ Olver, IN Smyth, JF Spitzer, TR Stewart, A AF Roila, F Del Favero, A Gralla, RJ Tonato, M Aapro, MS Andrews, PLR Ballatori, E De Mulder, PHM Dicato, MA du Bois, A Feyer, PC Gandara, DR Gralla, RJ Gralla, RJ Groshen, S Grunberg, SM Herrstedt, J Hesketh, PJ Joss, RA Kris, MG Marty, MM Morrow, GR Naylor, RJ Olver, IN Smyth, JF Spitzer, TR Stewart, A CA Antiemetic Subcommittee Multinational As TI Prevention of chemotherapy- and radiotherapy-induced emesis: Results of the Perugia Consensus Conference SO ANNALS OF ONCOLOGY LA English DT Review DE antiemetics; chemotherapy and radiotherapy-induced emesis; 5-HT3 antagonists ID MODERATELY EMETOGENIC CHEMOTHERAPY; CISPLATIN-INDUCED EMESIS; METOCLOPRAMIDE PLUS DEXAMETHASONE; RANDOMIZED DOUBLE-BLIND; HIGH-DOSE CISPLATIN; BONE-MARROW TRANSPLANT; IV DOLASETRON MESILATE; QUALITY-OF-LIFE; INDUCED NAUSEA; ANTIEMETIC THERAPY AB Background. The need to review and summarize the evidence concerning preventive treatment of cancer chemotherapy- and radiotherapy-induced emesis. Design: After a survey among experts the Antiemetic Subcommittee of the MASCC planned and held a Consensus Conference on antiemetic therapy. Recommendations were provided on the basis of scientific confidence and the level of consensus among the participating experts. Results and conclusions: A 5-HT3 antagonist plus dexamethasone is the regimen of choice in the prevention of acute emesis induced by single high, and low and repeated doses of cisplatin, and of acute emesis induced by moderately-high emetogenic chemotherapy (i.e., cyclophosphamide, doxorubicin, epirubicin, carboplatin, used alone or in combination) in both adults and children. In the prevention of delayed emesis induced by cisplatin the most efficacious choice is a combination of dexamethasone with either metoclopramide or a 5-HT3 antagonist, while in moderately-high emetogenic chemotherapy dexamethasone alone or a 5-HT3 antagonist alone or their combination should be used. No evidence or consensus exists regarding antiemetic treatment for patients receiving low emetogenic chemotherapy, or about the optimal rescue treatment for patients failing antiemetic prophylaxis. The best treatment for anticipatory emesis is the best possible control of acute and delayed emesis. Although 5-HT3 antagonists have some efficacy in the prevention of acute emesis induced by high-dose chemotherapy, more studies should be carried out to determine the best preventive treatment. For prevention of acute emesis induced by highly/moderately emetogenic radiotherapy (TBI, irradiation of the upper part of the abdomen or of the whole abdomen/radiotherapy of the thorax, pelvis and lower body half) a 5-HT3 antagonist is the best choice. C1 Inst Multidisciplinaire Oncol, Genolier, Switzerland. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Univ Aquila, I-67100 Laquila, Italy. Univ Nijmegen Hosp, NL-6500 HB Nijmegen, Netherlands. Univ Perugia, I-06100 Perugia, Italy. Ctr Hosp, Luxembourg, Luxembourg. St Vincentius Hosp, Karlsruhe, Germany. Humboldt Univ, D-1086 Berlin, Germany. Univ Calif Davis, Sacramento, CA 95817 USA. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Univ So Calif, Los Angeles, CA USA. Univ Vermont, Burlington, VT USA. Univ Copenhagen, Herlev Hosp, DK-1168 Copenhagen, Denmark. St Elizabeths Med Ctr, Boston, MA USA. Kantonsspital Luzern, Luzern, Switzerland. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Hop St Louis, Paris, France. Univ Rochester, Ctr Canc, Rochester, NY 14627 USA. Univ Bradford, Bradford BD7 1DP, W Yorkshire, England. Royal Adelaide Hosp, Adelaide, SA 5000, Australia. Univ Perugia, Monteluce Policlin, Perugia, Italy. Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Christie Hosp, Manchester, Lancs, England. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. EM oncmedpg@krenet.in RI Olver, Ian/I-1518-2015 OI Olver, Ian/0000-0001-5478-1576 NR 103 TC 137 Z9 140 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 1998 VL 9 IS 8 BP 811 EP 819 PG 9 WC Oncology SC Oncology GA 125ZD UT WOS:000076266900010 ER PT J AU Campo, E Gaulard, P Zucca, E Jaffe, ES Harris, NL Diebold, J Schlegelberger, B Feller, AC Delsol, C Gisselbrecht, C Montserrat, E AF Campo, E Gaulard, P Zucca, E Jaffe, ES Harris, NL Diebold, J Schlegelberger, B Feller, AC Delsol, C Gisselbrecht, C Montserrat, E CA European Task Force Lymphomas TI Report of the European task force on lymphomas: Workshop on peripheral T-cell lymphomas SO ANNALS OF ONCOLOGY LA English DT Editorial Material DE extranodal lymphomas; non-Hodgkin's lymphomas; peripheral T-cell lymphomas ID MONOCLONAL-ANTIBODY ALK1; NON-HODGKINS-LYMPHOMA; B-CELL; ANGIOIMMUNOBLASTIC LYMPHADENOPATHY; AMERICAN CLASSIFICATION; CYTOGENETIC FINDINGS; INTERFERON-GAMMA; ORGANIZATION; EXPRESSION; NEOPLASMS C1 Univ Barcelona, Hosp Clin Barcelona, Pathol Lab, Hematopathol Sect, E-08036 Barcelona, Spain. Univ Barcelona, Hosp Clin Barcelona, Dept Hematol, E-08036 Barcelona, Spain. CHU Henri Mondor, Pathol Lab, F-94010 Creteil, France. San Giovanni Hosp, Div Oncol, Bellinzona, Switzerland. NCI, Pathol Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Pathol Lab, Boston, MA 02114 USA. Hotel Dieu, Pathol Lab, Paris, France. Univ Kiel, Dept Human Genet, Kiel, Germany. Univ Lubeck, D-2400 Lubeck, Germany. Hop Purpan, Pathol Lab, Toulouse, France. Hop St Louis, Inst Hematol, Paris, France. RP Campo, E (reprint author), Univ Barcelona, Hosp Clin Barcelona, Pathol Lab, Hematopathol Sect, Villarroel 170, E-08036 Barcelona, Spain. EM campo@medicina.ub.es RI Feller, Alfred/E-3853-2010; OI Campo, elias/0000-0001-9850-9793 NR 32 TC 24 Z9 24 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 1998 VL 9 IS 8 BP 835 EP 843 DI 10.1023/A:1008439620513 PG 9 WC Oncology SC Oncology GA 125ZD UT WOS:000076266900013 PM 9789605 ER PT J AU Ung, F Lazor, JB Montgomery, WW AF Ung, F Lazor, JB Montgomery, WW TI Cervical thorotrast granuloma: A review of the literature and a new treatment modality SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE contrast medium complications; doxycycline sclerosis; neck; thorium dioxide; Thorotrast; thorotrastoma; wound healing ID HEMORRHAGE; MORTALITY AB Extravasation of thorium dioxide after transcervical carotid angiography has resulted in persistent open draining neck wounds. These difficult problems have remained a challenge for the treating head and neck surgeon. Neck dissection has been the mainstay of treatment in the past; however, this has been fraught with complications. The application of doxycycline sclerosis is described in the successful resolution of a large Thorotrast granulomatous neck Round. A review of the literature and the management options of Thorotrast granulomas are discussed. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Montgomery, WW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 4 Z9 4 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 AUG PY 1998 VL 107 IS 8 BP 708 EP 712 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 108ND UT WOS:000075271600014 PM 9716875 ER PT J AU Nakfoor, BM Willett, CG Shellito, PC Kaufman, DS Daly, WJ AF Nakfoor, BM Willett, CG Shellito, PC Kaufman, DS Daly, WJ TI The impact of 5-fluorouracil and intraoperative electron beam radiation therapy on the outcome of patients with locally advanced primary rectal and rectosigmoid cancer SO ANNALS OF SURGERY LA English DT Article ID HIGH-DOSE LEUCOVORIN; PREOPERATIVE IRRADIATION; CHEMOTHERAPY; FLUOROURACIL; CARCINOMAS; SURGERY AB Objective To analyze the effects of 5-fluorouracil (5-FU) chemotherapy combined with preoperative irradiation and the role of intraoperative electron beam irradiation (IOERT) on the outcome of patients with primary locally advanced rectal or rectosigmoid cancer. Methods From 1978 to 1996, 145 patients with locally advanced rectal cancer underwent moderate- to high-dose preoperative irradiation followed by surgical resection. Ninety-three patients received 5-FU as a bolus for 3 days during the first and last weeks of radiation therapy (84 patients) or as a continuous infusion throughout irradiation (9 patients). At surgery, IOERT was administered to the surgical bed of 73 patients with persistent tumor adherence or residual disease in the pelvis. Results No differences in sphincter preservation, pathologic downstaging, or resectability rates were observed by 5-FU use. However, there were statistically significant improvements in 5-year actuarial local control and disease-specific survival in patients receiving 5-FU during irradiation compared with patients undergoing irradiation without 5-FU. For the 73 patients selected to receive IOERT, local control and disease-specific survival correlated with resection extent. For the 45 patients undergoing complete resection and IOERT, the 5-year actuarial local control and disease-specific survival were 89% and 63%, respectively. These figures were 65% and 32%, respectively, for the 28 patients undergoing IOERT for residual disease. The overall 5-year actuarial complication rate was 11%. Conclusions Treatment strategies using 5-FU during irradiation and IOERT for patients with locally advanced rectal cancer are beneficial and well tolerated. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Gen Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Med Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Willett, CG (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 12 TC 57 Z9 58 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 1998 VL 228 IS 2 BP 194 EP 200 DI 10.1097/00000658-199808000-00008 PG 7 WC Surgery SC Surgery GA 108ZY UT WOS:000075297600008 PM 9712564 ER PT J AU Glatter, RD Goldberg, JS Schomacker, KT Compton, CC Flotte, TJ Bua, DP Greaves, KW Nishioka, NS Sheridan, RL AF Glatter, RD Goldberg, JS Schomacker, KT Compton, CC Flotte, TJ Bua, DP Greaves, KW Nishioka, NS Sheridan, RL TI Carbon dioxide laser ablation with immediate autografting in a full-thickness porcine burn model SO ANNALS OF SURGERY LA English DT Article ID THERMAL-DAMAGE; BLOOD-LOSS; SKIN INCISIONS; HEPATITIS-C; CO2-LASER; EXCISION; SCALPEL; TRANSFUSION; TISSUE; WOUNDS AB Objective To compare the long-term clinical and histologic outcome of immediate autografting of full-thickness burn wounds ablated with a high-power continuous-wave CO2 laser to sharply debrided wounds in a porcine model. Summary Background Data Continuous-wave CO2 lasers have performed poorly as tools for burn excision because the large amount of thermal damage to viable subeschar tissues precluded successful autografting. However, a new technique, in which a high-power laser is rapidly scanned over the eschar, results in eschar vaporization without significant damage to underlying viable tissues, allowing successful immediate autografting. Methods Full-thickness paravertebral burn wounds measuring 36 cm(2) were created on 11 farm swine. Wounds were ablated to adipose tissue 48 hours later using either a surgical blade or a 150-Watt continuous-wave CO2 laser deflected by an x-y galvanometric scanner that translated the beam over the tissue surface, removing 200 mu m of tissue per scan. Both sites were immediately autografted and serially evaluated clinically and histologically for 180 days. Results The laser-treated sites were nearly bloodless. The mean residual thermal damage was 0.18 +/- 0.05 mm. The mean graft take was 96 +/- 11% in manual sites and 93 +/- 8% in laser sites. On postoperative day 7, the thickness of granulation tissue at the graft-wound bed interface was greater in laser-debrided sites. By postoperative day 180, the manual and laser sites were histologically identical. Vancouver scar assessment revealed no differences in scarring at postoperative day 180. Conclusions Long-term scarring, based on Vancouver scar assessments and histologic evaluation, was equivalent at 6 months in laser-ablated and sharply excised sites. Should this technology become practical, the potential clinical implications include a reduction in surgical blood loss without sacrifice of immediate engraftment rates or long-term outcome. C1 Massachusetts Gen Hosp, Shriners Burns Inst, Trauma & Burn Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Sheridan, RL (reprint author), Massachusetts Gen Hosp, Shriners Burns Inst, Trauma & Burn Serv, Suite 930,51 Blossom St, Boston, MA 02114 USA. NR 46 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 1998 VL 228 IS 2 BP 257 EP 265 DI 10.1097/00000658-199808000-00016 PG 9 WC Surgery SC Surgery GA 108ZY UT WOS:000075297600016 PM 9712572 ER PT J AU Fischman, AJ Babich, JW Bonab, AA Alpert, NM Vincent, J Callahan, RJ Correia, JA Rubin, RH AF Fischman, AJ Babich, JW Bonab, AA Alpert, NM Vincent, J Callahan, RJ Correia, JA Rubin, RH TI Pharmacokinetics of [F-18]trovafloxacin in healthy human subjects studied with positron emission tomography SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO ACTIVITY; F-18 LABELED FLUCONAZOLE; TROVAFLOXACIN CP-99,219; ANAEROBIC-BACTERIA; STREPTOCOCCUS-PNEUMONIAE; ANTIMICROBIAL ACTIVITY; FLUOROQUINOLONE; CIPROFLOXACIN; FLEROXACIN; NAPHTHYRIDONE AB Tissue pharmacokinetics of trovafloxacin, a new broad-spectrum fluoroquinolone antimicrobial agent, were measured by positron emission tomography (PET) with [F-18]trovafloxacin in 16 healthy volunteers (12 men and 4 women). Each subject received a single oral dose of trovafloxacin (200 mg) daily beginning 5 to 8 days before the PET measurements. Approximately 2 h after the final oral dose, the subject was positioned in the gantry of the PET camera, and 1 h later 10 to 20 mCi of [F-18]trovafloxacin was infused intravenously over 1 to 2 min. Serial PET images and blood samples were collected for 6 to 8 h, starting at the initiation of the infusion. Drug concentrations were expressed as the percentage of injected dose per gram, and absolute concentrations were estimated by assuming complete absorption of the final oral dose. In most tissues, there was rapid accumulation of the radiolabeled drug, with high levels achieved within 10 min after tracer infusion. Peak concentrations of more than five times the MIC at which 90% of the isolates are inhibited (MIC90) for most members of Enterobacteriaceae and anaerobes (> 10-fold for most organisms) were achieved in virtually all tissues, and the concentrations remained above this level for more than 6 to 8 h. Particularly high peak concentrations (micrograms per gram; mean +/- standard error of the mean [SEM]) were achieved in the liver (35.06 +/- 5.89), pancreas (32.36 +/- 20.18), kidney (27.20 +/- 10.68), lung (22.51 +/- 7.11), and spleen (21.77 +/- 11.33). Plateau concentrations (measured at 2 to 8 h; micrograms per gram; mean +/- SEM) were 3.25 +/- 0.43 in the myocardium, 7.23 +/- 0.95 in the lung, 11.29 +/- 0.75 in the liver, 9.50 +/- 2.72 in the pancreas, 4.74 +/- 0.54 in the spleen, 1.32 +/- 0.09 in the bowel, 4.42 +/- 0.32 in the kidney, 1.51 +/- 0.15 in the bone, 2.46 +/- 0.17 in the muscle, 4.94 +/- 1.17 in the prostate, and 3.27 +/- 0.49 in the uterus. In the brain, the concentrations (peak, similar to 2.63 +/- 1.49 mu g/g; plateau, similar to 0.91 +/- 0.15 mu g/g) exceeded the MIC(90)s for such common causes of central nervous system infections as Streptococcus pneumoniae (MIC90, <0.2 mu g/ml), Neisseria meningitidis (MIC90, <0.008 mu g/ml), and Haemophilus influenzae (MIC90, <0.03 mu g/ml). These PET results suggest that trovafloxacin will be useful in the treatment of a broad range of infections at diverse anatomic sites. C1 Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA. MIT, Harvard Mit Div Hlth Sci & Technol, Ctr Expt Pharmacol & Therapeut, Cambridge, MA 02139 USA. Pfizer Inc, Div Cent Res, Groton, CT 06340 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 46 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1998 VL 42 IS 8 BP 2048 EP 2054 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 106LV UT WOS:000075131800029 PM 9687405 ER PT J AU Fournier, B Hooper, DC AF Fournier, B Hooper, DC TI Effects of mutations in GrlA of topoisomerase IV from Staphylococcus aureus on quinolone and coumarin activity SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; DNA GYRASE; PRIMARY TARGET; RESISTANCE; FLUOROQUINOLONES; LOCUS; GENE AB The grlA genes of Staphylococcus aureus ISP794 (wild type), MT5224c4 (grlA [Phe-80]), MT5224c2 (grlA [Pro-116]), and MT111 (grlA [Glu-116]) were cloned in pSK950, a shuttle vector, and introduced into S, aureus strains derived from strain RN4220. The mutations at position 116 of GrlA (Ala-->Pro or Glu) caused an increase in the level of fluoroquinolone resistance and a decrease in the level of coumarin susceptibility, whereas the mutation at position 80 (Ser-->Phe) caused only an increase in the level of fluoroquinolone resistance. In multicopy alleles, both types of mutations were codominant for fluoroquinolone resistance, and mutations at position 116 were also codominant for coumarin resistance. C1 Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Med Serv, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI023988, AI23988, R37 AI023988] NR 18 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1998 VL 42 IS 8 BP 2109 EP 2112 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 106LV UT WOS:000075131800040 PM 9687416 ER PT J AU Hall, SM Reus, VI Munoz, RF Sees, KL Humfleet, G Hartz, DT Frederick, S Triffleman, E AF Hall, SM Reus, VI Munoz, RF Sees, KL Humfleet, G Hartz, DT Frederick, S Triffleman, E TI Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID LONGITUDINAL PSYCHIATRIC DATA; NICOTINE DEPENDENCE; DEPRESSIVE SYMPTOMS; WITHDRAWAL SYMPTOMS; YOUNG-ADULTS; DOUBLE-BLIND; CESSATION; SMOKERS; ABSTINENCE; CLONIDINE AB Background: A history of major depressive disorder (MDD) predicts failure to quit smoking. We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD. The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence. Methods: This was a 2 (nortriptyline vs placebo) x 2 (cognitive-behavioral therapy vs control) x 2 (history of MDD vs no history) randomized trial. The participants were 199 cigarette smokers. The outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 38, and 64. Mood, withdrawal, and depression were measured at 3, 5, and 8 days after the smoking quit date, Results: Nortriptyline produced higher abstinence rates than placebo, independent of depression history. Cognitive;behavioral therapy was more effective for participants with a history of depression. Nortriptyline alleviated a negative affect occurring after smoking cessation. Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessments for MDD history-negative smokers. There was also a sex-by-depression history interaction; MDD history-positive women were less likely to be abstinent than MDD history-negative women, but depression history did not predict abstinence for men. Conclusions: Nortriptyline is a promising adjunct for smoking cessation. Smokers with a history of depression are aided by more intensive psychosocial treatments. Mood and diagnosis interact to predict relapse. Increases in negative affect after quitting smoking are attenuated by nortriptyline. C1 Univ Calif San Francisco, Treatment Res Ctr, Dept Psychiat, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Psychiat Serv, San Francisco, CA USA. RP Hall, SM (reprint author), Univ Calif San Francisco, Treatment Res Ctr, Dept Psychiat, Box 0984TRC,401 Parnassus Ave, San Francisco, CA 94143 USA. RI reus, victor/I-7923-2015 OI reus, victor/0000-0002-8193-5697 FU NIDA NIH HHS [P50 DA 09253, R01 DA 23652, T32 DA 07250] NR 33 TC 256 Z9 260 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1998 VL 55 IS 8 BP 683 EP 690 DI 10.1001/archpsyc.55.8.683 PG 8 WC Psychiatry SC Psychiatry GA 107EE UT WOS:000075193400001 PM 9707377 ER PT J AU Barsky, AJ Fama, JM Bailey, ED Ahern, DK AF Barsky, AJ Fama, JM Bailey, ED Ahern, DK TI A prospective 4- to 5-year study of DSM-III-R hypochondriasis SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; MEDICAL OUTPATIENTS; SOMATOSENSORY AMPLIFICATION; TRANSIENT HYPOCHONDRIASIS; MENTAL-HEALTH; PRIMARY-CARE; SELF-REPORT; DISORDERS; VALIDITY; ILLNESS AB Background: Although hypochondriasis is generally thought to be a chronic and stable condition with a relatively low remission rate, this disorder remains understudied. Methods: This is a 4- to 5-year prospective case-control study of DSM-III-R hypochondriasis. Medical outpatients meeting DSM diagnostic criteria for hypochondriasis completed an extensive research battery assessing hypochondriacal symptoms, medical and psychiatric co morbidity, functional status and role impairment, and medical care. A comparison group of nonhypochondriacal patients from the same setting underwent the same battery. Four to 5 years later, both cohorts were, re interviewed. Results: One hundred twenty hypochondriacal and 133 nonhypochondriacal comparison patients were originally studied. Follow-up was obtained on 73.5% (n = :186) of all patients. At follow-up, the hypochondriacal sample was significantly (P<.001) less hypochondriacal and had less somatization (P<.001) and disability than at inception, but 63.5% (n=54) still met DSM-III-R diagnostic criterial. When compared with the comparison group using repeated measures multivariate analysis of variance, these changes remained statistically significant (P<.0001). Changes in medical and psychiatric comorbidity did not differ between the 2 groups. When hypochondriacal patients who did and did not meet diagnostic criteria at follow-up were compared; the latter had significantly less disease conviction (P<.05) and somatization (P<.01) at inception, and their incidence of major medical illness during the follow-up period was significantly (P<.05) greater. Conclusions: Hypochondriacal patients show a considerable decline in symptoms and improvement in role functioning over 4 to 5 years but two thirds of them still meet diagnostic criteria. Hypochondriasis, therefore, carries a very substantial, long-term burden of morbidity, functional impairment, and personal distress. C1 Brigham & Womens Hosp, Div Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. RP Barsky, AJ (reprint author), Brigham & Womens Hosp, Div Psychiat, 75 Francis St, Boston, MA 02115 USA. EM ajbarsky@bics.bwh.harvard.edu FU NIMH NIH HHS [MH-40487] NR 42 TC 73 Z9 75 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1998 VL 55 IS 8 BP 737 EP 744 DI 10.1001/archpsyc.55.8.737 PG 8 WC Psychiatry SC Psychiatry GA 107EE UT WOS:000075193400009 PM 9707385 ER PT J AU Growdon, JH AF Growdon, JH TI Apolipoprotein E and Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID EPSILON-4; ALLELE C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Growdon, JH (reprint author), Massachusetts Gen Hosp, Dept Neurol, 32 Fruit St, Boston, MA 02114 USA. NR 10 TC 19 Z9 19 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 1998 VL 55 IS 8 BP 1053 EP 1054 DI 10.1001/archneur.55.8.1053 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 107WU UT WOS:000075234600001 PM 9708953 ER PT J AU Vamvakas, EC AF Vamvakas, EC TI Meta-analyses of studies of the diagnostic accuracy of laboratory tests - A review of the concepts and methods SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED TRIALS; URINARY-TRACT INFECTION; PAP TEST ACCURACY; PUBLICATION BIAS; CLINICAL-TRIALS; DISEASE VERIFICATION; METAANALYTIC METHODS; CONSORT STATEMENT; MEDICAL-RESEARCH; SELECTION BIAS AB Objective.-To provide practicing pathologists and other laboratory professionals with the necessary background for reading and evaluating published reports of meta-analyses of studies of the diagnostic accuracy of laboratory tests. Study Selection.-English language literature, 1980 to present, pertaining to the rationale, objectives, and interpretation of meta-analyses of randomized controlled trials, and meta-analyses of studies of the diagnostic accuracy of laboratory tests. Conclusions.-Meta-analysis has several applications in the investigation of the diagnostic accuracy of laboratory tests. It can improve the quality of future primary studies by drawing attention to the methodologic deficiencies of existing reports; it can identify reasons for the variation in the results of those reports; and it can generate valid summary estimates of the diagnostic accuracy of laboratory tests based on all completed investigations, providing that the available primary studies are of high scientific validity. Several statistical techniques for integrating data from reports on diagnostic test accuracy have either been developed or are under development, but meta-analysis is often limited by the poor quality of the primary studies and the effect of publication bias. Meta-analysis can evolve into a reliable tool for assessing the accuracy of laboratory tests if both investigators and editors strive to improve the quality of the primary studies and to reduce the extent of publication bias in this area of the literature. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Blood Transfus Serv, Boston, MA USA. RP Vamvakas, EC (reprint author), Vet Adm Med Ctr, Pathol & Lab Med Serv, 6N,423 E 23rd St, New York, NY 10010 USA. NR 104 TC 113 Z9 117 U1 0 U2 3 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 1998 VL 122 IS 8 BP 675 EP 686 PG 12 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 106XV UT WOS:000075177300004 PM 9701328 ER PT J AU Ticho, BS Neufeld, EJ Newburger, JW Harris, N Baker, A Rifai, N AF Ticho, BS Neufeld, EJ Newburger, JW Harris, N Baker, A Rifai, N TI Utility of direct measurement of low-density lipoprotein cholesterol in dyslipidemic pediatric patients SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID DIRECT LDL; PLASMA; ASSAY; SERUM AB Background: Low-density lipoprotein cholesterol (LDL-C) levels are the primary basis for treatment guidelines established for hyperlipidemic children and adolescents. Levels of LDL-C are commonly monitored by means of the Friedewald formula, an indirect calculation that requires an overnight fast. A new method has been developed for the direct measurement of LDL-C (DLDL-C) that does not require fasting. We evaluated the clinical utility of this method. Design: We determined LDL-C concentrations simultaneously by the DLDL-C method, Friedewald equation, and P-quantification (reference procedure). Setting: Pediatric dyslipidemia clinic at Children's Hospital, Boston, Mass. Patients: Ninety-two fasting hyperlipidemic pediatric patients. Results: At the LDL-C concentration cutoffs commonly used for making therapeutic decisions, the DLDL-C method had a significant negative bias (P less than or equal to .05) and misclassified patients into incorrect treatment groups more often than the Friedewald method. The negative predictive value for the DLDL-C method was lower than that for the Friedewald method (P less than or equal to .05), and the cost of determining LDL-C level with the new method was 3 times greater. Conclusions: The misclassification potential for LDL-C, and the assay costs, were greater for the DLDL-C method than for the Friedewald calculation. Despite the apparent advantages of the DLDL-C method, we conclude that for hyperlipidemic children the utility of this new method is not advantageous over the conventional Friedewald method. In some conditions, such as in diabetes or marked hypertriglyceridemia, the DLDL-C method may be useful. C1 Childrens Hosp, Dana Farber Canc Inst, Dept Lab Med, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Cardiol, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rifai, N (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Lab Med, 300 Longwood Ave, Boston, MA 02115 USA. EM rifai@al.tch.harvard.edu RI Neufeld, Ellis/F-9331-2011 NR 17 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD AUG PY 1998 VL 152 IS 8 BP 787 EP 791 PG 5 WC Pediatrics SC Pediatrics GA 106JQ UT WOS:000075126500012 PM 9701139 ER PT J AU Legro, MW Reiber, GD Smith, DG del Aguila, M Larsen, J Boone, D AF Legro, MW Reiber, GD Smith, DG del Aguila, M Larsen, J Boone, D TI Prosthesis evaluation questionnaire for persons with lower limb amputations: Assessing prosthesis-related quality of life SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID HEALTH-STATUS; MOOD STATES; SHORT-FORM; PROFILE; REHABILITATION; RELIABILITY; AMPUTEE; PEOPLE; ANKLE; KNEE AB Objective: To develop a self-report questionnaire for persons with lower limb amputations who use a prosthesis. The resulting scales were intended to be suitable to evaluate the prosthesis and life with the prosthesis. The conceptual framework was health-related quality of life. Design: Multiple steps of scale development, terminating with test-retest of the Prosthesis Evaluation Questionnaire (PEQ) by mail. Source of Sample: Records from two Seattle hospitals. Patients: Ninety-two patients with lower limb amputations who varied by age, reason for amputation, years since amputation, and amputation level. Main Outcome Measures: The 10 scales used were 4 prosthesis function scales (Usefulness, Residual Limb Health, Appearance, and Sounds), 2 mobility scales (Ambulation and Transfers), 3 psychosocial scales (Perceived Responses, Frustration, and Social Burden), and 1 Well-being scale. Validation measures were the Medical Outcomes Study Short Form-36, the Social Interaction subscale from the Sickness Impact Profile, and the Profile of Mood States-short form. Results: Nine PEQ scales demonstrated high internal consistency. All met test-retest criteria for comparing group results. Validity was described based on methods used to gather original items, distribution of scores, and comparison of scores with criterion variables. Conclusions: The PEQ scales displayed good psychometric properties. Future work will assess responsiveness of PEQ scales to changes in prosthetic components. We conclude that they will be useful in evaluation of prosthetic care. (C) 1998 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Puget Sound Hlth Care Syst, Div Hlth Serv Res & Dev, Seattle Div, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Orthopaed, Seattle, WA 98195 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Orthopaed Surg Unit, Seattle Div, Seattle, WA USA. Prosthet Res Study, Seattle, WA USA. RP Legro, MW (reprint author), MEDTAP Int Inc, 2101 4th Ave,Suite 2200, Seattle, WA 98121 USA. NR 31 TC 147 Z9 152 U1 6 U2 20 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 AUG PY 1998 VL 79 IS 8 BP 931 EP 938 DI 10.1016/S0003-9993(98)90090-9 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 108MJ UT WOS:000075269800009 PM 9710165 ER PT J AU Buckwalter, JA Mankin, HJ AF Buckwalter, JA Mankin, HJ TI Articular cartilage repair and transplantation SO ARTHRITIS AND RHEUMATISM LA English DT Review ID GROWTH-FACTOR-BETA; OSTEOCHONDRAL ALLOGRAFTS; POSTTRAUMATIC DEFECTS; ARTHROSCOPIC LAVAGE; PERIOSTEAL GRAFTS; CONTROLLED TRIAL; FEMORAL CONDYLE; RABBIT KNEE; FOLLOW-UP; OSTEOARTHRITIS C1 Univ Iowa, Coll Med, Dept Orthopaed, Iowa City, IA 52242 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Buckwalter, JA (reprint author), Univ Iowa, Coll Med, Dept Orthopaed, Pappajohn Pavil, Iowa City, IA 52242 USA. NR 144 TC 313 Z9 324 U1 1 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD AUG PY 1998 VL 41 IS 8 BP 1331 EP 1342 DI 10.1002/1529-0131(199808)41:8<1331::AID-ART2>3.0.CO;2-J PG 12 WC Rheumatology SC Rheumatology GA 108ZT UT WOS:000075297100001 PM 9704631 ER PT J AU Shepherd, PR Withers, DJ Siddle, K AF Shepherd, PR Withers, DJ Siddle, K TI Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling SO BIOCHEMICAL JOURNAL LA English DT Review ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; RAT SKELETAL-MUSCLE; P70 S6 KINASE; GROWTH-FACTOR-I; STIMULATED GLUCOSE-TRANSPORT; PLECKSTRIN HOMOLOGY DOMAINS; RECEPTOR SUBSTRATE-1 IRS-1; GTPASE-ACTIVATING PROTEIN; ACTIVE PHOSPHATIDYLINOSITOL 3-KINASE AB Insulin plays a key role in regulating a wide range of cellular processes. However, until recently little was known about the signalling pathways that are involved in linking the insulin receptor with downstream responses. It is now apparent that the activation of class la phosphoinositide 3-kinase (PI 3-kinase) is necessary and in some cases sufficient to elicit many of insulin's effects on glucose and lipid metabolism. The lipid products of PI 3-kinase act as both membrane anchors and allosteric regulators, serving to localize and activate downstream enzymes and their protein substrates. One of the major ways these lipid products of PI 3-kinase act in insulin signalling is by binding to pleckstrin homology (PH) domains of phosphoinositide-dependent protein kinase (PDK) and protein kinase B (PKB) and in the process regulating the phosphorylation of PKB by PDR. Using mechanisms such as this, PI 3-kinase is able to act as a molecular switch to regulate the activity of serine/threonine-specific kinase cascades important in mediating insulin's effects on endpoint responses. C1 UCL, Dept Biochem & Mol Biol, London WC1E 6BT, England. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge CB2 2QR, England. RP Shepherd, PR (reprint author), UCL, Dept Biochem & Mol Biol, Gower St, London WC1E 6BT, England. EM p.shepherd@biochem.ucl.ac.uk RI Withers, Dominic/D-7671-2014 OI Withers, Dominic/0000-0002-8009-7521 NR 334 TC 716 Z9 725 U1 2 U2 18 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 1 PY 1998 VL 333 BP 471 EP 490 PN 3 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 110NJ UT WOS:000075387000002 PM 9677303 ER PT J AU Moyers, JS Zhu, J Kahn, CR AF Moyers, JS Zhu, J Kahn, CR TI Effects of phosphorylation on function of the Rad GTPase SO BIOCHEMICAL JOURNAL LA English DT Article ID DEPENDENT PROTEIN-KINASE; C-MEDIATED PHOSPHORYLATION; BINDING PROTEIN; CALMODULIN; SITE; SUBSTRATE; FAMILY; MUSCLE; P21 AB Rad, Gem and Kir possess unique structural features in comparison with other Ras-like GTPases, including a C-terminal 31-residue extension that lacks typical prenylation motifs. We have recently shown that Rad and Gem bind calmodulin in a Ca2+-dependent manner via this C-terminal extension, involving residues 278-247 in human Rad. This domain also contains several consensus sites for serine phosphorylation, and Rad is complexed with calmodulin-dependent protein kinase II (CaM-KII) in C2C12 cells. Here we show that Rad serves as a substrate for phosphorylation by CaMKII, cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and casein kinase II (CKII) with stoichiometries in vitro of 0.2-1.3 mol of phosphate/mol of Rad. By deletion and point mutation analysis we show that phosphorylation by CaMKII and PKA occurs on a single serine residue at position 273, whereas PKC and CKII phosphorylate multiple C-terminal serine residues, including Ser(214), Ser(257), Ser(273), Ser(290) and Ser(299). Incubation of Rad with PKA decreases GTP binding by 60-70 %, but this effect seems to be independent of phosphorylation, as it is observed with the Ser(273) --> Ala mutant of Rad containing a mutation at the site of PKA phosphorylation. The remainder of the serine kinases have no effect on Rad GTP binding, intrinsic GTP hydrolysis or GTP hydrolysis stimulated by the putative tumour metastasis suppressor nm23. However, phosphorylation of Rad by PKC and CKII abolishes the interaction of Rad with calmodulin. These findings suggest that the binding of Rad to calmodulin, as well as its ability to bind GTP, might be regulated by the activation of several serine kinases. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM kahnr@joslab.harvard.edu FU NIDDK NIH HHS [T32DK 07260, DK 45935, P30 DK36836] NR 21 TC 22 Z9 22 U1 1 U2 1 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD AUG 1 PY 1998 VL 333 BP 609 EP 614 PN 3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 110NJ UT WOS:000075387000018 PM 9677319 ER PT J AU Williamson, PTF Watts, J Grobner, G Miller, KW Watts, A AF Williamson, PTF Watts, J Grobner, G Miller, KW Watts, A TI Solid state NMR studies of ligands bound to the nicotinic acetylcholine receptor. SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 665th Meeting of the Royal-Irish-Academy-Lecture on Peptide Metabolism in Cytoplasm of Brain Cells CY MAR 31-APR 02, 1998 CL UNIV SOUTHAMPTON, HANTS, ENGLAND SP Royal Irish Acad Lecture HO UNIV SOUTHAMPTON ID MEMBRANES C1 Univ Oxford, Dept Biochem, Biomembrane Struct Unit, Oxford OX1 4QU, England. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02114 USA. RP Williamson, PTF (reprint author), Univ Oxford, Dept Biochem, Biomembrane Struct Unit, S Parks Rd, Oxford OX1 4QU, England. RI Williamson, Philip/A-3362-2008 OI Williamson, Philip/0000-0002-0231-8640 NR 6 TC 2 Z9 2 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD AUG PY 1998 VL 26 IS 3 BP S297 EP S297 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 115XX UT WOS:000075692600151 PM 9766016 ER PT J AU Lees, S AF Lees, S TI Interpreting the equatorial diffraction pattern of collagenous tissues in the light of molecular motion SO BIOPHYSICAL JOURNAL LA English DT Article ID TURKEY LEG TENDON; GENERALIZED PACKING MODEL; NEUTRON-DIFFRACTION; WATER-CONTENT; ELECTRON-MICROSCOPY; SOFT-TISSUES; H-2 NMR; BONE; FIBRILS; HARD AB The equatorial diffraction pattern associated with collagenous tissues, particularly type I collagen, is diffuse and clearly unlike that from crystals. Hukins and Woodhead-Galloway proposed a statistical model that they termed a "liquid crystal" for collagen fibers in tendons. Fratzl et al. applied this model to both unmineralized and mineralized turkey leg tendon, a model that ignores the organization imposed by the well-known cross-linking. The justification for adopting this model is that the curve fits the data. It is shown that the data can be equally well matched by fitting a least-squares curve consisting of a second-order polynomial plus a Gaussian. The peak of the Gaussian is taken as the equatorial spacing of the collagen. A physical explanation for this model is given, as is a reason for the changes in the spacing with changes in water content of the tissue. The diffusion is attributed to thermally driven agitation of the molecules, in accordance with the Debye-Waller theory including the Gaussian distribution. The remainder of the diffusion is attributed to other scattering sources like the mineral crystallites. C1 Forsyth Dent Ctr, Boston, MA 02115 USA. RP Lees, S (reprint author), Forsyth Dent Ctr, 140 Fenway, Boston, MA 02115 USA. EM slees@forsyth.org NR 25 TC 9 Z9 9 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 1998 VL 75 IS 2 BP 1058 EP 1061 PG 4 WC Biophysics SC Biophysics GA 107KB UT WOS:000075206000048 PM 9675207 ER PT J AU Kowluru, A Metz, SA AF Kowluru, A Metz, SA TI Purine nucleotide- and sugar phosphate-induced inhibition of the carboxyl methylation and catalysis of protein phosphatase-2A in insulin-secreting cells: Protection by divalent cations SO BIOSCIENCE REPORTS LA English DT Article; Proceedings Paper CT 16th International-Diabetes-Federation Congress CY JUL 20-25, 1997 CL HELSINKI, FINLAND SP Int Diabet Federat DE carboxyl methylation; protein phosphatase 2A; insulin secretion; pancreatic beta cell ID PANCREATIC BETA-CELLS; OKADAIC ACID; RAT ISLETS; BINDING PROTEINS; LANGERHANS; PHOSPHORYLATION; CALCIUM; 2A; SECRETAGOGUES; EXOCYTOSIS AB Recently, we demonstrated that the 36 kDa catalytic subunit of protein phosphatase 2A (PP2Ac) undergoes methylation at its C-terminal leucine in normal rat islets, human islets and isolated beta cells; this modification increases the catalytic activity of PP2A [Kowluru el al. Endocrinology. 137:2315-2323, 1996]. Previous studies have suggested that adenine and guanine nucleotides or glycolytic intermediates [which are critical mediators in beta cell function] also modulate phosphatase activity in the pancreatic beta cell. Therefore, we examined whether these phosphorylated molecules specifically regulate the carboxyl methylation and the catalytic activity of PP2A in beta cells. Micromolar concentrations of ATP, ADP, GTP or GDP each inhibited the carboxyl methylation of PP2Ac and, to a lesser degree, the catalytic activity of PP2A. Likewise, the carboxyl methylation of PP2Ac and its catalytic activity were inhibited by [mono- or di-] phosphates of glucose or fructose. Additionally, however, the carboxyl methylation of PP2Ac was significantly stimulated by divalent metal ions (Mn2+ > Mg2+ > Ca2+ > control). The nucleotide or sugar phosphate-mediated inhibition of carboxyl methylation of PP2Ac and the catalytic activity of PP2A were completely prevented by Mn2+ or Mg2+. These data indicate that divalent metal ions protect against the inhibition by purine nucleotides or sugar phosphates of the carboxyl methylation of PP2Ac perhaps permitting PP2A to function under physiologic conditions. Therefore, these data warrant caution in interpretation of extant data on the regulation of phosphatase function by purine nucleotides. C1 William S Middleton Mem Vet Adm Med Ctr, Res Serv, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Med Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Endocrinol Sect, Madison, WI 53792 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53792 USA. Pacific NW Res Inst, Seattle, WA 98122 USA. RP Kowluru, A (reprint author), Ctr Clin Sci, H4-568,600 Highland Ave, Madison, WI 53792 USA. FU NIDDK NIH HHS [DK 37312] NR 37 TC 11 Z9 11 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0144-8463 J9 BIOSCIENCE REP JI Biosci. Rep. PD AUG PY 1998 VL 18 IS 4 BP 171 EP 186 DI 10.1023/A:1020148729747 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 148DP UT WOS:000077489500002 PM 9877231 ER PT J AU Kowluru, A Kowluru, RA AF Kowluru, A Kowluru, RA TI Subcellular localization and characterization of nucleoside diphosphate kinase in rat retina: Effect of diabetes SO BIOSCIENCE REPORTS LA English DT Article DE nucleoside diphosphate kinase; nucleotide triphosphates; G-proteins; retina; diabetes ID GTP-BINDING-PROTEINS; PANCREATIC BETA-CELLS; DIPHOSPHOKINASE ACTIVITY; INSULIN-SECRETION; MAST-CELLS; ABNORMALITIES; METABOLISM; EXPRESSION; FAMILY AB Nucleoside diphosphate kinase (NDP kinase) catalyzes the transfer of terminal phosphate from nucleotide triphosphates (e.g. ATP) to nucleotide diphosphates (e.g. GDP) to yield nucleotide triphosphates (e.g. GTP). Since guanine nucleotides play critical role(s) in GTP-binding protein (G-protein)-mediated signal transduction mechanisms in retina, we quantitated NDP kinase activity in subcellular fraction-derived from normal rat retina. A greater than 85% of the total specific activity was present in the soluble fraction, which was stimulated (up to 7 fold) by 2 mM magnesium. NDP kinase exhibited saturation kinetics towards di- and tri-phosphate substrates, and was inhibited by known inhibitors of NDP kinase, uridine diphosphate (UDP) or cromoglycate (CRG). We have previously reported significant abnormalities in the activation of G-proteins in streptozotocin (STZ)-diabetic rat retina (Kowluru er al. Diabetologia 35:624-631, 1992). Since NDP kinase has been implicated in direct interaction with and/or activation of various G-proteins, we quantitated both basal and magnesium-stimulated NDP kinase activity in soluble and particulate fractions of retina derived from STZ-diabetic rats to examine whether abnormalities in G-protein function in diabetes are attributable to alterations in retinal NDP kinase. There was no effect of diabetes either on the basal or the magnesium-activated retinal NDP kinase activity. This study represents the first characterization of NDP kinase activity in rat retina, and suggests that in diabetes, this enzyme may not be rate-limiting and/or causal for the observed alterations in retinal G-protein functions. C1 William S Middleton Mem Vet Adm Med Ctr, Diabet Res Lab, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Madison, WI 53706 USA. RP Kowluru, A (reprint author), Ctr Clin Sci, Room H4-568,600 Highland Ave, Madison, WI 53792 USA. NR 31 TC 1 Z9 2 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0144-8463 J9 BIOSCIENCE REP JI Biosci. Rep. PD AUG PY 1998 VL 18 IS 4 BP 187 EP 198 DI 10.1023/A:1020100813818 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 148DP UT WOS:000077489500003 PM 9877232 ER PT J AU Richardson, PG Elias, AD Krishnan, A Wheeler, C Nath, R Hoppensteadt, D Kinchla, NM Neuberg, D Waller, EK Antin, JH Soiffer, R Vredenburgh, J Lill, M Woolfrey, AE Bearman, SI Iacobelli, M Fareed, J Guinan, EC AF Richardson, PG Elias, AD Krishnan, A Wheeler, C Nath, R Hoppensteadt, D Kinchla, NM Neuberg, D Waller, EK Antin, JH Soiffer, R Vredenburgh, J Lill, M Woolfrey, AE Bearman, SI Iacobelli, M Fareed, J Guinan, EC TI Treatment of severe veno-occlusive disease with defibrotide: Compassionate use results in response without significant toxicity in a high-risk population SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; ACUTE-RENAL-FAILURE; POLYDEOXYRIBONUCLEOTIDE-DERIVED DRUG; HEPATIC VENOOCCLUSIVE DISEASE; ANTITHROMBOTIC AGENT; LIVER; IDENTIFICATION; GENERATION; ACTIVATION; PARAMETERS AB Hepatic veno-occlusive disease (VOD) is the most common of the regimen-related toxicities accompanying stem cell transplantation (SCT). Despite aggressive therapies, including the combination of tissue plasminogen activator (t-PA) and heparin, severe VOD is almost uniformly fatal. Defibrotide (DF) is a polydeoxyribonucleotide with activity in several vascular disorders and, unlike t-PA and heparin, produces no systemic anticoagulant effects. Nineteen patients who developed severe VOD after SCT were treated with DF on a compassionate-use basis. Patients had clinically established VOD and met risk criteria predicting progression and fatality. At the initiation of DF, all 19 patients had evidence of multiorgan dysfunction; median bilirubin was 22.3 mg/dL, 12 patients had renal insufficiency (5 dialysis dependent), 14 required oxygen supplementation, and encephalopathy was present in 8 patients. Beginning a median of 6 days after diagnosis of VOD, DF was administered intravenously in doses ranging from 5 to 60 mg/kg/d for a planned minimum course of 14 days. In no case was DF discontinued for attributable toxicity. No severe hemorrhage related to DF administration was observed. Resolution of VOD (bilirubin <2 mg/dL with improvement in other symptoms and signs) was seen in 8 patients (42%). Six of 8 responders survived past day +100, contrasted with the 2% predicted survival reported in comparable patients. The observed response rate, survival to day +100, and absence of significant DF treatment-associated toxicity are compelling end warrant further evaluation. (C) 1998 by The American Society of Hematology. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Beth Israel Hosp, Div Hematol Oncol, Boston, MA 02215 USA. Loyola Univ, Med Ctr, Chicago, IL 60611 USA. Emory Univ, Med Ctr, Atlanta, GA 30322 USA. Western Penn Canc Inst, Pittsburgh, PA USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Colorado, Ctr Hlth, Denver, CO 80202 USA. Univ Calif Los Angeles, Med Ctr, Div Hematol Oncol, Los Angeles, CA 90024 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Crinos SPA, Como, Italy. Childrens Hosp, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5PO1-CA 39542]; NHLBI NIH HHS [P50 HL54785]; NIAID NIH HHS [P01-AI 35225] NR 42 TC 157 Z9 159 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 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1998 VL 92 IS 3 BP 737 EP 744 PG 8 WC Hematology SC Hematology GA 104UY UT WOS:000075035300003 PM 9680339 ER PT J AU Urashima, M Teoh, G Chauhan, D Ogata, A Shirahama, S Kaihara, C Matsuzaki, M Matsushima, H Akiyama, M Yuza, Y Maekawa, K Anderson, KC AF Urashima, M Teoh, G Chauhan, D Ogata, A Shirahama, S Kaihara, C Matsuzaki, M Matsushima, H Akiyama, M Yuza, Y Maekawa, K Anderson, KC TI MDM2 protein overexpression inhibits apoptosis of TF-1 granulocyte-macrophage colony-stimulating factor-dependent acute myeloblastic leukemia cells SO BLOOD LA English DT Article ID WILD-TYPE P53; GM-CSF; HEMATOPOIETIC-CELLS; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; MULTIPLE-MYELOMA; MESSENGER-RNA; GENE; LINE; AMPLIFICATION AB Granulocyte-macrophage colony-stimulating factor (GMCSF) is a growth factor for acute myeloblastic leukemia (AML) cells. Murine double minute 2 (MDM2) oncoprotein, a potent inhibitor of wild-type p53 (wtp53), can function both to induce cell proliferation and enhance cell survival, and is frequently overexpressed in leukemias. Therefore, we focused on the importance of MDM2 protein in GM-CSF-dependent versus GM-CSF- independent growth of AML cells. The TF-1 AML cell line, which has both wtp53 and mutant p53 genes, showed GM-CSF-dependent growth; deprivation of GM-CSF resulted in G1 growth arrest and apoptosis, MDM2 mRNA and protein were highly expressed ire proliferating TF-1 cells in the presence of GM-CSF and decreased significantly with deprivation of GM-CSF. In contrast, p53 protein increased with GM-CSF deprivation, Ectopic overexpression of MDM2 in TF-1 AML cells conferred resistance to GM-CSF deprivation, and is associated with decreased p53 protein expression. Moreover, a variant of TF-1 cells that grows in a GM-CSF-independent fashion also expressed high levels of MDM2 and low levels of p53, These results suggest that GM-CSF-independent growth of AML cells is associated with overexpression of MDM2 protein and related modulation of p53 expression. (C) 1998 by The American Society of Hematology. C1 Jikei Univ, Sch Med, Dept Pediat, Minato Ku, Tokyo 105, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. SRL Inc, Tokyo, Japan. RP Urashima, M (reprint author), Jikei Univ, Sch Med, Dept Pediat, Minato Ku, 3-25-8 Nishi Shinbashi, Tokyo 105, Japan. EM urashima@jikei.ac.jp NR 55 TC 10 Z9 12 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1998 VL 92 IS 3 BP 959 EP 967 PG 9 WC Hematology SC Hematology GA 104UY UT WOS:000075035300029 PM 9680365 ER PT J AU Furuta, GT Ackerman, SJ Lu, L Williams, RE Wershil, BK AF Furuta, GT Ackerman, SJ Lu, L Williams, RE Wershil, BK TI Stem cell factor influences mast cell mediator release in response to eosinophil-derived granule major basic protein SO BLOOD LA English DT Article ID C-KIT LIGAND; CATIONIC PROTEINS; HISTAMINE-RELEASE; PROTEASES; RECEPTOR; BASOPHIL; INVIVO; HETEROGENEITY; PROLIFERATION; MATURATION AB Stem cell factor (SCF) is an important mast cell growth, differentiation, and survival factor. We investigated whether SCF influenced the response of mouse mast cells to an IgE-independent stimulus, eosinophil-derived granule major basic protein (MBP). Mouse bone marrow cultured mast cells (BMCMC) were derived in either concanavalin-stimulated mouse spleen conditioned medium (CM) or SCF, The cloned growth, factor-independent mast cell line CI.MC/C57.1 was also studied. BMCMC in SCF exhibited cytochemical staining properties, protease and histamine content, and increased serotonin uptake consistent with more mature differentiated mast cells as compared with BMCMC in CM or CI.MC/C57.1 cells. BMCMC in SCF released serotonin, C-14-labeled arachidonic acid metabolites and tumor necrosis factor-alpha (TNF-alpha) on stimulation with MBP, while no response was seen from either BMCMC in CM or CI.MC/C57.1 cells. All three mast cell populations released mediators on stimulation with the cationic MBP analog, poly-L-arginine, indicating that the cationic charge did not explain the selective response of BMCMC in SCF to eosinophil-derived granule MBP. These findings show that SCF significantly influences mast cell differentiation and the responsiveness of mast cells to eosinophil-derived granule MBP. (C) 1998 by The American Society of Hematology. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Childrens Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Expt Pathol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Illinois, Dept Biochem & Mol Biol, Chicago, IL USA. RP Wershil, BK (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, 149 13th St 1493404, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK46819, DK33506, DK40561] NR 39 TC 22 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1998 VL 92 IS 3 BP 1055 EP 1061 PG 7 WC Hematology SC Hematology GA 104UY UT WOS:000075035300039 PM 9680375 ER PT J AU Lein, M Koenig, F Jung, K Mcgovern, FJ Skates, SJ Schnorr, D Loening, SA AF Lein, M Koenig, F Jung, K Mcgovern, FJ Skates, SJ Schnorr, D Loening, SA TI The percentage of free prostate specific antigen is an age-independent tumour marker for prostate cancer: establishment of reference ranges in a large population of healthy men SO BRITISH JOURNAL OF UROLOGY LA English DT Article DE prostate specific antigen; free PSA; tumour marker; reference range ID SERUM; ALPHA-1-ANTICHYMOTRYPSIN; ADENOCARCINOMA; HYPERPLASIA; COMPLEX; CELLS AB Objective To define the reference range for the ratio of free to total prostate-specific antigen (fPSA%) in a population of healthy men with no clinically evident prostate cancer and to assess the influence of age on this tumour marker, thus determining the utility of fPSA% in enhancing the discriminatory power of PSA to differentiate healthy men and patients with benign prostatic hyperplasia from those with prostate cancer. Subjects and methods In a prospective cohort study between May and August 1996, 1160 white men aged 20-89 years (957 were 40-69 years old, 82% of all subjects) from nine European and eight non-European countries were assessed. None of the participants who had a history of prostate cancer had undergone prostatectomy. A standard clinical examination including a digital rectal examination was performed to exclude the presence of prostate cancer. Transrectal ultrasonography was not an inclusion criterion, as it was not available in every case, Total PSA (tPSA) and free PSA (fPSA) were determined in 61 laboratories using the appropriate Enzymun-Test(R) for tPSA and fPSA (Boehringer Mannheim Diagnostics, Mannheim, Germany). Serum tPSA, fPSA and fPSA% were then assessed as a function of the subjects' age, Results The serum tPSA and fPSA were significantly different among age decades 2-8 (P<0.001), with increasing median values, indicating that both variables depend on age. The recommended upper reference limit (95th percentile) for tPSA is 1.78 ng/mL for men aged 30-39 years, 1.75 ng/mL for 40-49 years, 2.27 ng/mL for 50-59 years, 3.48 ng/mL for 60-69 years and 4.26 ng/mL for 70-79 years. The fPSA% was not significantly different between decades 3-8 (P=0.06), Those aged 20-29 years had a slightly higher median value (P=0.03) than the other age groups. The recommended lower reference limit (fifth percentile) for fPSA% is 12.6%. Conclusion The fPSA% for clinically relevant age groups in healthy men was independent of age, which simplifies the use and interpretation of this relatively new tumour marker. C1 Humboldt Univ, Dept Urol, Hosp Charite, Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr, Boston, MA USA. RP Loening, SA (reprint author), Humboldt Univ, Dept Urol, Hosp Charite, Berlin, Germany. NR 29 TC 24 Z9 26 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1331 J9 BRIT J UROL JI Br. J. Urol. PD AUG PY 1998 VL 82 IS 2 BP 231 EP 236 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 108TB UT WOS:000075280600011 PM 9722758 ER PT J AU Lalonde, J Turgay, A Hudson, JI AF Lalonde, J Turgay, A Hudson, JI TI Attention-deficit hyperactivity disorder subtypes and comorbid disruptive behaviour disorders in a child and adolescent mental health clinic SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE DSM-IV; attention-deficit hyperactivity disorder; oppositional defiant disorder; conduct disorder; disruptive behaviour disorders ID DIAGNOSTIC-CRITERIA; CONDUCT DISORDER; SAMPLE AB Objective: To assess demographic characteristics and patterns of comorbid disruptive behaviour disorders (oppositional defiant disorder [ODD] or conduct disorder [CD]) in subtypes of attention-deficit hyperactivity disorder (ADHD). Method,, One hundred youths consecutively referred to a community child and adolescent mental health clinic and subsequently diagnosed with ADHD by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria were evaluated. The diagnosis was made by a child psychiatrist and was based on information from physicians, parents, teachers, and diagnostic interviews with the youths and their parents. Results: The major findings were: 1) ADHD combined (C) type was diagnosed in 78% of the subjects, while 15% had inattentive (I) type and 7% had hyperactive-impulsive (HI) type, and 2) patterns of comorbid disruptive behavioural disorders significantly differed among subtypes. Specifically subjects with the I type showed lower rates of comorbid ODD than those with the C type (33% and 85%; P < 0.001) and HI type (33% and 100%; P = 0.005), subjects with the HI type displayed a higher prevalence of CD than those with the I type (57% and 0%; P = 0.005) and C type (57% and 8%; P = 0.003). These results should be considered tentative because the reliability of the diagnostic procedures was not formally assessed and the number of subjects in the I and HI groups was small. Conclusion: ADHD subtypes showed significant differences in the distribution of comorbid disruptive behaviour disorders. These results support the utility of ADHD subtypes but should be replicated with a larger sample of I and HI type subjects using more rigorous diagnostic methods. C1 McLean Hosp, Biol Psychiat Lab, Belmont, MA 02178 USA. Massachusetts Gen Hosp, McLean Hosp Program, Belmont, MA USA. Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada. Michigan State Univ, E Lansing, MI 48824 USA. Harvard Med Sch, Dept Psychiat, Boston, MA USA. RP Lalonde, J (reprint author), McLean Hosp, Biol Psychiat Lab, 115 Mill St, Belmont, MA 02178 USA. NR 15 TC 28 Z9 32 U1 0 U2 1 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 260-441 MACLAREN ST, OTTAWA, ONTARIO K2H 2P3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD AUG PY 1998 VL 43 IS 6 BP 623 EP 628 PG 6 WC Psychiatry SC Psychiatry GA 112ZD UT WOS:000075524000011 PM 9729691 ER PT J AU Avigan, D Richardson, P Elias, A Demetri, G Shapiro, M Schnipper, L Wheeler, C AF Avigan, D Richardson, P Elias, A Demetri, G Shapiro, M Schnipper, L Wheeler, C TI Neutropenic enterocolitis as a complication of high dose chemotherapy with stem cell rescue in patients with solid tumors - A case series with a review of the literature SO CANCER LA English DT Review DE stem cell transplantation; pneumatosis intestinalis; typhlitis; neutropenic enterocolitis; solid tumor ID ACUTE-LEUKEMIA; SURGICAL INTERVENTION; CHILDHOOD LEUKEMIA; TYPHLITIS; CANCER; MANAGEMENT; COLITIS; ADULTS; EXPERIENCE; CHILDREN AB BACKGROUND. This case series with an accompanying review of the literature describes neutropenic enterocolitis as a complication of high dose chemotherapy viith stem cell rescue in patients with solid tumors. METHODS. Neutropenic enterocolitis is documented in two patients undergoing autologous stem cell transplantation. A review of MEDLINE from 1970 to the present was performed to delineate the prior related disease settings in which this condition has been described. The nature of the clinical syndrome and controversies regarding management are discussed. RESULTS. The authors report two patients who each received autologous stem cell transplantation for the treatment of a solid tumor. Both patients presented with progressive abdominal pain, signs of peritoneal irritation on examination, and pneumatosis intestinalis. In the first case, the syndrome developed rapidly over several hours, requiring emergent surgical intervention during the period of postchemotherapy nadir. In the second case, the patient developed a slowly progressive clinical picture that was managed successfully with medical therapy alone. A review of the literature suggests that neutropenic enterocolitis arises due to drug-induced bowel wall mucosal injury followed by superinfection with colonic and opportunistic organisms. Surgical intervention potentially is beneficial in patients who develop an acute syndrome that is unresponsive to antibiotic and supportive therapy. Those patients who can be stabilized with medical management often will recover once reengraftment occurs. CONCLUSIONS, Neutropenic enterocolitis is described in two patients undergoing autologous stem cell transplantation for solid tumors. The management of this life-threatening complication is controversial and governed by the nature of the clinical presentation. Cancer 1998;83:409- 14. (C) 1998 American Cancer Society. C1 Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Avigan, D (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. OI Shapiro, Michael/0000-0001-7491-6490 NR 37 TC 33 Z9 34 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 AUG 1 PY 1998 VL 83 IS 3 BP 409 EP 414 DI 10.1002/(SICI)1097-0142(19980801)83:3<409::AID-CNCR7>3.0.CO;2-J PG 6 WC Oncology SC Oncology GA 103XA UT WOS:000074982100007 PM 9690531 ER PT J AU Boral, AL Dessain, S Chabner, BA AF Boral, AL Dessain, S Chabner, BA TI Clinical evaluation of biologically targeted drugs: Obstacles and opportunities SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 13th Bristol-Myers-Squibb Nagoya International Cancer Treatment Symposium CY OCT 17-18, 1997 CL NAGOYA, JAPAN SP Bristol-Myers Squibb DE molecular mechanisms; apoptosis; telomerase; angiogenesis; antisense; metastasis ID NON-HODGKINS-LYMPHOMA; VASCULAR-PERMEABILITY FACTOR; TUMOR-CELL-LINES; C-RAF KINASE; ANTISENSE PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES; REVERSE-TRANSCRIPTASE INHIBITORS; POSITRON EMISSION TOMOGRAPHY; INVASIVE BREAST-CARCINOMA; BCL-2 PROTEIN EXPRESSION; HUMAN ENDOTHELIAL-CELLS AB Recent insights into the molecular mechanisms of cancer have indicated that a variety of fundamental cellular processes are dysregulated in malignant cells. These processes include cell cycle control, signal transduction pathways, apoptosis, telomere stability, angiogenesis, and interactions with the extracellular matrix. Remarkable advances in molecular genetics, enzymology, and medicinal chemistry have permitted the design of compounds that modulate some of these processes with specificity that was unimaginable a decade ago. As these novel, biologically targeted compounds enter the clinic, they will require a strategy for clinical evaluation and development different from that used commonly for cytotoxic antineoplastic agents. This review examines the development of cancer drugs directed against angiogenesis, metastasis, signal transduction, telomerase, and molecular message (antisense), outlines strategies for the clinical testing of agents directed at these processes, and contrasts these efforts with traditional approaches to cancer drug testing. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Cox Bldg 640,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [5T32CA09172-23] NR 177 TC 23 Z9 23 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD AUG PY 1998 VL 42 SU S BP S3 EP S21 DI 10.1007/s002800051075 PG 19 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 120EN UT WOS:000075942100002 PM 9750025 ER PT J AU Seetharam, S Nodzenski, E Beckett, MA Heimann, R Cha, A Margulies, I Pastan, I Kufe, DW Weichselbaum, RR AF Seetharam, S Nodzenski, E Beckett, MA Heimann, R Cha, A Margulies, I Pastan, I Kufe, DW Weichselbaum, RR TI Modulation of apoptotic response of a radiation-resistant human carcinoma by Pseudomonas exotoxin-chimeric protein SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-ALPHA; MEDIATED APOPTOSIS; CARBOXYL-TERMINUS; DNA FRAGMENTATION; DIPHTHERIA-TOXIN; FACTOR RECEPTOR; BLADDER-CANCER; CELLS; CERAMIDE; CYTOTOXICITY AB Strategies to sensitize human tumors that are resistant to apoptosis have been clinically unsuccessful. We demonstrate that a structurally modified chimeric Pseudomonas exotoxin, PE Delta 53L/TGF-alpha/KDEL, with binding specificity for the epidermal growth factor receptor, markedly enhances sensitivity of human xenografts to radiation killing. Exposure to PE Delta 53L/TGF-alpha/KDEL decreases the apoptotic threshold through protein synthesis inhibition and simultaneous production of ceramide in tumor cells that lack functional p53 protein. In contrast, no increase in local or systemic toxicity was observed with the chimeric toxin and radiation. We conclude that biochemical targeting of the chimeric toxin and physical targeting of ionizing radiation may increase the therapeutic ratio in the treatment of human cancers with alterations of p53 expression. This strategy offers a high therapeutic potential for Pseudomonas exotoxin A chimeric proteins and irradiation. C1 Univ Chicago Hosp, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Pharmacol, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago Hosp, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. EM rrw@rover.uchicago.edu FU NCI NIH HHS [CA-42596, CA-55241] NR 31 TC 4 Z9 4 U1 0 U2 0 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 AUG 1 PY 1998 VL 58 IS 15 BP 3215 EP 3220 PG 6 WC Oncology SC Oncology GA 105ZD UT WOS:000075104500005 PM 9699644 ER PT J AU Tanaka, T Cao, YH Folkman, J Fine, HA AF Tanaka, T Cao, YH Folkman, J Fine, HA TI Viral vector-targeted antiangiogenic gene therapy utilizing an angiostatin complementary DNA SO CANCER RESEARCH LA English DT Article ID PRIMARY HUMAN ASTROCYTOMAS; GROWTH-FACTOR; TUMOR ANGIOGENESIS; HUMAN GLIOMAS; IN-VITRO; INHIBITION; SUPPRESSION; THROMBOSPONDIN-1; TRANSDUCTION; CONTRIBUTE AB Despite recent advances in neurosurgery, radiation, and chemotherapy, the prognosis of patients with malignant gliomas remains dismal. Based on the observation that solid tumor growth is angiogenic dependent, and gliomas are among the most angiogenic of all tumors, therapeutic strategies aimed at inhibiting angiogenesis are theoretically attractive. Angiostatin, an internal peptide fragment of plasminogen, has recently been shown to potently inhibit endothelial proliferation irt vitro and tumor growth in vivo. Long-term systemic delivery of proteins, however, poses a number of difficult logistic and pharmacological problems and may not be necessary or optimal for treating locally aggressive tumors such as gliomas. We now demonstrate that retroviral and adenoviral vectors that transduce the angiostatin cDNA can be used to inhibit endothelial cell growth in vitro and angiogenesis in vivo. Vector-mediated inhibition of tumor-associated angiogenesis results in increased apoptotic tumor fell death, Leading to inhibition of tumor growth. These studies support a potential role of vector-mediated transduction of the cDNA encoding angiostatin as a potential novel therapeutic strategy for the treatment of malignant brain tumors and confirm the antitumor activity; of angiostatin and the concept of dormancy therapy. C1 Harvard Univ, Ctr Neurooncol, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Lab Canc Pharmacol, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. Karolinska Inst, Inst Genom Res, Stockholm, Sweden. RP Fine, HA (reprint author), Harvard Univ, Ctr Neurooncol, Sch Med, Dana Farber Canc Inst, Dana 1234,44 Binney St, Boston, MA 02115 USA. NR 24 TC 135 Z9 149 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 AUG 1 PY 1998 VL 58 IS 15 BP 3362 EP 3369 PG 8 WC Oncology SC Oncology GA 105ZD UT WOS:000075104500028 PM 9699667 ER PT J AU Maroni, JM Oelberg, DA Pappagianopoulos, P Boucher, CA Systrom, DM AF Maroni, JM Oelberg, DA Pappagianopoulos, P Boucher, CA Systrom, DM TI Maximum cardiac output during incremental exercise by first-pass radionuclide ventriculography SO CHEST LA English DT Article DE cardiac output; cardiopulmonary exercise testing; first pass radionuclide ventriculography; pulmonary artery catheter ID MAGNETIC-RESONANCE SPECTROSCOPY; PULMONARY-ARTERY CATHETER; CONGESTIVE-HEART-FAILURE; AORTIC REGURGITATION; ANAEROBIC THRESHOLD; FICK METHOD; DISEASE; TRANSPLANTATION; THERMODILUTION; COMPLICATIONS AB Study objective: To validate a noninvasive first-pass radionuclide ventriculographic (FPRV) measurement of maximum cardiac output (Qv) during exercise. Design: Comparison of Qv to that measured by the Fick principle (Qf) at peak exercise, Setting: Academic cardiopulmonary exercise laboratory. Patients: Seventy-eight consecutive patients without a history of septal defect undergoing clinically indicated maximum incremental cardiopulmonary exercise testing with pulmonary arterial catheterization and FPRV. Measurements and results: Ventilation and gas exchange were measured breath-by-breath or by a mixing chamber/mass spectrometer system, Arterial and mixed venous O-2 content were measured each minute during exercise. When patients without left-to-right ventricular stroke count ratio evidence for left-sided regurgitation were isolated, peak Qv was linearly related to Qf (r = 0.75, p = 0.0001), To account for a small systematic overestimation (bias) of Qf by Qv, the linear equation for the Qv/Qf relation was derived for patients studied between 1990 and 1993 and applied to those studied subsequently. The resulting corrected peak Qv was tightly related to peak Qf (r = 0.90, p < 0.001) with confidence intervals for slope and intercept overlapping identity. Conclusion: FPRV can reasonably estimate maximum cardiac output during incremental exercise in patients for whom the technique has ruled out left-sided cardiac regurgitant lesions. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Systrom, DM (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [T32 HL07874] NR 37 TC 4 Z9 4 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 AUG PY 1998 VL 114 IS 2 BP 457 EP 461 DI 10.1378/chest.114.2.457 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 110ER UT WOS:000075367700022 PM 9726730 ER PT J AU Nobel, CK Duerinckx, AJ Mas-Estelles, F Oren, A AF Nobel, CK Duerinckx, AJ Mas-Estelles, F Oren, A TI Dyspnea and chest pain associated with lung mass SO CHEST LA English DT Article ID PULMONARY-EMBOLISM C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Serv Radiol, Los Angeles, CA 90073 USA. RP Nobel, CK (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 8 TC 1 Z9 1 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 AUG PY 1998 VL 114 IS 2 BP 618 EP 620 DI 10.1378/chest.114.2.618 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 110ER UT WOS:000075367700046 PM 9726754 ER PT J AU DeSanctis, RW AF DeSanctis, RW TI Thomas Woodward Smith SO CLINICAL CARDIOLOGY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Cardiac Unit, Ctr Ambulatory Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP DeSanctis, RW (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Ctr Ambulatory Care, 15 Parkman St,Suite 467, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 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 AUG PY 1998 VL 21 IS 8 BP 607 EP 608 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 106PE UT WOS:000075137400015 ER PT J AU Hooper, DC AF Hooper, DC TI Bacterial topoisomerases, anti-topoisomerases, and anti-topoisomerase resistance SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Bacterial Resistance - Laboratory Explanations and Clinical Consequences CY APR 15-17, 1996 CL SURREY, ENGLAND ID COLI DNA GYRASE; N-TERMINAL FRAGMENT; F-PLASMID PROTEINS; SEX FACTOR-F; ESCHERICHIA-COLI; QUINOLONE RESISTANCE; STAPHYLOCOCCUS-AUREUS; MICROCIN B17; FLUOROQUINOLONE RESISTANCE; LETD CCDB AB Topoisomerases are ubiquitous enzymes necessary for controlling the interlinking and twisting of DNA molecules. Among the four topoisomerases identified in eubacteria, two, DNA gyrase and topoisomerase IV, have been exploited by nature and the pharmaceutical industry as antibacterial targets. Natural products that are inhibitors of one or both of these topoisomerases include the coumarin and cyclothialidine classes, which interfere with adenosine triphosphate hydrolysis, cinodine, flavones, and terpenoid derivatives. The plasmid-encoded bacterial peptides microcin B17 and CcdB also inhibit DNA gyrase. The quinolones, a synthetic class of antibacterials that act on both DNA gyrase and topoisomerase IV, have had the broadest clinical applications, however, Quinolone congeners differ in their relative potencies for DNA gyrase and topoisomerase IV. Studies of an expanding set of resistant mutant enzymes and the crystal structure of the homologous enzyme in yeast have contributed to our understanding of interactions of these drugs with topoisomerase-DNA complexes and the ways in which mutations effect resistance. C1 Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. NR 132 TC 70 Z9 74 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1998 VL 27 SU 1 BP S54 EP S63 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 110BB UT WOS:000075358400010 PM 9710672 ER PT J AU Lewandrowski, KU Bonassar, L Uhthoff, HK AF Lewandrowski, KU Bonassar, L Uhthoff, HK TI Mechanical properties of perforated and partially demineralized bone grafts SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID YAG LASER ABLATION; OSTEOINDUCTION; ALLOGRAFTS; TISSUE AB Changes in flexural rigidity and compression strength of 18 sheep tibias were investigated after laser perforation and partial demineralization. Test bones were divided into three groups: Group 1, no treatment; Group 2, laser hole grid; and Group 3, laser hole grid and partial demineralization, Starting in the anterior direction at the tibial tuberosity, the flexural rigidity was determined using a nondestructive four-point bending test. The elliptical distribution of the flexural rigidity before and after a specific treatment was compared. After the bending test, a cylindrical center section of each test bone was loaded axially to failure to determine subsequent changes in compression strength. Results showed that perforation alone produced minimal reduction of rigidity and insignificant changes in compression strength. However, additional partial demineralization resulted in larger reductions, In compression testing, perforated and partially demineralized bone specimen showed marked decrease of the ultimate failure stress, The observed increase in failure strain appeared to be related to compression of the laser holes. The findings of this study suggest that partial demineralization and perforation can be applied to diaphyseal bone grafts and that their decreased mechanical properties are a function of the bone volume reductions produced by both processes. C1 Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Ruhr Univ Bochum, Dept Surg, Berufsgenossenschaftliche Kliniken Bergmannsheil, D-4630 Bochum, Germany. Ottawa Gen Hosp, Bone & Joint Res Lab, Ottawa, ON K1H 8L6, Canada. RP Lewandrowski, KU (reprint author), Massachusetts Gen Hosp, Orthopaed Res Labs, WACC 508,15 Parkman St, Boston, MA 02114 USA. RI Bonassar, Lawrence/C-2103-2016 OI Bonassar, Lawrence/0000-0003-1094-6433 NR 14 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD AUG PY 1998 IS 353 BP 238 EP 246 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 113GH UT WOS:000075541700028 PM 9728180 ER PT J AU Boland, GWL AF Boland, GWL TI Teleradiology: Another revolution in radiology? SO CLINICAL RADIOLOGY LA English DT Review ID WAVELET COMPRESSION; WORKSTATION; RADIOGRAPHS; IMAGES; STANDARD AB Teleradiology systems are rapidly being deployed by an increasing number of radiological services. Many articles have already been published on the technological developments of teleradiology but little attention has been given to its expected impact on the delivery of health care. This review article will therefore outline the historical and current technological developments of teleradiology and its potential future implementation into mainstream radiology. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 33 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD AUG PY 1998 VL 53 IS 8 BP 547 EP 553 DI 10.1016/S0009-9260(98)80145-1 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 111UA UT WOS:000075455300001 PM 9744579 ER PT J AU Kanwisher, N Tong, F Nakayama, K AF Kanwisher, N Tong, F Nakayama, K TI The effect of face inversion on the human fusiform face area SO COGNITION LA English DT Article DE fusiform face area; face inversion; fMRI; face perception ID RECOGNITION AB Inversion severely impairs the recognition of greyscale faces and the ability to see the stimulus as a face in two-tone Mooney images. We used functional magnetic resonance imaging to study the effect of face inversion on the human fusiform face area (FFA). MR signal intensity from the FFA was reduced when greyscale faces were presented upside-down, but this effect was small and inconsistent across subjects when subjects were required to attend to both upright and inverted faces. However when two-tone faces were inverted, the MR signal from the FFA was substantially reduced for all subjects. We conclude that (i) the FFA responds to faces per se, rather than to the low-level visual features present in faces, and (ii) inverted greyscale faces can strongly activate this face-specific mechanism. (C) 1998 Elsevier Science B.V. All rights reserved. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Kanwisher, N (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. FU NIMH NIH HHS [NIMH 56037] NR 17 TC 172 Z9 178 U1 3 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD AUG PY 1998 VL 68 IS 1 BP B1 EP B11 DI 10.1016/S0010-0277(98)00035-3 PG 11 WC Psychology, Experimental SC Psychology GA 115VF UT WOS:000075686100003 PM 9775518 ER PT J AU Maeda, M Vanlandingham, BD Ye, HQ Lu, PCS Azar, DT AF Maeda, M Vanlandingham, BD Ye, HQ Lu, PCS Azar, DT TI Immunoconfocal localization of gelatinase B expressed by migrating intrastromal epithelial cells after deep annular excimer keratectomy SO CURRENT EYE RESEARCH LA English DT Article DE confocal microscopy; corneal wound healing; excimer laser; gelatinase B; intrastromal migration ID MATRIX METALLOPROTEINASE; BASEMENT-MEMBRANE; GROWTH-FACTOR; ACTIN; EPIKERATOPLASTY; FIBROBLASTS; COLLAGENASE; CHEMOTAXIS; ULCERATION; MECHANISM AB Purpose. Intrastromal epithelial migration occurs following deep excimer annular keratectomy. Our purpose is to determine the localization of gelatinase B expression and its relationship to migrating intrastromal epithelial cells following deep annular excimer keratectomy. Methods. Rabbit corneas were treated with deep annular ablation and harvested 3, 5, 7 and 14 days following surgery. Histological examination was performed. Confocal microscopy was used to determine the lime and the pattern of gelatinase B expression. This was compared to AE-5, vimentin, and alpha-smooth muscle actin immunolocalization. Results. Histologic examination revealed islands of epithelial cells within the corneal stroma after deep annular excimer ablation, whereas eyes treated with superficial annular keratectomy did not show intrastromal epithelial migration. Immunoconfocal microscopy using monoclonal anti-matrix metalloproteinase-9 (MMP-9) antibody demonstrated the presence of gelatinase B at the outer borders of the intrastromal epithelial islands following deep annular excimer keratectomy. Conclusion. Gelatinase B may be involved in the process of intrastromal epithelial migration following deep annular excimer keratectomy. C1 Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Cornea Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM azard@vision.eri.harvard.edu FU NEI NIH HHS [EY10101] NR 38 TC 21 Z9 21 U1 0 U2 0 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD AUG PY 1998 VL 17 IS 8 BP 836 EP 843 DI 10.1076/ceyr.17.8.836.5155 PG 8 WC Ophthalmology SC Ophthalmology GA 105BW UT WOS:000075053300012 PM 9724000 ER PT J AU Johnson, RP Desrosiers, RC AF Johnson, RP Desrosiers, RC TI Protective immunity induced by live attenuated simian immunodeficiency virus SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-LYMPHOCYTE RESPONSES; RHESUS MACAQUES; HIV TYPE-1; ANTIBODY-RESPONSES; VACCINE PROTECTION; DELETION MUTANT; INFECTED CELLS; NEF GENE; CHALLENGE; SIV AB Lack of information on the mechanisms of protective immunity to AIDS virus infection represents a major obstacle to the development of a rational strategy for an effective HIV vaccine. In macaques, immunization with live attenuated simian immunodeficiency viruses has induced the most potent protective immunity and continued study promises a better understanding of the nature of protective immune responses. Recent evidence supports involvement of both cytotoxic T lymphocytes and neutralizing antibodies in protective immunity against infection by simian immunodeficiency virus, but more detailed studies are needed to document their relative importance. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Microbiol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. NR 61 TC 116 Z9 118 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 1998 VL 10 IS 4 BP 436 EP 443 DI 10.1016/S0952-7915(98)80118-0 PG 8 WC Immunology SC Immunology GA 110XH UT WOS:000075406500012 PM 9722920 ER PT J AU Staecker, H Van de Water, TR AF Staecker, H Van de Water, TR TI Factors controlling hair-cell regeneration/repair in the inner ear SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID CHINCHILLA CRISTA-AMPULLARIS; LIGHT-MICROSCOPIC EVIDENCE; SENSORY EPITHELIA; SUPPORTING CELL; ACOUSTIC TRAUMA; GROWTH-FACTOR; REGENERATIVE PROLIFERATION; BASILAR PAPILLA; ORGAN-CULTURES; CHICK COCHLEA AB Damaged hair cells in the avian basilar papilla are replaced by regenerative proliferation of supporting cells and transdifferentiation of supporting cells into hair cells. In the mammalian vestibular system, transdifferentiation and, possibly, the repair of damaged hair cells appear to play significant roles. Several growth factors have been found to be associated with the regeneration/repair process: insulin, insulin-like growth factor 1 (IGF-1), and fibroblast growth factors are important for avian inner ear regeneration/repair, whereas epidermal growth factor, transforming growth factor a, insulin, IGF-1, and IGF-2 are important for regeneration/repair in the mammalian labyrinth. Increasing evidence suggests that regeneration/repair of mammalian auditory hair cells is possible during the early neonatal period and may exist to a very limited degree at later times. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Otolaryngol, Kennedy Ctr, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Kennedy Ctr, Bronx, NY 10461 USA. RP Staecker, H (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM vandewat@aecom.yu.edu OI Staecker, Hinrich/0000-0002-0348-3015 NR 52 TC 50 Z9 54 U1 1 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD AUG PY 1998 VL 8 IS 4 BP 480 EP 487 DI 10.1016/S0959-4388(98)80035-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 120ME UT WOS:000075959500007 PM 9751665 ER PT J AU Vaina, LM AF Vaina, LM TI Complex motion perception and its deficits SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID SUPERIOR TEMPORAL AREA; OPTIC FLOW STIMULI; MACAQUE MONKEY; EYE-MOVEMENTS; MST NEURONS; EXPANSION CONTRACTION; RESPONSE SELECTIVITY; SPEED DISCRIMINATION; SPATIAL INTEGRATION; INTRAPARIETAL AREA AB Within the hierarchy of motion perception, the dorsolateral middle superior temporal area (MSTd) is optimally suited for the analysis of the complex motion patterns that are directly useful for visually guided behaviour (e.g. computation of heading). Recent electrophysiological and psychophysical evidence suggests the existence of 'detectors' in MSTd that are specialised for complex motion patterns and advocates the necessity of combining retinal and extraretinal signals received by MSTd neurones for the accurate perception of heading. In some neurological patients, of which only a small number have been reported to date, lesions involving the human homologue of MST have devastating effects on their ability to navigate in their surroundings. It has been reported that these patients have impaired performance of psychophysical tasks of complex motion discrimination. C1 Boston Univ, Brain & Vis Res Lab, Dept Biochem Engn, Boston, MA 02215 USA. Boston Univ, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02215 USA. RP Vaina, LM (reprint author), Boston Univ, Brain & Vis Res Lab, Dept Biochem Engn, 44 Cummington St, Boston, MA 02215 USA. EM vaina@enga.bu.edu FU NEI NIH HHS [EY-2RO1-O781-09, R01 EY007861] NR 75 TC 40 Z9 41 U1 1 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD AUG PY 1998 VL 8 IS 4 BP 494 EP 502 DI 10.1016/S0959-4388(98)80037-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 120ME UT WOS:000075959500009 PM 9751663 ER PT J AU Roberts, DJ Smith, DM Goff, DJ Tabin, CJ AF Roberts, DJ Smith, DM Goff, DJ Tabin, CJ TI Epithelial-mesenchymal signaling during the regionalization of the chick gut SO DEVELOPMENT LA English DT Article DE Shh; Bmp4; Hoxd-13; chick; gut development; epithelial-mesenchymal interaction ID SONIC-HEDGEHOG; HOMEOBOX GENE; HOX GENES; DIFFERENTIAL EXPRESSION; INTESTINAL ENDODERM; PATTERN-FORMATION; PROGENITOR CELLS; DIGESTIVE-TRACT; FAMILY MEMBER; MOUSE EMBRYO AB The development of the vertebrate gut requires signaling between the endoderm and mesoderm for establishing its normal anteroposterior (AP) axis and for tissue-specific differentiation. Factors implicated in positional specification of the AP regions of the gut include endodermally expressed Sonic hedgehog (Shh), mesodermally expressed Bmp4 and members of the Hox gene family, We have investigated the roles of these factors during AP regional specification of the chick embryonic gut. Early in gut development, the endoderm sends inductive signals to the mesoderm, Shh has been implicated as one of these signals. We find a differential response to exposure of the inductive influence of Shh along the AP axis of the gut. Virally mediated misexpression of Shh results in ectopic upregulation of its receptor Ptc and a cellular proliferation throughout the gut mesoderm, Although ectopic Shh can induce Bmp4 in the mesoderm of the midgut and hindgut, Bmp4 is not induced in the stomach region of the foregut, The stomach region has a thicker layer of mesoderm than the rest of the gut suggesting that the normal function of Bmp4 could be to limit mesodermal growth in the non-stomach regions of the gut. Ectopic Bmp4 expression in the stomach results in a reduction of the mesodermal component consistent with this hypothesis. In addition to the regional restriction on Bmp4 induction, Shh can only induce Hoxd-13 in the mesoderm of the hindgut, These findings suggest that a prepattern exists in the primitive gut mesoderm prior to expression of Shh in the endoderm, The gut mesoderm is subsequently responsible for inducing region-specific differentiation of its overlying endoderm, We tested the role of Hoxd-13, normally restricted in its mesodermal expression to the most posterior region of the hindgut (cloaca), in controlling adjacent endodermal differentiation. When virally mediated Hoxd-13 is misexpressed in the primitive midgut mesoderm, there is a transformation of the endoderm to the morphology and mucin content of the hindgut, Thus, the positionally restricted expression of a Hox gene in the gut mesoderm influences the inductive signaling that leads to regionally specific differentiation of gut endoderm. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Roberts, DJ (reprint author), Brigham & Womens Hosp, Dept Pathol, Fruit St, Boston, MA 02114 USA. EM robertsd@helix.mgh.harvard.edu FU NICHD NIH HHS [HD01060, R55HD34448] NR 59 TC 241 Z9 249 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD AUG PY 1998 VL 125 IS 15 BP 2791 EP 2801 PG 11 WC Developmental Biology SC Developmental Biology GA 111RW UT WOS:000075452200004 PM 9655802 ER PT J AU Tufarelli, C Fujiwara, Y Zappulla, DC Neufeld, EJ AF Tufarelli, C Fujiwara, Y Zappulla, DC Neufeld, EJ TI Hair defects and pup loss in mice with targeted deletion of the first cut repeat domain of the Cux/CDP homeoprotein gene SO DEVELOPMENTAL BIOLOGY LA English DT Article ID CCAAT DISPLACEMENT PROTEIN; SENSORY ORGAN IDENTITY; DNA-BINDING; HOMEODOMAIN PROTEIN; NONSENSE MUTATIONS; GLOBIN GENE; DROSOPHILA; EXPRESSION; PROMOTER; TRANSCRIPTION AB CDP, a ubiquitous homeoprotein homologous to Drosophila cut, is implicated as a transcriptional repressor in several developmental systems. It contains four independent DNA binding domains: three "cut repeats" plus the homeodomain. The murine Cux/CDP gene spans more than 200 kb and is composed of at least 21 exons. We designed a targeting construct to replace the first cut repeat with a neomycin resistance cassette, introducing a nonsense mutation after position 1319 of the 4.5-kb reading frame of Cux/CDP. We expected to generate a truncated product of approximate to 60 kDa with this construct, but instead rye obtained mice expressing a mutant form of the protein, with an internal deletion of 246 amino acids encompassing cut repeat 1, but intact in the C-terminal region. Ribonuclease protection assays and direct sequencing of mutant cDNA obtained by RT-PCR demonstrate skipping of exons 10 and 11 in the mutant. Homozygous mutant mice, designated Cux/CDP Delta CR1, display a phenotype characterized by curly vibrissae and wavy hair. We also observed a high degree of pup loss in litters born to mutant females, most likely on a nutritional basis. The mutant protein is present at levels slightly greater than wild-type, but exhibits the same tissue distribution as wild-type protein, and has approximately normal affinity for known target sequences (though no DNA targets identified to date require the first cut repeat for binding). These results support the hypothesis that the different DNA binding domains of the ubiquitous Cux/CDP protein are responsible for regulation of different genes in diverse tissues during development. (C) 1998 Academic Press. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Tufarelli, C (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. RI Zappulla, David/C-7818-2009; Neufeld, Ellis/F-9331-2011; OI Zappulla, David/0000-0001-8242-3493 FU NHLBI NIH HHS [HL49196] NR 44 TC 33 Z9 33 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 1998 VL 200 IS 1 BP 69 EP 81 DI 10.1006/dbio.1998.8950 PG 13 WC Developmental Biology SC Developmental Biology GA 110DU UT WOS:000075365500007 PM 9698457 ER PT J AU Hayashi, T Hirshman, MF Kurth, EJ Winder, WW Goodyear, LJ AF Hayashi, T Hirshman, MF Kurth, EJ Winder, WW Goodyear, LJ TI Evidence for 5 ' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport SO DIABETES LA English DT Article ID RAT SKELETAL-MUSCLE; INSULIN; ACTIVATION; INHIBITION; EXERCISE; CELLS; DISSOCIATION; METABOLISM; WORTMANNIN; RIBOSIDE AB The intracellular signaling proteins that lead to exercise-stimulated glucose transport in skeletal muscle have not been identified, although it is clear that there are separate signaling mechanisms for exercise- and insulin-stimulated glucose transport, mie have hypothesized that the 5'AMP-activated protein kinase (AMPK) functions as a signaling intermediary in exercise-stimulated glucose uptake. This hypothesis was based on recent studies showing the following: 1) muscle contraction increases AMPK activity and 2) perfusion of rat hindlimb skeletal muscles with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a compound that results in increased AMPK activity, increased insulin-stimulated glucose uptake. In the current study, isolated rat epitrochlearis muscles were treated to contract in vitro (via electrical stimulation for 10 min) and/or incubated in the absence or presence of AICAR (2 mmol/l), insulin (1 mu mol/l), or wortmannin (100 nmol/l). Both contraction and AICAR significantly increased AMPK activity, while the enzyme was not activated by insulin. AICAR, contraction, and insulin all increased 3-O-methylglucose (3MG) transport by threefold to fivefold above basal. The phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin completely blocked insulin-stimulated transport, but did not inhibit AICAR- or contraction-stimulated transport. The increase in glucose transport with the combination of maximal AICAR plus maximal insulin treatments was partially additive, suggesting that these stimuli increase glucose transport by different mechanisms. In contrast, there was no additive effect on glucose transport with the combination of AICAR plus contraction. These data suggest that AICAR and contraction stimulate glucose transport by a similar insulin-independent signaling mechanism and are consistent with the hypothesis that AMPK is involved in exercise-stimulated glucose uptake. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham Young Univ, Dept Zool, Provo, UT 84602 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIAMS NIH HHS [AR-41438, AR-42238] NR 24 TC 562 Z9 579 U1 2 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 1998 VL 47 IS 8 BP 1369 EP 1373 DI 10.2337/diabetes.47.8.1369 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 106XW UT WOS:000075177400031 PM 9703344 ER PT J AU Hollander, PA Elbein, SC Hirsch, IB Kelley, D McGill, J Taylor, T Weiss, SR Crockett, SE Kaplan, RA Comstock, J Lucas, CP Lodewick, PA Canovatchel, W Chung, J Hauptman, J AF Hollander, PA Elbein, SC Hirsch, IB Kelley, D McGill, J Taylor, T Weiss, SR Crockett, SE Kaplan, RA Comstock, J Lucas, CP Lodewick, PA Canovatchel, W Chung, J Hauptman, J TI Role of orlistat in the treatment of obese patients with type 2 diabetes - A 1-year randomized double-blind study SO DIABETES CARE LA English DT Article ID VISCERAL ADIPOSE-TISSUE; WEIGHT-LOSS; FAT DISTRIBUTION; MELLITUS; INSULIN; NIDDM; REDUCTION; BENEFITS; GAIN AB OBJECTIVE - Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications. RESEARCH DESIGN AND METHODS - In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged >18 years, had a BMI of 28-40 kg/m(2), and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured. RESULTS - After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost greater than or equal to 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA(1c) (P < 0.001) and lasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P ( 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients. CONCLUSIONS - Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile. C1 Baylor Univ, Med Ctr, Ruth Collins Care Ctr, Dallas, TX 75246 USA. Vet Adm Hosp, Houston, TX USA. Univ Washington, Med Ctr, Seattle, WA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Washington Univ, Sch Med, St Louis, MO USA. Georgetown Univ, Sch Med, Washington, DC USA. San Diego Endocrine & Med Clin, San Diego, CA USA. E Bay Clin Trial Ctr, Concord, CA USA. Florida Hosp Diabet Program, Orlando, FL USA. William Beaumont Hosp, Birmingham, MI USA. William Beaumont Hosp, Birmingham, MI USA. Diabet Care Ctr, Birmingham, AL USA. F Hoffmann La Roche, Nutley, NJ USA. RP Hollander, PA (reprint author), Baylor Univ, Med Ctr, Ruth Collins Care Ctr, 3500 Gaston Ave, Dallas, TX 75246 USA. NR 32 TC 378 Z9 389 U1 2 U2 20 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 1998 VL 21 IS 8 BP 1288 EP 1294 DI 10.2337/diacare.21.8.1288 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 106YA UT WOS:000075177900015 PM 9702435 ER PT J AU Levy, CJ Kinsley, BT Bajaj, M Simonson, DC AF Levy, CJ Kinsley, BT Bajaj, M Simonson, DC TI Effect of glycemic control on glucose counterregulation during hypoglycemia in NIDDM SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; INSULIN-INDUCED HYPOGLYCEMIA; BETA-ENDORPHIN; NEUROENDOCRINE RESPONSES; HYPOTHALAMIC-PITUITARY; HORMONAL RESPONSES; PLASMA-LEVELS; SYMPTOMS; IDDM; SECRETION AB OBJECTIVE - We examined the effect of glycemic control of NIDDM on counterregulatory hormone responses to hypoglycemia and compared the effect with that seen in patients with IDDM. RESEARCH DESIGN AND METHODS - Eleven subjects with NIDDM and eight age- and weight-matched control subjects and ten subjects with IDDM and ten age- and weight-matched control subjects were studied. All subjects underwent a stepped hypoglycemic-hyperinsulinemic clamp study during which plasma glucose levels were lowered in a stepwise manner from 5.0 to 2.2 mmol/l in steps of 0.6 mmol/l every 30 min. Counterregulatory hormones (epinephrine, norepinephrine, glucagon, ACTH, cortisol, and growth hormone [GH]) were measured, and a symptom survey was administered during the last 10 min of each 30-min interval. RESULTS - The threshold for release of epinephrine, norepinephrine, ACTH, and cortisol occurred at higher plasma glucose levels in NIDDM than in IDDM patients (P < 0.05-0.01). The glucose threshold for release of epinephrine and norepinephrine correlated with glycemic control as measured by glycosylated hemoglobin (P < 0.05-0.01). However, for a given level of glycemic control, the threshold for release of epinephrine and norepinephrine occurred at a higher glucose level in NIDDM versus IDDM patients (P < 0.05-0.01). At the nadir level of hypoglycemia, glucagon, ACTH, and cortisol levels were all higher in NIDDM compared with IDDM subjects, whereas GH levels were lower. CONCLUSIONS - Glycemic control alters counterregulatory responses to hypoglycemia in NIDDM as has been previously reported in IDDM. However, at similar levels of glycemic control, NIDDM patients release counterregulatory hormones at a higher plasma glucose level than patients with IDDM. In addition, subjects with NIDDM maintain their glucagon response to hypoglycemia. These data suggest that patients with NIDDM may be at reduced risk of severe hypoglycemia when compared with a group of IDDM patients in similar glycemic control, thus providing a more favorable risk-benefit ratio for intensive diabetes therapy in NIDDM. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Levy, CJ (reprint author), Mt Sinai Med Ctr, Div Endocrinol Diabet & Metab, 1 Gustave L Levy Pl,Box 1055, New York, NY 10029 USA. RI Bajaj, Mandeep/B-6060-2009 FU NCRR NIH HHS [RR-02635]; NIDDK NIH HHS [DK-36836] NR 66 TC 46 Z9 46 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 1998 VL 21 IS 8 BP 1330 EP 1338 DI 10.2337/diacare.21.8.1330 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 106YA UT WOS:000075177900023 PM 9702443 ER PT J AU Arora, S Smakowski, P Frykberg, RG Simeone, LR Freeman, R LoGerfo, FW Veves, A AF Arora, S Smakowski, P Frykberg, RG Simeone, LR Freeman, R LoGerfo, FW Veves, A TI Differences in foot and forearm skin microcirculation in diabetic patients with and without neuropathy SO DIABETES CARE LA English DT Article ID ACETYLCHOLINE; ETIOLOGY; DENSITY; ROLES; RISK AB OBJECTIVE - We have compared the hyperemic response to heal and the endothelium-dependent and endothelium-independent vasodilatation between the dorsum of the foot and the forearm in diabetic neuropathic and non-neuropathic patients and healthy control subjects. RESEARCH DESIGN AND METHODS - We studied the cutaneous microcirculation in the forearm and foot in 15 diabetic patients with neuropathy, in 14 diabetic patients without neuropathy, and in 15 control subjects matched for age, sex, BMI, and in the case of diabetic patients, for the duration of diabetes. Patients with peripheral vascular disease and/or renal impairment were excluded. The cutaneous microcirculation of the dorsum of the foot and the flexor aspect of the forearm was tested in all subjects. Single-point laser Doppler was employed to measure the maximal hyperemic response to heating of the skin to 44 degrees C and laser Doppler imaging scanner was used to evaluate the response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent response) and 1% sodium nitroprusside (NaNP) (endothelium-independent response). RESULTS - The transcutaneous oxygen tension was lower in the neuropathic group at both foot and forearm level, while the maximal hyperemic response to heat was similar at the foot and forearm level in all three groups. The endothelium-dependent vasodilatation (percent increase over baseline) was lower in the foot compared to the forearm in the neuropathic group (23 +/- 4 vs. 55 +/- 10 [mean +/- SEM]; P < 0.01)], the non-neuropathic group (33 +/- 6 vs. 88 +/- 14; P < 0.01), and the control subjects (43 +/- 6 vs. 93 +/- 13; P < 0.001). Similar results were observed during the iontophoresis of NaNP (P < 0.05). No differences were found among the three groups when the ratio of the forearm:foot response was calculated for both the endothelium-dependent (neuropathic group, 2.25 +/- 0.24; non-neuropathic group, 2.55 +/- 0.35; and control subjects, 2.11 +/- 0.26; P = NS) and endothelium-independent vasodilatation (neuropathic group, 1.54 +/- 0.27; non-neuropathic group, 2.08 +/- 0.33; and control subjects, 2.77 +/- 1.03; P = NS). The vasodilatory response, which is related to the C nociceptive fiber action, was reduced at the foot level during iontophoresis of Ach in the neuropathic group. In contrast, no difference was found during the iontophoresis of NaNP at the foot and forearm level and of Ach at the forearm level among all three groups. CONCLUSIONS - In healthy subjects, the endothelial-dependent and endothelial-independent vasodilatation is lower at the foot level when compared to the forearm, and a generalized impairment of the microcirculation in diabetic patients with neuropathy preserves this forearm-foot gradient. These changes may be a contributing factor for the early involvement of the foot with neuropathy when compared to the forearm. C1 Beth Israel Deaconess Med Ctr, Deaconess Joslin Foot Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Vasc Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Podiatry, Boston, MA 02115 USA. RP Veves, A (reprint author), Beth Israel Deaconess Med Ctr, Deaconess Joslin Foot Ctr, 1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu NR 25 TC 84 Z9 85 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 1998 VL 21 IS 8 BP 1339 EP 1344 DI 10.2337/diacare.21.8.1339 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 106YA UT WOS:000075177900024 PM 9702444 ER PT J AU Nishi, M Ekawa, K Anaguchi, R Sanke, T Nanjo, K AF Nishi, M Ekawa, K Anaguchi, R Sanke, T Nanjo, K TI Apolipoprotein E gene polymorphism and diabetic vascular complications in Japanese Type 2 patients SO DIABETES NUTRITION & METABOLISM LA English DT Article DE apolipoprotein E; gene polymorphism; diabetic vascular complication; retinopathy; nephropathy; ischemic heart disease ID CORONARY-ARTERY DISEASE; E PHENOTYPE; ALZHEIMERS-DISEASE; RISK; NEPHROPATHY; CHOLESTEROL; ALLELE; MICE; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS AB We investigated the relationship between apolipoprotein E (apoE) gene common polymorphism (E2, E3, and E4) and diabetic vascular complications in 166 Japanese patients with Type 2 diabetes mellitus (T2DM) (79 men and 87 women, age 61.6+/-0.7 yr, duration 14.9+/-0.5 yr, mean+/-SE). Allele frequencies of E2, E3 or E4 were 4.2%, 86.5 % or 9.3 %, respectively, and not significantly different from those of 94 non-diabetic controls (E2:5.8 %, E3:86.7%, E3:86.7%, E4:7.5 %). We divided T2DM patients into three groups according to apoE genotype; E2 group (E2/E2 and E2/E3), E3 group (E3/E3), and E4 group (E3/E4 and E4/E4), Among these three groups, there were no significant differences in age, sex, duration of T2DM, body mass index, HbA(1c) and plasma lipid levels (total cholesterol, HDL cholesterol, and triglyceride), In the frequencies of hypertension, hyperlipidemia, ischemic heart disease, and nephropathy, no significant differences were observed among the three groups. In contrast to them, the frequency of preproliferative/proliferative retinopathy in the E4 group was significantly higher than that in the others. Our results suggest that apoE gene E4 allele is a risk factor of diabetic retinopathy in Japanese T2DM patients. C1 Wakayama Univ Med Sch, Dept Med 1, Wakayama 640, Japan. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Nishi, M (reprint author), Wakayama Univ Med Sch, Dept Med 1, 27 Nanaban Cho, Wakayama 640, Japan. NR 29 TC 0 Z9 1 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-3402 J9 DIABETES NUTR METAB JI Diabetes Nutr. Metab. PD AUG PY 1998 VL 11 IS 4 BP 249 EP 253 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 178DN UT WOS:000079251200006 ER PT J AU Porte, D Seeley, RJ Woods, SC Baskin, DG Figlewicz, DP Schwartz, MW AF Porte, D Seeley, RJ Woods, SC Baskin, DG Figlewicz, DP Schwartz, MW TI Obesity, diabetes and the central nervous system SO DIABETOLOGIA LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; HYPOTHALAMIC NEUROPEPTIDE-Y; REDUCES FOOD-INTAKE; BETA-CELL FUNCTION; MESSENGER-RIBONUCLEIC-ACID; BODY-WEIGHT REGULATION; BROWN ADIPOSE-TISSUE; BLOOD-BRAIN-BARRIER; LEPTIN RECEPTOR; CEREBROSPINAL-FLUID C1 Univ Washington, Dept Med, Seattle, WA 98109 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98109 USA. Univ Washington, Dept Psychol, Seattle, WA 98109 USA. VA Puget Sound Hlth Care Syst, Div Endocrinol & Metab, Seattle, WA 98109 USA. RP Porte, D (reprint author), Univ Washington, Dept Med, 1660 S Columbian Way, Seattle, WA 98109 USA. RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK 12829, DK 17844, DK17047] NR 232 TC 139 Z9 141 U1 1 U2 8 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1998 VL 41 IS 8 BP 863 EP 881 DI 10.1007/s001250051002 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 108RB UT WOS:000075278300001 PM 9726588 ER PT J AU Almind, K Bernal, D Urhammer, S Hansen, T Berglund, L Reneland, R Lithell, H White, M Pedersen, O AF Almind, K Bernal, D Urhammer, S Hansen, T Berglund, L Reneland, R Lithell, H White, M Pedersen, O TI Studies of the potential influence of an amino acid variant in IRS-2 on insulin secretion in two Scandinavian populations SO DIABETOLOGIA LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Steno Diabet Ctr, DK-2820 Gentofte, Denmark. Univ Uppsala, Dept Geriatr, S-75105 Uppsala, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1998 VL 41 SU 1 MA 121 BP A33 EP A33 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109ZG UT WOS:000075353800127 ER PT J AU Frykberg, RG Lavery, LA Pham, H Harkless, LB Veves, A AF Frykberg, RG Lavery, LA Pham, H Harkless, LB Veves, A TI The risk of ulceration in diabetic patients with high foot pressures and neuropathy SO DIABETOLOGIA LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Deaconess Joslin Foot Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1998 VL 41 SU 1 MA 282 BP A73 EP A73 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109ZG UT WOS:000075353800287 ER PT J AU Jonas, JC Sharma, A Ilkova, H Patane, G Bonner-Weir, S Weir, GC AF Jonas, JC Sharma, A Ilkova, H Patane, G Bonner-Weir, S Weir, GC TI Hyperglycemia increases lactate dehydrogenase mRNA levels in islets from 90% pancreatectomized rats. SO DIABETOLOGIA LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1998 VL 41 SU 1 MA 259 BP A67 EP A67 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109ZG UT WOS:000075353800262 ER PT J AU Klupa, T Malecki, MT Davidson, MB Sieradzka, J Frey, J Sieradzki, J Krolewski, AS AF Klupa, T Malecki, MT Davidson, MB Sieradzka, J Frey, J Sieradzki, J Krolewski, AS TI Amino acid variants of the vitamin D-binding protein are not associated with type 2 diabetes in Caucasians. SO DIABETOLOGIA LA English DT Meeting Abstract C1 Jagiellonian Univ, Dept Metab Dis, Cracow, Poland. Joslin Diabet Ctr, Dept Genet & Epidemiol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1998 VL 41 SU 1 MA 438 BP A113 EP A113 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109ZG UT WOS:000075353800442 ER PT J AU Lautier, C Macari, F El Mkadem, SA Renard, E Rokiki, D Bringer, J Jaffiol, C Smith, R Grigorescu, F AF Lautier, C Macari, F El Mkadem, SA Renard, E Rokiki, D Bringer, J Jaffiol, C Smith, R Grigorescu, F TI Pathogenic role of mutations in insulin and IGF-1 receptors and IRS-1 genes in insulin resistance. SO DIABETOLOGIA LA English DT Meeting Abstract C1 IURC, Montpellier, France. Joslin Diabet Ctr, Boston, MA 02215 USA. RI macari, francoise/E-9941-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1998 VL 41 SU 1 MA 666 BP A171 EP A171 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109ZG UT WOS:000075353800671 ER PT J AU Nishiyama, T Kahn, CR AF Nishiyama, T Kahn, CR TI Cloning of new members of signaling inositol 5-phosphatases family. SO DIABETOLOGIA LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1998 VL 41 SU 1 MA 199 BP A52 EP A52 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109ZG UT WOS:000075353800203 ER PT J AU Rebrin, K Steil, GM Van Antwerp, WP Mastrototaro, JJ AF Rebrin, K Steil, GM Van Antwerp, WP Mastrototaro, JJ TI Reliability of interstitial glucose measurements by subcutaneous glucose sensors in humans SO DIABETOLOGIA LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. MiniMed Inc, Sylmar, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1998 VL 41 SU 1 MA 880 BP A228 EP A228 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109ZG UT WOS:000075353800883 ER PT J AU Seufert, J Habener, JF AF Seufert, J Habener, JF TI Autoregulation of insulin gene transcriptional repressor C/EBP beta in pancreatic beta-cells SO DIABETOLOGIA LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1998 VL 41 SU 1 MA 180 BP A47 EP A47 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109ZG UT WOS:000075353800185 ER PT J AU Veves, A Arora, S Smakowski, P Pham, H LoGerfo, FW AF Veves, A Arora, S Smakowski, P Pham, H LoGerfo, FW TI Microvascular reactivity in the neuropathic foot remains impaired after successful revascularization SO DIABETOLOGIA LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Microcirculat Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1998 VL 41 SU 1 MA 1076 BP A279 EP A279 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109ZG UT WOS:000075353801079 ER PT J AU Vicent, D Maratos-Flier, E Kahn, CR AF Vicent, D Maratos-Flier, E Kahn, CR TI A new isoprenyl synthase, which is over-expressed in obesity and induced by adipogenesis, synthesizes the prenyl, moiety used in G-protein prenylation. SO DIABETOLOGIA LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RI Vicent, David/O-2255-2014 OI Vicent, David/0000-0002-6663-0350 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1998 VL 41 SU 1 MA 744 BP A191 EP A191 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 109ZG UT WOS:000075353800748 ER PT J AU Fan, HX Gulley, ML Gascoyne, RD Horsman, DE Adomat, SA Cho, CG AF Fan, HX Gulley, ML Gascoyne, RD Horsman, DE Adomat, SA Cho, CG TI Molecular methods for detecting t(11;14) translocations in mantle-cell lymphomas SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE mantle-cell lymphoma; bcl1; 11q13; cyclin D1; southern blot analysis; polymerase chain reaction ID POLYMERASE CHAIN-REACTION; PARAFFIN-EMBEDDED TISSUES; BCL-1 GENE REARRANGEMENT; CYCLIN D1 GENE; LYMPHOPROLIFERATIVE DISORDERS; CHROMOSOME-TRANSLOCATION; CENTROCYTIC LYMPHOMA; BREAKPOINTS; EXPRESSION; OVEREXPRESSION AB The t(11;14)(q13;q32) and its molecular counterpart, bcl1/JH, are characteristic of mantle-cell lymphomas (MCL). Molecular detection of the translocation is useful in diagnosis and classification, and also shows promise in detecting minimal residual disease. The purpose of this study was to determine the frequency of detecting bcl1/JH by polymerase chain reaction (PCR) compared with Southern blot analysis in cases proven by cytogenetic analysis to harbor t(11;14). Southern blot analysis using two probes targeting the major translocation cluster (MTC) and a third probe targeting the p94 region was performed, along with PCR using two different bell MTC primers, on is cases of MCL known to have t(11;14). Southern blot analysis revealed bell rearrangement in 13 of 18 cases (72%), 12 with MTC breakpoints and 1 with a p94 breakpoint. The 2.1-kb MTC probe "b" was superior to the smaller 700-bp probe "a" in detecting these rearrangements. The MTC translocation was identified by PCR in 10 of 12 cases, and both primer sets that were tested performed equally well. This study illustrates the frequency with which molecular methods detect known t(11,14) translocations in MCLs. These results may help clinical laboratory scientists optimize their procedure for detecting bell translocations by molecular methods at initial diagnosis and for purposes of detecting minimal residual disease. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. RP Gulley, ML (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 30 TC 20 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD AUG PY 1998 VL 7 IS 4 BP 209 EP 214 DI 10.1097/00019606-199808000-00005 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 156WQ UT WOS:000078025700005 PM 9917131 ER PT J AU Evans, RL Connis, RT Haselkorn, JK AF Evans, RL Connis, RT Haselkorn, JK TI Hospital-based rehabilitative care versus outpatient services: effects on functioning and health status SO DISABILITY AND REHABILITATION LA English DT Article DE home-based rehabilitation; physical disability ID SOCIAL SUPPORT; STROKE; ADJUSTMENT; PROGRAMS; ILLNESS; INDEX AB Purpose: The goal of this clinical trial was to examine the long-term impact of rehabilitative care on the health status of patients diagnosed with a disabling disorder. Method: Study patients consisted of first-time hospitalizations from diagnostic groups commonly admitted for inpatient rehabilitation, including nervous, circulatory, and musculoskeletal disorders or injury. Patients were randomly assigned to inpatient rehabilitation (n = 43) or to outpatient follow-up (n = 42) in which the usual medical services were provided but no scheduled rehabilitative therapies were offered. Specific objectives of the study were to determine the effects of inpatient rehabilitation on: (1) functional ability, (2) health and mental health status, (3) personal adjustment, and (4) family function. Cost and use of health-care resources were descriptively assessed. Results: Analysis of covariance found no significant treatment effects, either at 6 months or at 1 year, for any of the variables under study. In addition, there were no differences between groups in their use of nursing homes, length of hospital stay, mortality, or in the number of hospital readmissions or clinic visits during the first year after hospital discharge. Use of rehabilitation services and cost of care was significantly higher than outpatient services. The findings were consistent with previous studies for most outcomes, with the major exception being functional improvements. Contrary to earlier studies, rehabilitation was not found to effectively produce lasting functional outcomes. However, study conditions may not have fully corresponded to those of previous studies, and further research is needed. The patient sample was representative of a full inpatient service and therefore more heterogeneous than samples reported in prior studies, but the small sample size (due to reductions in the number of admitted patients to the rehabilitation unit during the course of the study) precluded subgroup analysis of diagnostic groupings. Conclusions: The findings suggest that hospital-based rehabilitative care does not have lasting benefits, and that alternative care or supportive follow-up by a subacute-care facility may be needed to assist patients in maintaining functional gains and health benefits. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Evans, RL (reprint author), VA Puget Sound Hlth Care Syst, 122,1660 S Columbian Way, Seattle, WA 98108 USA. NR 32 TC 6 Z9 6 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0963-8288 J9 DISABIL REHABIL JI Disabil. Rehabil. PD AUG PY 1998 VL 20 IS 8 BP 298 EP 307 PG 10 WC Rehabilitation SC Rehabilitation GA ZV308 UT WOS:000074291600003 PM 9651688 ER PT J AU Wolff, BG Bolton, J Baum, R Chetanneau, A Pecking, A Serafini, AN Fischman, AJ Hoover, HC Klein, JL Wynant, GE Subramanian, R Goroff, DK Hanna, MG AF Wolff, BG Bolton, J Baum, R Chetanneau, A Pecking, A Serafini, AN Fischman, AJ Hoover, HC Klein, JL Wynant, GE Subramanian, R Goroff, DK Hanna, MG TI Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium Tc 99m 88BV59H21-2V67-66 (HumaSPECT (R)-Tc), a totally human monoclonal antibody - Patient management benefit from a phase III multicenter study SO DISEASES OF THE COLON & RECTUM LA English DT Article DE human monoclonal antibody; monoclonal antibody imaging; technetium; colorectal cancer; 88BV59; HumaSPECT (R)-Tc ID COLON CANCER; CARCINOMA; RECTUM; IMMUNOSCINTIGRAPHY; INTERFERENCE; DIAGNOSIS AB PURPOSE: The study contained herein was undertaken to evaluate the accuracy of radiolabeled human monoclonal antibody, 88BV59H21-2V67-66 (88BV59 or HumaSPECT(R)-Tc), in predicting disease resectability in presurgical subjects with recurrent, metastatic, or occult colorectal carcinoma. METHODS: A total of 219 patients with disease visualized on computed tomographic scan (recurrent or metastatic disease) or with negative or equivocal computed tomographic scan and rising carcinoembryonic antigen serum levels (occult group) received technetium Te 99m-labeled 88BV59 intravenously. Planar and single photon emission computed tomographic images were obtained 14 to 20 hours postinfusion, before surgery. The ability of computed tomographic and HumaSPECT(R)-Tc imaging to define the extent of disease and to predict resectability was evaluated based on surgical and histopathologic results. RESULTS: In patients with recurrent or metastatic disease (170 evaluable patients), the accuracy of predicting nonresectability of disease was significantly greater (P < 0.001) for HumaSPECT(R)-Tc than for computed tomography (60 vs. 29 percent). Computed tomography understaged 41 percent of patients believed to have resectable disease compared with 27 percent for HumaSPECT(R)-Tc (P < 0.001). In occult disease patients (29 computed tomographic and 28 HumaSPECT(R)-Tc evaluable patients), the overall accuracy of predicting resectability/nonresectability was 68 percent for HumaSPECT(R)=Tc compared with 24 percent for computed tomography. Administration of HumaSPECT(R)=Tc had no effect on monoclonal antibody-based in vitro diagnostic assays. Only a single patient demonstrated an anti-antibody response (90 ng/ml) at nine weeks postinfusion. CONCLUSION: HumaSPECT(R)-Tc was more accurate than computed tomography in determining disease resectability in patients with metastatic, recurrent, or occult cancer. The addition of HumaSPECT(R)-Tc imaging can play a significant role in patient management decisions. C1 Mayo Clin, Dept Colorectal & Gen Surg, Rochester, MN USA. Alton Ochsner Med Fdn & Ochsner Clin, Dept Surg, New Orleans, LA 70121 USA. Univ Frankfurt, Dept Nucl Med, Med Ctr, D-6000 Frankfurt, Germany. Ctr Rene Gauducheau, Ctr Reg Lutte Contre Canc, St Herblain, France. Ctr Rene Huguenin, Nucl Med Serv, St Cloud, France. Univ Miami, Sch Med, Div Nucl Med, Miami, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Lehigh Valley Hosp, Allentown, PA USA. INTRACEL Corp, Rockville, MD 20850 USA. RP Hanna, MG (reprint author), INTRACEL Corp, 1330 Piccard Dr, Rockville, MD 20850 USA. RI Bolton, John/A-5509-2011 NR 21 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD AUG PY 1998 VL 41 IS 8 BP 953 EP 962 DI 10.1007/BF02237380 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 109XJ UT WOS:000075349400001 PM 9715149 ER PT J AU Sentovich, SM Wong, WD Blatchford, GJ AF Sentovich, SM Wong, WD Blatchford, GJ TI Accuracy and reliability of transanal ultrasound for anterior anal sphincter injury SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT Meeting of the American-Society-of-Colon-and-Rectal-Surgeons CY JUN 21-27, 1997 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Colon & Rectal Surgeons DE transanal ultrasonography; accuracy; reliability; anal sphincter injury; fecal incontinence ID FECAL INCONTINENCE; ENDOLUMINAL ULTRASOUND; NORMAL ANATOMY; ENDOSONOGRAPHY; DEFECTS; MANOMETRY; ELECTROMYOGRAPHY AB INTRODUCTION: Although transanal ultrasound has rapidly become the test of choice for the diagnosis of anal sphincter injury, the accuracy and reliability of this technique are unknown. This study evaluates the accuracy and reliability of transanal ultrasound for anterior (obstetric-related) anal sphincter injury. METHODS: Sixty-two women underwent transanal ultrasound with hard-copy images obtained at 0.5-cm intervals from the anal verge to 2.5 cm into the anal canal. All transanal ultrasound procedures were also recorded on videotape. Two experienced ultrasonographers blinded as to the patients' clinical history and examination independently reviewed the images and videotape recordings for the presence or absence of anal sphincter injury. RESULTS: The accuracy of transanal ultrasound in 22 incontinent women with known anal sphincter injury was 100 percent. The accuracy of transanal ultrasound in 20 nulliparous women with intact anal sphincters was only 35 percent but improved to 50 percent after the "real time" videotape was reviewed (P = 0.16) and further improved to 85 percent when interpretation was limited to the distal 1.5 cm of the anal canal (P = 0.004). In these nulliparous women, intact internal sphincters were more accurately predicted than intact external sphincters (95 vs. 85 percent; P = 0.24). Measurement agreement between the two ultrasonographers was 68 percent (fair; kappa, 0.26) but significantly improved to 78 percent (moderate; kappa, 0.48; P = 0.0001) when interpretation was limited to the distal 1.5 cm of the anal canal. Overall clinical agreement (final scan interpretation) was good (81 percent agreement; kappa, 0.61). Agreement was better for the internal sphincter (74 percent; fair; kappa, 0.36) than the external sphincter (61 percent; poor; kappa, 0.17; P = 0.0002). CONCLUSIONS: Although transanal ultrasound can accurately identify anterior anal sphincter injury when present, transanal ultrasound falsely identifies sphincter injury in at least 5 to 25 percent of normal anal sphincters. Only fair agreement in the interpretation of transanal ultrasound exists between experienced ultrasonographers. Both the accuracy and reliability of transanal ultrasound are significantly improved by limiting transanal ultrasound to the distal 1.5 cm of the anal canal. C1 Beth Israel Deacones Med Ctr, Dept Surg, Boston, MA 02215 USA. Univ Minnesota, Sch Med, Div Colon & Rectal Surg, Minneapolis, MN 55455 USA. Creighton Univ, Sch Med, Sect Colon & Rectal Surg, Omaha, NE USA. RP Sentovich, SM (reprint author), Beth Israel Deacones Med Ctr, Dept Surg, 110 Francis St,Suite 3A, Boston, MA 02215 USA. NR 19 TC 40 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD AUG PY 1998 VL 41 IS 8 BP 1000 EP 1004 DI 10.1007/BF02237390 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 109XJ UT WOS:000075349400011 PM 9715156 ER PT J AU Damon, SE Maddison, L Ware, JL Plymate, SR AF Damon, SE Maddison, L Ware, JL Plymate, SR TI Overexpression of an inhibitory insulin-like growth factor binding protein (IGFBP), IGFBP-4, delays onset of prostate tumor formation SO ENDOCRINOLOGY LA English DT Article ID FACTOR-I RECEPTOR; SIMIAN-VIRUS-40 T-ANTIGEN; HUMAN-BREAST-CANCER; ACID MESSENGER-RNA; EPITHELIAL-CELLS; INDUCED APOPTOSIS; PRIMARY CULTURES; GENE-EXPRESSION; BENIGN; FIBROBLASTS AB Insulin-like growth factor (IGF) binding proteins (IGFBPs) have been shown to either inhibit or enhance the action of IGF, or act in an IGF-independent manner in the prostate. We have overexpressed the IGF-inhibitory IGFBP-4 in the malignant M12 prostate epithelial cell line to determine the effects on tumor formation and apoptosis. Overexpression was determined by Not-them, Western immunoblot and Western radioligand blot analysis. IGF induced proliferation was reduced in the IGFBP-4 transfected cells compared with control cells (P less than or equal to 0.01). Colony formation in soft agar was significantly inhibited up to 14 days after plating in the IGFBP-4 transfected cells when compared with the M12 controls (P less than or equal to 0.01): however, in the presence of des(1-3)IGF-I, there was no significant difference between the control and IGFBP-4 transfectants in colony formation in soft, agar. Apoptosis in an IGFBP-4 transfected cell Line was significantly increased in response to induction by B-hydroxyurea compared with the control Line. When injected sc into male athymic/nude mice, a marked delay was noted in tumor formation in animals receiving IGFBP-4 transfected cells (P less than or equal to 0.01). Interestingly, IGFBP-2 protein levels were reduced in the conditioned media of all IGFBP-4 transfected cell cultures. These data indicate that an inhibitory IGFBP may significantly delay the growth of malignant prostate epithelial cells and enhance the sensitivity of these cells to apoptosis. C1 VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Amer Lake Div, Tacoma, WA 98493 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pathol, Richmond, VA 23298 USA. RP Plymate, SR (reprint author), VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Amer Lake Div, Tacoma, WA 98493 USA. EM splymate@u.washington.edu FU NIDDK NIH HHS [DK 96-005] NR 48 TC 71 Z9 71 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1998 VL 139 IS 8 BP 3456 EP 3464 DI 10.1210/en.139.8.3456 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102KC UT WOS:000074922600013 PM 9681496 ER PT J AU Oelberg, DA Medoff, BD Markowitz, DH Pappagianopoulos, PP Ginns, LC Systrom, DM AF Oelberg, DA Medoff, BD Markowitz, DH Pappagianopoulos, PP Ginns, LC Systrom, DM TI Systemic oxygen extraction during incremental exercise in patients with severe chronic obstructive pulmonary disease SO EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY AND OCCUPATIONAL PHYSIOLOGY LA English DT Article DE COPD; exercise; skeletal muscle; oxygen extraction ID CHRONIC RESPIRATORY-FAILURE; SKELETAL-MUSCLE METABOLISM; LUNG-DISEASE; ANAEROBIC THRESHOLD; MAGNETIC-RESONANCE; LACTIC-ACIDOSIS; COPD; CAPACITY AB To determine if decreased systemic oxygen (O-2) extraction contributes to the exercise limit in severe chronic obstructive pulmonary disease (COPD), 40 consecutive incremental cycle ergometer exercise tests performed by such patients, from which a "log-log" lactate threshold (LT) was identified, were compared to those of 8 patients with left ventricular failure (LVF) and IO normal controls. Pulmonary gas exchange and minute ventilation were measured continuously and arterial blood gas tensions, pH and lactate concentrations were sampled each minute. Cardiac output ((Q) over dot(c)) was measured by first-pass radionuclide ventriculography. The systemic O-2 extraction ratio (O2ER) was calculated as arterial - mixed venous O-2 content difference CaO2 - CvO2/CaO2. Peak exercise O-2 uptake ((V) over dot O-2peak) was markedly reduced in both COPD and LVF [41 (3) and 42 (3)% predicted, respectively], compared to controls [89 (2)% predicted, P < 0.0001 for each]. Similarly, the LT occurred at a low percentage of predicted maximal oxygen consumption in both COPD and LVF [25 (2) and 27 (3)%] compared to normals [46 (3)%, P < 0.0001 for each]. The systemic O2ER at peak exercise was severely reduced in COPD [0.36 (0.02)] compared to the other groups [P < 0.0001 for each], for whom it was nearly identical [0.58 (0.03) vs 0.63 (0.03), LVF vs control, P > 0.05]. In the COPD group, an early LT correlated with reduced systemic O2ER at peak exercise (r = 0.64, P < 0.0001), but not with any index of systemic O-2 delivery. These data suggest that lactic acidemia during exercise in patients with severe COPD is better related to abnormal systemic O-2 extraction than to its delivery and contributes to the exercise limit. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lung Transplant Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Systrom, DM (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. NR 45 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0301-5548 J9 EUR J APPL PHYSIOL O JI Eur. J. Appl. Physiol. Occup. Physiol. PD AUG PY 1998 VL 78 IS 3 BP 201 EP 207 DI 10.1007/s004210050408 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 106KJ UT WOS:000075128200004 PM 9720997 ER PT J AU Neymark, N Kiebert, W Torfs, K Davies, L Fayers, P Hillner, B Gelber, R Guyatt, G Kind, P Machin, D Nord, E Osoba, D Revicki, D Schulman, K Simpson, K AF Neymark, N Kiebert, W Torfs, K Davies, L Fayers, P Hillner, B Gelber, R Guyatt, G Kind, P Machin, D Nord, E Osoba, D Revicki, D Schulman, K Simpson, K TI Methodological and statistical issues of quality of life (QoL) and economic evaluation in cancer clinical trials: Report of a workshop SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE cancer; quality of life; economic evaluation; costs ID HEALTH-STATUS; COSTS AB In recent years, quality of life (QoL) and economic evaluations have become increasingly important as additional outcome measures in cancer clinical trials. However, both fields of research are relatively new and in need of finding solutions to a substantial number of specific methodological problems. This paper reports on the proceedings of a symposium aimed at summarising and discussing some of the most contentious methodological and statistical issues in QoL and economic evaluations. In addition, possible solutions are indicated and the most pertinent areas of research are identified. Issues specific to QoL evaluations that are addressed include clinically meaningful changes in QoL scores; how to analyse QoL data and to handle missing and censored data and integration of length of life and QoL outcomes. Issues specific to economic evaluations are the advantages and disadvantages of various outcome measures; statistical methods to analyse economic data and choice of decision criteria and analytical perspective. How to perform QoL and economic evaluations in large and simple trials and whether the gap between QoL and utility measures can be bridged are also discussed. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Eortc Data Ctr, Brussels, Belgium. Medtap Int, London, England. Janssen Res Fdn, B-2340 Beerse, Belgium. Univ York, Ctr Hlth Econ, York YO1 5DD, N Yorkshire, England. MRC, Canc Trials Off, Cambridge, England. Virginia Commonwealth Univ, Med Coll Virginia, Div Gen Internal Med, Richmond, VA 23298 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON L8S 4L8, Canada. Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada. MRC, Canc Trials Off, Cambridge, England. Natl Inst Publ Hlth, Oslo, Norway. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Medtap Int, Bethesda, MD USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Chiron Diagnost, Emeryville, CA USA. RP Neymark, N (reprint author), Eortc Data Ctr, Av E Mounier 83,Bte 11, Brussels, Belgium. RI Hillner, Bruce/A-6852-2009; Fayers, Peter/A-5999-2010; OI Davies, Linda/0000-0001-8801-3559; Fayers, Peter/0000-0003-4778-1513 NR 23 TC 40 Z9 41 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD AUG PY 1998 VL 34 IS 9 BP 1317 EP 1333 DI 10.1016/S0959-8049(98)00074-4 PG 17 WC Oncology SC Oncology GA 108XG UT WOS:000075290600007 PM 9849412 ER PT J AU Weissleder, R Cheng, HC Marecos, E Kwong, K Bogdanov, A AF Weissleder, R Cheng, HC Marecos, E Kwong, K Bogdanov, A TI Non-invasive in vivo mapping of tumour vascular and interstitial volume fractions SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE tumour; neovascularity; angiogenesis; vascular architecture; MR imaging ID DTPA ENHANCED MRI; GD-DTPA; THERAPEUTIC AGENTS; BREAST-CARCINOMA; CONTRAST AGENTS; BLOOD-FLOW; PERMEABILITY; RAT; ANGIOGENESIS; MICROCIRCULATION AB Non-invasive measurement of haemodynamic parameters and imaging of neovasculature architecture is of importance in determining tumour prognosis, in directing tissue sampling and in assessing treatment efficacy. In the current research we investigated a dual tracer nuclear magnetic resonance (NMR) technique to map the tumour vascular (VVF) and interstitial volume fraction (IVF) noninvasively in vivo. We hypothesised that a NMR signal emanating after intravenous administration of a vascular paramagnetic probe (MPEG-PL-GdDTPA) can be maximised so that additional signal after administration of a second interstitial probe (GdDTPA) would only reflect the IVF but not the VVF. The method and its assumptions were verified and experimental conditions optimised both in phantoms and in C6 glioma bearing rats. Data derived from in vivo studies show tumoral VVF and IVF values that are consistent with histology data and literature values; the relative ranking order of values was tumour>muscle>brain. Image maps showed intratumoral and intertumoral heterogeneity of both parameters at submillimetre pixel resolution. The method is applicable to a wide variety of tumour models and can theoretically be performed repeatedly to study tumour growth or involution during therapy. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Room 5403, Charlestown, MA 02129 USA. FU NCI NIH HHS [2RO1 CA54886-04A1, 5RO1CA59649-03] NR 40 TC 45 Z9 45 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD AUG PY 1998 VL 34 IS 9 BP 1448 EP 1454 DI 10.1016/S0959-8049(98)00195-6 PG 7 WC Oncology SC Oncology GA 108XG UT WOS:000075290600025 PM 9849430 ER PT J AU Bilan, PJ Moyers, JS Kahn, CR AF Bilan, PJ Moyers, JS Kahn, CR TI The Ras-related protein Rad associates with the cytoskeleton in a non-lipid-dependent manner SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID PLASMA-MEMBRANE; CAAX MOTIF; DOMAIN; FAMILY; LOCALIZATION; MUSCLE; GENE; GERANYLGERANYL; SUPERFAMILY; SEQUENCE AB Rad is the prototypic member of a new family of Ras-related proteins (Rad, Gem, and Kir) which lack typical C-terminal amino acid motifs for isoprenylation, In mouse C2C12 muscle cell Lines about 50% of Rad protein resides in the cytosol and behaves as a hydrophilic protein partitioning away from TX-114. The remainder of Rad is associated with plasma and internal membranes. The association of Rad with the membrane does not occur through the lipid bilayer, but instead depends on the interaction of Rad with the cytoskeleton or membrane skeleton. In contrast to Ras, biosynthetic labeling of cellular proteins in C2C12 cells with [H-3]palmitic acid demonstrates that Rad is not modified with this fatty acid, and inhibition of isoprenylation with lovastatin treatment has no effect on Rad subcellular distribution. Furthermore, removal of the C-terminal 11 amino acids that are precisely conserved in all three Rad family members has no effect on Rad subcellular distribution. Addition of the 9 amino acids from the C-terminus of H-Ras to the truncated Rad protein results in a redistribution of Rad from the cytosol to the membrane skeleton without the presence of any detectable lipid modification of the chimeric protein. These data suggest that Rad possesses unique cellular localization signals which, in contrast to other Ras-related family members, do not depend on the lipid modification of the C-terminus. (C) 1998 Academic Press. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM kahnr@joslab.harvard.edu FU NIDDK NIH HHS [DK 45935, DK 07260] NR 37 TC 23 Z9 23 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 1 PY 1998 VL 242 IS 2 BP 391 EP 400 DI 10.1006/excr.1998.4092 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 110UT UT WOS:000075399700002 PM 9683526 ER PT J AU Little, MT Griffin, JD AF Little, MT Griffin, JD TI Bcr-Abl mediated resistance to apoptosis is not related to changes in the levels of expression of either Bcl-2, Bcl-(xl), or Bax SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 157 BP 725 EP 725 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600159 ER PT J AU Koh, PS Hughes, GC Faulkner, GR Keeble, WW Bagby, GC AF Koh, PS Hughes, GC Faulkner, GR Keeble, WW Bagby, GC TI The Fanconi anemia group C gene product modulates apoptotic responses to tumor necrosis factor receptor superfamily proteins but does not suppress expression of these receptors. SO EXPERIMENTAL HEMATOLOGY 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 CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 164 BP 726 EP 726 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600166 ER PT J AU Boggs, SS Trevisan, M Patrene, K Georgopoulos, K AF Boggs, SS Trevisan, M Patrene, K Georgopoulos, K TI Lack of NK cell precursors in fetal liver of Ikaros knockout mutant mice SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 246 BP 750 EP 750 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600248 ER PT J AU Salgia, R Quackenbush, E Ewaniuk, D von Andrean, UH Griffin, JD AF Salgia, R Quackenbush, E Ewaniuk, D von Andrean, UH Griffin, JD TI BCR/ABL transformed hematopoietic cells do not respond to the chemokine SDF-1 alpha. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, 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 CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 265 BP 757 EP 757 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600267 ER PT J AU Markewitz, M Yamashita, T Asano, S Joenje, H Kupfer, G AF Markewitz, M Yamashita, T Asano, S Joenje, H Kupfer, G TI Interaction of the Fanconi Anemia proteins in a novel signaling pathway. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Tokyo, Japan. Free Univ, Rotterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 271 BP 759 EP 759 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600273 ER PT J AU Lu, L Li, YX Wang, L Heinrich, MC Broxmeyer, HE AF Lu, L Li, YX Wang, L Heinrich, MC Broxmeyer, HE TI Transduction of human c-kit hematopoietic stem/progenitor cells from cord blood enhances erythroid cell containing colony formation in the absence of steel factor SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Indiana Univ Sch Med, Dept Microbiol Immunol, Indianapolis, IN USA. Indiana Univ Sch Med, Walther Oncol Ctr, Indianapolis, IN USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 292 BP 764 EP 764 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600294 ER PT J AU Pharr, P Goldsmith, MA Mikami, A You, Y Liu, KD Thomas, L Longmore, GD AF Pharr, P Goldsmith, MA Mikami, A You, Y Liu, KD Thomas, L Longmore, GD TI Divergent cytokine receptors support terminal red blood cell differentiation in vivo SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. Univ Calif San Francisco, Sch Med, Dept Med, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol, St Louis, MO 63110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 291 BP 764 EP 764 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600293 ER PT J AU Sato, T Laver, JH Ogawa, M AF Sato, T Laver, JH Ogawa, M TI A clonal cell culture assay for human natural killer cell progenitors. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Div Pediat & Med, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 342 BP 776 EP 776 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600344 ER PT J AU Theodore, PR Simon, AR Warrens, AN Sackstein, R Sykes, M AF Theodore, PR Simon, AR Warrens, AN Sackstein, R Sykes, M TI Divergence of integrin function in hematopoiesis in the pig to human xenogeneic combination: Implications for bone marrow induced donor-specific tolerance SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, BMT Sect,Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 347 BP 778 EP 778 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600349 ER PT J AU Sykes, M Ohdan, H Wekerle, T Yang, YG AF Sykes, M Ohdan, H Wekerle, T Yang, YG TI Mixed hematopoietic chimerism and tolerance. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,BMT Sect, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 431 BP 799 EP 799 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600433 ER PT J AU Yang, L Embree, L Tsai, S Hickstein, DD AF Yang, L Embree, L Tsai, S Hickstein, DD TI Oncoprotein TLS interacts with serine-arginine (SR) proteins involved in RNA splicing SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 450 BP 805 EP 805 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600452 ER PT J AU Rebel, VI Chan, M Finberg, R Sieff, CA AF Rebel, VI Chan, M Finberg, R Sieff, CA TI Expression of coxsackievirus and adenovirus receptor (CAR) protein is important for adenovirus entry imo hematopoietic cells. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 454 BP 806 EP 806 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600456 ER PT J AU North, M Dallalio, G Means, RT AF North, M Dallalio, G Means, RT TI Effects of ceramide on human erythroid colony formation: Involvement in the inhibition induced by gamma-interferon. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. RI Means, Robert/A-4454-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1998 VL 26 IS 8 MA 462 BP 809 EP 809 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 118GT UT WOS:000075830600464 ER PT J AU Tao, XJ Sayegh, RA Tilly, JL Isaacson, KB AF Tao, XJ Sayegh, RA Tilly, JL Isaacson, KB TI Elevated expression of the proapoptotic BCL-2 family member, BAK, in the human endometrium coincident with apoptosis during the secretory phase of the cycle SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 18-22, 1997 CL SAN DIEGO, CALIFORNIA SP Soc Gynecol Invest DE BAK; BCL-2; endometrium; apoptosis; uterus; menstrual cycle ID CELL-DEATH; MENSTRUAL-CYCLE; HOMOLOG BAK; DISTINCT AB Objective: To characterize the distribution of BAK (BCL-2 homologous antagonist/killer) protein in the human endometrium relative to the occurrence of apoptosis. Design: A prospective, controlled study. Setting: An academic hospital. Patient(s): Premenopausal women with histologically normal endometrium who were undergoing hysterectomy and curettage. Intervention(s): Endometrial tissues were collected. Main Outcome Measure(s): Detection of BAK protein by immunohistochemical and immunoblot analyses, and of apoptosis by in situ DNA end-labeling. Result(s): BAK protein was detected in secretory endometrium and was confined to the glandular epithelial cells of the functionalis layer. Immunoreactive BAK was absent from most of the cells of the proliferative endometrium. By immunoblot analysis, we confirmed the immunohistochemical data by demonstrating that a 30-kD protein corresponding to BAK was elevated in lysates prepared from secretory, as compared with proliferative, endometrium. The elevated levels of BAK coincided with the onset of apoptosis in endometrial glandular epithelial cells during the secretory phase of the menstrual cycle. Conclusion(s): BAK protein localizes to glandular epithelial cells on the verge of apoptosis in the human endometrium. Thus, BAK likely functions with other members of the BCL-2 family in the regulation of apoptosis in the human uterus. (Fertil Steril(R) 1998;70:338-43. (C)1998 by American Society for Reproductive Medicine.). C1 Harvard Univ, Sch Med,Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Dept Obstet Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Reprod Biol & Infertil, Boston, MA 02114 USA. RP Isaacson, KB (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Dept Obstet Gynecol, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R01-HD34226] NR 22 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD AUG PY 1998 VL 70 IS 2 BP 338 EP 343 DI 10.1016/S0015-0282(98)00129-0 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 105UN UT WOS:000075092100027 PM 9696231 ER PT J AU Heller, RS Stoffers, DA Hussain, MA Miller, CP Habener, JF AF Heller, RS Stoffers, DA Hussain, MA Miller, CP Habener, JF TI Misexpression of the pancreatic homeodomain protein IDX-1 by the Hoxa-4 promoter associated with agenesis of the cecum SO GASTROENTEROLOGY LA English DT Article ID CONTAINING GENE HOX-1.4; EXPRESSION; HOMEOBOX; TRANSCRIPTION; RAT; ISLETS; FIBER; CELLS; MICE AB Background & Aims: The endoderm-specific homeodomain transcription factor IDX-1 is critical for pancreas development and for the regulation of islet cell-specific genes. During development, IDX-1 is expressed in the epithelial cells of the endoderm in the pancreatic anlage of the foregut. The aim of this study was to determine whether IDX-1 may have potential properties of a master homeotic determinant of pancreas and/or gut development. Methods: Transgenic mice were generated in which the expression of IDX-1 was misdirected by a promoter of the mesoderm-specific homeodomain protein Hoxa-4 known to express in the stomach and hindgut during development. The expectation was the formation of ectopic pancreatic tissue or alterations of gut patterning or morphology. Results: Although no ectopic induction of pancreatic markers was found in these transgenic mice, they manifested an altered midgut-hindgut union and agenesis of the cecum. Further, IDX-1 binds to the gut-specific homeodomain protein Cdx-2 and inhibits transactivation of the sucrase-isomaltase promoter by Cdx-2. Conclusions: These findings further support the emerging understanding that interactions among different classes of homeodomain proteins, expressed in a spatially and temporally restricted manner during development, determine the pattern of organogenesis. A possible mechanism for the dysmorphogenesis of the proximal colon may be an inhibition of Cdx-2 actions by IDX-1. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, 32 Fruit St, Boston, MA 02114 USA. EM habenerj@a1.mgh.harvard.edu RI Heller, R.Scott/A-7279-2008; Stoffers, Doris/H-6157-2012 FU NIDDK NIH HHS [DK 30457] NR 30 TC 39 Z9 40 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 AUG PY 1998 VL 115 IS 2 BP 381 EP 387 DI 10.1016/S0016-5085(98)70204-5 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 108YE UT WOS:000075293400020 PM 9679043 ER PT J AU Dyson, N AF Dyson, N TI The regulation of E2F by pRB-family proteins SO GENES & DEVELOPMENT LA English DT Review ID TRANSCRIPTION FACTOR E2F; CELL-CYCLE REGULATION; RETINOBLASTOMA GENE-PRODUCT; S-PHASE ENTRY; ADENOVIRUS E1A PROTEINS; UBIQUITIN-PROTEASOME PATHWAY; DIHYDROFOLATE-REDUCTASE GENE; DNA-BINDING ACTIVITY; IN-VIVO; COMPLEX-FORMATION C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Dyson, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA64402]; NIGMS NIH HHS [GM53203] NR 194 TC 1698 Z9 1726 U1 7 U2 55 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 1 PY 1998 VL 12 IS 15 BP 2245 EP 2262 DI 10.1101/gad.12.15.2245 PG 18 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 109YU UT WOS:000075352600001 PM 9694791 ER PT J AU Jackson, SA Wang, ML Goodman, HM Jiang, JM AF Jackson, SA Wang, ML Goodman, HM Jiang, JM TI Application of fiber-FISH in physical mapping of Arabidopsis thaliana SO GENOME LA English DT Article DE fluorescence in situ hybridization; DNA fibers; physical mapping; genome analysis ID IN-SITU HYBRIDIZATION; EXTENDED DNA FIBERS; RIBOSOMAL-RNA GENES; REPETITIVE DNA; REGIONS; GENOME; CHROMOSOME-2; SEQUENCES; CHROMATIN; MAP AB Arabidopsis thaliana has become a model plant species for genetic studies because of its small genome and short juvenility period. However, the small chromosomes of this species are not suitable for classical cytogenetic studies. Here we demonstrate that the fluorescence in situ hybridization (FISH) technique using extended DNA fibers can be a powerful tool in the physical mapping of the A. thaliana genome. Using a refined fiber-FISH technique we were able to measure DNA clusters as long as 1.71 Mb, more than 1% of the A. thaliana genome. Several small DNA loci, including the telomeres and a dispersed repetitive DNA sequence, mi167, were also analyzed with this technique. The results show that without known adjacent DNA markers such small DNA loci cannot be mapped precisely using fiber-FISH. One of the most difficult obstacles in physical mapping by contig assembly is closing the gaps that are present between adjacent contigs. Currently available molecular techniques are not sufficient to accurately estimate the physical sizes of these gaps. We isolated bacterial artificial chromosome (BAC) clones bordering Saps 2 and 3 on the physical contig map of A. thaliana chromosome II. The BAC clones were used in fiber-FISH analysis and the physical sizes of the two gaps were estimated as 31 kb and more than 500 kb, respectively. Thus, we have demonstrated that fiber-FlSH is an efficient technique for determining the physical size of gaps on molecular contig maps. C1 Univ Wisconsin, Dept Hort, Madison, WI 53706 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Jiang, JM (reprint author), Univ Wisconsin, Dept Hort, 1575 Linden Dr, Madison, WI 53706 USA. RI Jiang, Jiming/A-9614-2009 NR 43 TC 114 Z9 128 U1 0 U2 10 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0831-2796 J9 GENOME JI Genome PD AUG PY 1998 VL 41 IS 4 BP 566 EP 572 DI 10.1139/gen-41-4-566 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 130CP UT WOS:000076501900011 PM 9796106 ER PT J AU Fusco, C Reymond, A Zervos, AS AF Fusco, C Reymond, A Zervos, AS TI Molecular cloning and characterization of a novel retinoblastoma-binding protein SO GENOMICS LA English DT Article ID E2F TRANSCRIPTION FACTOR; ADENOVIRUS E1A PROTEINS; CELL-CYCLE; GENE-PRODUCT; SUSCEPTIBILITY GENE; INSITU HYBRIDIZATION; NEGATIVE MODULATION; RB PROTEIN; LARGE-T; MYC AB We describe the isolation and characterization of a novel cDNA encoding a polypeptide that interacts in a yeast two-hybrid system as well as in mammalian cells with the retinoblastoma (RB) protein. This new protein, which we call Rim, consists of 897 amino acids, has two leucine zipper motifs, and has a LECEE sequence previously identified as an RE-binding domain. Rim also has an E1A/CtBP-binding motif and four putative nuclear localization signals. Rim mRNA is expressed ubiquitously at low levels in all human adult tissues tested and at much higher levels in several tumor cell lines. The Rim gene (HG;MW-approved symbol RBBP8) is localized on human chromosome 18q11.2. (C) 1998 Academic Press C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Charlestown, MA 02129 USA. RP Zervos, AS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. NR 48 TC 48 Z9 49 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 1 PY 1998 VL 51 IS 3 BP 351 EP 358 DI 10.1006/geno.1998.5368 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 115PN UT WOS:000075674000005 PM 9721205 ER PT J AU Fenner, MH Parrish, JE Boyd, Y Reed, V MacDonald, M Nelson, DL Isselbacher, KJ Shioda, T AF Fenner, MH Parrish, JE Boyd, Y Reed, V MacDonald, M Nelson, DL Isselbacher, KJ Shioda, T TI MSG1 (melanocyte-specific gene 1): mapping to chromosome Xq13.1, genomic organization, and promoter analysis SO GENOMICS LA English DT Article ID X-INACTIVATION CENTER; MOUSE; PROTEIN; IDENTIFICATION; TRANSCRIPTION; EXPRESSION; ZEBRAFISH; ENCODES; CELLS; MAPS AB MSG1 (melanocyte-specific gene 1) is a recently isolated gene predominantly expressed in cultured normal melanocytes and pigmented melanoma cells, MSG1 encodes a 27-kDa nuclear protein that has strong intrinsic transcriptional transactivating activity. In this report, the human MSG1 gene was mapped to chromosome Xq13.1 using X chromosome-specific somatic cell hybrids, and the mouse Msg1 gene was mapped 1.9 +/- 1.3 cM proximal to Xist using an interspecific backcross panel. Both the human and the mouse MSG1 genes consist of three exons and two introns within 5 kb of genomic DNA, and their genomic structures are highly conserved. Southern blot analysis suggests the existence of MSG1 homologues in chicken, zebrafish, and Drosophila. A 2.0-kb fragment of the 5'-flanking region of the mouse Msg1 gene contains a TATA box and potential binding sites for several transcription factors including USF, Brn-3, Brn-2, TFE3, Oct-1, AP-2, and Spl. This promoter fragment activates transcription of a reporter gene in pigmented melanoma cells, but not in amelanotic melanoma cells or nonmelanocytic cells, indicating that Msg1 expression is at least partially regulated at the transcriptional level, (C) 1998 Academic Press C1 Massachusetts Gen Hosp, Ctr Canc, Lab Tumor Biol, Charlestown, MA 02129 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. MRC, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Ctr Canc, Lab Tumor Biol, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Fenner, Martin/A-7225-2008 OI Fenner, Martin/0000-0003-1419-2405 FU PHS HHS [H6.00210] NR 32 TC 18 Z9 19 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 1 PY 1998 VL 51 IS 3 BP 401 EP 407 DI 10.1006/geno.1998.5383 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 115PN UT WOS:000075674000010 PM 9721210 ER PT J AU Jette, AM Rooks, D Lachman, M Lin, TH Levenson, C Heislein, D Giorgetti, MM Harris, BA AF Jette, AM Rooks, D Lachman, M Lin, TH Levenson, C Heislein, D Giorgetti, MM Harris, BA TI Home-based resistance training: Predictors of participation and adherence SO GERONTOLOGIST LA English DT Article DE community-dwelling older adults; exercise programs; adherence ID PHYSICAL-ACTIVITY; OLDER ADULTS; EXERCISE PROGRAM; SELF-EFFICACY; DISEASE; HEALTH; WOMEN; MAINTENANCE; MOBILITY; BELIEFS AB This study identified factors associated with exercise participation and adherence in a sample of 102 sedentary, functionally limited, community-dwelling adults aged 60 to 94 years who participated in a home-based resistance training program. Stepwise regression analyses revealed that baseline physical factors (i.e., higher levels of mobility, weaker muscle strength, and fewer numbers of new medical conditions) were associated with higher rates of participation in the home program. Positive attitudes and a sense of control toward exercise, lower levels of confusion and depressive moods, and the development of fewer new medical problems during the program were related to higher levels of adherence to the program. Findings revealed that although physical health variables were the primary indicators of an older person's overall participation in the program, it was the psychological factors that were most important to adherence to this home-based program. C1 Boston Univ, Sargent Coll Hlth & Rehabil Sci, Boston, MA 02215 USA. Brandeis Univ, Waltham, MA 02254 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA USA. RP Jette, AM (reprint author), Boston Univ, Sargent Coll Hlth & Rehabil Sci, 635 Commonwealth Ave, Boston, MA 02215 USA. EM ajette@bu.edu FU NIA NIH HHS [P50 AG11669] NR 53 TC 114 Z9 114 U1 3 U2 12 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 1998 VL 38 IS 4 BP 412 EP 421 PG 10 WC Gerontology SC Geriatrics & Gerontology GA 111MC UT WOS:000075440300002 PM 9726128 ER PT J AU Cariappa, A Sands, B Forcione, D Finkelstein, D Podolsky, DK Pillai, S AF Cariappa, A Sands, B Forcione, D Finkelstein, D Podolsky, DK Pillai, S TI Analysis of MHC class II DP, DQ and DR alleles in Crohn's disease SO GUT LA English DT Article DE Crohn's disease; inflammatory bowel disease; genetic susceptibility; major histocompatibility complex; HLA class II genes ID INFLAMMATORY BOWEL-DISEASE; MYELIN BASIC-PROTEIN; MULTIPLE-SCLEROSIS; SUSCEPTIBILITY LOCUS; HLA; GENES; ASSOCIATION; CHROMOSOME-16; LYMPHOCYTES; GENETICS AB Background-Although inflammation in Crohn's disease is believed to be mediated by activated T cells, genotyping of all MHC class II alleles in white people with this disease has not been reported. Aims-To perform a detailed molecular analysis of HLA DPB, DQB, and DRB genes in white patients with Crohn's disease and controls in order to determine if the inheritance of any class II genes confers susceptibility or resistance to this disease. Methods-Complete molecular typing of HLA class II DPB, DQB, and DRB alleles was performed in 58 white patients with Crohn's disease and 93 healthy controls using a polymerase chain reaction-sequence specific oligonucleotide based approach. Results-No significant association with any DPB or DQB alleles was noted in patients with Crohn's disease. Since our previous studies had shown a strong association of an HLA DRB3(star)0301/DRB1(star)1302 haplotype with Crohn's disease, we re-examined this association using more stringent genotyping criteria. This haplotype was present in 20.7% of patients and 5.4% of controls (p = 0.0066; relative risk = 4.59). Conclusions-The DRB3(star)0301/DRB1(star)1302 haplotype is the only significant MHC class II association noted in white people with Crohn's disease and represents the strongest association of any MHC or non-MHC locus with this disease. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02129 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St,Charlestown Navy Yard, Boston, MA 02129 USA. FU NIAID NIH HHS [AI-33507]; NIDDK NIH HHS [P30DK43351] NR 27 TC 32 Z9 35 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD AUG PY 1998 VL 43 IS 2 BP 210 EP 215 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 104JZ UT WOS:000075012100012 PM 10189846 ER PT J AU Nakfoor, BM Spiro, IJ Wang, CC Martins, P Montgomery, W Fabian, R AF Nakfoor, BM Spiro, IJ Wang, CC Martins, P Montgomery, W Fabian, R TI Results of accelerated radiotherapy for supraglottic carcinoma: A Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary experience SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE altered fractionation; supraglottic cancer; local control; voice preservation; complications ID SQUAMOUS-CELL CARCINOMA; LARYNX AB Background. Carcinoma of the supraglottic larynx is a relatively common malignancy treated with either surgery, radiotherapy, or a combined approach. Methods. The radiotherapy records of 190 patients with carcinoma of the supraglottic larynx treated at the Massachusetts General Hospital (MGH) and Massachusetts Eye and Ear Infirmary (MEEI) from 1981 to 1992 were reviewed. Of these patients, 164 were available for evaluation for local control and 169 for disease-specific survival. The patients were treated with accelerated hyperfractionated radiotherapy to 67.2-72 Gy/1.6 Gy per fraction twice a day in 6 weeks. The median follow-up was 56 months. Five-year actuarial local and regional control, relapse-free and overall survival, and voice-preservation rates were analyzed, Results. For T1, T2, T3, and T4 tumors, local control rates were 96%, 86%, 76%, and 43%, respectively (p <.01), and the corresponding relapse-free survival rates were 78%, 82%, 64%, and 40% (p <.01). For the patients with NO, N1, and N2-3 disease, local control rates at the primary site were 86%, 74%, and 46%, respectively (p <.01), and the corresponding relapse-free survival rates were 79%, 53%, and 39% (p <.01), Including surgical salvage, the ultimate local control rates were 96%, 93%, 88%, and 51%, respectively (p <.01). Voice preservation rate for the entire group was 79% and for T1, T2, T3, and T4 tumors, rates were 96%, 80%, 72%, and 43%, respectively. Conclusions. Our experience with accelerated hyperfractionated radiotherapy for supraglottic carcinoma showed excellent locoregional control, relapse-free survival, and laryngeal preservation. The radiation toxicity was acceptable. The T and N stages were significant predictors of outcome, and the T4 tumors and node-positive neck disease portended a poor prognosis and therefore should be considered for protocols that include adjuvant therapies. (C) 1998 John Wiley & Sons, Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. RP Wang, CC (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. NR 9 TC 22 Z9 24 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD AUG PY 1998 VL 20 IS 5 BP 379 EP 384 DI 10.1002/(SICI)1097-0347(199808)20:5<379::AID-HED4>3.0.CO;2-V PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA ZW063 UT WOS:000074370200004 PM 9663664 ER PT J AU Allen, JD Sorensen, G Stoddard, AM Colditz, G Peterson, K AF Allen, JD Sorensen, G Stoddard, AM Colditz, G Peterson, K TI Intention to have a mammogram in the future among women who have underused mammography in the past SO HEALTH EDUCATION & BEHAVIOR LA English DT Article ID BREAST SELF-EXAMINATION; SCREENING MAMMOGRAPHY; MEXICAN-AMERICAN; HEALTH PROMOTION; UNITED-STATES; BLACK-WOMEN; PAP SMEAR; CANCER; BEHAVIOR; EFFICACY AB This study investigated associations between confidence in one's ability to discuss mammography with health providers and to obtain regular mammograms (self-efficacy), social network members' attitudes toward mammograms (social influence), mammography experiences, and intention to have a mammogram in the next 1 to 2 years among women who were not in adherence with screening guidelines. Data were collected as part of a baseline assessment for a work site intervention study. Women 52 years and older completed a self-administered survey. Those not in compliance with screening guidelines (n = 194) were included in the analyses. Logistic regression revealed that self-efficacy and strong supportive social influences were significantly associated with mammography intention (odds ratio [OR] = 2.50, OR = 2.22, respectively), adjusting for prior mammography use. Findings suggest that interventions designed to promote mammography should build women's confidence in their ability to discuss mammography with health providers and to obtain regular mammograms. Intervention among social networks may also be an effective means of promoting mammography. C1 Dana Farber Canc Inst, Div Canc Epidemiol & Control, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Allen, JD (reprint author), Dana Farber Canc Inst, Div Canc Epidemiol & Control, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. EM jennifer_allen@dfci.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [R01 CA 66038] NR 48 TC 34 Z9 34 U1 0 U2 1 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 AUG PY 1998 VL 25 IS 4 BP 474 EP 488 DI 10.1177/109019819802500406 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 102PP UT WOS:000074933300006 PM 9690105 ER PT J AU Langley, RGB Sober, AJ AF Langley, RGB Sober, AJ TI Clinical recognition of melanoma and its precursors SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; CONGENITAL MELANOCYTIC NEVI; WESTERN-CANADA-MELANOMA; DYSPLASTIC NEVI; RISK-FACTORS; LENTIGO MALIGNA; SKIN; DIAGNOSIS; LESIONS; MARKERS AB This article reviews the essential clinical features of cutaneous melanoma, as well as those of the more common benign pigmented lesions that need to be distinguished on clinical examination. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Sober, AJ (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. NR 62 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 1998 VL 12 IS 4 BP 699 EP + DI 10.1016/S0889-8588(05)70019-8 PG 18 WC Oncology; Hematology SC Oncology; Hematology GA 117CX UT WOS:000075764000003 PM 9759575 ER PT J AU Haines, JL Terwedow, HA Burgess, K Pericak-Vance, MA Rimmler, JB Martin, ER Oksenberg, JR Lincoln, R Zhang, DY Banatao, DR Gatto, N Goodkin, DE Hauser, SL AF Haines, JL Terwedow, HA Burgess, K Pericak-Vance, MA Rimmler, JB Martin, ER Oksenberg, JR Lincoln, R Zhang, DY Banatao, DR Gatto, N Goodkin, DE Hauser, SL TI Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity SO HUMAN MOLECULAR GENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; AFFECTED RELATIVE PAIRS; CLASS-II REGION; DISEASE ASSOCIATION; NO EVIDENCE; T-CELLS; POLYMORPHISMS; SUSCEPTIBILITY; STRATEGIES AB Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system, While its etiology is not well understood, genetic factors are clearly involved, Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases, The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6, Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies, Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association, Three highly polymorphic markers (HLA-DR, D6S273 and TNF beta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001), Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles, These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS, This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC. C1 Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Duke Univ, Med Ctr, Med Genet Sect, Durham, NC USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Haines, JL (reprint author), Vanderbilt Univ, Program Human Genet, 221 Kirkland Hall, Nashville, TN 37232 USA. EM jonathan@ruth.mc.vanderbilt.edu RI Haines, Jonathan/C-3374-2012; Hauser, Stephen/J-2978-2016 FU NINDS NIH HHS [NS26799, NS32830] NR 56 TC 186 Z9 189 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG PY 1998 VL 7 IS 8 BP 1229 EP 1234 DI 10.1093/hmg/7.8.1229 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 106TV UT WOS:000075167300005 PM 9668163 ER PT J AU Singh, JP Larson, MG Tsuji, H Evans, JC O'Donnell, CJ Levy, D AF Singh, JP Larson, MG Tsuji, H Evans, JC O'Donnell, CJ Levy, D TI Reduced heart rate variability and new-onset hypertension - Insights into pathogenesis of hypertension: The Framingham Heart Study SO HYPERTENSION LA English DT Article DE heart rate; hypertension, essential; Framingham Heart Study; autonomic nervous system; pathogenesis ID SPECTRAL-ANALYSIS; MORTALITY; DISEASE; WOMEN; RISK AB Heart rate variability (HRV) is a useful noninvasive tool to assess cardiac autonomic function. The purpose of this study was to (1) compare measures of HRV between hypertensive and normotensive subjects and (2) examine the role of HRV as a predictor of new-onset hypertension. The first 2 hours of ambulatory ECG recordings obtained from 931 men and 1111 women attending a routine examination at the Framingham Heart Study were processed for HRV. Three time-domain and 5 frequency-domain variables were studied: standard deviation of normal RR intervals (SDNN), percentage of differences between adjacent normal RR intervals exceeding 50 milliseconds, square root of the mean of squared differences between adjacent normal RR intervals, total power (0.01 to 0.40 Hz), high frequency power (HF, 0.15 to 0.40 Hz), low frequency power (LF, 0.04 to 0.15 Hz), very low frequency power (0.01 to 0.04 Hz), and LF/HF ratio. On cross-sectional analysis, HRV was significantly lower in hypertensive men and women. Among 633 men and 801 women who were normotensive at baseline (systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg and not receiving antihypertensive treatment), 119 men and 125 women were newly hypertensive at follow-up 4 years later. After adjustment for factors associated with hypertension, multiple logistic regression analysis revealed that LF was associated with incident hypertension in men (odds ratio per SD decrement [OR], 1.38; 95% confidence interval [CI], 1.04 to 1.83) but not in women (OR, 1.12; 95% CI, 0.86 to 1.46). SDNN, HF, and LF/HF were not associated with hypertension in either sex. HRV is reduced in men and women with systemic hypertension. Among normotensive men, lower HRV was associated with greater risk for developing hypertension. These findings are consistent with the hypothesis that autonomic dysregulation is present in the early stage of hypertension. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA USA. Beth Israel Hosp, Div Cardiol, Boston, MA 02215 USA. Beth Israel Hosp, Div Clin Epidemiol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, Boston, MA USA. Kansai Med Univ, Osaka, Japan. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. EM dan@fram.nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-38038] NR 29 TC 234 Z9 259 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD AUG PY 1998 VL 32 IS 2 BP 293 EP 297 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 112RV UT WOS:000075508700016 PM 9719057 ER PT J AU James, JA Harley, JB AF James, JA Harley, JB TI B-cell epitope spreading in autoimmunity SO IMMUNOLOGICAL REVIEWS LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; LA SS-B; SEQUENTIAL AUTOANTIGENIC DETERMINANTS; GLUTAMIC-ACID DECARBOXYLASE; VESICULAR STOMATITIS-VIRUS; DRUG-INDUCED LUPUS; T-CELLS; RO RIBONUCLEOPROTEIN; MURINE LUPUS; 60-KDA RO AB How the immune response matures from recognizing a single or a few structures of the antigen to many is an obviously important process. Models of B-cell epitope spreading have been developed in a variety of systems. For example, immunization of animals with PPPGMRPP, one of the earliest B-cell epitopes in the anti-Sm response found in human lupus, leads to antispliceosomal autoimmunity and features of lupus. The humoral immune response spreads from PPPGMRPP to other structures of the spliceosome in an apparently reproducible sequence. B-cell epitope spreading has provided the experimental basis from which a relationship between lupus and Epstein-Barr virus was suspected. An understanding of B-cell epitope spreading is likely to lead to important principles in basic immunology and to answers to human disease problems. C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Dept Med, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Harley, JB (reprint author), Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Dept Med, 825 NE 13Th St, Oklahoma City, OK 73104 USA. EM john-harley@omrf.ouhsc.edu FU NIAID NIH HHS [AI42471]; NIAMS NIH HHS [AR42474, AR42460] NR 81 TC 88 Z9 89 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 1998 VL 164 BP 185 EP 200 DI 10.1111/j.1600-065X.1998.tb01220.x PG 16 WC Immunology SC Immunology GA 124AQ UT WOS:000076158500019 PM 9795776 ER PT J AU Burgess, JF Wilson, PW AF Burgess, JF Wilson, PW TI Variation in inefficiency among US hospitals SO INFOR LA English DT Article ID DATA ENVELOPMENT ANALYSIS; FRONTIER PRODUCTION FUNCTION; DECISION-MAKING UNITS; TECHNICAL EFFICIENCY; MODEL; REGRESSION; CARE AB This study analyzes the impact of policy variables and other factors on hospital technical inefficiency in the US. Distance functions are used to estimate technical efficiency for each hospital relative to contemporaneous technologies. The resulting panel of efficiency estimates are then regressed on exogenous factors to gain insight into various issues impacting the debate over health-care reform in the US. Methodologically, we extend previous work by recognizing data envelopment analysis (DEA) efficiency scores as estimates, and by dealing with a censoring problem at the estimated technology frontier. We use annual data on US hospitals operated by the US Department of Veterans Affairs (VA), state and local governments, and for-profit as well as nonprofit organizations from 1985 to 1988. C1 US Dept Vet Affairs, Management Sci Grp, Bedford, MA 01730 USA. Univ Texas, Dept Econ, Austin, TX 78712 USA. RP Burgess, JF (reprint author), US Dept Vet Affairs, Management Sci Grp, Bedford, MA 01730 USA. NR 38 TC 21 Z9 21 U1 3 U2 5 PU INFOR PI DOWNSVIEW ONTARIO PA UNIV TORONTO PRESS, JOURNALS DEPT,5201 DUFFERIN ST, DOWNSVIEW ONTARIO, TORONTO M3H 5T8, CANADA SN 0315-5986 J9 INFOR JI Infor PD AUG PY 1998 VL 36 IS 3 BP 84 EP 102 PG 19 WC Computer Science, Information Systems; Operations Research & Management Science SC Computer Science; Operations Research & Management Science GA 123MF UT WOS:000076128400003 ER PT J AU Cunningham, K Ackerly, H Claflin, L Collins, J Wu, PQ Ford, C Lansford, R Alt, F Dunnick, WA AF Cunningham, K Ackerly, H Claflin, L Collins, J Wu, PQ Ford, C Lansford, R Alt, F Dunnick, WA TI Germline transcription and recombination of a murine VDJ(mu delta gamma)1 transgene SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE heavy chain switch; CD40 ligand; IL-4 ID IMMUNOGLOBULIN HEAVY-CHAIN; SWITCH REGION RECOMBINATION; PRE-B CELLS; INTERFERON-GAMMA; SOMATIC MUTATION; LINE TRANSCRIPTS; CONSTANT-REGION; 3' END; C-MYC; EXPRESSION AB To investigate the regulation of Ig switch recombination, we have constructed mice with a 56 kb VDJ(mu delta gamma)1 transgene, This transgene included an anti-nitrophenyl VDJ segment, S-mu, C-mu, C-delta, I(gamma)1, S(gamma)1, C(gamma)1 and the C(gamma)1 membrane exons from the murine Igh(a) haplotype. Two founder lines were produced, with very similar characteristics. Transgenic B cells expressed normal amounts of C-mu (which is >95% transgenic), C-delta and other cell surface markers, and normal amounts of VDJ and C-mu RNA, yl germline transcription of the transgenes is properly regulated since stable transcripts were not expressed in B cells treated with lipopolysaccharide (LPS) alone, nor in thymus or non-lymphoid tissues, but were expressed after treatment of B cells with LPS + IL-4 or CD40L + IL-4, B cells from both lines of transgenic mice expressed transgenic gamma 1(a) after in vitro culture with CD40L + IL-4, but not after culture with CD40L alone. However, the CD40L + IL-4 induced IgG1 precursor frequency is much lower for VDJ(mu delta gamma)1 transgenic B cells (1:240-760) than for nontransgenic B cells (1:9), Analysis of DNA from transgenic hybridomas indicated that switch recombination can take place in switch (S) regions, but can also take place outside S regions. These results indicate that targeting of switch recombinase to S regions must include regulation beyond the S regions themselves and correct germline transcription. This additional regulation might include cis-acting elements or appropriate spacing or arrangement of the recombining elements. C1 Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, HHMI Res Labs, Boston, MA 02115 USA. RP Dunnick, WA (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. RI Lansford, Rusty/C-6956-2014 FU NCI NIH HHS [CA39068]; NIAID NIH HHS [AI20047, AI31541] NR 49 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD AUG PY 1998 VL 10 IS 8 BP 1027 EP 1037 DI 10.1093/intimm/10.8.1027 PG 11 WC Immunology SC Immunology GA 111GY UT WOS:000075430000002 PM 9723688 ER PT J AU Brazitikos, PD D'Amico, DJ Bochow, TW Hmelar, M Marcellino, GR Stangos, NT AF Brazitikos, PD D'Amico, DJ Bochow, TW Hmelar, M Marcellino, GR Stangos, NT TI Experimental ocular surgery with a high-repetition-rate erbium : YAG laser SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 21-26, 1996 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID ER-YAG; VITREORETINAL SURGERY; RELAXING RETINOTOMIES; CLINICAL-EXPERIENCE; EXCIMER-LASER; ABLATION; MODEL; SCLEROSTOMIES; CORNEA; DAMAGE AB PURPOSE. TO evaluate the performance in ocular surgery and the ocular tissue interactions resulting from increasing the maximum repetition rate of a pulsed-mode erbium:YAG laser system from 30 to 200 pulses per second. METHODS. An erbium:YAG laser was used that emitted at 2.94 mu m with an output graduated from 0.2 mJ to 25 mJ and a repetition rate from 2 Hz to 200 Hz and that was equipped with a flexible optical fiber attached to various interchangeable 20-gauge endoprobes to perform ocular surgery in enucleated pig eyes. The specific maneuvers were performed in close contact in nontransmitting aqueous media and included inner retinal ablation, retinotomy, lens capsulotomy, lens ablation, iridotomy, and iridectomy. Selected tissue specimens were examined by light microscopy. RESULTS. Increasing the repetition rate to the 200-Hz range significantly improved the smoothness, continuity, and speed of all surgical maneuvers. Compared with the 30-Hz rate, substantially lower energies per pulse were efficient with the 200-Hz rate. The "sticking effect" between the tip of the probe and the target tissue at low-repetition rates, which resulted in discontinuation of the surgical maneuver, particularly during lens surgery, was eliminated with the use of high-repetition rates. Use of high-repetition rates produced a zone of residual thermal damage less than 30 mu m in all ocular tissues. The histologic findings of tissue interactions were comparable to those obtained in published studies in which the same wavelength and low hertz rates were used. CONCLUSIONS. The high-repetition-rate erbium:YAG laser technology described is advantageous, compared with low-repetition-rate erbium:YAG lasers, and is applicable in a variety of ocular surgical procedures. Innovations in endoprobe design and further study will determine its role in contemporary ocular surgery. C1 Democritus Univ Thrace, Dept Ophthalmol, Alexandroupolis, Greece. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Coherent Med, Palo Alto, CA USA. RP Brazitikos, PD (reprint author), Agias Sophias 10 St, Salonika 54622, Greece. NR 30 TC 32 Z9 33 U1 1 U2 3 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 AUG PY 1998 VL 39 IS 9 BP 1667 EP 1675 PG 9 WC Ophthalmology SC Ophthalmology GA 106DE UT WOS:000075113800018 PM 9699556 ER PT J AU Escalante, A Fischbach, M AF Escalante, A Fischbach, M TI Searching for the Gulf War Syndrome SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Editorial Material C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Immunol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Escalante, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Immunol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM escalanie@uihscsa.edu NR 10 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD AUG PY 1998 VL 4 IS 4 BP 171 EP 172 DI 10.1097/00124743-199808000-00001 PG 2 WC Rheumatology SC Rheumatology GA 115ZT UT WOS:000075697000001 PM 19078284 ER PT J AU Alterman, AI McDermott, PA Cacciola, JS Rutherford, MJ Boardman, CR McKay, JR Cook, TG AF Alterman, AI McDermott, PA Cacciola, JS Rutherford, MJ Boardman, CR McKay, JR Cook, TG TI A typology of antisociality in methadone patients SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID ADDICTION SEVERITY INDEX; III PERSONALITY-DISORDERS; CLUSTER-ANALYSIS; SUBSTANCE-ABUSERS; RELIABILITY; VALIDITY; SCALE; SOCIOPATHY; ALCOHOLICS; ALGORITHMS AB Multistage cluster analyses with replications were used to sort score profiles of 252 methadone maintained men on 4 continuous measures of antisociality-childhood conduct disorder and adult antisocial personality disorder symptoms, the revised Psychopathy Checklist, and the Socialization scale of the California Psychological Inventory. The analysis yielded 6 replicable and temporally stable cluster groups varying in degree and pattern of antisociality. The groups were statistically compared on sets of external criterion variables-Addiction Severity Index measures of past and recent substance abuse and functioning and lifetime criminal history, Axis I and II symptomatology, anxiety and depression, object relations and reality testing, hostility, guilt, and machiavellianism. The expression of antisociality in the 6 groups and differences found among them on the external variables supported the validity of a more complex conceptualization of antisociality than is provided by antisocial personality disorder. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Childrens Hosp, Philadelphia, PA 19104 USA. RP Alterman, AI (reprint author), Dept Psychiat, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM alterman@research.trc.upenn.edu FU NIDA NIH HHS [DA-05858, DA05186] NR 63 TC 32 Z9 32 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD AUG PY 1998 VL 107 IS 3 BP 412 EP 422 DI 10.1037/0021-843X.107.3.412 PG 11 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 109BB UT WOS:000075300400005 PM 9715576 ER PT J AU Bal, BS Vandelune, D Gurba, DM Jasty, M Harris, WH AF Bal, BS Vandelune, D Gurba, DM Jasty, M Harris, WH TI Polyethylene wear in cases using femoral stems of similar geometry, but different metals, porous layer, and modularity SO JOURNAL OF ARTHROPLASTY LA English DT Article DE acetabular component; osteolysis; taper; monoblock; modular head ID HIP; COMPONENTS; CORROSION AB Ln this report, 83 total hip arthroplasties in 75 patients with femoral stems of similar geometry but different metals, porous surfaces, and femoral head-neck; design were compared at a mean follow-up of 66 months (range, 40-104 months). One type of acetabular component and polyethylene were implanted in all hips. The femoral stem was monoblock in 25 hips, and in 58 it had a modular head-neck piece; 70 stems had chrome-cobalt heads, and 13 heads were titanium. Equally satisfactory clinical results were obtained with either type of femoral implant (i.e., modular and monoblock). The calculated average annual linear polyethylene wear was significantly higher for the titanium stems with a plasma-spray porous surface and chrome-cobalt head on a Morse taper than the chrome-cobalt, beaded,monoblock stems (0.22 mm/year vs 0.07 mm/year, P < .0001). The prevalence of periprosthetic osteolysis was higher for these modular sterns (15.7% vs 0%), but this difference was not statistically significant (P = .09). Gross corrosion was present on the taper surfaces of an autopsy-retrieved femoral implant with a modular cobalt-chrome head on a titanium stem. Particles of chromium 3-orthophosphate were present at the taper rim and in the periarticular tissues. C1 Massachusetts Gen Hosp, Hip & Implant Unit, Dept Orthopaed Surg, Orthopaed Biomech Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Hip & Implant Unit, Dept Orthopaed Surg, Orthopaed Biomech Lab, Boston, MA 02114 USA. OI Bal, B. Sonny/0000-0002-9615-8632 NR 27 TC 5 Z9 5 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 J9 J ARTHROPLASTY JI J. Arthroplast. PD AUG PY 1998 VL 13 IS 5 BP 492 EP 499 DI 10.1016/S0883-5403(98)90046-8 PG 8 WC Orthopedics SC Orthopedics GA 111BQ UT WOS:000075417800002 PM 9726312 ER PT J AU Eroglu, A Toner, M Leykin, L Toth, TL AF Eroglu, A Toner, M Leykin, L Toth, TL TI Cytoskeleton and polyploidy after maturation and fertilization of cryopreserved germinal vesicle stage mouse oocytes SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE cryopreservation; cytoskeleton; digyny; fertilization; oocyte; pronuclear formation ID MEIOTIC SPINDLE; DEVELOPMENTAL CAPACITY; INVITRO; CONFIGURATIONS; CHROMOSOMES; VITRO AB Purpose: Our purpose was to assess the effect of cryopreservation on cytoskeleton of germinal vesicle (GV) mouse oocytes and determine whether irreversible spindle damage and related digyny associated with cryopreservation of metaphase II (MII) oocytes can be avoided. Methods: The GV oocytes were cryopreserved using a slow-cooling (0.5 degrees C/min) and slow-thawing (8 degrees C/min) protocol in 1.5 M dimethylsulfoxide supplemented with 0.2 M sucrose and analyzed before and during fertilization by multiple-label fluorescence and differential interference contrast microscopy techniques, Results: When examined after in vitro maturation, the vast majority (>95%) of cryopreserved and control oocytes displayed nor mal microfilament and microtubule organization. With respect to barrel-shaped spindle and nor mal chromosome alignment, no significant differences were observed between cryopreservation (78 and 86%, respectively) and control (85 and 95%, respectively) groups. In fertilization experiments, spindle rotation, formation of the second polar body, and pronuclear migration were displayed by similar percentages of cryopreserved (96, 94, and 37%, respectively) and control (98, 97 and 45%, respectively) oocytes, indicating normal functionality of the cytoskeleton during this period. However; pronuclear formation was significantly, inhibited by cryopreservation (81%) compared with controls (100%). Regarding digyny and polyspermy, no significant increase was observed after cryopreservation (3 and 10%, respectively) compared with controls (3 and 6%, respectively). Conclusions: Cryopreservation of mouse oocytes at the GV stage is particularly advantageous to circumvent the spindle damage and increased digyny noted after cryopreservation of MII oocytes. C1 Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Toth, TL (reprint author), Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Vincent 2, Boston, MA 02114 USA. NR 24 TC 33 Z9 37 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD AUG PY 1998 VL 15 IS 7 BP 447 EP 454 DI 10.1007/BF02744940 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA 110QY UT WOS:000075392900009 PM 9717122 ER PT J AU Canver, CC Cooler, SD Nichols, RD AF Canver, CC Cooler, SD Nichols, RD TI The influence of cardiopulmonary function on outcome of veterans undergoing resectional therapy for lung cancer SO JOURNAL OF CARDIOVASCULAR SURGERY LA English DT Article DE lung neoplasms; veterans; treatment outcome; lung surgery ID MORTALITY; COMPLICATIONS; MORBIDITY; SURGERY AB Background. The unknown but presumably poor preoperative cardiopulmonary function of U.S, Armed Forces veterans with bronchogenic cancer may dissuade surgeons performing necessary major lung resection, The purpose of this study was to investigate the relationship between preoperative cardiopulmonary risk and the outcome of veterans undergoing pulmonary resection for bronchogenic carcinoma. Methods. A retrospective chart review a-as performed on 79 veterans who underwent lung resection for bronchogenic cancer between March 1990 and June 1995 Preoperative cardiac function was assessed by 1) history of heart disease (myocardial infarction, previous open heart surgery, and hypertension), 2) electrocardiogram, EKG, and 3) transthoracic echocardiography, TTE (ejection fraction and left ventricular wall motion abnormalities). Pulmonary reserve was evaluated by 1) history of lung disease (active smoking, known chronic obstructive pulmonary disease, COPD), and 2) spirometry (forced expiratory volume in 1 second, FEV1, and minute ventilation volume, MVV). Resections were performed by standard pulmonary techniques and follow-up data was available in all patients. Results. All patients were males except one, with a mean age of 66 +/- 1.0 yrs (range=32 to 81 yrs). Fifty-one patients (64.6%) had a history of COPD while one-third of the veterans were smoking and using excessive alcohol just prior to surgery. Twenty-four patients (29%) had abnormal preoperative EKG and only 10 (15%) had prior myocardial infarction, Eleven patients (13.9%) had undergone previous coronary bypass surgery. Average preoperative left ventricular ejection fraction was 63 +/- 2% (range=41 to 80%) and left ventricular wall motion abnormalities were present in only 6 patients (8%), Mean preoperative FEV, was 2.2 +/- 0.1 L (range=0.6-4.1 L) and MVV was 87 +/- 4 L/min (range = 26-198 L/min). A lobectomy was performed in 68 patients (86.1%), pneumonectomy in 10 (12.7%), and wedge resection in 1 (1.2%). The most common types of cancer were squamous cell. (36 patients) and adenocarcinoma (31 patients). While pulmonary complications (atelectasis, prolonged air leak, pneumonia) occurred in 8 patients (10%), only two (3%) suffered nonpulmonary complications (ischemic bowel disease). For all veterans with bronchogenic canter, early (30-day) mortality after major lung resection was 3.9% (3/79): 1.5% (1/68) after lobectomy, and 20% (2/10) after pneumonectomy (p=not significant). Overall survival at 5 years was 39.5%. Conclusions. Preoperative cardiopulmonary risk for veterans with bronchogenic cancer is acceptable and lung resection can be performed with good outcomes in this distinct patient population. C1 Univ Wisconsin, Sch Med, William S Middleton Mem Vet Hosp, Sect Cardiothorac Surg, Madison, WI USA. RP Canver, CC (reprint author), Univ Wisconsin, Sch Med, Div Cardiothorac Surg, Ctr Clin Sci, H4-352,600 Highland Ave, Madison, WI 53792 USA. NR 12 TC 9 Z9 10 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0021-9509 J9 J CARDIOVASC SURG JI J. Cardiovasc. Surg. PD AUG PY 1998 VL 39 IS 4 BP 497 EP 501 PG 5 WC Cardiac & Cardiovascular Systems; Surgery; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Surgery GA 125UF UT WOS:000076254900021 PM 9788800 ER PT J AU Chang, SW Benson, A Azar, DT AF Chang, SW Benson, A Azar, DT TI Corneal light scattering with stromal reformation after laser in situ keratomileusis and photorefractive keratectomy SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID EXCIMER-LASER; MYOPIA; IMMUNOFLUORESCENCE; ABLATION; SURGERY; EYE AB Objective: To correlate corneal light scattering with keratocyte and extracellular matrix reformation after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). Setting: Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland, USA. Methods: Sixteen pigmented rabbit eyes were randomly divided into 2 groups. Group 1 (n=8) hand a 5.0 mm, -10.0 diopter (D) LASIK treatment and Group 2 (n=8), a 5.0 mm, -10.0 D surface PRK treatment after mechanical epithelial debridement. The stromal surface exposed at surgery was stained with dichlorotriazinylaminofluorescein (DTAF) solution. Slitlamp biomicroscopic and objective measurement of corneal light scattering using a scatterometer were performed 1 and 2 days and 1, 2, 3, 4, 8, and 12 weeks after surgery. In each group, 2 corneas were harvested at 1 week and 1 month and 4 corneas were harvested at 12 weeks. Tissue sections were examined by light and fluorescence microscopy. The percentage of newly formed stromal tissue was calculated and correlated with the scatterometry index. Results: In Group 1, corneas remained clear and healed without significant scarring throughout the study. In Group 2, subepithelial scarring was noted. Extracellular matrix reformation peaked at 1 month and showed a slight regression thereafter. The percentage of extracellular matrix reformation was strongly correlated with the scatterometry index (r = .86, P < .001). Conclusions: In this study, significant subepithelial stromal tissue reformation followed PRK. The percentage of extracellular matrix reformation correlated well with the objective corneal light scattering measurements. C1 Johns Hopkins Univ Hosp, Wilmer Ophthalmol Inst, Baltimore, MD 21205 USA. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Corneal Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 28 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC CATARACT REFRACTIVE SURGERY PI FAIRFAX PA 4000 LEGATO RD, SUITE 850, FAIRFAX, VA 22030 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD AUG PY 1998 VL 24 IS 8 BP 1064 EP 1069 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 111AU UT WOS:000075415800012 PM 9719965 ER PT J AU Ware, MF Wells, A Lauffenburger, DA AF Ware, MF Wells, A Lauffenburger, DA TI Epidermal growth factor alters fibroblast migration speed and directional persistence reciprocally and in a matrix-dependent manner SO JOURNAL OF CELL SCIENCE LA English DT Article DE motility; growth factor; extracellular matrix ID SMOOTH-MUSCLE CELLS; MAMMARY ADENOCARCINOMA CELLS; ACTIVATED PROTEIN-KINASE; CORNEAL EPITHELIAL-CELLS; PROSTATE CARCINOMA-CELLS; FACTOR RECEPTOR; EGF-RECEPTOR; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; IN-VITRO AB Growth factors stimulate sustained cell migration as well as inducing select acute motility-related events such as membrane ruffling and disruption of focal adhesions. However, an in-depth understanding of the characteristics of sustained migration that are regulated by growth factor signals is lacking: how the biochemical signals are related to physical processes underlying locomotion, and how these events are coordinately influenced by interplay between growth factor and matrix substratum signals. To address these issues, we studied sustained migration of NR6 fibroblasts on a complex human matrix substratum, Amgel, comparing effects of epidermal growth factor (EGF) treatment across a range of Amgel levels. In the absence of EGF, cell migration speed and directional persistence are relatively independent of Amgel level, whereas in the presence of EGF speed is increased at intermediate Amgel levels but not at low and high Amgel levels while directional persistence is decreased at intermediate but not at low and high Amgel levels. The net effect of EGF is to increase the frequency of changes in the cell direction, and at the same time to slightly increase the path-length and thereby greatly enhance random dispersion of cells. Despite increasing migration speed during long-term sustained migration EGF treatment does not lead to significantly increased absolute rates of membrane extension in contrast to its well-known elicitation of membrane ruffling in the short term. However, EGF treatment does decrease cell spread area, yielding an apparent enhancement of specific membrane extension rate, i,e, normalized to cell spread area. Cell movement speed and directional persistence are thus, respectively, directly related and indirectly related to the increase in specific membrane extension rate (alternatively, the decrease in cell spread area) induced by EGF treatment during sustained migration,These results indicate that growth factor rind matrix substrata coordinately regulate sustained cell migration through combined governance of underlying physical processes. C1 MIT, Ctr Biomed Engn, Cambridge, MA 02139 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35294 USA. RP Lauffenburger, DA (reprint author), MIT, Ctr Biomed Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM lauffen@mit.edu OI Wells, Alan/0000-0002-1637-8150 FU NCI NIH HHS [CA69213] NR 53 TC 106 Z9 108 U1 0 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG PY 1998 VL 111 BP 2423 EP 2432 PN 16 PG 10 WC Cell Biology SC Cell Biology GA 117AW UT WOS:000075758400013 PM 9683636 ER PT J AU Guo, ZM Heydari, AR Wu, WT Yang, H Sabia, MR Richardson, A AF Guo, ZM Heydari, AR Wu, WT Yang, H Sabia, MR Richardson, A TI Characterization of gene-specific DNA repair by primary cultures of rat hepatocytes SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID CYCLOBUTANE PYRIMIDINE DIMERS; TRANSCRIPTION-COUPLED REPAIR; HAMSTER OVARY CELLS; GEL-ELECTROPHORESIS; MONOLAYER-CULTURE; ACTIVE GENE; STRAND; EXPRESSION; INDUCTION; MUTATIONS AB At present, almost all the information on gene-specific DNA repair in mammals comes from studies with transformed cell lines and proliferating primary cells obtained from rodents and humans. In the present study, we measured the repair of specific DNA regions in primary cultures of nondividing rat hepatocytes (parenchymal cells). DNA damage was induced by irradiating the primary cultures of hepatocytes with ultraviolet (UV) light, and the presence of cyclobutane pyrimidine dimers (CPDs) was measured by using T4 endonuclease V in the following: a 21-kb BamHI fragment containing the albumin gene, a 14-kb BamHI fragment containing the H-ras gene, and the genome overall. The frequency of CPDs in the two BamHI fragments and the genome overall were similar and ranged from 0.5 to 1.3 CPDs per 10 kb for UV doses of 5-30 J/m(2). However, the removal of CPDs from the DNA fragment containing the albumin gene was significantly higher than from that of the genome overall and the DNA fragment containing the H-ras gene. Within 24 hr, approximately 67% of the CPDs was removed from the DNA fragment containing the albumin gene versus less than 40% for the genome overall and the DNA fragment containing the H-ras gene. The lower repair observed for the 14-kb fragment containing the H-ras gene is probably indicative of repair of the nontranscribed region of this fragment because the H-ras gene makes up only 2.4 kb of the 14-kb fragment. Primary cultures of hepatocytes removed CPDs from the transcribed strand of albumin fragment more efficiently than from the nontranscribed strand; however, no differences were observed in the repair of the two strands of the fragment containing the H-ras gene. These results demonstrate that primary cultures of nondividing rat hepatocytes show differential repair of UV-induced DNA damage that is comparable to what has been reported for transformed, proliferating mammalian cell lines. (C) 1998 Wiley-Liss, Inc. C1 S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. RP Richardson, A (reprint author), Audie L Murphy Mem Vet Hosp, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG15134, AG01548] NR 40 TC 7 Z9 7 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 1998 VL 176 IS 2 BP 314 EP 322 DI 10.1002/(SICI)1097-4652(199808)176:2<314::AID-JCP9>3.0.CO;2-R PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ZV411 UT WOS:000074301900009 PM 9648918 ER PT J AU Abboud, SL Woodruff, KA Choudhury, GG AF Abboud, SL Woodruff, KA Choudhury, GG TI Retroviral-mediated gene transfer of CSF-1 into op/op stromal cells to correct defective in vitro osteoclastogenesis SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; OP OP MOUSE; BONE-MARROW; FACTOR-I; HUMAN GLUCOCEREBROSIDASE; OSTEOBLASTIC CELLS; GROWTH-FACTORS; CODING REGION; EXPRESSION; MICE AB Colony-stimulating factor-1 (CSF-1) released by stromal cells in the bone microenvironment is essential for the proliferation of osteoclast progenitors. in op/op mutant mice, a thymidine insertion in the coding sequence of the CSF-1 gene results in CSF-1 deficiency that in turn leads to decreased osteoclast production and osteopetrosis. Because the osteopetrotic defect is due to the failure of stromal cells to produce CSF-1, we determined if retroviral-mediated gene transfer of the wild-type CSF-1 cDNA into op/op stromal cells would restore their ability to support osteoclast formation in vitro. A retroviral vector, L-CSF-1-SN, was constructed by inserting 1,867 bp of the wild-type CSF-1 cDNA into pLXSN. After transduction with L-CSF-1-SN or LXSN constructs, a stable PA317 packaging cell line that produced a high viral titre was isolated. Viral supernatant from this line was used to infect op/op bone marrow stromal cells. Stable L-CSF-1-SN op/op stromal clones overexpressed CSF-1 mRNA and released CSF-1 into conditioned medium, compared with no CSF-1 released by LXSN op/op stroma. The amount of CSF-1 produced by two clones was similar to the physiologic level released by normal littermate stroma. Southern blot analysis confirmed the presence of intact proviral sequences in transduced cells. In coculture assays, L-CSF-1-SN, but not LXSN, op/op stromal cells supported the formation of TRAP-positive multinucleated cells in the absence of exogenous CSF-1. These findings indicate that genetically engineered stromal cells may be used to improve defective osteoclastogenesis and suggest that targeting stromal cells to bone is a potentially useful therapeutic modality for treating bone disorders. (C) 1998 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Vet Affairs Med Ctr, San Antonio, TX USA. RP Abboud, SL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAMS NIH HHS [R01 AR042306, AR42306]; NIDDK NIH HHS [DK50190] NR 45 TC 10 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 1998 VL 176 IS 2 BP 323 EP 331 DI 10.1002/(SICI)1097-4652(199808)176:2<323::AID-JCP10>3.3.CO;2-T PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA ZV411 UT WOS:000074301900010 PM 9648919 ER PT J AU Kalechstein, AD Hinkin, CH van Gorp, WG Castellon, SA Satz, P AF Kalechstein, AD Hinkin, CH van Gorp, WG Castellon, SA Satz, P TI Depression predicts procedural but not episodic memory in HIV-1 infection SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; FRONTAL-LOBE; SYMPTOMS; HYPOMETABOLISM; PERFORMANCE; INDIVIDUALS; SKILL; MOTOR AB Forty-three homosexual/bisexual males with HIV-1 infection participated in a study that sought to determine: (1) whether increased levels of self-reported depressive symptomatology were associated with poorer performance on episodic or procedural memory tasks, (2) the relative strength of association between the affective/cognitive or somatic symptoms of depression and memory deficits and level of immunosuppression, and (3) whether increased depression or neuropsychological deficits are associated with degree of immunosuppression. Linear regression analyses revealed that increased affective/cognitive symptomatology was correlated with poorer performance on a procedural memory task, but was not correlated with performance on an episodic memory task or degree of immunosuppression. In contrast, somatic symptoms showed the strongest association with level of immunosuppression, but were not correlated with performance on the memory tasks. These findings underscore the complex interplay between neuropsychiatric and neuropsychological symptomatology in HIV-1 infection. C1 Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Cornell Univ, Med Ctr, White Plains, NY 10605 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Kalechstein, AD (reprint author), Univ Calif Los Angeles, Drug Abuse Res Ctr, 1100 Glendon Ave,Suite 763, Los Angeles, CA 90024 USA. FU CSR NIH HHS [RG000974]; NIDA NIH HHS [2T32 DA07272]; NIMH NIH HHS [R03 MH54465] NR 22 TC 14 Z9 14 U1 0 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD AUG PY 1998 VL 20 IS 4 BP 529 EP 535 DI 10.1076/jcen.20.4.529.1473 PG 7 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 153JY UT WOS:000077831000010 PM 9892056 ER PT J AU Melmed, S Jackson, I Kleinberg, D Klibanski, A AF Melmed, S Jackson, I Kleinberg, D Klibanski, A TI Current treatment guidelines for acromegaly SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ANALOG SMS 201-995; GROWTH-FACTOR-I; CONTINUOUS SUBCUTANEOUS INFUSION; TERM OCTREOTIDE THERAPY; SLOW-RELEASE LANREOTIDE; SOMATOSTATIN ANALOG; HORMONE-SECRETION; BROMOCRIPTINE TREATMENT; PITUITARY-ADENOMAS; SANDOSTATIN-LAR AB Acromegaly, an indolent disorder of growth hormone (GH) hypersecretion is most typically caused by a somatotroph cell adenoma and may be treated by several modalities. Transsphenoidal surgical resection of micro-adenomas by experienced neurosurgeons results in biochemical normalization (postglucose GH <2 ng/mL, assay-dependent, age- and sex-matched IGF-I levels) in 70% of patients. However, over 65% of GH-secreting adenomas are invasive or macroadenomas, and over 50% of these patients have persistent postoperative GH hypersecretion. Irradiation of adenomas results in attenuation of GH secretion to more than 5 ng/mL in 50% of subjects after 12 yr. However, the percent of parents who normalize IGF-I levels is less certain. Most of these patients develop associated pituitary failure and rarely develop other local adverse effects. About 60% of patients receiving somatostatin analogs achieve normalized IGF-I levels. Efficacy of medical management with somatostatin analogs may be improved by increasing injection frequency, changing delivery modes to depot preparations, and in the future, development of novel SRIF receptor subtype-specific analogs. An integrated approach to acromegaly management based upon relative risks and benefits of the currently available therapeutic modes is presented that allows for a national individualized strategy designed to achieve maximal biochemical control. of GH hypersecretion and elevated IGF-I levels. C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Cedars Sinai Res Inst, Los Angeles, CA 90048 USA. Brown Univ, Rhode Isl Hosp, Sch Med, Providence, RI 02903 USA. NYU Med Ctr, New York, NY 10016 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. RP Melmed, S (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Cedars Sinai Res Inst, 8700 Beverly Blvd,Room B-131, Los Angeles, CA 90048 USA. NR 82 TC 159 Z9 165 U1 0 U2 1 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 AUG PY 1998 VL 83 IS 8 BP 2646 EP 2652 DI 10.1210/jc.83.8.2646 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 108KL UT WOS:000075265300007 PM 9709926 ER PT J AU Miller, K Corcoran, C Armstrong, C Caramelli, K Anderson, E Cotton, D Basgoz, N Hirschhorn, L Tuomala, R Schoenfeld, D Daugherty, C Mazer, N Grinspoon, S AF Miller, K Corcoran, C Armstrong, C Caramelli, K Anderson, E Cotton, D Basgoz, N Hirschhorn, L Tuomala, R Schoenfeld, D Daugherty, C Mazer, N Grinspoon, S TI Transdermal testosterone administration in women with acquired immunodeficiency syndrome wasting: A pilot study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CLINICAL-RESEARCH CENTER; QUALITY-OF-LIFE; LEAN BODY-MASS; MEGESTROL-ACETATE; PROTEIN-SYNTHESIS; MEDICAL OUTCOMES; MUSCLE STRENGTH; HYPOGONADAL MEN; WEIGHT; AIDS AB Although human immunodeficiency virus (HIV) disease is increasing rapidly among women, no prior studies have investigated gender-based therapeutic strategies for the treatment of acquired immunodeficiency syndrome (AIDS) and its complications in this population. Markedly decreased serum androgen levels have been demonstrated in women with AIDS and may be a contributing factor to the wasting syndrome in this population. To assess the effects of androgen replacement therapy in women with AIDS wasting, we conducted a randomized, placebo-controlled, pilot study of transdermal testosterone administration. The primary aim of the study was to determine efficacy in terms of the change in serum testosterone levels, safety parameters and tolerability. A secondary aim of the study was to investigate testosterone effects on weight, body composition, quality of life, and functional indexes. Fifty-three ambulatory women with the AIDS wasting syndrome defined as weight less than 90% of ideal body weight or weight loss of more than 10% of the preillness maximum, free of new opportunistic infection within 6 weeks of study initiation, and with screening serum levels of free testosterone less than the mean of the normal reference range (<3 pg/mL) were enrolled in the study. Subjects were age 37 +/- 1 yr old (mean +/- SEM), weighed 92 +/- 2% of ideal body weight, and had lost 17 +/- 1% of their maximum weight. CD4 count was 324 +/- 36 cells/mm(3), and viral burden was 102,382 +/- 28,580 copies. Subjects were randomized into three treatment groups, in which two placebo patches (PP), one active/one placebo patch (AP group), or two active patches (AA group) were applied twice weekly to the abdomen for 12 weeks. The expected nominal delivery rates of testosterone were 150 and 300 mu g/day, respectively, for the AP and AA groups. Forty-five subjects completed the study (PP group, n = 13; AP group, n = 14; AA group, n = 18). Two additional subjects from the PP group and two from the AP group were included in the intent to treat analysis. Serum free testosterone levels increased significantly from 1.2 +/- 0.2 to 5.9 +/- 0.8 pg/mL (AP) and from 1.9 +/- 0.4 to 12.4 +/- 1.6 pg/mL (AA.) in response to testosterone administration (P < 0.0001 for comparison of AA vs. PP and AP vs. PP; normal range, 1.3-6.8 pg/mL). Testosterone administration was generally well tolerated locally and systemically, with no adverse trends in hirsutism scores, lipid profiles, or liver function tests. Weight increased significantly in the AP group (1.9 +/- 0.7 kg) us. the PP group (0.6 +/- 0.8 kg; P = 0.043), but did not increase significantly in the AA group (0.9 +/- 0.4 kg; P = 0.263 us. PP, by mixed effects model assessing the interaction of time and treatment on all available data, one-tailed test). Improved social functioning (P = 0.024, by one-tailed test) and a trend toward improved pain score (P = 0.059) were observed in the AP us, the PP-treated patients (RAND 36-Item Health Survey questionnaire). Five of six previously amenorrheic patients in the AP group had spontaneous resumption of menses compared to only one of four amenorrheic patients in the AA group (P = 0.045 for comparison of actual number of periods during the study). This study is the first investigation of testosterone administration in women with AIDS wasting. We demonstrate a novel method to augment testosterone levels in such patients that is safe and well tolerated during short term administration. At the lower of the two doses administered in this study, testosterone therapy was associated with positive trends in weight gain and quality of life. Higher, more supraphysiological, dosing was not associated with positive trends in weight or overall well-being. These data suggest that testosterone administration may improve the status of women with AIDS wasting. Further studies are needed to assess the effects of testosterone on weight in HIV-infected women and to define the optimal therapeutic window for testosterone administration in this population. C1 Massachusetts Gen Hosp, Neuroendocrine Dept, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Dimock Community Hlth Ctr, Boston, MA 02119 USA. TheraTech Inc, Salt Lake City, UT 84108 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Dept, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1-RR-01066]; NIDDK NIH HHS [P32-DK-07028] NR 37 TC 106 Z9 107 U1 2 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1998 VL 83 IS 8 BP 2717 EP 2725 DI 10.1210/jc.83.8.2717 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 108KL UT WOS:000075265300018 PM 9709937 ER PT J AU Goodman, WG Veldhuis, JD Belin, TR Van Herle, AJ Juppner, H Salusky, IB AF Goodman, WG Veldhuis, JD Belin, TR Van Herle, AJ Juppner, H Salusky, IB TI Calcium-sensing by parathyroid glands in secondary hyperparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CHRONIC-RENAL-FAILURE; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; HORMONE RELEASE; SET-POINT; IN-VIVO; BENIGN HYPERCALCEMIA; PTH RELEASE; INTACT; HYPERPLASIA; CALCITRIOL AB Calcium-sensing by the parathyroids is abnormal in familial benign hypocalciuric hypercalcemia and in primary hyperparathyroidism (1 degrees HPT), but the role of a calcium-sensing defect in uremic secondary hyperparathyroidism (2 degrees HPT) remains controversial. To study the regulation of PTH release by calcium, set point estimates were obtained using the four parameter model during in, vivo dynamic tests of parathyroid gland function in 31 patients with 2 degrees HPT, 8 patients with advanced 2 degrees HPT studied shortly before undergoing parathyroidectomy (Pre-PTX), 3 patients with 1 degrees HPT, and 20 subjects with normal renal function (NL); the response to 2-h iv calcium infusions was also evaluated. Neither blood ionized calcium (iCa(+2)) levels nor the set point for calcium-regulated PTH release differed between 2 degrees HPT and NL; iCa(+2) levels and set point values were moderately elevated in Pre-PTX and markedly elevated in 1 degrees HPT. Compared with values obtained in NL, the lowest serum PTH levels achieved during calcium infusions, expressed as a percentage of preinfusion values, were incrementally greater in 2 degrees HPT, Pre-PTX, and 1 degrees HPT, whereas the slope of the relationship between iCa+2 and PTH, expressed as the natural logarithm (In) of percent preinfusion values, decreased incrementally in 2 degrees HPT, Pre-PTX, and 1 degrees HPT. The inhibitory effect of calcium on PTH release is blunted both in 2 degrees HPT and 1 degrees HPT because of increases in parathyroid gland mass, but a calcium-sensing defect is a late, rather than early, consequence of renal 2 degrees HPT. C1 Univ Calif Los Angeles, Med Ctr, Sch Med, Dept Med,Div Nephrol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. Univ Virginia, Hlth Sci Ctr, Dept Internal Med, Div Endocrinol, Charlottesville, VA 22908 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Goodman, WG (reprint author), Univ Calif Los Angeles, Med Ctr, Sch Med, Dept Med,Div Nephrol, 7-155 Factor Bldg,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM wgoodman@ucla.edu FU NCRR NIH HHS [RR-00865]; NIDDK NIH HHS [DK-35423] NR 38 TC 40 Z9 41 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 AUG PY 1998 VL 83 IS 8 BP 2765 EP 2772 DI 10.1210/jc.83.8.2765 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 108KL UT WOS:000075265300025 PM 9709944 ER PT J AU Meneilly, GS Ryan, AS Minaker, KL Elahi, D AF Meneilly, GS Ryan, AS Minaker, KL Elahi, D TI The effect of age and glycemic level on the response of the beta-cell to glucose-dependent insulinotropic polypeptide and peripheral tissue sensitivity to endogenously released insulin SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GASTRIC-INHIBITORY POLYPEPTIDE; DIABETES-MELLITUS; SECRETION; RESISTANCE; GIP; INTOLERANCE; METABOLISM; DIAGNOSIS; TOLERANCE AB Normal aging is characterized by a progressive impairment in glucose tolerance. An important mechanism underlying the glucose intolerance of aging is an impairment in glucose-induced insulin release. These studies were conducted to determine whether the age-related impairment in insulin release was caused by a decreased beta-cell sensitivity to glucose-dependent insulinotropic polypeptide (GIP). Thirty-one Caucasian men were divided into four groups: two young groups (age range: 19-26 yr, n = 15) and two old groups (age range: 67-79 yr, n = 16). Each volunteer participated in three studies (n = 93 clamps). Hyperglycemic clamps were conducted at two doses [basal plasma glucose (G) + 5.4 mmol/L and G + 12.8 mmol/L] for 120 min. In the initial hyperglycemic clamp, only glucose was infused. In subsequent studies, GIP was infused at a final rate of 2 or 4 pmol/ kg(-1).min(-1) from 60-120 min. Basal plasma insulin and GIP levels were similar in the young (41 +/- 6 and 51 +/- 6 pmol/L) and the old subjects (42 +/- 6 and 66 +/- 12 pmol/L) in all studies. First- and second-phase insulin responses were similar during the control study and during the first 60 min of each GIP infusion study in both groups. The 90-120 min GIP values were similar between groups and between hyperglycemic plateaus during the 2 and 4 pmol/kg(-1).min(-1) GIP infusion (young: 342 +/- 28 and 601 +/- 44 pmol/L, old: 387 +/- 45 and 568 +/- 49 pmol/L). In response to the GIP infusions, significant increases in insulin occurred in young and old at both glucose levels (P < 0.01). The potentiation of the insulin response caused by GIP was greater in the young subjects than in the old, in the G + 5.4 mmol/L studies (P < 0.05). However, the insulin response to GIP was similar in both young and old during the G + 12.8 mmol/L clamps. The insulinotropic effect of the incretin was higher in the young and in the old, in the G + 12.8 mmol clamps, than in the G + 5.4 mmol/L clamps. We conclude that normal aging is characterized by a decreased beta-cell sensitivity to GIP during modest hyperglycemia, which may explain, in part, the age-related impairment in glucose-induced insulin release. We also find that the insulinotropic effect of GIP is increased with increasing levels of hyperglycemia. C1 Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Geriatr Res Lab,Geriatr Med Unit, Boston, MA 02114 USA. Harvard Univ, Beth Israel Hosp, Sch Med, Dept Med,Div Gerontol, Boston, MA 02215 USA. Univ British Columbia, Dept Med, Div Geriatr Med, Vancouver, BC V6T 1Z3, Canada. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Baltimore Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD 21201 USA. RP Elahi, D (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Geriatr Res Lab,Geriatr Med Unit, GRJ 1215,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-01032]; NIA NIH HHS [AG-00599, PGO-AG-12583] NR 35 TC 25 Z9 25 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 AUG PY 1998 VL 83 IS 8 BP 2925 EP 2932 DI 10.1210/jc.83.8.2925 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 108KL UT WOS:000075265300052 PM 9709971 ER PT J AU Stratakis, CA Kirschner, LS Taymans, SE Tomlinson, IPM Marsh, DJ Torpy, DJ Giatzakis, C Eccles, DM Theaker, J Houlston, RS Blouin, JL Antonarakis, SE Basson, CT Eng, C Carney, JA AF Stratakis, CA Kirschner, LS Taymans, SE Tomlinson, IPM Marsh, DJ Torpy, DJ Giatzakis, C Eccles, DM Theaker, J Houlston, RS Blouin, JL Antonarakis, SE Basson, CT Eng, C Carney, JA TI Carney complex, Peutz-Jeghers syndrome, Cowden disease, and Bannayan-Zonana syndrome share cutaneous and endocrine manifestations, but not genetic loci SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SPOTTY SKIN PIGMENTATION; DOMINANT INHERITANCE; GERMLINE MUTATIONS; LINKAGE ANALYSIS; CARDIAC MYXOMAS; CELL TUMORS; FOLLOW-UP; CANCER; OVERACTIVITY; NEOPLASIA AB Carney complex (CC), Peutz-Jeghers syndrome (PJS), Cowden disease (CD), and Bannayan-Zonana syndrome (BZS) share clinical features, such as mucocutaneous lentigines and multiple tumors (thyroid, breast, ovarian, and testicular neoplasms), and autosomal dominant inheritance. A genetic locus has been identified for CC on chromosome 2 (2p16), and the genes for PJS, CD, and BZS were recently identified; genetic heterogeneity appears likely in both CC and PJS. The genes for PJS and CD/BZS, STK11/LKB1 and PTEN, respectively, may act as tumor suppressors, because loss of heterozygosity (LOH) of the PJS and CD/BZS loci has been demonstrated in tumors excised from patients with these disorders. We studied 2 families with CC in whom the disease could not be shown to segregate with polymorphic markers from the 2p16 locus. Their members presented with lesions frequently seen in PJS and the other lentiginosis syndromes. We also tested 16 tumors and cell lines established from patients with CC for LOH involving the PJS and CD/BZS loci. DNA was extracted from peripheral blood, tumor cell lines, and tissues and subjected to PCR amplification with primers from microsatellite sequences flanking the STK11/LKB1 and PTEN genes on 19p13 and 10q23, respectively, and a putative PJS locus on 19q13. All loci were excluded as candidates in both families with LOD scores less than -2 and/or by haplotype analysis. LOR for these loci was not present in any of the tumors that were histologically identical to those seen in PJS. The overall rate of LOH for the PJS and CD/BZS loci in tumors from patients with CC was less than 10%. We conclude that despite substantial clinical overlap among CC, PJS, CD, and BZS, LOH for the STK11 and PTEN loci is an infrequent event in CC-related tumors. Linkage analysis excluded the PJS and CD/BZS loci on chromosomes 19 (19p13 and 19913) and 10 (10q23) from harboring the gene defect(s) responsible for the phenotype in these 2 families. C1 NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol, Dev Endocrinol Branch,NIH, Bethesda, MD 20892 USA. Cornell Univ, Med Ctr, New York Hosp, Dept Med,Cardiol Div, New York, NY 10021 USA. Cornell Univ, Med Ctr, New York Hosp, Dept Cell Biol & Anat, New York, NY 10021 USA. Mayo Clin, Emeritus Staff, Rochester, MN 55905 USA. Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Richard & Susan Smith Labs, Boston, MA 02115 USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Clin Med, Tumor Genet Grp, Oxford OX3 7HN, England. Inst Canc Res, Sutton SM2 5NG, Surrey, England. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. Princess Anne Hosp, Wessex Clin Genet Serv, Southampton SO16 5YA, Hants, England. Univ Geneva, Sch Med, Dept Genet, Div Med Genet, CH-1211 Geneva, Switzerland. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol, Dev Endocrinol Branch,NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC1862, Bethesda, MD 20892 USA. EM stratakc@cc1.nichd.nih.gov RI Marsh, Deborah/I-1491-2014; Antonarakis, Stylianos/N-8866-2014; OI Marsh, Deborah/0000-0001-5899-4931; Antonarakis, Stylianos/0000-0001-8907-5823; Eng, Charis/0000-0002-3693-5145; Houlston, Richard/0000-0002-5268-0242 NR 38 TC 35 Z9 35 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1998 VL 83 IS 8 BP 2972 EP 2976 DI 10.1210/jc.83.8.2972 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 108KL UT WOS:000075265300060 PM 9709978 ER PT J AU Gollob, JA Schnipper, CP Orsini, E Murphy, E Daley, JF Lazo, SB Frank, DA Neuberg, D Ritz, J AF Gollob, JA Schnipper, CP Orsini, E Murphy, E Daley, JF Lazo, SB Frank, DA Neuberg, D Ritz, J TI Characterization of a novel subset of CD8(+) T cells that expands in patients receiving interleukin-12 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE lymphocytes; activation; cytokines; immunotherapy; cancer ID NATURAL-KILLER-CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; INTERFERON-GAMMA PRODUCTION; STIMULATORY FACTOR NKSF; LYMPHOCYTES-T; IL-12 RECEPTOR; CYTOKINE; PROLIFERATION; EXPRESSION; INDUCTION AB IL-12 has significant antitumor activity in mice that may be mediated by CD8(+) T cells. We show in this report that repeated subcutaneous injections of IL-12 in patients with cancer resulted in the selective expansion of a subset of peripheral blood CD8(+) T cells. This T cell subset expressed high levels of CD18 and upregulated IL-12 receptor expression after IL-12 treatment in vivo. In normal subjects, these CD3(+)CD8(+)CD18(bright) T cells expressed IL-12 and IL-2 receptors and adhesion/costimulatory molecules to a greater degree than other CD8(+) and CD4(+) T cells. They appeared morphologically as large granular lymphocytes, although they did not express NK cell markers such as CD56, In addition, CD8(+)CD18(bright) T cells were almost exclusively T cell receptor (TCR) alpha beta(+), and exhibited a TCR V beta repertoire that was strikingly oligoclonal, whereas the V beta repertoire of CD18(dim) T cells was polyclonal. Although CD8(+)CD18(bright) T cells demonstrated little functional responsiveness to IL-12 or IL-2 alone in vitro, they responded to the combination of IL-12+IL-2 with strong IFN-gamma production and proliferation and enhanced non-MHC-restricted cytolytic activity. In contrast, CD18(dim) T cells were not activated by IL-12 or IL-2, alone or in combination. These findings demonstrate that CD8+CD18(bright) T cells are a unique population of peripheral blood lymphocytes with features of both memory and effector cells that are capable of TCR-independent activation through combined stimulation with IL-12+IL-2. As this activation results in IFN-gamma production and enhanced cytolytic activity, these T cells may play a role in innate as well as acquired immunity to tumors and infectious pathogens. Additional studies will be necessary to determine whether CD8+CD18(bright) T cells mediate the antitumor effect of IL-12 or IL-2 administered to cancer patients, and if so, whether maximal activation of these T cells with the combination of IL-12 + IL-2 in vivo can augment the clinical effectiveness of these cytokines. C1 Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Biostat, Boston, MA 02115 USA. RP Gollob, JA (reprint author), Beth Israel Deaconess Med Ctr, Dept Hematol & Oncol, East Campus,Kirstein Hall 1,Room KS-158,330 Brook, Boston, MA 02215 USA. EM jgollob@bidmc.harvard.edu RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619] NR 44 TC 35 Z9 36 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 1 PY 1998 VL 102 IS 3 BP 561 EP 575 DI 10.1172/JCI3861 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 109ND UT WOS:000075327900012 PM 9691093 ER PT J AU Tai, YT Lee, S Niloff, E Weisman, C Strobel, T Cannistra, SA AF Tai, YT Lee, S Niloff, E Weisman, C Strobel, T Cannistra, SA TI BAX protein expression and clinical outcome in epithelial ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSITIVE BREAST-CANCER; TUMOR-SUPPRESSOR P53; INDUCED APOPTOSIS; IN-VIVO; COMBINATION CHEMOTHERAPY; BCL-2 PROTEIN; CELL-LINES; CARCINOMA; GENE; PACLITAXEL AB Purpose: Expression of the pro-apoptotic protein BAX sensitizes ovarian cancer cell lines to paclitaxel in vitro by enhancing the pathway of programmed cell death. The present study was performed to determine the relationship between BAX expression and clinical outcome in 45 patients with newly diagnosed ovarian cancer. Methods: BAX protein expression was analyzed by immunohistochemistry, and its relationship with clinical outcome was determined. Assessment of BAX mRNA transcript levels and mutational analysis of the BAX coding region were also performed. Results: BAX protein was expressed at high levels (defined as greater than or equal to 50% of tumor cells positive) in tumor tissue from 60% of newly diagnosed patients. All patients whose tumors expressed high levels of BAX achieved a complete response (CR) to first-line chemotherapy that contained paclitaxel plus a platinum analogue, compared with 57% of patients in the low-BAX group (P=.036). After a median fallow-up of 1.9 years, the median disease-free survival (DFS) of patients in the high-BAX group has not been reached, compared with a median DFS of 1.1 years for low-BAX expressors (P=.0061). BAX retained independent prognostic significance in multivariate analysis when corrected for stage and histology. BAX mRNA transcripts were easily detected in samples with low BAX protein expression, and no BAX mutations were identified. Conclusion: The correlation between high BAX levels and improved clinical outcome suggests that an intact apoptotic pathway is an important determinant of chemoresponsiveness in ovarian cancer patients who receive paclitaxel. J Clin Oncol 16:2583-2590. (C) 1998 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Hosp, Dept Obstet & Gynecol, Boston, MA USA. RP Cannistra, SA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM stephen_cannistra@dfci.harvard.edu FU NCI NIH HHS [CA 60670] NR 44 TC 111 Z9 112 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1998 VL 16 IS 8 BP 2583 EP 2590 PG 8 WC Oncology SC Oncology GA 107NT UT WOS:000075215900003 PM 9704707 ER PT J AU Pegram, MD Lipton, A Hayes, DF Weber, BL Baselga, JM Tripathy, D Baly, D Baughman, SA Twaddell, T Glaspy, JA Slamon, DJ AF Pegram, MD Lipton, A Hayes, DF Weber, BL Baselga, JM Tripathy, D Baly, D Baughman, SA Twaddell, T Glaspy, JA Slamon, DJ TI Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185(HER2/neu) monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; CARCINOMA-CELLS; OVARIAN-CANCER; CIS-DIAMMINEDICHLOROPLATINUM; PROGNOSTIC VALUE; INCREASED RISK; GENE-PRODUCT; MAJOR ADDUCT; DNA-REPAIR; HER-2 NEU AB Purpose: To determine the toxicity, pharmacokinetics, response Kite, and response duration of intravenous (IV) administration of recombinant, humanized anti-p185(HER2) monoclonal antibody (rhuMAb HER2) plus cisplatin (CDDP) in a phase II, open-label, multicenter clinical trial for patients with HER2/neu-overexpressing metastatic breast cancer. Patients and Methods: The study population consisted of extensively pretreated advanced breast cancer patients with HER2/neu overexpression and disease progression during standard chemotherapy. Patients received a loading dose of rhuMAb HER2 (250 mg IV) on day 0, followed by weekly doses of 100 mg IV for 9 weeks. Patients received CDDP (75 mg/m(2)) on days 1, 29, and 57. Results: Of 37 patients assessable for response, nine (24.3%) achieved a PR, nine (24.3%) had a minor response or stable disease, and disease progression occurred in 19 (51.3%). The median response duration was 5.3 months (range, 1.6-18). Grade III or IV toxicity was observed in 22 of 39 patients (56%). The toxicity profile reflected that expected from CDDP alone with the most common toxicities being cytopenias (n = 10), nausea/vomiting (n = 9), and asthenia (n = 5). Mean pharmacokinetic parameters of rhuMAb HER2 were unaltered by coadministration of CDDP. Conclusion: The use of rhuMAb HER2 in combination with CDDP in patients with HER2/neu-overexpressing metastatic breast cancer results in objective clinical response Kites higher than those reported previously for CDDP alone, or rhuMAb HER2, alone. In addition, the combination results in no apparent increase in toxicity. Finally, the pharmacology of rhuMAb HEW was unaffected by coadministration with CDDP. J Clin Oncol 16: 2659-2671. (C) 1998 by American Society of Clinical Oncology. C1 Univ Calif Los Angeles, Ctr Hlth Sci, Dept Med Oncol, Los Angeles, CA 90095 USA. Milton S Hershey Med Ctr, Dept Med Oncol, Hershey, PA 17033 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Penn, Dept Med Oncol, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, Dept Med Oncol, New York, NY 10021 USA. Univ Calif San Francisco, Dept Med Oncol, San Francisco, CA 94143 USA. Genentech Inc, San Francisco, CA 94080 USA. RP Pegram, MD (reprint author), Univ Calif Los Angeles, Ctr Hlth Sci, Dept Med Oncol, 11-934 Factor Bldg,10833 Le Conte Ave,Campus Mail, Los Angeles, CA 90095 USA. EM mpegram@ucla.edu FU NCI NIH HHS [1K12CA01714] NR 51 TC 748 Z9 762 U1 2 U2 21 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1998 VL 16 IS 8 BP 2659 EP 2671 PG 13 WC Oncology SC Oncology GA 107NT UT WOS:000075215900012 PM 9704716 ER PT J AU Dalton, VMK Gelber, RD Li, F Donnelly, MJ Tarbell, NJ Sallan, SE AF Dalton, VMK Gelber, RD Li, F Donnelly, MJ Tarbell, NJ Sallan, SE TI Second malignancies in patients treated for childhood acute lymphoblastic leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FARBER-CANCER-INSTITUTE; INTENSIVE ASPARAGINASE; CRANIAL IRRADIATION; TUMORS; NEOPLASMS; INDUCTION; CHILDREN; THERAPY; METHOTREXATE; SURVIVORS AB Purpose: Second malignant neoplasms (SMN) are devastating late complications of childhood acute lymphoblastic leukemia (ALL) and its treatment. We evaluated the incidence and type of SMN diagnosed before leukemic relapse in a large series of patients with ALL, Patients and Methods: We reviewed the outcome of all patients treated for childhood ALL between 1972 and 1995 on Dana-Farber Cancer Institute (DFCI) and DFCI ALL Consortium protocols, The follow-vp time from diagnosis of ALL to induction failure, relapse, remission death, or SMN, whichever occurred first, ranged from 0 to 24.0 years (median, 7.6 years; mean, 6.7 years). Results: Thirteen SMNs were diagnosed among 1,597 patients, Eight tumors occurred in a radiation field (five in the CNS and three in the head and neck), two occurred outside of a radiation field (one adenocarcinoma of the sigmoid colon and one epithelioid sarcoma of the chest wall), and three were hematopoietic malignancies. The median rime to occurrence was 6.7 years (range, 1.0 to 17.2 years) and the cumulative incidence of second malignancy before another first event was 2.7% (95% confidence interval, 0.7 to 4.7), The risk of a first event, which included induction failure, relapse, or remission death, was 31.0% (95% confidence interval, 28.5 to 33.5), Conclusion: We found a more than 10-fold risk of other first events when compared with SMN, Thus, we conclude that SMN before first relapse is a relatively uncommon occurrence among survivors of childhood ALL. Future therapeutic regimens must focus on reducing leukemia relapse and enhancing quality of life, as well as preventing SMNs. J Clin Oncol 16:2848-2853. (C) 1998 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Dalton, VMK (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Dana 308, Boston, MA 02115 USA. EM virginia_dalton@dfci.harvard.edu NR 42 TC 71 Z9 72 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1998 VL 16 IS 8 BP 2848 EP 2853 PG 6 WC Oncology SC Oncology GA 107NT UT WOS:000075215900034 ER PT J AU Tondo, L Baldessarini, RJ Hennen, J Floris, G Silvetti, F Tohen, M AF Tondo, L Baldessarini, RJ Hennen, J Floris, G Silvetti, F Tohen, M TI Lithium treatment and risk of suicidal behavior in bipolar disorder patients SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; MANIC-DEPRESSIVE PATIENTS; RECURRENT MOOD DISORDERS; MAINTENANCE TREATMENT; MORTALITY; DISCONTINUATION; ANTIDEPRESSANTS; PROPHYLAXIS; ILLNESS; PREVENTION AB Background: Lithium may exert an antisuicidal effect in bipolar disorder patients, but this hypothesis requires further testing by direct comparison of patients with and without lithium treatment. Method: Risk of life-threatening suicidal acts over time and associated factors were analyzed in 310 patients with DSM-IV bipoIar I (N = 186) or II (N = 124) disorder evaluated for a mean of 8.3 years before, and prospectively during, a mean of 6.4 years of lithium maintenance in a mood disorder clinic; 185 were also followed for a mean of 3.7 years after clinically discontinuing lithium. Results: In 5233 patient-years of observation, 58 patients made 90 suicide attempts (8 were fatal). Survival analyses with Weibull modeling with adjustments for covariates indicated a highly significant 6.4-fold adjusted hazard ratio during versus before and 7.5-fold ratio after versus during lithium maintenance. Suicidal acts were more common early in the course of illness before lithium and were associated with prior suicide attempts, greater proportion of time depressed, and younger age. After the discontinuation of lithium, suicidal acts were mon frequent in the first year than at later times or before start of lithium treatment. Fatalities were 9 times more frequent after versus during treatment. Conclusion: Lithium maintenance was associated with marked reduction of life-threatening suicidal acts, the number of which sharply increased after discontinuing lithium. Suicidal behavior was strongly associated with prior suicide attempts, more time depressed, and younger age or recent onset. Greater attention to suicidal risk in patients with bipolar depression and assessment of all proposed mood-stabilizing agents for antisuicidal effects are strongly encouraged. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Bipolar & Psychot Disorders Program, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Univ Cagliari, Dept Psychiat, Cagliari, Italy. Lucio Bini Psychiat Ctr, Cagliari, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02178 USA. EM rjb@mrc309.mclean.org FU NIMH NIH HHS [MH-47370] NR 73 TC 113 Z9 117 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 1998 VL 59 IS 8 BP 405 EP 414 DI 10.4088/JCP.v59n0802 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 111CE UT WOS:000075419100002 PM 9721820 ER PT J AU Goff, DC Posever, T Herz, L Simmons, J Kletti, N Lapierre, K Wilner, KD Law, CG Ko, GN AF Goff, DC Posever, T Herz, L Simmons, J Kletti, N Lapierre, K Wilner, KD Law, CG Ko, GN TI An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; ANTIPSYCHOTIC-DRUGS; RECEPTOR ANTAGONIST; DOPAMINE; OCCUPANCY; D-2; CP-88,059-01; ICI-169,369; RACLOPRIDE; RITANSERIN AB Ninety patients with schizophrenia or schizoaffective disorder according to DSM-III-R criteria participated in this double-blind, exploratory, dose-ranging trial. After a single-blind washout period of 4 to 7 days, patients were randomly assigned to receive one of four fixed doses of the new antipsychotic, ziprasidone 4 (N = 19), 10 (N = 17), 40 (N = 17), or 160 (N = 20) mg/day or haloperidol 15 mg/day (N = 17) for 4 weeks. A dose-response relationship among ziprasidone groups was established for improvements in Clinical Global impression Severity (CGI-S) score (p = 0.002) but not in Brief Psychiatric Rating Scale (BPRS) total score (p = 0.08). The intent-to-treat analysis of mean changes from baseline in the BPRS total, BPRS Psychosis core, and CGI-S scores demonstrated that ziprasidone 160 mg/day was comparable with haloperidol in reducing overall psychopathology and positive symptoms and was superior to ziprasidone 4 mg/day. Despite the small sample size and short duration of the trial, the improvement in CGI-S with both ziprasidone 160 mg/day and haloperidol 15 mg/day was statistically significantly greater than with ziprasidone 4 mg/day (p = 0.001 and p = 0.005, respectively). The percentage of patients classified as responders on both the BPRS total (greater than or equal to 30% improvement) and CGI-Improvement (score of 1 or 2) scales in the ziprasidone 160 mg/day group was similar to that in the haloperidol group and nonsignificantly greater than that in the ziprasidone 4 mg/day group. On all assessments of clinical efficacy, the improvements associated with ziprasidone 4 mg/day, 10 mg/day, and 40 mg/day were similar. Concomitant benztropine use at any time during the study was less frequent with ziprasidone 160 mg/day (15%) than with haloperidol (53%). Haloperidol was associated with a sustained hyperprolactinemia, unlike ziprasidone, where only transient elevations in prolactin that returned to normal within the dosing interval were observed. Ziprasidone was well tolerated, and the incidence of adverse events was similar in all groups. The results of this study suggest that ziprasidone 160 mg/day is as effective as haloperidol 15 mg/day in reducing overall psychopathology and positive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder but has a lower potential to induce extrapyramidal symptoms. C1 Massachusetts Gen Hosp, Psychot Disorders Program, Boston, MA 02114 USA. New England Med Ctr, Boston, MA 02111 USA. Bedford VA Hosp, Bedford, MA USA. Tewksbury State Hosp, Tewskbury, MA USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Pfizer Inc, Pfizer Cent Res, Groton, CT 06340 USA. RP Goff, DC (reprint author), Erich Lindemann Mental Hlth Ctr, Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. NR 17 TC 144 Z9 146 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1998 VL 18 IS 4 BP 296 EP 304 DI 10.1097/00004714-199808000-00009 PG 9 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 102VK UT WOS:000074946000007 PM 9690695 ER PT J AU Fukae, M Tanabe, T Uchida, T Lee, SK Ryu, OH Murakami, C Wakida, K Simmer, JP Yamada, Y Bartlett, JD AF Fukae, M Tanabe, T Uchida, T Lee, SK Ryu, OH Murakami, C Wakida, K Simmer, JP Yamada, Y Bartlett, JD TI Enamelysin (Matrix metalloproteinase-20): Localization in the developing tooth and effects of pH and calcium on amelogenin hydrolysis SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE matrix metalloproteinase; dental enamel; dentin; ameloblast; odontoblast; Tomes' process ID BOVINE ENAMEL; GEL ELECTROPHORESIS; PORCINE ENAMEL; COLLAGENASE; PROTEINS; RAT; IDENTIFICATION; INHIBITORS; CLEAVAGE; DENTIN AB The formation of dental Enamel is a precisely regulated and dynamic developmental process. The forming enamel starts as a soft, protein-rich tissue and ends as a hard tissue that is over 95% mineral by weight. intact amelogenin and its proteolytic cleavage products are the most abundant proteins present within the developing enamel. Proteinases are also present within the enamel matrix and are thought to help regulate enamel development and to expedite the removal of proteins prior to enamel maturation. Recently, a novel matrix metalloproteinase named enamelysin was cloned from the porcine enamel organ. Enamelysin transcripts have previously been observed in the enamel organ and dental papillae of the developing tooth. Here, we show that the sources of the enamelysin transcripts are the ameloblasts of the enamel organ and the odontoblasts of the dental papilla. Furthermore, we show that enamelysin is present within the forming enamel and that it is transported in secretory vesicles prior to its secretion from the ameloblasts. We also characterize the ability of recombinant enamelysin (rMMP-20) to degrade amelogenin under conditions of various pHs and calcium ion concentrations. Enamelysin displayed the greatest activity at neutral pH (7.2) and high calcium ion concentration (10 mM). During the initial stages of enamel formation, the enamel matrix maintains a neutral pH of between 7.0 and 7.4. Thus, enamelysin may play a role in enamel and dentin formation by cleaving proteins that are also present during these initial developmental stages. C1 Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. Tsurumi Univ, Sch Dent Med, Dept Biochem, Tsurumi Ku, Yokohama, Kanagawa 230, Japan. Hiroshima Univ, Sch Dent, Dept Oral Anat, Hiroshima 734, Japan. NIDR, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat Dent, San Antonio, TX 78284 USA. RP Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE 12098, R29 DE012098] NR 40 TC 82 Z9 86 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD AUG PY 1998 VL 77 IS 8 BP 1580 EP 1588 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 111QG UT WOS:000075448700005 PM 9719031 ER PT J AU Thyen, U Terres, NM Yazdgerdi, SR Perrin, JM AF Thyen, U Terres, NM Yazdgerdi, SR Perrin, JM TI Impact of long-term care of children assisted by technology on maternal health SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE home care; technology; maternal depression; social support ID PHYSICALLY-HANDICAPPED CHILDREN; FAMILY ENVIRONMENT SCALE; SOCIAL SUPPORT; PSYCHOLOGICAL ADJUSTMENT; CHRONIC ILLNESS; DEPRESSIVE SYMPTOMS; FUNCTIONAL STATUS; PARENTING STRESS; CYSTIC-FIBROSIS; MENTAL-HEALTH AB This study examines the health outcomes of mothers of children assisted by technology and their associations with condition severity and family social support. The 6-month postdischarge status of 65 mothers of children (matched for age and sex) hospitalized for acute illnesses. We measured maternal health, emotional well-being (Center for Epidemiologic Studies Depression Scale), severity of the child's condition, family functioning, social support, and sociodemographic data. Mothers in the study group reported impaired health related to pain, vitality, social functioning, and mental health and substantially more depressive symptoms than mothers in the control group (p < .001), with almost half having scores suggesting clinical depression. Family supportiveness and opportunities for recreational and cultural activities were significantly lower in families with children assisted by technology. After controlling for sociodemographic variables, high condition severity (p < .01), lack of family support (p = .05), low social support appraisal (p < .01), and high levels of receipt of social support (p < .01) were associated with more depressive symptoms of mothers in the study group. Six months after diagnosis or major hospitalization, the severity of the condition was highly associated with maternal emotional well-being, with family support and social support appraisal having moderate independent positive effects. The receipt of social support indicated need rather than support and was negatively associated with well-being. Discharge planning and support systems need to focus on both the child and the prevention of secondary social and psychological morbidity of caretakers. C1 Med Univ Lubeck, Klin Padiat, D-23538 Lubeck, Germany. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Thyen, U (reprint author), Med Univ Lubeck, Klin Padiat, Kahlhorststr 31-35, D-23538 Lubeck, Germany. NR 65 TC 22 Z9 22 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD AUG PY 1998 VL 19 IS 4 BP 273 EP 282 DI 10.1097/00004703-199808000-00006 PG 10 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 109VT UT WOS:000075345200006 PM 9717137 ER PT J AU Gropper, A Doyle, S Dreyer, K AF Gropper, A Doyle, S Dreyer, K TI Enterprise-scale image distribution with a Web PACS SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Computer-Applications-in-Radiology CY JUN 04-07, 1998 CL BALTIMORE, MARYLAND SP Soc Comp Applicat Radiol (SCAR), Amer Coll Radiol (ACR) AB The integration of images with existing and new health care information systems poses a number of challenges in a multi-facility network: image distribution to clinicians; making DICOM image headers consistent across information systems; and integration of teleradiology into PACS, A novel, Web-based enterprise PACS architecture introduced at Massachusetts General Hospital provides a solution. Four AMICAS Web/Intranet Image Servers were installed as the default DICOM destination of 10 digital modalities, A fifth AMICAS receives teleradiology studies via the Internet, Each AMICAS includes: a Java-based interface to the IDXrad radiology information system (RIS), a DICOM autorouter to tape-library archives and to the Agfa PACS, a wavelet image compressor/decompressor that preserves compatibility with DICOM workstations, a Web server to distribute images throughout the enterprise, and an extensible interface which permits links between other HIS and AMICAS. Using wavelet compression and Internet standards as its native formats, AMICAS creates a bridge to the DICOM networks of remote imaging centers via the Internet. This teleradiology capability is integrated into the DICOM network and the PACS thereby eliminating the need for special teleradiology workstations. AMICAS has been installed at MGH since March of 1997. During that time, it has been a reliable component of the evolving digital image distribution system. As a result, the recently renovated neurosurgical ICU will be filmless and use only AMICAS workstations for mission-critical patient care. Copyright (C) 1998 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gropper, A (reprint author), 52 Marshall St, Watertown, MA 02172 USA. NR 0 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD AUG PY 1998 VL 11 IS 3 SU 1 BP 12 EP 17 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 111NH UT WOS:000075443600005 PM 9735424 ER PT J AU Emanuel, EJ Goldman, L AF Emanuel, EJ Goldman, L TI Protecting patient welfare in managed care: Six safeguards SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Article ID PHYSICIANS CLINICAL DECISIONS; UNIVERSAL HEALTH-INSURANCE; FINANCIAL INCENTIVES; PROMOTE QUALITY; JOINT VENTURES; OF-INTEREST; CONFLICTS; PERFORMANCE; THERAPY; PLAN AB The public is very suspicious and fearful that managed care threatens their health because of its interest in reducing costs. Because physicians' decisions control 75 percent of all health care spending, managed care organizations are focusing their cost-cutting strategies on influencing physician decision making through financial incentives and guidelines. These two techniques have had some important contributions, especially in enhancing efficiency and standardizing care to a high level. Nevertheless, they pose a threat-and are perceived by the public to pose a threat-to patients' health and well-being. How can we mitigate the threats to patient welfare posed by financial incentives and guidelines? We propose and analyze six safeguards. These safeguards are not an attempt to revive the fee-for-service system, but an effort to make managed care ethical and to focus it on improving patient welfare. They are designed to work together to ensure that patient welfare remains the primary focus of managed care organizations; they try to create institutional structures that emphasize quality over mere cost reductions. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Emanuel, EJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 70 TC 16 Z9 16 U1 1 U2 3 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 0361-6878 J9 J HEALTH POLIT POLIC JI J. Health Polit. Policy Law PD AUG PY 1998 VL 23 IS 4 BP 635 EP 659 PG 25 WC Health Care Sciences & Services; Health Policy & Services; Medicine, Legal; Social Issues; Social Sciences, Biomedical SC Health Care Sciences & Services; Legal Medicine; Social Issues; Biomedical Social Sciences GA 110DV UT WOS:000075365600003 PM 9718517 ER PT J AU Zhao, Y Swenson, K Sergio, JJ Sykes, M AF Zhao, Y Swenson, K Sergio, JJ Sykes, M TI Pig MHC mediates positive selection of mouse CD4(+) T cells with a mouse MHC-restricted TCR in pig thymus grafts SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-II MHC; CLONAL DELETION; HEMATOPOIETIC-CELLS; NEGATIVE SELECTION; XENOGENEIC BARRIER; ANTIGEN RECEPTOR; HELPER-CELLS; TOLERANCE; DIFFERENTIATION; LYMPHOCYTES AB Remarkably normal immune function and specific T cell tolerance to discordant xenogeneic donors can be achieved by grafting fetal pig thymus and liver (FP THY/LIV) tissue to T cell and NK cell-depleted, thymectomized (ATX) mice. To determine whether or not host class II MHC molecules participate in the positive selection of mouse CD4(+) T cells in FP THY/LIV grafts, ne compared their development in ATX, "AND" TCR-transgenic mice with positive selecting or nonselecting host MHC genotypes, Mouse TCR-transgenic CD4 single positive T cells repopulated the periphery significantly and to a similar extent in both T/NK cell-depleted, ATX AND mice with positive-selecting or nonselecting MHC backgrounds after grafting with FP THY/LIV. Therefore, MHC molecules from a widely disparate xenogeneic species can positively select T cells bearing a host class II MHC-restricted TCR without a contribution from the host MHC. These results, in combination with previous studies performed in this model, suggest that the T cell repertoire that is generated by the combination of positive selection on xenogeneic MHC and negative selection on both recipient and xenogeneic porcine MHC is tolerant of both donor and recipient and has sufficient cross-reactivity with host MHC/foreign peptide complexes to confer a high level of immunocompetence. The results hale implications for the potential clinical applicability of xenogeneic thymic transplantation and also suggest a predominant role for the TCR recognition of species-conserved MHC residues in positive selection. C1 Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Sch Med,Surg Serv, Bone Marrow Transplantat Sec, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Sch Med,Surg Serv, Bone Marrow Transplantat Sec, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [P01-AI39755] NR 49 TC 28 Z9 31 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1998 VL 161 IS 3 BP 1320 EP 1326 PG 7 WC Immunology SC Immunology GA 102VA UT WOS:000074944900034 PM 9686594 ER PT J AU Merchant, SN Ravicz, ME Voss, SE Peake, WT Rosowski, JJ AF Merchant, SN Ravicz, ME Voss, SE Peake, WT Rosowski, JJ TI Middle ear mechanics in normal, diseased and reconstructed ears SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Article; Proceedings Paper CT Meeting of the-Royal-Society-of-Medicine CY NOV 07, 1997 CL LONDON, ENGLAND SP Royal Soc Med DE ear, middle; hearing loss, conductive; tympanoplasty ID V TYMPANOPLASTY; REPLACEMENT PROSTHESES; SURGICAL IMPLICATIONS; INPUT IMPEDANCE; COCHLEA; IV; EXPERIENCE; SURGERY; HEARING; MODELS AB A review of the structure-function relationships in normal, diseased and reconstructed middle ears is presented. Variables used to describe the system are sound pressure, volume velocity and acoustic impedance. We discuss the following: (1) Sound can be transmitted from the ear canal to the cochlea via two mechanisms: the tympano-ossicular system (ossicular coupling) and direct acoustic stimulation of the oval and round windows (acoustic coupling). In the normal ear, middle-ear pressure gain, which is the result of ossicular coupling, is frequency-dependent and smaller than generally believed. Acoustic coupling is negligibly small in normal ears, but can play a significant role in some diseased and reconstructed ears. (2) The severity of conductive hearing loss due to middle-ear disease or after tympanoplasty surgery can be predicted by the degree to which ossicular coupling, acoustic coupling, and stapes-cochlear input impedance are compromised. Such analyses are used to explain the air-bone gaps associated with lesions such as ossicular interruption, ossicular fixation and tympanic membrane perforation. (3) With type IV and V tympanoplasty, hearing is determined solely by acoustic coupling. A quantitative analysis of structure-function relationships can both explain the wide range of observed postoperative hearing results and suggest surgical guidelines in order to optimize the post-operative results. (4) In tympanoplasty types I, II and III, the hearing result depends on the efficacy of the reconstructed tympanic membrane, the efficacy of the reconstructed ossicular chain and adequacy of middle-ear aeration. Currently, our knowledge of the mechanics of these three factors is incomplete. The mechanics of mastoidectomy and stapedectomy are also discussed. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Sci Program, Boston, MA USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P01 DC00119, P01 DC000119, R29 DC003657] NR 47 TC 35 Z9 39 U1 2 U2 3 PU HEADLEY BROTHERS LTD PI ASHFORD PA INVICTA PRESS, ASHFORD, KENT, ENGLAND TN24 8HH SN 0022-2151 J9 J LARYNGOL OTOL JI J. Laryngol. Otol. PD AUG PY 1998 VL 112 IS 8 BP 715 EP 731 PG 17 WC Otorhinolaryngology SC Otorhinolaryngology GA 111ZV UT WOS:000075469600003 PM 9850313 ER PT J AU Kabakibi, A Morse, CR Laposata, M AF Kabakibi, A Morse, CR Laposata, M TI Fatty acid ethyl esters and HepG2 cells: intracellular synthesis and release from the cells SO JOURNAL OF LIPID RESEARCH LA English DT Article DE hepatoblastoma cells; alcohol; ethyl ester; secretion; lipoprotein; albumin ID NONOXIDATIVE ETHANOL-METABOLISM; TRANS-GOLGI CISTERNAE; BREFELDIN-A; ENDOPLASMIC-RETICULUM; SYNTHASE ACTIVITY; APOLIPOPROTEIN-B; LIVER-MICROSOMES; HUMAN MYOCARDIUM; G2 CELLS; PROTEINS AB Fatty acid ethyl esters (FAEE), esterification prodlucts of fatty acid and ethanol, have been implicated as mediators of ethanol-induced organ damage. To understand the molecular and cellular events in FAEE synthesis and secretion, we developed a system in which HepG2 cells synthesize and release FAEE into the culture medium upon incubation with ethanol. The synthesis of FAEE was observed within 5 min of the addition of ethanol, with a plateau for FAEE synthesis after 2 h of incubation. It was also observed that FAEE are synthesized by both a microsomal FAEE synthase, which preferentially uses fatty acyl-CoA as a substrate, and a cytosolic FAEE synthase, which accepts both unesterified fatty acid and fatty acyl-CoA as substrates with a slight preference for fatty acyl-CoA. Although the kinetics of cellular FAEE synthesis await further characterization, the intracellular fatty acid substrate appears to be derived principally from glycerolipids and other esters, FAEE were released into the culture medium by a mechanism independent of the vesicular transport pathway. Lipoprotein particles and albumin were found to be carriers of FAEE after FAEE secretion from the cell. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Div Clin Labs, Boston, MA 02114 USA. RP Laposata, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Div Clin Labs, 32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-37454] NR 63 TC 26 Z9 26 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 1998 VL 39 IS 8 BP 1568 EP 1582 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 107WH UT WOS:000075233600004 PM 9717716 ER PT J AU Corbitt, J Vivekananda, J Wang, SS Strong, R AF Corbitt, J Vivekananda, J Wang, SS Strong, R TI Transcriptional and posttranscriptional control of tyrosine hydroxylase gene expression during persistent stimulation of pituitary adenylate cyclase-activating polypeptide receptors on PC12 cells: Regulation by protein kinase A-dependent and protein kinase A-independent pathways SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE tyrosine hydroxylase; tyrosine hydroxylase mRNA; pituitary adenylate cyclase; activating polypeptide (PACAP); gene transcription; mRNA stability ID ADRENAL CHROMAFFIN CELLS; NERVE GROWTH-FACTOR; SUPERIOR CERVICAL-GANGLION; DOPAMINE-BETA-HYDROXYLASE; MESSENGER-RNA STABILITY; COLD STRESS; SHORT-TERM; 3'-UNTRANSLATED REGION; PHEOCHROMOCYTOMA CELLS; NEURITE OUTGROWTH AB Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates catecholamine release and biosynthesis in sympathetic postganglionic cells. Moreover, PACAP receptor activation in cultured adrenal chromaffin and superior cervical ganglion cells has been reported to increase the expression of the gene coding for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. However, the relative contribution of transcriptional and posttranscriptional mechanisms to the effects of PACAP on TH gene expression has not been evaluated. Therefore, in this study we compared the temporal effects of PACAP on TH gene transcription with the duration of its effects on TH mRNA levels. We had previously shown that vasoactive intestinal polypeptide, peptide histidine isoleucine, and secretin, peptides closely related to PACAP, induce TH gene expression through a cyclic AMP (cAMP)-dependent pathway. Therefore, using a mutant PC12 cell line deficient in cAMP-dependent protein kinase II (PKA),we also evaluated the role of the cAMP pathway in the effect of PACAP on TH gene expression. Continuous treatment of wildtype PC12 cells with PACAP (1 nM) increased TH mRNA levels maximally by 12 h and maintained TH mRNA at near maximal levels for at least 2 days. In contrast, the rate of TH gene transcription, as measured by a nuclear run-on assay, was maximal by 1 h and returned to basal levels by 3 h, The fact that a new steady-state level of TH mRNA was achieved and maintained for days in the absence of a sustained increase in TH gene transcription supports the involvement of posttranscriptional mechanisms. Removal of PACAP after 12 h, a time at which TH gene transcription was at basal levers, resulted in a subsequent return of TH mRNA to unstimulated levels within 36 h. Thus, continuous PACAP stimulation is required to maintain sustained increases in TH mRNA levels in the absence of a sustained elevation of transcription. To examine the role of the cAMP pathway in these effects, we compared the effects of PACAP in wild-type PC12 cells and in a mutant PC12 cell line (A126-1B2) that is deficient in PKA. PACAP failed to stimulate either TH mRNA levels or TH gene transcription in the mutant cells, In contrast to the effects of PACAP, dexamethasone increased TH mRNA levels by the same magnitude in both cell lines. It is noteworthy that stimulation of the PKA-deficient mutant cells with a combination of PACAP and dexamethasone (1 mu M) produced a synergistic increase in TH mRNA levels, which was nearly twice that induced by dexamethasone stimulation alone. This synergistic effect was not transcriptionally mediated. The effect of the combined treatment on TH gene transcription was identical to the effect of dexamethasone alone. Taken together, these data indicate that PACAP regulates TH gene expression through a transcriptional mechanism requiring an intact cAMP pathway and through posttranscriptional mechanisms under the control of a cAMP-independent pathway(s). C1 Audie L Murphy Mem Vet Hosp, Ctr Geriatr Res Educ & Clin 182, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. RP Strong, R (reprint author), Audie L Murphy Mem Vet Hosp, Ctr Geriatr Res Educ & Clin 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG 09557]; NIDDK NIH HHS [DK 52543] NR 58 TC 39 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1998 VL 71 IS 2 BP 478 EP 486 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 102FB UT WOS:000074912800004 PM 9681437 ER PT J AU Counihan, TJ Penney, JB AF Counihan, TJ Penney, JB TI Regional dopamine transporter gene expression in the substantia nigra from control and Parkinson's disease brains SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE mesencephalon; in situ hybridisation; parkinsonism; amine transporter ID MESSENGER-RNA EXPRESSION; TYROSINE-HYDROXYLASE; MESENCEPHALIC NEURONS; MIDBRAIN NEURONS; RECEPTOR; COCAINE; RAT; SUBPOPULATIONS; NEUROTOXIN; BINDING AB Objective-To test the hypothesis that differential regional dopamine transporter (DAT) gene expression may underlie the selective vulnerability of certain nigral dopaminergic neurons in Parkinson's disease, DAT mRNA expression was examined in neuronal subpopulations of human postmortem ventral mesencephalon from patients with Parkinson's disease and controls. Methods-Radioactive in situ hybridisation histochemistry using a polymerase chain reaction derived ribonucleotide probe for DAT was performed on sections of ventral mesencephalon from the brains of five donors with no history of neurological illness and from five patients with pathologically established Parkinson's disease. The number of silver grains overlying melanised neurons from the paranigral nucleus, dorsal and ventral tier, and pars lateralis of the substantia nigra pars compacta were compared with each other and to background labelling by using a one way factorial analysis of variance (ANOVA) with a significance level of 5%. Results-In control brains, there was intense DAT mRNA expression in the ventral midbrain with no significant difference in mRNA concentrations among the four regions studied. In the Parkinson's disease brains, there was an overall decrease in the intensity of DAT mRNA expression in the surviving dopaminergic neurons. There were no significant differences in signal between regions in either the control or parkinsonian brains. Conclusion-Taken together, these findings do not support the hypothesis that differential regional DAT gene expression underlies the selective vulnerability of certain nigral dopaminergic neurons in Parkinson's disease, as the vulnerable neurons of the substantia nigra pars compacta do not express more DAT mRNA than the resistant paranigral neurons. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Penney, JB (reprint author), Massachusetts Gen Hosp, Neurol Serv, Warren 408,Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS31579] NR 42 TC 15 Z9 17 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD AUG PY 1998 VL 65 IS 2 BP 164 EP 169 DI 10.1136/jnnp.65.2.164 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 105QG UT WOS:000075084700006 PM 9703165 ER PT J AU Simon, DK Rodriguez, ML Frosch, MP Quackenbush, EJ Feske, SK Natowicz, MR AF Simon, DK Rodriguez, ML Frosch, MP Quackenbush, EJ Feske, SK Natowicz, MR TI A unique familial leukodystrophy with adult onset dementia and abnormal glycolipid storage: a new lysosomal disease? SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE leukodystrophy; dementia; lysosomal disorder ID ORTHOCHROMATIC LEUKODYSTROPHY; ADRENOLEUKODYSTROPHY; DIAGNOSIS; DISORDERS; CARRIERS AB Two adult siblings with early onset dementia are described. At presentation, in their early 30s, they showed poor judgment and disinhibition. A progressive dementia ensued over several years. Brain MRI disclosed diffusely increased T2 signal in the cerebral white matter, suggestive of a leukodystrophy. Numerous lysosomal enzyme assays including leucocyte arylsulphatase A and galactocerebrosidase activities, plasma and fibroblast very long chain fatty acid concentrations, and urinary sulphatide concentrations were normal, as were CSF analyses. A brain biopsy disclosed periodic acid Schiff (PAS) and Sudan black positive material in perivascular macrophages which, by electron microscopy, consisted of stacks of straight or curvilinear paired membranes within angulate lysosomes, indicative of abnormal glycolipid accumulation. The combination of clinical, radiological, biochemical, and pathological features of this degenerative disease is not consistent with that of any of the known leukodystrophies or lysosomal storage disorders. These findings suggest a previously undescribed familial glycolipid storage disorder causing an adult onset leukodystrophy and presenting with behavioural symptoms that mimic a psychiatric disorder. C1 Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriver Ctr, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Simon, DK (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. NR 16 TC 4 Z9 5 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD AUG PY 1998 VL 65 IS 2 BP 251 EP 254 DI 10.1136/jnnp.65.2.251 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 105QG UT WOS:000075084700023 PM 9703182 ER PT J AU Berezovska, O Xia, MQ Hyman, BT AF Berezovska, O Xia, MQ Hyman, BT TI Notch is expressed in adult brain, is coexpressed with presenilin-1, and is altered in Alzheimer disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; brain; immunohistochemistry; Notch; presenilin; Western blot ID DROSOPHILA-NOTCH; NEUROBLAST SEGREGATION; CAENORHABDITIS-ELEGANS; PARAXIAL MESODERM; MESSENGER-RNA; GENE; HOMOLOG; NEUROGENESIS; LOCALIZATION; RECEPTOR AB In C. elegans, the Notch family member Lin-12 has been shown to have a genetic interaction with sel-12, the homologue of the Alzheimer disease-associated presenilin (PS) genes in humans. Mutations in PS genes cause autosomal dominant Alzheimer disease, with age of onset frequently in the 40s. Notch is known as a developmental protein that plays an important role in lateral inhibition and specifying cell fate decisions in proliferating immature cells, and is not known to be present in adult neurons. We reasoned that, if Notch/PS-1 interaction is relevant in Alzheimer disease, Notch1 would also need to be expressed in neurons in adult brain and colocalized with PS-1. We found that Notch1, Notch2, and a Notch ligand, Jagged1, are expressed in adult brain in mouse and in human, with strongest expression in the kippocampal formation and Purkinje cells of the cerebellum Double immunofluorescent staining demonstrates neuronal colocalization of Notch1 with PS-I. Moreover, Notchl expression in sporadic Alzheimer disease hippocampus is elevated more than 2-fold in comparison to that in control human hippocampus by both immunohistochemistry and Western blot analysis (p < 0.007). These results support the hypothesis that Notch1 continues to play a role in terminally differentiated neurons, and that Notch1/PS-1 interactions may occur in adult mammalian brain. The alteration in Notchl expression in sporadic Alzheimer disease raises the possibility that disruption of Notch1/PS-1 functional interactions may occur in Alzheimer disease. C1 Massachusetts Gen Hosp, Neurol Serv, Alzheimer Res Unit, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Neurol Serv, Alzheimer Res Unit, Rm 6405,149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG 11337, AG 14744] NR 44 TC 98 Z9 106 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD AUG PY 1998 VL 57 IS 8 BP 738 EP 745 DI 10.1097/00005072-199808000-00003 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 111PQ UT WOS:000075447200003 PM 9720489 ER PT J AU Costigan, M Mannion, RJ Kendall, G Lewis, SE Campagna, JA Coggeshall, RE Meridith-Middleton, J Tate, S Woolf, CJ AF Costigan, M Mannion, RJ Kendall, G Lewis, SE Campagna, JA Coggeshall, RE Meridith-Middleton, J Tate, S Woolf, CJ TI Heat shock protein 27: Developmental regulation and expression after peripheral nerve injury SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dorsal root ganglion; axotomy; differential gene expression; apoptosis; spinal cord; regeneration ID ROOT GANGLION NEURONS; GAP-43 MESSENGER-RNA; INDUCED CELL-DEATH; RAT SPINAL-CORD; SENSORY NEURONS; GROWTH-FACTOR; GENE-EXPRESSION; DORSAL HORN; CONFERS RESISTANCE; DROSOPHILA HSP27 AB The heat shock protein (HSP) 27 is constitutively expressed at low levels in medium-sized lumbar dorsal root ganglion (DRG) cells in adult rats. Transection of the sciatic nerve results in a ninefold upregulation of HSP27 mRNA and protein in axotomized neurons in the ipsilateral DRG at 48 hr, without equivalent changes in the mRNAs encoding HSP56, HSP60, HSP70, and HSP90. Dorsal rhizotomy, injuring the central axon of the DRG neuron, does not upregulate HSP27 mRNA levers. After peripheral axotomy, HSP27 mRNA and protein are present in small, medium, and large DRG neurons, and HSP27 protein is transported anterogradely, accumulating in the dorsal horn and dorsal columns of the spinal cord, where it persists for several months. Axotomized motor neurons also upregulate HSP27. Only a minority of cultured adult DRG neurons are HSP27-immunoreactive soon after dissociation, but all express HSP27 after 24 hr in culture with prominent label throughout the neuron, including the growth cone. HSP27 differs from most axonal injury-regulated and growth-associated genes, which are typically present at high levels in early development and downregulated on innervation of their targets, in that its mRNA is first detectable in the DRG late in development and only approaches adult levels by postnatal day 21. In non-neuronal cells, HSP27 has been shown to be involved both in actin filament dynamics and in protection against necrotic and apoptotic cell death. Therefore, its upregulation after adult peripheral nerve injury may both promote survival of the injured neurons and contribute to alterations in the cytoskeleton associated with axonal growth. C1 UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ Texas, Med Branch, Dept Anat & Neurobiol, Galveston, TX 77551 USA. Glaxo Wellcome Res & Dev Ltd, Gene Funct Unit, Stevenage SG1 2NY, Herts, England. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. NR 56 TC 131 Z9 139 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 1998 VL 18 IS 15 BP 5891 EP 5900 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 103RN UT WOS:000074971800030 PM 9671676 ER PT J AU Asch, DA AF Asch, DA TI Tensions between the theory and practice of palliative care - Commentary SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Editorial Material ID ASSISTED SUICIDE; EUTHANASIA C1 Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. RP Asch, DA (reprint author), Univ Penn, Sch Med, Div Gen Internal Med, 317 Ralston House,3615 Chestnut St, Philadelphia, PA 19104 USA. NR 6 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD AUG PY 1998 VL 16 IS 2 BP 135 EP 136 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 113VG UT WOS:000075574100013 PM 9737107 ER PT J AU Vernacchio, L Neufeld, EJ MacDonald, K Kurth, S Murakami, S Hohne, C King, M Molrine, D AF Vernacchio, L Neufeld, EJ MacDonald, K Kurth, S Murakami, S Hohne, C King, M Molrine, D TI Combined schedule of 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal vaccine in children and young adults with sickle cell disease SO JOURNAL OF PEDIATRICS LA English DT Article ID POLYSACCHARIDE; INFANTS AB We compared the immunogenicity of 7-valent pneumococcal-conjugate vaccine plus 23-valent pneumococcal vaccine to immunization with 23-valent vaccine only in individuals greater than or equal to 2 years of age with sickle cell disease. IgG pneumococcal antibody concentrations were higher in the combined schedule group with no increase in side effects observed after immunization with 23-valent vaccine. C1 Dana Farber Canc Inst, Infect Dis Lab, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Molrine, D (reprint author), Dana Farber Canc Inst, Infect Dis Lab, 44 Binney St, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011; OI Vernacchio, Louis/0000-0002-2012-5404 FU NCRR NIH HHS [M01RR02172]; NICHD NIH HHS [5T32HD0748802] NR 12 TC 73 Z9 75 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 1998 VL 133 IS 2 BP 275 EP 278 DI 10.1016/S0022-3476(98)70235-5 PG 4 WC Pediatrics SC Pediatrics GA 109BC UT WOS:000075300500025 PM 9709721 ER PT J AU Daws, LC Toney, GM Gerhardt, GA Frazer, A AF Daws, LC Toney, GM Gerhardt, GA Frazer, A TI In vivo chronoamperometric measures of extracellular serotonin clearance in rat dorsal hippocampus: Contribution of serotonin and norepinephrine transporters SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID FREELY MOVING RATS; NUCLEUS-ACCUMBENS; UPTAKE INHIBITORS; FIBER ELECTRODES; DOPAMINE; STRIATUM; BRAIN; ANTIDEPRESSANT; DEPRESSION; REUPTAKE AB The effects of blockade of serotonin (5-HT) and norepinephrine (NE) transporters (SERT and NET, respectively) on the removal of locally applied 5-HT from extracellular fluid (ECF) were examined using in vivo chronoamperometry. Male Sprague-Dawley rats were anesthetized with chloratose/urethane, and a Nafion-coated, carbon fiber electrode attached to a multibarrel micropipette was positioned into either the dentate gyrus or CA3 region of the dorsal hippocampus. Pressure ejection of 5-HT elicited reproducible electrochemical signals of similar peak amplitude and time course in both structures. Local application of the selective serotonin reuptake inhibitors (SSRI) fluvoxamine and citalopram prolonged the clearance of 5-HT in both brain regions and also increased signal amplitude in the CA3 region. These effects were abolished in rats pretreated with 5,7-dihydroxytryptamine (5,7-DHT), a selective 5-HT neurotoxin. The NE uptake inhibitors desipramine (DMI) and protriptyline did not alter the 5-HT signal in the CA3 region but prolonged the clearance of 5-HT in the dentate gyrus; this effect was absent in rats pretreated with 6-hydroxydopamine (6-OHDA), a selective catecholamine neurotoxin. The prolongation of the removal of 5-HT from the ECF in the dentate gyrus caused by fluvoxamine or desipramine was of comparable magnitude and was dose dependent. Furthermore, per picomole of 5-HT applied, the signal amplitude and clearance time were significantly increased in the dentate gyrus of rats lesioned with either 5,7-DHT or 6-OHDA. Only 5,7-DHT treatment caused this effect in the CA3 region. From these data, it is inferred that in certain regions of brain (dentate gyrus), both the SERT and NET contribute to the active clearance of exogenously applied 5-HT. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Colorado, Hlth Sci Ctr, Neurosci Training Program, Dept Pharmacol, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Neurosci Training Program, Dept Psychiat, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Rocky Mt Ctr Sensor Technol, Denver, CO USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Daws, LC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG06434]; NIMH NIH HHS [MH29094]; NINDS NIH HHS [NS09199] NR 40 TC 50 Z9 50 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1998 VL 286 IS 2 BP 967 EP 976 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110BP UT WOS:000075359600051 PM 9694957 ER PT J AU Green, DS George, AL Cannon, SC AF Green, DS George, AL Cannon, SC TI Human sodium channel gating defects caused by missense mutations in S6 segments associated with myotonia: S804F and V1293I SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID HYPERKALEMIC PERIODIC PARALYSIS; MUSCLE NA+ CHANNEL; PARAMYOTONIA-CONGENITA; SLOW INACTIVATION; EXPRESSION; DISORDERS; FAMILIES AB 1. Missense mutations in the alpha-subunit of the human skeletal muscle sodium channel (hSkM1) have been detected In some heritable forms or myotonia. By recording Na+ currents from cells transfected with cDNA encoding either wild-type or mutant hSkM1, we characterized the functional consequences of two myotonia-associated mutations that lie at the cytoplasmic end of the sixth transmembrane segment in domain II (S804F) or domain III (V1293I). 2. Both mutations caused modest, but unequivocal, alterations in the voltage-dependent gating behaviour of hSkM1. For S804F, the abnormalities were limited to fast inactivation: the persistent Na+ cnrrent at the end of a 50 ms depolarization was increased 3-fold, the rate of inactivation from the open state was slowed 2-fold, and the voltage dependence of fast inactivation (h(infinity)) was shifted by +3 mV. V1293I also disrupted fast inactivation, as evidenced by a 3-fold faster rate of recovery at hyperpolarized potentials (less than or equal to -70 mV). Activation was altered as well for V1293I: the voltage dependence was shifted by -6 mV (hyperpolarized). 3. Slow inactivation was not altered by S804F or V1293I. 4. We conclude that S804F and V1293I are not benign polymorphisms. Either mutation causes detectable alterations in channel gating and, in model simulations, the magnitude of the defects is sufficient to produce runs of myotonic discharges. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Cannon, SC (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM cannon@helix.mgh.harvard.edu FU NIGMS NIH HHS [GM15605, F31 GM015605]; NINDS NIH HHS [R01 NS032387, R01-NS32387]; PHS HHS [R01-42703] NR 25 TC 37 Z9 37 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD AUG 1 PY 1998 VL 510 IS 3 BP 685 EP 694 DI 10.1111/j.1469-7793.1998.685bj.x PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 111PW UT WOS:000075447700003 PM 9660885 ER PT J AU Otsuji, Y Gilon, D Jiang, L He, SQ Leavitt, M Roy, MJ Birmingham, MJ Levine, RA AF Otsuji, Y Gilon, D Jiang, L He, SQ Leavitt, M Roy, MJ Birmingham, MJ Levine, RA TI Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: Evidence for increased valve tethering SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PAPILLARY-MUSCLE DYSFUNCTION; ACUTE MYOCARDIAL-ISCHEMIA; CORONARY-ARTERY DISEASE; HEART-FAILURE; SEPTAL SEPARATION; DOPPLER-ECHOCARDIOGRAPHY; DILATED CARDIOMYOPATHY; COLOR-FLOW; E-POINT; REGURGITATION AB Objectives. We tested the hypothesis that patients with incomplete systolic mitral leaflet closure (IMLC: apically displaced coaptation) also have restricted diastolic leaflet opening that is independent of mitral inflow volume and provides evidence supporting increased leaflet tethering. Background. Competing hypotheses for functional mitral regurgitation (MR) with IMLC include global left ventricular (LV) dysfunction per se (reduced leaflet closing force) versus geometric distortion of the mitral apparatus by LV dilation (augmented leaflet tethering). These are inseparable in systole, but restricted leaflet motion has also been observed in diastole, and attributed to reduced mitral inflow. Methods. Diastolic mitral leaflet excursion and orifice area were measured by two-dimensional echocardiography in 58 patients with global LV dysfunction, 36 with and 22 without IMLC, compared with 21 normal subjects. The biplane Simpson's method was used to calculate LV ejection volume, which equals mitral inflow volume in the absence of aortic regurgitation. Results. The diastolic mitral leaflet excursion angle was markedly reduced in patients with IMLC compared with those without IMLC, whose ventricles were smaller, and normal subjects (17 +/- 10 degrees vs. 58 +/- 13 degrees vs. 67 +/- 8 degrees, p < 0.0001). Excursion angle was dissociated from mitral inflow volume (r(2) = 0.04); excursion was reduced in patients with IMLC despite a normal inflow volume in the larger ventricles with MR (60 +/- 25 vs. 61 +/- 12 ml in normal subjects, p = NS), and excursion was nearly normal in patients without IMLC despite reduced inflow volume (40 +/- 10 ml, p < 0.001 vs. normal subjects). The anterior leaflet when maximally open coincided well with the line connecting its attachments to the anterior annulus and papillary muscle tip (angular difference = 3 +/- 7 degrees vs. 25 +/- 9 degrees vs. 32 +/- 10 degrees in patients with and without IMLC vs. normal subjects, p < 0.0001). In patients with IMLC, the leaflet tip orifice was smaller in an anteroposterior direction but wider than in the other groups, giving a normal total area (6.8 +/- 1.8 vs. 7.1 +/- 1.2 vs. 6.9 +/- 0.8 cm(2), p = NS). Conclusions. Patients with LV dysfunction and systolic IMLC also have restricted diastolic leaflet excursion that is independent of inflow volume, coincides with the tethering line connecting the annulus and papillary muscle and reflects limitation of anterior motion relative to the posteriorly placed papillary muscles without a decrease in total orifice area. These observations are consistent with increased tethering by displaced mitral leaflet attachments in the dilated ventricles of patients,vith IMLC that can restrict both diastolic opening and systolic closure. (C) 1998 by the American College of Cardiology. C1 Harvard Univ, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. RP Levine, RA (reprint author), Harvard Univ, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Sch Med,Dept Med, VBK 508,32 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 38176]; PHS HHS [53702] NR 53 TC 50 Z9 52 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 AUG PY 1998 VL 32 IS 2 BP 398 EP 404 DI 10.1016/S0735-1097(98)00237-X PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 108NW UT WOS:000075273200015 PM 9708467 ER PT J AU Lamich, R Ballester, M Marti, V Brossa, V Aymat, R Carrio, I Berna, L Camprecios, M Puig, M Estorch, M Flotats, A Bordes, R Garcia, J Auge, JM Padro, JM Caralps, JM Narula, J AF Lamich, R Ballester, M Marti, V Brossa, V Aymat, R Carrio, I Berna, L Camprecios, M Puig, M Estorch, M Flotats, A Bordes, R Garcia, J Auge, JM Padro, JM Caralps, JM Narula, J TI Efficacy of augmented immunosuppressive therapy for early vasculopathy in heart transplantation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; MYOCARDIAL PERFUSION SCINTIGRAPHY; CARDIAC TRANSPLANTATION; ALLOGRAFT VASCULOPATHY; VASCULAR REJECTION; RECIPIENTS; TL-201; ARTERIOSCLEROSIS; ATHEROSCLEROSIS; REINNERVATION AB Objectives. The present study was undertaken to prospectively and comparatively evaluate the role of serial myocardial per fusion imaging and coronary angiography for the detection of early vasculopathy in a large patient population and also to determine the short- and long-term efficacy of augmented immunosuppressive therapy in the potential reversal of the early vasculopathy. Background. Allograft vasculopathy is the commonest cause of death after the first year of heart transplantation. Anecdotal studies have reported the efficacy of augmented immunosuppressive therapy after early detection of vascular involvement. However, no prospective study has evaluated the feasibility of early detection and treatment of allograft vasculopathy. Methods. In 76 cardiac allograft recipients, 230 coronary angiographic and 376 scintigraphic studies were performed in a follow-up period of 8 years. Angiography was performed at 1 month and every pear after transplantation, and thallium-201 scintigraphy at 1, 3, 6 and It months after transplantation and twice a year thereafter, Prospective follow up of 76 patients showed that 18 developed either angiographic or scintigraphic evidence of coronary vasculopathy. All episodes were treated with 3-day methylprednisolone pulse and antithymocyte globulin. Results. Twenty-two episodes of vasculopathy were diagnosed and treated in these 18 patients. Of these 22 episodes, tffo were detected only by angiography, seven by both angiography and scintigraphy, four by scintigraphy and histologic evidence of vasculitis and nine episodes only by thallium-201 scintigraphy studies. Angiographic and/or scintigraphic resolution was observed in 15 of the 22 episodes (68%) with augmented immunosuppression. The likelihood of regression was higher when treatment was instituted within the first year of transplantation (92%) than after the first gear (40%) (p = 0.033). Eighty percent of patients who responded to follow-up. Conclusions. The present study suggests that early detection of allograft coronary vasculopathy is feasible with surveillance myocardial perfusion or coronary angiographic studies. When identified early after transplantation, immunosuppressive treatment may result in regression of coronary disease. (C) 1998 by the American College of Cardiology. C1 Hosp Santa Cruz & San Pablo, Cardiomyopathy & Transplantat Program, E-08025 Barcelona, Spain. Hosp Santa Cruz & San Pablo, Nucl Med Serv, E-08025 Barcelona, Spain. Hosp Santa Cruz & San Pablo, Dept Pathol, E-08025 Barcelona, Spain. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Ballester, M (reprint author), Hosp Santa Cruz & San Pablo, Cardiomyopathy & Transplantat Program, Sant Antoni M Claret 167, E-08025 Barcelona, Spain. RI PUIG CAMPMANY, MIREIA/G-3580-2016 OI PUIG CAMPMANY, MIREIA/0000-0001-6416-3341 NR 30 TC 34 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1998 VL 32 IS 2 BP 413 EP 419 DI 10.1016/S0735-1097(98)00234-4 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 108NW UT WOS:000075273200017 PM 9708469 ER PT J AU Dretler, SP AF Dretler, SP TI Contemporary urological intervention for cystinuric patients: Immediate and long-term impact and implications - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dretler, SP (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1998 VL 160 IS 2 BP 344 EP 345 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 102MM UT WOS:000074928200011 ER PT J AU Letran, JL Blase, AB Loberiza, FR Meyer, GE Ransom, SD Brawer, MK AF Letran, JL Blase, AB Loberiza, FR Meyer, GE Ransom, SD Brawer, MK TI Repeat ultrasound guided prostate needle biopsy: Use of free-to-total prostate specific antigen ratio in predicting prostatic carcinoma SO JOURNAL OF UROLOGY LA English DT Article DE prostate-specific antigen; prostatic neoplasms; biopsy, needle ID CANCER; SERUM; MEN; DENSITY AB Purpose: Despite being the most useful tumor marker for the diagnosis of patients with prostate cancer, serum prostate specific antigen (PSA) is still hampered by lack of specificity. A negative prostate biopsy is associated with a 20 to 40% incidence of positive repeat biopsy in men with persistently elevated serum PSA levels. We determine whether the free-to-total PSA ratio could be predictive of prostate cancer in men undergoing repeat biopsy. Materials and Methods: Archival sera, drawn before the first biopsy, were gathered from 51 men with a total serum PSA of 2 to 15 ng./ml. who underwent repeat prostate needle biopsy for various indications. The percent free PSA was calculated using the Hybritech Tandem-R dagger free and total PSA as well as Dianon Systems free double dagger and Hybritech total PSA assays. The free-to-total PSA ratio results between the cancer and noncancer groups were compared using Student's t test. Results: The median Hybritech free-to-total PSA ratio was significantly lower in patients with positive repeat prostate needle biopsy compared to those with negative biopsy (14.9 versus 19.4%, p = 0.05). Total PSA as well as the percent Dianon free-to-Hybritech total PSA ratio were not significantly different between the 2 groups of men. Conclusions: For total PSA in the range of 2 to 15 ng./ml. Hybritech free-to-total PSA ratio appeared to aid in the prediction of cancer on repeat biopsy. C1 Univ Washington, Med Ctr, Dept Urol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Urol Sect, Seattle, WA USA. Hybritech Inc, San Diego, CA USA. Univ Iowa, Dept Psychiat Prevent Med, Iowa City, IA USA. RP Brawer, MK (reprint author), NW Prostate Inst, 1560 N 115th St,Suite 209, Seattle, WA 98133 USA. NR 20 TC 36 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1998 VL 160 IS 2 BP 426 EP 429 DI 10.1016/S0022-5347(01)62915-X PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 102MM UT WOS:000074928200036 PM 9679891 ER PT J AU McDougal, WS Lunz, ME Hirst, G AF McDougal, WS Lunz, ME Hirst, G TI Postgraduate education: Does it improve the knowledge base of practitioners with time? SO JOURNAL OF UROLOGY LA English DT Article DE education, medical, continuing; education, medical, graduate AB Purpose: We evaluate the effect of the provision of postgraduate educational material on improving practitioner knowledge base during a 3-year period. Materials and Methods: A total of 210 urologists were provided 67 monographs in a 2-year period. They were given a pretest before and posttest 1 year after receipt of all monographs. Results: There was significant improvement in posttest scores for the group as a whole. Improvement correlated with years post-training and number of monographs read. Multivariate analysis revealed the number of monographs read was the only independent predictor of outcome. Conclusions: Although the improvement in test scores was significant and did correlate with the postgraduate educational material read, it was modest. This finding raises significant concerns about the usefulness of this format for graduate medical education. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,GRB 1102, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1998 VL 160 IS 2 BP 502 EP 504 DI 10.1016/S0022-5347(01)62940-9 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 102MM UT WOS:000074928200061 PM 9679913 ER PT J AU Swartz, MA Kaipainen, AH Slavin, SA Jain, RK AF Swartz, MA Kaipainen, AH Slavin, SA Jain, RK TI Quantification of lymphatic function: Effects of lymphedema and lymphangiogenesis SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Steele Lab Tumor Biol, Boston, MA 02114 USA. RI Swartz, Melody/B-7633-2009; Swartz, Melody/F-9563-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PD AUG PY 1998 VL 35 SU 2 MA o52 BP 14 EP 14 PG 1 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 136YN UT WOS:000076886800052 ER PT J AU Wagner, CT Durante, W Christodoulides, N Hellums, JD Schafer, AI AF Wagner, CT Durante, W Christodoulides, N Hellums, JD Schafer, AI TI Hemodynamic forces induce the expression of heme oxygenase in cultured vascular smooth muscle cells SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract C1 Rice Univ, Cox Lab Biomed Engn, Houston, TX 77251 USA. Houston VA Med Ctr, Med Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PD AUG PY 1998 VL 35 SU 2 MA p75 BP 42 EP 42 PG 1 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 136YN UT WOS:000076886800163 ER PT J AU Sckell, A Safabakhsh, N Dellian, M Jain, PK AF Sckell, A Safabakhsh, N Dellian, M Jain, PK TI Primary tumor induced inhibition of angiogenesis at a secondary site - Effects on physiological properties of newly formed vessels. SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. Univ Bern, Inselspital, Dept Orthopaed Surg, CH-3010 Bern, Switzerland. Temple Sch Med, Philadelphia, PA USA. Univ Munich, Klinikum Grosshadern, Dept Otorhinolaryngol Head & Neck Surg, D-8000 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PD AUG PY 1998 VL 35 SU 2 MA p212 BP 76 EP 76 PG 1 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 136YN UT WOS:000076886800297 ER PT J AU Fukumura, D Chen, Y Gohongi, T Seed, B Jain, RK AF Fukumura, D Chen, Y Gohongi, T Seed, B Jain, RK TI Simultaneous monitoring of VEGF promoter activity and tissue PO2 in vivo. SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PD AUG PY 1998 VL 35 SU 2 MA p216 BP 77 EP 77 PG 1 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 136YN UT WOS:000076886800301 ER PT J AU Juang, JH Kuo, CH Hsu, BRS AF Juang, JH Kuo, CH Hsu, BRS TI Effects of vascular endothelial growth factor on the neovascularization of islet isografts SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Howard Univ, Dept Anat, Washington, DC 20059 USA. RI Juang, Jyuhn-Huarng /C-2465-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PD AUG PY 1998 VL 35 SU 2 MA p215 BP 77 EP 77 PG 1 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 136YN UT WOS:000076886800303 ER PT J AU Lichtenbeld, HC Munn, LL Kopesky, PW Leak, LV Jain, RK AF Lichtenbeld, HC Munn, LL Kopesky, PW Leak, LV Jain, RK TI Response of lymphatic endothelial cells to tumor interstitial fluid. SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Howard Univ, Dept Anat, Washington, DC 20059 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PD AUG PY 1998 VL 35 SU 2 MA p217 BP 77 EP 77 PG 1 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 136YN UT WOS:000076886800300 ER PT J AU Hansen-Algenstaedt, N Fukumura, D Helmingler, G Jain, RK AF Hansen-Algenstaedt, N Fukumura, D Helmingler, G Jain, RK TI Metabolic microenvironment during tumor growth, regression and relapse. SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Hartford, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PD AUG PY 1998 VL 35 SU 2 MA p292 BP 96 EP 96 PG 1 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 136YN UT WOS:000076886800377 ER PT J AU Abbott, WM AF Abbott, WM TI Leadership or survival In the health care revolution: Choices for the vascular surgeon SO JOURNAL OF VASCULAR SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. RP Abbott, WM (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, 15 Parkman St,ACC 458, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 1998 VL 28 IS 2 BP 353 EP 353 DI 10.1016/S0741-5214(98)70173-9 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 109VM UT WOS:000075344600025 PM 9719333 ER PT J AU Gertler, JP AF Gertler, JP TI Quality assessment and vascular disease: The analytic imperatives confronting vascular surgeons in the new era SO JOURNAL OF VASCULAR SURGERY LA English DT Editorial Material ID OF-LIFE; OUTCOMES; ISCHEMIA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA 02114 USA. RP Gertler, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, ACC 464,15 Parkman St, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 1998 VL 28 IS 2 BP 354 EP 357 DI 10.1016/S0741-5214(98)70174-0 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 109VM UT WOS:000075344600026 PM 9719334 ER PT J AU Mort, EA AF Mort, EA TI Managing the demand for vascular surgery: The imperative, the opportunity SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Joint Annual Meeting of the Society-for-Vascular-Surgery / North-American-Chapter of the International-Society-for-Cardiovascular-Surgery CY JUN 01-04, 1997 CL BOSTON, MASSACHUSETTS SP Soc Vasc Surg, Int Soc Cardiovasc Surg, N Amer Chapter ID SELF-CARE EDUCATION; DECISION-MAKING; BREAST-CANCER; PATIENT; PARTICIPATION; QUALITY; INFORMATION; PREFERENCES; PROGRAM; DOCTOR C1 Massachusetts Gen Hosp, Operat Improvement & Decis Support Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Internal Med Div, Boston, MA 02114 USA. RP Mort, EA (reprint author), Massachusetts Gen Hosp, Operat Improvement & Decis Support Unit, 712 Founders House,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 1 Z9 2 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 1998 VL 28 IS 2 BP 361 EP 364 DI 10.1016/S0741-5214(98)70176-4 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 109VM UT WOS:000075344600028 PM 9719336 ER PT J AU Abbott, WM AF Abbott, WM TI The Operations Improvement Program at Massachusetts General Hospital: A paradigm for change SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Joint Annual Meeting of the Society-for-Vascular-Surgery / North-American-Chapter of the International-Society-for-Cardiovascular-Surgery CY JUN 01-04, 1997 CL BOSTON, MASSACHUSETTS SP Soc Vasc Surg, Int Soc Cardiovasc Surg, N Amer Chapter C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. RP Abbott, WM (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, 15 Parkman St,ACC 458, Boston, MA 02114 USA. NR 2 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 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD AUG PY 1998 VL 28 IS 2 BP 381 EP 383 DI 10.1016/S0741-5214(98)70181-8 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 109VM UT WOS:000075344600033 PM 9719341 ER PT J AU Gauduin, MC Glickman, RL Means, R Johnson, RP AF Gauduin, MC Glickman, RL Means, R Johnson, RP TI Inhibition of simian immunodeficiency virus (SIV) replication by CD8(+) T lymphocytes from macaques immunized with live attenuated SIV SO JOURNAL OF VIROLOGY LA English DT Article ID ANTI-HIV ACTIVITY; PERIPHERAL-BLOOD; RHESUS-MONKEYS; SUPPRESSIVE FACTORS; DELETION MUTANT; TROPIC HIV-1; NEF GENE; CELL; INFECTION; MIP-1-ALPHA AB Characterization of immune responses induced by live attenuated simian immunodeficiency virus (SIV) strains may yield clues to the nature of protective immunity induced by this vaccine approach. We investigated the ability of CD8+ T lymphocytes from rhesus macaques immunized with the live, attenuated SIV strain SIVmac239 Delta nef or SIVmac239 Delta 3 to inhibit SIV replication. CD8+ T lymphocytes from immunized animals were able to potently suppress SN replication in autologous SIV-infected CD4+ T cells. Suppression of SIV replication by unstimulated CD8+ T cells required direct contact and was major histocompatibility complex (MRC) restricted. However, CD3-stimulated CD8+ T cells produced soluble factors that inhibited SIV replication in an MHC-unrestricted fashion as much as 30-fold. Supernatants from stimulated CD8+ T cells were also able to inhibit replication of both CCR5- and CXCR4-dependent human immunodeficiency virus type I (HIV-1) strains. Stimulation of CD8+ cells with cognate cytotoxic T-lymphocyte epitopes also induced secretion of soluble factors able to inhibit SIV replication. Production of RANTES, macrophage inhibitory protein 1 alpha (MTP-la), or MIP-IP from stimulated CD8+ T cells of vaccinated animals was almost 10-fold higher than that from stimulated CD8+ T cells of control animals. However, addition of antibodies that neutralize these beta-chemokines, either alone or in combination, only partly blocked inhibition of SIV and HIV replication by soluble factors produced by stimulated CD8+ T cells. Our results indicate that inhibition of SIV replication by CD8+ T cells from animals immunized with live attenuated SIV strains involves both MHC-restricted and -unrestricted mechanisms and that MHC-unrestricted inhibition of SIV replication is due principally to soluble factors other than RANTES, MIP-1 alpha, and MIP-1 beta. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Microbiol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. FU NCRR NIH HHS [K26 RR000168, P51 RR000168]; NIAID NIH HHS [P01 AI035365, U01 AI035365] NR 59 TC 67 Z9 67 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 AUG PY 1998 VL 72 IS 8 BP 6315 EP 6324 PG 10 WC Virology SC Virology GA ZZ446 UT WOS:000074730200006 PM 9658070 ER PT J AU Sullivan, N Sun, Y Binley, J Lee, J Barbas, CF Parren, PWHI Burton, DR Sodroski, J AF Sullivan, N Sun, Y Binley, J Lee, J Barbas, CF Parren, PWHI Burton, DR Sodroski, J TI Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID FC-GAMMA-R; V3 LOOP; HIV-1 GP120; COMBINATORIAL LIBRARIES; SYNCYTIUM FORMATION; RECEPTOR-BINDING; MEMBRANE-FUSION; V1/V2 REGION; CELL-LINES; NEUTRALIZATION AB Infection by some human immunodeficiency virus type 1 (HIV-1) isolates is enhanced by the binding of subneutralizing concentrations of soluble receptor, soluble CD4 (sCD4), or monoclonal antibodies directed against the viral envelope glycoproteins. In this work, we studied the abilities of different antibodies to mediate activation of the envelope glycoproteins of a primary HIV-1 isolate, YU2, and identified the regions of gp120 envelope glycoprotein contributing to activation. Binding of antibodies to a variety of epitopes on gp120, including the CD4 binding site, the third variable (V3) loop, and CD4-induced epitopes, enhanced the entry of viruses containing YU2 envelope glycoproteins. Fab fragments of antibodies directed against either the CD4 binding site or V3 loop also activated YU2 virus infection. The activation phenotype was conferred on the envelope glycoproteins of a laboratory-adapted HIV-1 isolate (HXBc2) by replacing the gp120 V3 loop or V1/V2 and V3 loops with those of the YU2 virus. Infection by the YU2 virus in the presence of activating antibodies remained inhibitable by macrophage inhibitory protein Ip, indicating dependence on the CCR5 coreceptor on the target cells. Thus, antibody enhancement of YU2 entry involves neither Fc receptor binding nor envelope glycoprotein cross-linking, is determined by the same variable loops that dictate enhancement by sCD4, and probably proceeds by a process fundamentally similar to the receptor-activated virus entry pathway. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div Human Retrovirol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. NYU, Sch Med, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div Human Retrovirol, 44 Binney St,Jimmy Fund Bldg,Room JFB 824, Boston, MA 02115 USA. EM Joseph_Sodroski@dfci.harvard.edu OI Parren, Paul/0000-0002-4365-3859 FU NIAID NIH HHS [AI 31783, AI 24755, R01 AI031783, R37 AI024755] NR 82 TC 99 Z9 102 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 AUG PY 1998 VL 72 IS 8 BP 6332 EP 6338 PG 7 WC Virology SC Virology GA ZZ446 UT WOS:000074730200008 PM 9658072 ER PT J AU Zeitels, SM Kim, J AF Zeitels, SM Kim, J TI Soft-palate reconstruction with a "SCARF" superior-constrictor advancement-rotation flap SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 31-FEB 02, 1997 CL BOSTON, MASSACHUSETTS SP Amer Laryngol Rhinol & Otol Soc, E Sect DE palate cancer; tonsil cancer; palate reconstruction; velopharynx reconstruction; oropharynx ID TEMPORALIS MUSCLE FLAP; LASER SURGERY; ORAL CAVITY; CARCINOMA; CO2-LASER; DEFECTS; HEAD AB Reconstruction of hemi-soft-palate defects after tumor resection is usually done by means of a regional flap, free-tissue transfer or a prosthesis. These options vary in complexity and have a number of shortcomings. A local myomucosal flap was designed that employs a superior-constrictor advancement-rotation flap (SCARF) to achieve circumferential closure of the velopharynx and to re-establish its valvular sphincteric function. Ten patients underwent a SCARF reconstruction of the velopharynx after 35% to 65% of the soft palate was resected. All patients reestablished normal velopharyngeal function without significant phonatory or deglutitive disability. Two patients did require a second-stage reinforcement of the suture line after partial dehiscence, The SCARF reconstruction of the soft palate is simple, fast, and reliable and there is no significant donor site morbidity, Patients resume oral intake earlier than standard reconstructive approaches. The SCARF can be done transorally, which allows for primary resection and discontinuous neck dissection. These factors facilitate short hospitalization and effective use of resources. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Boston Vet Affairs Med Ctr, Otolaryngol Sect, Boston, MA USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 18 Z9 19 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 1998 VL 108 IS 8 BP 1136 EP 1140 DI 10.1097/00005537-199808000-00006 PN 1 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 108GK UT WOS:000075257600006 PM 9707231 ER PT J AU Metson, R Gliklich, RE Cosenza, M AF Metson, R Gliklich, RE Cosenza, M TI A comparison of image guidance systems for sinus surgery SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 30-FEB 01, 1998 CL NEW YORK, NEW YORK SP Amer Laryngol Rhinol & Otol Soc, Eastern Sect AB Objective: Intraoperative computed tomographic guidance systems are available which utilize either electromagnetic (radiofrequency) or optical (infrared) signals to localize instruments within the surgical field. The objective of this study was to compare the use of these two different image guidance technologies for sinus surgery. Study Design: Prospective cohort study. Methods: The electromagnetic-based InstaTrak system (n = 24) and the optical-based Stealth-Station (n = 49) were compared in a series of 73 consecutive sinus series which utilized image guidance technology, Results: Both the electromagnetic and optical systems provided anatomic localization to within 2 mm during surgery. Intraoperative reregistration was effective in correcting for any anatomic drift. There were no intraoperative complications. Mean operative times were 156.3 +/- 8.9 minutes for the electromagnetic and 139.2 +/- 17.7 minutes for the optical system (P < .05), The average intraoperative blood loss did not differ significantly between groups (electromagnetic, 190.6 +/- 28.7 mL; optical, 172.4 +/- 23.0 mL). Each system was noted to have limitations. The presence of metallic objects in the operative field interfered with functioning of the electromagnetic system, whereas the optical system required a clear line of sight to be maintained between the infrared camera and surgical handpiece. Both systems required specialized headsets to be worn by patients during surgery to monitor head position. The electromagnetic system also required these headsets to be worn during the preoperative computed tomography scan. Conclusion: Although these two image guidance systems both proved valuable for anatomic localization during sinus surgery, individual preferences can be based on distinct differences in their design and operation. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Grandview Hosp & Med Ctr, Dept Otolaryngol, Dayton, OH USA. RP Metson, R (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. NR 13 TC 95 Z9 97 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 1998 VL 108 IS 8 BP 1164 EP 1170 DI 10.1097/00005537-199808000-00012 PN 1 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 108GK UT WOS:000075257600012 PM 9707237 ER PT J AU Stone, RM AF Stone, RM TI Overview of randomized trials of growth factors in acute myeloid leukemia SO LEUKEMIA & LYMPHOMA LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; ELDERLY PATIENTS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG PY 1998 VL 30 SU 1 BP 38 EP 40 DI 10.3109/10428199809058628 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 130WC UT WOS:000076542500020 ER PT J AU Kelly, K AF Kelly, K TI The uncomplicated guide to diabetes complications. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Kelly, K (reprint author), Massachusetts Gen Hosp, Treadwell 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 AUG PY 1998 VL 123 IS 13 BP 123 EP 123 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 108XR UT WOS:000075291800262 ER PT J AU Moore, SA Lopez, A Richardson, A Pahlavani, MA AF Moore, SA Lopez, A Richardson, A Pahlavani, MA TI Effect of age and dietary restriction on expression of heat shock protein 70 in rat alveolar macrophages SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE aging; dietary restriction; macrophage; heat shock protein; rat ID PERITONEAL-MACROPHAGES; SPLEEN LYMPHOCYTES; SUPEROXIDE ANION; MICE; ADHERENCE; INVITRO; TRANSCRIPTION; INTERLEUKIN-2; RETARDATION; MODULATION AB Dietary restriction (DR) is the only effective experimental manipulation known to retard aging in rodents, and this manipulation has been shown to alter a variety of processes that change with age. However, there is no information on the effect of DR on macrophage function. In the present study, the effect of aging and DR on the ability of alveolar macrophages (AMs) to express the heat shock gene, hsp70 was studied. AMs were isolated by lavage from the lungs of young (4-6 months) and old (24-26 months) rats fed either ad libitum (AL) or a restricted diet (60% of AL). There was no age-related change in the number of cells recovered from young and old rats fed AL. However, the number of cells recovered from the lungs of the DR rats was reduced, and this decrease was statistically significant in young rats. The expression of heat shock protein 70 (hsp70) was measured by the level of the hsp70 mRNA transcript in total RNA isolated from AMs cultured under two conditions: in suspension and after adherence to plastic. When AMs were incubated at 37 degrees C in suspension, no detectable hsp70 expression was observed; however, hsp70 expression was induced at 37 degrees C when the AMs adhered to the plastic culture dishes. Hsp70 mRNA levels were rapidly induced by heat shock (43 degrees C, 1 h) in AMs cultured both in suspension and on plastic. The induction of hsp70 expression did not change significantly with either age or DR in AMs cultured in suspension. In contrast, the induction of hsp70 mRNA levels by AMs adherent to plastic culture plates decreased approximately 70% with age, and hsp70 induction was greater in AMs isolated from DR rats; this difference was statistically significant in young rats. The induction of hsp70 by heat shock (43 degrees C, 1 h) also decreased with age in the adherent AMs, and DR increased the induction of hsp70 expression three- to fourfold in adherent AMs from both young and old rats. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Audie L Murphy Mem Vet Hosp, S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182, 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, Geriatr Res Educ & Clin Ctr 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM pahlavani@uthscsa.edu FU NIA NIH HHS [AG00677, AG01548, AG00205] NR 59 TC 22 Z9 24 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD AUG 1 PY 1998 VL 104 IS 1 BP 59 EP 73 DI 10.1016/S0047-6374(98)00052-9 PG 15 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 112AQ UT WOS:000075471800005 PM 9751432 ER PT J AU Lee, SJ Liljas, B Neumann, PJ Weinstein, MC Johannesson, M AF Lee, SJ Liljas, B Neumann, PJ Weinstein, MC Johannesson, M TI The impact of risk information on patients' willingness to pay for autologous blood donation SO MEDICAL CARE LA English DT Article DE blood transfusion; risks; information; cost-effectiveness; cost-benefit; contingent valuation; willingness to pay ID COST-EFFECTIVENESS; UNITED-STATES; HEALTH-CARE; TO-PAY; TRANSFUSION; PERCEPTIONS; COLLECTION; VALUATION; RESPONSES; PROGRAMS AB OBJECTIVES. For contingent valuation to provide valid values for policy making, it is important that respondents be well informed about the goods they are asked to value. Few studies, however, have tested the impact of providing this information This study assessed the impact of risk information on patients' willingness to pay for autologous blood donation and derived the willingness to pay in a sample of informed patients. METHODS. Patients were randomized either to receive information about the risks of complications from allogeneic (volunteer) blood transfusions or to base their willingness to pay responses on their own prior knowledge. Four hundred twelve autologous blood donors were recruited from three study sites. Self-administered questionnaires collected information on willingness to pay, risk perceptions, and socioeconomic information. RESULTS. As predicted by our theoretical model, providing risk information reduced the variance in the willingness to pay for autologous blood donation. A tendency for information to reduce the willingness to pay was also found, suggesting that uninformed patients, on average, overestimate the risks of allogeneic blood transfusions. The median willingness to pay in the informed sample was approximately $750 to $1,100, depending on the estimation method, compared with $800 to $1,900 in the uninformed group. Willingness to pay was significantly related to perceived transfusion risk, personal income, and dread of transfusions. CONCLUSIONS. Our results are consistent with an economic model where individuals update their prior risk perceptions with new information. The willingness to pay in the informed sample was far higher than the costs of autologous blood donation, suggesting that total benefits outweigh the costs of the procedure. C1 Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Program Econ Evaluat Med Technol, Boston, MA 02115 USA. Univ Lund, Dept Econ, Lund, Sweden. Ctr Hlth Econ, Stockholm, Sweden. Stockholm Sch Econ, S-11383 Stockholm, Sweden. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 454 Brookline Ave,Suite 23, Boston, MA 02115 USA. EM sjlee@bics.bwh.harvard.edu RI Johannesson, Magnus/E-9680-2011 OI Johannesson, Magnus/0000-0001-8759-6393 NR 41 TC 24 Z9 24 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1998 VL 36 IS 8 BP 1162 EP 1173 DI 10.1097/00005650-199808000-00005 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 107RY UT WOS:000075224200005 PM 9708589 ER PT J AU Petersen, LA Burstin, HR O'Neil, AC Orav, EJ Brennan, TA AF Petersen, LA Burstin, HR O'Neil, AC Orav, EJ Brennan, TA TI Nonurgent emergency department visits - The effect of having a regular doctor SO MEDICAL CARE LA English DT Article; Proceedings Paper CT National Meeting of the Society-of-General-Internal-Medicine CY APR 28, 1994 CL WASHINGTON, D.C. SP Soc Gen Internal Med DE primary health care; emergency services, hospital; emergency department utilization; health services need; choice behavior; emergency medicine; adult ID PUBLIC HOSPITAL EMERGENCY; PRIMARY-CARE; ROOM USE; MEDICAL-CARE; ACCESS AB OBJECTIVES. The authors assess the association between having a regular doctor and presentation for nonurgent versus urgent emergency department visits while controlling for potential confounders such as sociodemographics, health status, and comorbidity. METHODS. A cross-sectional study was conducted in emergency departments of five urban teaching hospitals in the northeast. Adult patients presenting with chest pain, abdominal pain, or asthma (n = 1696; 88% of eligible) were studied. Patients completed a survey on presentation, reporting sociodemographics, health status, comorbid diseases, and relationship with a regular doctor. Urgency on presentation was assessed by chart review using explicit criteria. RESULTS. Of the 1,696 study participants, 852 (50%) presented with nonurgent complaints. In logistic regression analyses, absence of a relationship with a regular physician was an independent correlate of presentation for a nonurgent emergency department visit (odds ratio 1.6; 95% confidence interval 1.2, 2.2) when controlling for age, gender, marital status, health status, and comorbid diseases. Race, lack of insurance, and education were not associated with nonurgent use. CONCLUSIONS. Absence of a relationship with a regular doctor was correlated with use of the emergency department for selected nonurgent conditions when controlling for important potential confounders. Our study suggests that maintaining a relationship with a regular physician may reduce nonurgent use of the emergency department regardless of insurance status or health status. C1 Brockton W Roxbury Vet Affairs Med Ctr, Hlth Serv Res & Dev, W Roxbury, MA USA. Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 02115 USA. Brigham & Womens Hosp, Clin Initiat Dev Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Petersen, LA (reprint author), Houston VA Med Ctr, Hlth Serv Res & Dev 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 25 TC 80 Z9 81 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1998 VL 36 IS 8 BP 1249 EP 1255 DI 10.1097/00005650-199808000-00012 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 107RY UT WOS:000075224200012 PM 9708596 ER PT J AU Viviani, MA De Marie, S Graybill, JR Yamaguchi, H Anaissie, E Caillot, D AF Viviani, MA De Marie, S Graybill, JR Yamaguchi, H Anaissie, E Caillot, D TI New approaches to antifungal chemotherapy SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT XIVth Congress of the International-Society-for-Human-and-Animal-Mycology CY JUN 08-13, 1997 CL PARMA, ITALY SP Int Soc Human & Anim Mycol DE antifungal chemotherapy; invasive mycoses; lipid-based amphotericin B; new antifungals; antifungal combined therapy ID INVASIVE PULMONARY ASPERGILLOSIS; HUMAN-IMMUNODEFICIENCY-VIRUS; RESISTANT CANDIDA-ALBICANS; LIPOSOMAL AMPHOTERICIN-B; IN-VITRO ACTIVITY; MURINE CRYPTOCOCCAL MENINGITIS; SYSTEMIC FUNGAL-INFECTIONS; ANTIBIOTIC BENANOMICIN-A; CELL-WALL SYNTHESIS; AIR CRESCENT SIGN AB The antifungal agents currently available to treat invasive fungal infections are limited in both number and usefulness. Treatment with the polyene amphotericin B (AmB), and with several azoles, in particular fluconazole and itraconazole, is the mainstay of antifungal chemotherapy. However, the clinical usefulness of these drugs is hampered by drawbacks associated with their safety and/or efficacy. There are two approaches to overcome this situation. One is to discover and develop new antifungal agents or formulations with advantages over and/or complementary to existing drugs. For this purpose, the following three categories of new drugs have been the major targets of study and development: (i) lipid formulations of polyenes, (ii) azoles (including cyclodextrin-complexes), and (iii) nonazole compounds, particularly those of microbial origin (antibiotics). C1 Univ Milano, Ist Igiene & Med Prevent, Milano, Italy. Univ Rotterdam Hosp, Dept Med Microbiol & Infect Dis, Rotterdam, Netherlands. Univ Texas, Dept Infect Dis, Ctr Hlth Sci, San Antonio, TX USA. Vet Adm Hosp, San Antonio, TX USA. Teikyo Univ, Sch Med, Dept Immunol & Microbiol, Tokyo 173, Japan. Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Ctr Hosp Reg Univ, Hop Bocage, Serv Hematol Clin, Dijon, France. RP Viviani, MA (reprint author), Univ Milano, Ist Igiene & Med Prevent, Milano, Italy. NR 176 TC 15 Z9 15 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD AUG PY 1998 VL 36 SU 1 BP 194 EP 206 PG 13 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 115LG UT WOS:000075665900022 PM 9988508 ER PT J AU McGinnis, MR Pasarell, L Sutton, DA Fothergill, AW Cooper, CR Rinaldi, MG AF McGinnis, MR Pasarell, L Sutton, DA Fothergill, AW Cooper, CR Rinaldi, MG TI In vitro activity of voriconazole against selected fungi SO MEDICAL MYCOLOGY LA English DT Article DE Amphotericin B; fluconazole; itraconazole; voriconazole ID IN-VITRO; EXPERIMENTAL-MODEL; ANTIFUNGAL AGENT; UK-109,496; FLUCONAZOLE; TRIAZOLE; ASPERGILLOSIS; ITRACONAZOLE AB Fifty-nine isolates consisting of 14 genera and 33 species of ascomycetes, basidiomycetes, and zygomycetes were tested against amphotericin B, fluconazole, itraconazole and voriconazole using an in vitro modified macrobroth dilution procedure based upon the NCCLS M27-A standard method for yeasts. The triazoles voriconazole and itraconazole had similar MIC values, except for Acremonium alabamensis, A. strictum, Fusarium oxysporum, F. solani and Wangiella dermatitidis, which had substantially lower voriconazole MIC values. Voriconazole MIC values were lower than those for itraconazole for the 17 species of Trichosporon tested. Fluconazole had high MIC values, often greater than 128 mu g ml(-1). C1 Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77555 USA. WHO, Collaborating Ctr Trop Dis, Galveston, TX USA. Univ Texas, Hlth Sci Ctr, Fungus Testing Lab, San Antonio, TX USA. Audie L Murphy Mem Vet Hosp, Clin Microbiol Labs, San Antonio, TX 78284 USA. RP McGinnis, MR (reprint author), Univ Texas, Med Branch, Dept Pathol, 301 Univ Blvd,Keiller Bldg 1-116, Galveston, TX 77555 USA. NR 17 TC 64 Z9 67 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD AUG PY 1998 VL 36 IS 4 BP 239 EP 242 DI 10.1080/02681219880000361 PG 4 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 112LA UT WOS:000075495100008 PM 9776841 ER PT J AU Akamatsu, Y Oettinger, MA AF Akamatsu, Y Oettinger, MA TI Distinct roles of RAG1 and RAG2 in binding the V(D)J recombination signal sequences SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STRUCTURE REQUIREMENTS; MOUSE THYMOCYTES; DNA-SEQUENCE; 2 STEPS; INITIATION; CLEAVAGE; PROTEINS; RECOGNITION; 12/23-RULE; DEFINITION AB The RAG1 and RAG2 proteins initiate V(D)J recombination by introducing double-strand breaks at the border between a recombination signal sequence (RSS) and a coding segment. To understand the distinct functions of RAG1 and RAG2 in signal recognition, we have compared the DNA binding activities of RAG1 alone and RAG1 plus RAG2 by gel retardation and footprinting analyses. RAG1 exhibits only a three- to fivefold preference for binding DNA containing an RSS over random sequence DNA. Although direct binding of RAG2 by itself was not detected, the presence of both RAG1 and RAG2 results in the formation of a RAG1-RAG2-DNA complex which is more stable and more specific than the RAG1-DNA complex: and is active in V(D)J cleavage. These results suggest that biologically effective discrimination between an RSS and nonspecific sequences requires both RAG1 and RAG2. Unlike the binding of RAG1 plus RAG2, RAG1 can bind to DNA in the absence of a divalent metal ion and does not require the presence of coding flank sequence. Footprinting of the RAG1-RAG2 complex with 1,10-phenanthroline-copper and dimethyl sulfate protection reveal that both the heptamer and the nonamer are involved. The nonamer is protected, with extensive protein contacts within the minor groove. Conversely, the heptamer is rendered more accessible to chemical attack, suggesting that binding of RAG1 plus RAG2 distorts the DNA near the coding/signal border. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM48026, R01 GM048026] NR 39 TC 100 Z9 105 U1 1 U2 5 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 AUG PY 1998 VL 18 IS 8 BP 4670 EP 4678 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 102WX UT WOS:000074950000028 PM 9671477 ER PT J AU Kim, DR Oettinger, MA AF Kim, DR Oettinger, MA TI Functional analysis of coordinated cleavage in V(D)J recombination SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STRUCTURE REQUIREMENTS; MOUSE THYMOCYTES; JOINING SIGNALS; MU TRANSPOSASE; RAG2 PROTEINS; DNA-SEQUENCE; 2 STEPS; INITIATION; 12/23-RULE; RECOGNITION AB V(D)J recombination in vivo requires a pair of signals with distinct spacer elements of 12 and 23 bp that separate conserved heptamer and nonamer motifs, Cleavage in vitro by the RAG1 and RAG2 proteins can occur at individual signals when the reaction buffer contains Mn2+, but cleavage is restricted to substrates containing two signals when Mg2+ is the divalent cation. By using a novel V(D)J cleavage substrate, we show that while the RAG proteins alone establish a moderate preference for a 12/23 pair versus a 12/12 pair, a much stricter dependence of cleavage on the 12/23 signal pair is produced by the inclusion of HMG1 and competitor double-stranded DNA, The competitor DNA serves to inhibit the cleavage of substrates carrying a 12/12 or 23/23 pair, as well as the cutting at individual signals in 12/23 substrates. We show that a 23/33 pair is more efficiently recombined than a 12/33 pair, suggesting that the 12/23 rule can be generalized to a requirement for spacers that differ from each other by a single helical turn. Furthermore, we suggest that a fixed spatial orientation of signals is required for cleavage, In general, the same signal variants that can be cleaved singly can function under conditions in which a signal pair is required. However, a chemically modified substrate with one noncleavable signal enables us to show that formation of a functional cleavage complex is mechanistically separable from the cleavage reaction itself and that although cleavage requires a pair of signals, cutting does not have to occur simultaneously at both. The implications of these results are discussed with respect to the mechanism of V(D)J recombination and the generation of chromosomal translocations. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM58026] NR 34 TC 56 Z9 56 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1998 VL 18 IS 8 BP 4679 EP 4688 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 102WX UT WOS:000074950000029 PM 9671478 ER PT J AU Gu, L Okada, Y Clinton, SK Gerard, C Sukhova, GK Libby, P Rollins, BJ AF Gu, L Okada, Y Clinton, SK Gerard, C Sukhova, GK Libby, P Rollins, BJ TI Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice SO MOLECULAR CELL LA English DT Article ID SMOOTH-MUSCLE CELLS; COLONY-STIMULATING FACTOR; HUMAN ENDOTHELIAL-CELLS; C-C CHEMOKINES; MONOCLONAL-ANTIBODIES; FUNCTIONAL EXPRESSION; CHEMOTACTIC PROTEIN-1; APOLIPOPROTEIN-E; GENE-EXPRESSION; KNOCKOUT MICE AB Recruitment of blood monocytes into the arterial subendothelium is one of the earliest steps in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1), a CC chemokine, is one likely signal involved in this process. To test MCP-l's role in atherogenesis, low density lipoprotein (LDL) receptor-deficient mice were made genetically deficient for MCP-1 and fed a high cholesterol diet. Despite having the same amount of total and fractionated serum cholesterol as LDL receptor-deficient mice with wild-type MCP-1 alleles, LDL receptor/MCP-1-deficient mice had 83% less lipid deposition throughout their aortas. Consistent with MCP-l's monocyte chemoattractant properties, compound-deficient mice also had fewer macrophages in their aortic walls. Thus, MCP-1 plays a unique and crucial role in the initiation of atherosclerosis and may provide a new therapeutic target in this disorder. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Ina Sue Perlmutter Labs, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 51 TC 1093 Z9 1144 U1 1 U2 35 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 AUG PY 1998 VL 2 IS 2 BP 275 EP 281 DI 10.1016/S1097-2765(00)80139-2 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 115TK UT WOS:000075681400014 PM 9734366 ER PT J AU Alt, FW Frank, K Sekiguchi, J Gao, Y Gu, Y Chaudhuri, J Rathbun, G Seidl, KJ Weaver, D AF Alt, FW Frank, K Sekiguchi, J Gao, Y Gu, Y Chaudhuri, J Rathbun, G Seidl, KJ Weaver, D TI Generally expressed gene products involved in VDJ recombination and DNA repair SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract ID V(D)J RECOMBINATION; KU70-DEFICIENT C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 7 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 1998 VL 35 IS 11-12 BP 681 EP 682 DI 10.1016/S0161-5890(98)90357-1 PG 2 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 131BA UT WOS:000076554800025 ER PT J AU Shcherbina, AY Rosen, FS Remold-O'Donnell, E AF Shcherbina, AY Rosen, FS Remold-O'Donnell, E TI Platelet destruction in patients with Wiskott-Aldrich Syndrome SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract C1 HMS, Ctr Blood Res, Boston, MA USA. Res Inst Pediat Hematol, Moscow, Russia. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 1998 VL 35 IS 11-12 BP 735 EP 735 DI 10.1016/S0161-5890(98)90406-0 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 131BA UT WOS:000076554800074 ER PT J AU Blacker, D Wilcox, MA Laird, NM Rodes, L Horvath, SM Go, RCP Perry, R Watson, B Bassett, SS McInnis, MG Albert, MS Hyman, BT Tanzi, RE AF Blacker, D Wilcox, MA Laird, NM Rodes, L Horvath, SM Go, RCP Perry, R Watson, B Bassett, SS McInnis, MG Albert, MS Hyman, BT Tanzi, RE TI Alpha-2 macroglobulin is genetically associated with Alzheimer disease SO NATURE GENETICS LA English DT Article ID RECEPTOR-RELATED PROTEIN; APOLIPOPROTEIN-E; DEGRADATION; ALPHA(2)-MACROGLOBULIN; BINDING; COMPLEX; ALLELE AB Alpha-2-macroglobulin (alpha-M-2; encoded by the gene A2M) is a serum pan-protease inhibitor that has been implicated in Alzheimer disease (AD) based on its ability to mediate the clearance and degradation of A beta, the major component of beta-amyloid deposits. Analysis of a deletion in the A2M gene at the 5' splice site of 'exon II' of the bait region (exon 18) revealed that inheritance of the deletion (A2M-2) confers increased risk for AD (Mantel-Haenzel odds ratio=3.56, P=0.001). The sibship disequilibrium test (SDT) also revealed a significant association between A2M and AD (P=0.00009). These values were comparable to those obtained for the APOE-epsilon 4 allele in the same sample, but in contrast to APOE-epsilon 4. A2M-2 did not affect age of onset. The observed association of A2M with AD did not appear to account for the previously published linkage of AD to chromosome 12, which we were unable to confirm in this sample. A2M, LRP1 (encoding the alpha-M-2 receptor) and the genes for two other LRP ligands, APOE and APP (encoding the amyloid P-protein precursor), have now all been genetically linked to AD, suggesting that these proteins may participate in a common neuropathogenic pathway leading to AD. C1 Massachusetts Gen Hosp, Genet & Aging Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL USA. Johns Hopkins Med Inst, Dept Psychiat, Baltimore, MD USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Genet & Aging Unit, Boston, MA 02114 USA. RI McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 FU NIMH NIH HHS [K21 MH01118, U01 MH46281, U01 MH51066] NR 33 TC 496 Z9 511 U1 2 U2 19 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 AUG PY 1998 VL 19 IS 4 BP 357 EP 360 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 106AM UT WOS:000075107600018 PM 9697696 ER PT J AU Shimodaira, H Filosi, N Shibata, H Suzuki, T Radice, P Kanamaru, R Friend, SH Kolodner, RD Ishioka, C AF Shimodaira, H Filosi, N Shibata, H Suzuki, T Radice, P Kanamaru, R Friend, SH Kolodner, RD Ishioka, C TI Functional analysis of human MLH1 mutations in Saccharomyces cevevisiae SO NATURE GENETICS LA English DT Article ID DNA MISMATCH REPAIR; COLON-CANCER; CEREVISIAE; YEAST; GENETICS; HOMOLOG; GENES; HNPCC AB Hereditary non-polyposis colorectal cancer (HNPCC; OMIM 120435-6) is a cancer-susceptibility syndrome(1) linked to inherited defects in human mismatch repair (MMR) genes(2). Germline missense human MLH1 (hMLH1) mutations are frequently detected in HNPCC (ref. 3), making functional characterization of mutations in hMLH1 critical to the development of genetic testing for HNPCC. Here, we describe a new method for detecting mutations in hMLHI using a dominant mutator effect of hMLH1 cDNA expressed in Saccharomyces cerevisiae. The majority of hMLH1 missense mutations identified in HNPCC patients abolish the dominant mutator effect. Furthermore, PCR amplification of hMLHI cDNA from mRNA from a HNPCC patient, followed by in vivo recombination into a gap expression vector, allowed detection of a heterozygous loss-of-function missense mutation in hMLH1 using this method. This functional assay offers a simple method for detecting and evaluating pathogenic mutations in hMLH1. C1 Tohoku Univ, Dept Clin Oncol, Inst Dev Aging & Canc, Sendai, Miyagi 9808575, Japan. Dana Farber Canc Inst, Charles A Dana Div Human Canc Genet, Boston, MA 02115 USA. Ist Nazl Tumori, Div Expt Oncol, I-20133 Milan, Italy. Fred Hutchinson Canc Res Ctr, Seattle Project, Seattle, WA 98109 USA. RP Ishioka, C (reprint author), Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. RI Radice, Paolo/O-3119-2013 FU NIGMS NIH HHS [GM44704] NR 20 TC 106 Z9 108 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1998 VL 19 IS 4 BP 384 EP 389 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 106AM UT WOS:000075107600024 PM 9697702 ER PT J AU Hahn, TM Breininger, JF Baskin, DG Schwartz, MW AF Hahn, TM Breininger, JF Baskin, DG Schwartz, MW TI Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons SO NATURE NEUROSCIENCE LA English DT Article ID NEUROPEPTIDE-Y; MESSENGER-RNA; ARCUATE NUCLEUS; EXPRESSION; LEPTIN; OBESITY; AGOUTI; MICE; RECEPTOR; MOUSE C1 Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98108 USA. Univ Washington, Harborview Med Ctr, Dept Biol Struct, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Schwartz, MW (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Schwartz, Michael/H-9950-2012; Wilkinson, Stuart/C-2802-2013 FU NIDDK NIH HHS [DK-12829, DK-52989]; NINDS NIH HHS [NS-32273] NR 15 TC 664 Z9 678 U1 1 U2 26 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD AUG PY 1998 VL 1 IS 4 BP 271 EP 272 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 127QD UT WOS:000076361300007 PM 10195157 ER PT J AU Heckers, S Rauch, SL Goff, D Savage, CR Schacter, DL Fischman, AJ Alpert, NM AF Heckers, S Rauch, SL Goff, D Savage, CR Schacter, DL Fischman, AJ Alpert, NM TI Impaired recruitment of the hippocampus during conscious recollection in schizophrenia SO NATURE NEUROSCIENCE LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; EPISODIC MEMORY; FUNCTIONAL NEUROANATOMY; RECOGNITION MEMORY; TEMPORAL-LOBE; DYSFUNCTION; BRAIN; MEDICATION; ACTIVATION AB Poor attention and impaired memory are enduring and core features of schizophrenia. These impairments have been attributed either to global cortical dysfunction or to perturbations of specific components associated with the dorsolateral prefrontal cortex (DLPFC), hippocampus and cerebellum. Here, we used positron emission tomography (PET) to dissociate activations in DLPFC and hippocampus during verbal episodic memory retrieval. We found reduced hippocampal activation during conscious recollection of studied words, but robust activation of the DLPFC during the effort to retrieve poorly encoded material in schizophrenic patients. This finding provides the first evidence of hippocampal dysfunction during episodic memory retrieval in schizophrenia. C1 Massachusetts Gen Hosp, Dept Psychiat, Psychot Disorders Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Positron Emiss Tomog Lab, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Heckers, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychot Disorders Unit, Boston, MA 02114 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIMH NIH HHS [MH01215, R01MH57915] NR 44 TC 412 Z9 418 U1 4 U2 17 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD AUG PY 1998 VL 1 IS 4 BP 318 EP 323 DI 10.1038/1137 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 127QD UT WOS:000076361300016 PM 10195166 ER PT J AU Endres, M Laufs, U AF Endres, M Laufs, U TI HMG-CoA reductase inhibitors and the risk of stroke. New mechanism(s) independent of cholesterol-lowering SO NERVENARZT LA German DT Article DE HMG-CoA reductase inhibitors; stroke; endothelial NO ID DEPENDENT CORONARY VASOMOTION; NITRIC-OXIDE SYNTHASE; FOCAL CEREBRAL-ISCHEMIA; L-ARGININE; HEART-DISEASE; PRAVASTATIN; ENDOTHELIUM; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS; PREVENTION AB HMG-CoA reductase inhibitors are potent cholesterol-lowering drugs. Recent clinical trials and meta-analyses show a 30% stroke reduction after treatment with HMG-CoA reductase inhibitors. Subgroup analyses and experimental findings support the notion that HMG-CoA reductase inhibitors improve endothelial function directly by mechanism(s) independent of cholesterol-lowering. They reduce inflammatory, proliferative and thrombogenic processes in atherosclerotic plaques and improve endothelial dysfunction. Recent findings demonstrate an enhanced production of endothelium-derived nitric oxide (NO) by HMG-CoA reductase inhibitors. Endothelial NO is an important vasodilator and plays a beneficial role in cerebral ischemic injury. Prophylactic treatment with HMG-CoA reductase inhibitors in mice selectively upregulates endothelial NO synthase expression and activity, increases cerebral blood flow at resting state and during ischemia, and reduces cerebral infarct size after experimental stroke. These findings provide a novel mechanism for the prophylactic treatment of ischemia-induced cerebral injury under non-hypercholesterolemic conditions. C1 Univ Lubeck, Neurol Klin, D-2400 Lubeck, Germany. Univ Cologne, Innere Med Klin 3, Koln, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. RP Endres, M (reprint author), Massachusetts Gen Hosp, Stroke Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. NR 42 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-2804 J9 NERVENARZT JI Nervenarzt PD AUG PY 1998 VL 69 IS 8 BP 717 EP 721 DI 10.1007/s001150050335 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 114FJ UT WOS:000075598200013 PM 9757426 ER PT J AU Neumeyer, AM Cros, D McKenna-Yasek, D Zawadzka, A Hoffman, EP Pegoraro, E Hunter, RG Munsat, TL Brown, RH AF Neumeyer, AM Cros, D McKenna-Yasek, D Zawadzka, A Hoffman, EP Pegoraro, E Hunter, RG Munsat, TL Brown, RH TI Pilot study of myoblast transfer in the treatment of Becker muscular dystrophy SO NEUROLOGY LA English DT Article ID TRANSPLANTATION AB We evaluated myoblast implantation therapy in three subjects with Becker muscular dystrophy who received 60 million myoblasts in one tibialis anterior (TA) muscle 2 months after beginning cyclosporine immunosuppression (5 to 10 mg/kg) that continued for 1 year. Strength of the implanted and control TA muscles was measured before and after treatment using a gauge to record TA contraction force. Our protocol controlled for the effects of cyclosporine and myoblast injections. In this pilot study, myoblast implantation did not improve strength of the implanted TA muscles. C1 Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Diacrin Inc, Charlestown, MA USA. Univ Pittsburgh, Sch Med, Dept Mol Genet, Pittsburgh, PA 15260 USA. Washington Regulatory Consultants, Princeton, NJ USA. New England Med Ctr, Neuromuscular Res Grp, Dept Neurol, Boston, MA 02111 USA. RP Brown, RH (reprint author), Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Bldg 149,13th St, Boston, MA 02129 USA. FU NICHD NIH HHS [K11-HD01002] NR 10 TC 39 Z9 40 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1998 VL 51 IS 2 BP 589 EP 592 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 110NN UT WOS:000075387400050 PM 9710042 ER PT J AU Lin, JW Sheng, M AF Lin, JW Sheng, M TI NSF and AMPA receptors get physical SO NEURON LA English DT Review ID TRANSPORT C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02114 USA. NR 19 TC 44 Z9 46 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 AUG PY 1998 VL 21 IS 2 BP 267 EP 270 DI 10.1016/S0896-6273(00)80534-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 114FK UT WOS:000075598300002 PM 9728906 ER PT J AU Mijovic-Prelec, D Chabris, CF Shin, LM Kosslyn, SM Wray, SH AF Mijovic-Prelec, D Chabris, CF Shin, LM Kosslyn, SM Wray, SH TI The judgement of absence in neglect SO NEUROPSYCHOLOGIA LA English DT Article; Proceedings Paper CT Meeting of the Cognitive-Neuroscience-Society CY MAR 27-29, 1994 CL SAN FRANCISCO, CALIFORNIA SP Cognit Neurosci Soc ID UNILATERAL VISUAL NEGLECT; SPATIAL NEGLECT; SEARCH; ATTENTION AB The usual way of looking at neglect is by investigating how neglect patients fail to detect that something is there. In this study, we look at how neglect patients correctly detect that something is not there. Patients with parietal lesions (11 with and 16 without neglect) and 23 control subjects indicated whether a dot target was or was not present in a geometrical display. While control subjects were consistently (and unexpectedly) faster in the no-dot than in the dot condition, the distinguishing response time pattern of right parietal patients with neglect was not-as one might expect-a relatively longer response time to left vs right targets, but a longer response time to target absence vs presence. This may be due to a serial search or, alternatively, it might result from double-checking for target absence, produced by lowered perceptual confidence. Since this "wariness" about stimulus absence seems to operate in parallel with neglect patients' denial of the deficit, ive conclude that the response time pattern observed in this study could be used as a measure of subjective (un)awareness of neglect. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mijovic-Prelec, D (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM mijovic@wjh.harvard.edu FU NINDS NIH HHS [NS P01 17778-09] NR 22 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD AUG PY 1998 VL 36 IS 8 BP 797 EP 802 DI 10.1016/S0028-3932(97)00144-9 PG 6 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 112NP UT WOS:000075500900009 PM 9751443 ER PT J AU Page, KJ Hollister, RD Hyman, BT AF Page, KJ Hollister, RD Hyman, BT TI Dissociation of apolipoprotein and apolipoprotein receptor response to lesion in the rat brain: An in situ hybridization study SO NEUROSCIENCE LA English DT Article DE apolipoprotein E; apolipoprotein J; LRP; VLDLr; GP330; Alzheimer's disease ID DENSITY-LIPOPROTEIN RECEPTOR; CENTRAL-NERVOUS-SYSTEM; E MESSENGER-RNA; ALZHEIMERS-DISEASE; CLUSTERIN SGP-2; GENE FAMILY; ADULT-RAT; PROTEIN; EXPRESSION; HIPPOCAMPUS AB The epsilon 4 allele of apolipoprotein E is associated with increased risk for developing Alzheimer's disease. To further understand the anatomical distribution of apolipoprotein E and its native receptors in the brain, we studied their messenger RNA expression in the adult rat brain under normal conditions and in response to an excitotoxic lesion to the hippocampus. In situ hybridization using oligonucleotide probes for apolipoprotein E, apolipoprotein J, the low density lipoprotein receptor, very low density lipoprotein receptor, low density lipoprotein receptor related protein, 39,000 mel. wt receptor-associated protein and glycoprotein 330/Megalin messenger RNA were performed on adjacent sections throughout the rat forebrain. Apolipoprotein E messenger RNA was abundantly expressed in the rat brain in both white and gray mailer localizing to astrocytes but not neurons. Low density lipoprotein receptor-related protein and receptor-associated protein messenger RNA had a similar regional distribution but low density lipoprotein receptor-related protein messenger RNA was expressed by both neurons and glia, while the expression of receptor-associated protein messenger RNA was more highly expressed in neurons. Apolipoprotein J messenger RNA was expressed by neurons, glia and choroid plexus. The low density lipoprotein receptor and very low density lipoprotein receptor messenger RNA were found in both neurons and glia. Glycoprotein 330/Megalin messenger RNA was not detectable in the adult rat brain. In response to hippocampal lesions, apolipoprotein E and apolipoprotein J messenger RNAs were significantly upregulated seven and 11 days post-lesion but the expression of low density lipoprotein receptor, low density lipoprotein receptor-related protein, receptor-associated protein, glycoprotein 330/Megalin, and very low density lipoprotein receptor messenger RNAs were unchanged. The expression of apolipoprotein E messenger RNA increased gradually beginning at three days while the expression of apolipoprotein J messenger RNA began to increase at seven days post-lesion. These findings further implicate apolipoproteins in the response of the brain to injury in vivo and suggest that transcriptional up-regulation of the apolipoprotein receptors studied is not a prominent feature in the response. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. FU NIA NIH HHS [AG-12406] NR 39 TC 47 Z9 49 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD AUG PY 1998 VL 85 IS 4 BP 1161 EP 1171 DI 10.1016/S0306-4522(97)00661-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA ZT531 UT WOS:000074097200015 PM 9681954 ER PT J AU Rogers, PL AF Rogers, PL TI Developing a curriculum for medical students in critical care medicine SO NEW HORIZONS-THE SCIENCE AND PRACTICE OF ACUTE MEDICINE LA English DT Article DE curriculum; education; students, medical; teaching; feedback; educational measurement; clinical clerkship; ICU; learning; clinical clerkship ID STRUCTURED CLINICAL EXAMINATION; RELIABILITY; COMPETENCE; EDUCATION AB Medical students need to learn the cognitive and psychomotor skills necessary to assess patients with life-threatening illness, initiate therapies to stabilize the patient, and develop management plans to deliver care, When organizing a curriculum, faculty should develop clear educational objectives, organize specific learning experiences, motivate the students, and develop tools to evaluate performance and provide feedback. C1 Univ Pittsburgh, Med Ctr, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA USA. RP Rogers, PL (reprint author), VA Pittsburgh Healthcare Syst, 124U, Pittsburgh, PA 15240 USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1063-7389 J9 NEW HORIZ-SCI PRACT JI New Horiz.-Sci. Pract. Acute Med. PD AUG PY 1998 VL 6 IS 3 BP 248 EP 254 PG 7 WC Emergency Medicine SC Emergency Medicine GA 126YP UT WOS:000076323200004 ER PT J AU Liu, W Su, W Roberts, TM AF Liu, W Su, W Roberts, TM TI Discovery of estrogen-responsive genes using an improved method which combines subtractive hybridization and PCR SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EXPRESSION; TRANSCRIPTION; STERILIZATION; PROTEINS; LIBRARY; MCF-7 AB Here we describe a reliable method for isolating genes, that are differentially expressed in two cell populations. The method is a combination of subtractive hybridization anti PCR, Among many improvements to previously described methods is the incorporation of a new technology into the procedure which sterilizes (inactivates) PCR amplicons, and thereby overcomes the limitation of similar procedures. To test this improved method, we conducted a search for estrogen-responsive genes. Estrogen-regulated genes dominated the subtracted libraries after four rounds of subtractive hybridizations. Four estrogen-regulated genes were identified from the initial screening. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Su, W (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Drop Code 0444, Indianapolis, IN 46285 USA. FU NCI NIH HHS [CA30002] NR 14 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 1 PY 1998 VL 26 IS 15 BP 3616 EP 3618 DI 10.1093/nar/26.15.3616 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 107CZ UT WOS:000075190600026 PM 9671829 ER PT J AU Garber, JE AF Garber, JE TI Predisposition testing for inherited breast cancer - The Cummings/Olopade article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID BRCA1 C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Epidemiol & Control, Boston, MA 02115 USA. RP Garber, JE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Epidemiol & Control, 44 Binney St, Boston, MA 02115 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD AUG PY 1998 VL 12 IS 8 BP 1241 EP 1242 PG 2 WC Oncology SC Oncology GA 111QN UT WOS:000075449300023 ER PT J AU Ayyala, RS Pieroth, L Vinals, AF Goldstein, MH Schuman, JS Netland, PA Dreyer, EB Cooper, ML Mattox, C Frangie, JP Wu, HK Zurakowski, D AF Ayyala, RS Pieroth, L Vinals, AF Goldstein, MH Schuman, JS Netland, PA Dreyer, EB Cooper, ML Mattox, C Frangie, JP Wu, HK Zurakowski, D TI Comparison of mitomycin C trabeculectomy, glaucoma drainage device implantation, and laser neodymium : YAG cyclophotocoagulation in the management of intractable glaucoma after penetrating keratoplasty SO OPHTHALMOLOGY LA English DT Article ID TRANSSCLERAL CYCLOPHOTOCOAGULATION; TUBE SHUNT AB Purpose: This study aimed to compare the surgical outcomes of mitomycin C trabeculectomy glaucoma drainage device (GDD) surgery and laser neodymium:YAG (Nd:YAG) cyclophotocoagulation (CPC) in the management of intractable glaucoma after penetrating keratoplasty (PKP) in a retrospective study. Design: Interventional case series. Participants/Methods: The medical charts of consecutive patients who had pre-existing glaucoma or who developed glaucoma after PKP and underwent a surgical procedure to control the glaucoma at the University Eye Associates of Boston University Medical Center, New England Eye Center, and Massachusetts Eye and Ear Infirmary between January 1991 and July 1995 were reviewed. Follow-up ranged from 6 months to 4 years after the glaucoma procedure. A total of 38 patients were included consisting of 17 patients who underwent mitomycin C, 10 patients who underwent GDD surgery, and 11 patients who had CPC. Intervention: Mitomycin C trabeculectomy, GDDs, or Nd:YAG CPC to control glaucoma after PKP was performed. Main Outcome Measures: Graft status, postoperative intraocular pressure (IOP), and visual acuity were the main outcome measures. Results: There were no differences among the three groups with respect to the follow-up time after the corneal graft operation (P = 0.15) or after the glaucoma operation (P = 0.98). At the final follow-up, the average decrease in the IOP was 17 mmHg (P < 0.001) after mitomycin C, 15 mmHg (P = 0.003) after GDD surgery, and 14.4 mmHg (P = 0.001) after CPC. There were no differences in the proportion of patients who developed postoperative IOP above 20 mmHg (P = 0.50) and in the proportion who developed hypotony (P = 0.10) among the three groups. Two grafts failed after mitomycin C and one failed after CPC. Among the three procedures, there were no differences in the proportion of patients who experienced either an improvement (P = 0.14) or a decrease (P = 0.22) in the visual acuity by more than one line after the glaucoma procedure. One patient each in the GDD group and the CPC group lost light perception after the procedure. The risk of graft failure was almost three times higher for each additional PKP (odds ratio = 2.80, P = 0.02). Conclusions: No differences were found among the three glaucoma procedures with respect to controlling IOP and graft failure. There was a trend for patients treated with CPC to have a higher incidence of graft failure, glaucoma failure, hypotony, and visual loss by more than one line, although this was not statistically significant. The number of PKPs was associated with graft failure, independent of the surgical procedure. C1 Boston Univ, Med Ctr, Univ Eye Associates, Boston, MA USA. Tufts Univ, New England Med Ctr Hosp, Sch Med, New England Eye Ctr, Boston, MA 02111 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Univ Tennessee, Dept Ophthalmol, Memphis, TN USA. Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol Res Comp & Biostat, Boston, MA USA. RP Ayyala, RS (reprint author), Univ S Florida, Inst Eye, 12901 Bruce B Downs Blvd,MDC 21, Tampa, FL 33612 USA. RI Schuman, Joel/K-7304-2012 OI Schuman, Joel/0000-0002-8885-3766 NR 24 TC 42 Z9 47 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1998 VL 105 IS 8 BP 1550 EP 1556 DI 10.1016/S0161-6420(98)98046-0 PG 7 WC Ophthalmology SC Ophthalmology GA 107VK UT WOS:000075231500047 PM 9709773 ER PT J AU Tearney, GJ Webb, RH Bouma, BE AF Tearney, GJ Webb, RH Bouma, BE TI Spectrally encoded confocal microscopy SO OPTICS LETTERS LA English DT Article AB An endoscope-compatible, submicrometer-resolution scanning confocal microscopy imaging system is presented. This approach, spectrally encoded confocal microscopy (SECM), uses a quasi-monochromatic light source and a transmission diffraction grating to detect the reflectivity simultaneously at multiple points along a transverse line within the sample. Since this method does not require fast spatial scanning within the probe, the equipment can be miniaturized and incorporated into a catheter or endoscope. Confocal images of an electron microscope grid were acquired with SECM to demonstrate the feasibility of this technique. (C) 1998 Optical Society of America. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 50 Blossom St,BAR 703, Boston, MA 02114 USA. NR 14 TC 139 Z9 143 U1 1 U2 9 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD AUG 1 PY 1998 VL 23 IS 15 BP 1152 EP 1154 DI 10.1364/OL.23.001152 PG 3 WC Optics SC Optics GA 104QC UT WOS:000075024400002 PM 18087457 ER PT J AU Spencer, T Biederman, J Wilens, T AF Spencer, T Biederman, J Wilens, T TI Growth deficits in children with attention deficit hyperactivity disorder SO PEDIATRICS LA English DT Article; Proceedings Paper CT 11th Annual Investigators Meeting of the National-Cooperative-Growth-Study on Guidance in Growth CY SEP 25-28, 1997 CL WASHINGTON, D.C. SP Natl Cooperat Growth Study, Childrens Natl Med Ctr, Washington DC, Genentech Inc, S San Francisco, California DE attention deficit hyperactivity disorder; growth deficit; height deficit; weight deficit; stimulant ID STIMULANT-DRUGS; METHYLPHENIDATE; HORMONE; PROLACTIN; RESPONSES; BOYS AB Stimulant-associated growth deficits in children with attention deficit hyperactivity disorder (ADHD) have long been a concern. Height deficits in preadolescence have been reported, but adult heights have been reported to be uncompromised. It is possible that the catch-up growth that occurs is related to ADHD-associated delayed maturation and not to the cessation of stimulant treatment. To date, no consistent neurohormonal pathophysiology to explain stimulant-associated height deficits has been identified nor have the initial associations of height and weight deficits been replicated. Attention deficit hyperactivity disorder is associated with dysregulation of several neurotransmitter systems, especially the catecholamines, that may alter neuroendocrine function and lead to growth delays. The literature on neuroendocrine aspects of growth and treatment in ADHD and on growth in boys with ADHD who are treated with psychotropics is reviewed, and the results of a controlled study in 124 boys with ADHD are presented. Small but significant differences in height were found between children with and without ADHD. However, the height deficits were evident in early, but not late, adolescence and were not related to the use of psychotropic medications. There was no evidence of weight deficits in children with ADHD relative to control subjects and no relationship between measures of malnutrition and short stature was found. These findings suggest that ADHD may be associated with temporary deficits in height gain through midadolescence that may normalize by late adolescence. This effect appears to be mediated by ADHD and not by its treatment. C1 Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Spencer, T (reprint author), Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, 15 Parkman St,WACC 725, Boston, MA 02114 USA. FU NIMH NIH HHS [K20 MH01169-01] NR 53 TC 54 Z9 58 U1 1 U2 4 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 AUG PY 1998 VL 102 IS 2 SU 2 BP 501 EP 506 PG 6 WC Pediatrics SC Pediatrics GA 108YB UT WOS:000075293100008 PM 9685453 ER PT J AU Walton, RL Beahm, EK Brown, RE Upton, J Reinke, K Fudem, G Banis, J Davidson, J Dabb, R Kalimuthu, R Kitzmiller, WJ Gottlieb, LJ Buncke, HJ AF Walton, RL Beahm, EK Brown, RE Upton, J Reinke, K Fudem, G Banis, J Davidson, J Dabb, R Kalimuthu, R Kitzmiller, WJ Gottlieb, LJ Buncke, HJ TI Microsurgical replantation of the lip: A multi-institutional experience SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Plastic-and-Reconstructive-Surgeons CY NOV 09-13, 1996 CL DALLAS, TEXAS SP Amer Soc Plast & Reconstruct Surgeons ID AMPUTATED UPPER LIP; MICROVASCULAR ANASTOMOSIS; SURVIVAL; NOSE AB Traumatic amputation of the lip is a rare yet devastating event affecting both form and function. Considering the available methods for reconstruction, replantation may offer a reasonable solution. We sought to characterize the variables associated with lip replantation and to assess the outcome in a retrospective review of 13 lip replantations performed in 12 institutions utilizing a form database and clinical and photographic analysis. Lip replantation was successful in all 13 patients; partial flap loss occurred in one patient owing to iatrogenic injury. Follow-up averaged 3.1 years. Average patient age at: the time of injury was 21.1 years. There were six male and seven female patients. Injuries in two patients were the result of a human bite, the remaining injuries resulted from dog bites. One patient had significant associated injuries. Average length of hospital stay was 11.9 days. Ten patients suffered amputations of the upper lip, and three suffered amputations of the lower lip. Average defect size was 10.6 cm(2). Operative time averaged 5.7 hours (range 2.5 to 12 hours). Warm ischemia time averaged 2.9 hours, and cold ischemia time averaged 2.7 hours. Donor and recipient veins were often scarce; all patients had at least one arterial anastomosis, whereas no vein was available in 7 of 13 patients; vein grafts were required in one patient. Leech therapy was employed in 11 of 13 patients. Anticoagulant therapy was administered in the majority of patients. Systemic heparin was utilized in 10 of 13 patients, low molecular weight dextran was used in 7 of 13 patients, and aspirin was given to 7 of 13 patients. One bleeding complication was incurred. An average of 6.2 units of packed red blood cells was administered to 12 of 13 patients (adjusted to 250 cc/unit). Antispasmodic therapy was employed in six of eight patients intraoperatively and in two of eight patients postoperatively. Intraoperative complications included difficulty identifying veins in 7 of 13 patients, arterial spasm in 1 of 13 patients, and vessel diameter <0.5 mm in 4 patients. Postoperatively, one patient suffered vein thrombosis requiring anastomotic revision. Broad spectrum antibiotics were administered to all patients, and there were no infections. Nearly one-third (4 of 13) patients suffered prolonged edema lasting >4 months. Color match of the replanted lip segment was rated excellent in all cases. Hypertrophic scarring occurred in 6 of 13 patients. A total of 12 revision procedures was performed in six patients. Interestingly, leech therapy resulted in permanent visible scarring as a result of the leech bite in 6 of 11 patients treated. Ten patients demonstrated active orbicularis muscle contraction in the replanted lip segment. Stomal continence was present in all lips. Sensibility return in the replanted lip segment was quite good with 12 of 13 patients demonstrating at least protective moving two-point sensibility (greater than or equal to 10 mm). Partial replant necrosis in one patient resulted in significant scar and contraction that compromised the aesthetic appearance. Overall, however, all patients were uniformly pleased with their final results. This clinical study is one of the largest of its kind on lip replantation. Although this represents a multi-institutional experience, the data are remarkably consistent. Re-establishment of venous outflow seems to be the most problematic technical challenge. By incorporating the adjuncts of anticoagulation, leech therapy, and antispasmodics, a successful outcome can be expected despite the paucity of vessels and small vessel size. The risks of blood transfusion, lengthy operative time, and hospital stay must be weighed against the functional benefits. C1 Univ Chicago Hosp, Sect Plast Surg, Chicago, IL USA. So Illinois Univ, Med Ctr, Div Plast Surg, Carbondale, IL 62901 USA. Beth Israel Deaconess Hosp, Div Plast Surg, Boston, MA USA. Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Div Plast Surg, Amherst, MA 01003 USA. Univ Louisville, Med Ctr, Div Plast Surg, Louisville, KY 40292 USA. Hop Hotel Dieu, Div Plast Surg, Kingston, ON, Canada. York Hosp, Div Plast Surg, York, PA USA. Univ Cincinnati, Med Ctr, Div Plast Surg, Cincinnati, OH 45267 USA. Davis Med Ctr, Microsurg Replantat Transplantat Dept, Davis, CA USA. RP Walton, RL (reprint author), Univ Chicago, Plast & Reconstruct Surg Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. NR 24 TC 36 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD AUG PY 1998 VL 102 IS 2 BP 358 EP 368 DI 10.1097/00006534-199808000-00009 PG 11 WC Surgery SC Surgery GA 106LE UT WOS:000075130100010 PM 9703070 ER PT J AU Glazer, WM AF Glazer, WM TI Defining best practices: A prescription for greater autonomy SO PSYCHIATRIC SERVICES LA English DT Editorial Material C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Glazer, WM (reprint author), 100 Beach Plum Lane, Menemsha, MA 02552 USA. NR 3 TC 7 Z9 7 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD AUG PY 1998 VL 49 IS 8 BP 1013 EP + PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 106KU UT WOS:000075129100002 PM 9712202 ER PT J AU Goldberg, SN Hahn, PF McGovern, FJ Fogle, RM Mueller, PR Gazelle, GS AF Goldberg, SN Hahn, PF McGovern, FJ Fogle, RM Mueller, PR Gazelle, GS TI Benign prostatic hyperplasia: US-guided transrectal urethral enlargement with radio frequency - Initial results in a canine model SO RADIOLOGY LA English DT Article DE prostate, hyperplasia; prostate, therapeutic radiology; prostate, US; radiofrequency (RF) ablation ID TRANSURETHRAL NEEDLE ABLATION; LASER-INDUCED PROSTATECTOMY; THERMAL ABLATION; TISSUE ABLATION; RADIOFREQUENCY; FEASIBILITY; EXPERIENCE; THERAPY; TUNA AB PURPOSE: To enlarge the prostatic urethra with thermal coagulation with transrectal radio-frequency (RF) application in dogs. MATERIALS AND METHODS: Eight aged dogs underwent RF ablation of periurethral prostatic tissue forb minutes. Eighteen-gauge electrodes were placed into the periurethral tissues with a transrectal approach and ultrasound (US) guidance. Prostatic and rectal temperatures were measured during RF application. US, conventional an computed tomographic (CT) retrograde urethrography (RUG), and CT were performed immediately (n = 8) and at 3-96 days (n = 6) after ablation. Histopathologic analysis was performed at sacrifice immediately (n = 2), at 28 days (n = 2), or at 3 months (n = 4) after treatment. RESULTS: All procedures were successful with no complications and were performed in less than 30 minutes. Rectal mucosal temperature did not exceed 38 degrees C. Immediately after treatment, CT and US demonstrated 1.2-cm foci of altered periurethral tissue that corresponded to solid coagulated tissue at histopathologic analysis. By day 3, CT, RUG, and US demonstrated that these foci had begun to cavitate, resulting in enlargement of the urethra. Complete cavitation was demonstrated by day 28. Minimal reduction in the degree of urethral enlargement was noted by day 60, but narrowing, urethral strictures, or fistulas were not observed at 3 months. At histopathologic analysis, focal cavitary enlargement with at least doubling of the urethral diameter and with normal urothelium was noted in all dogs surviving at least 28 days. CONCLUSION: Transrectal RF urethral enlargement is feasible and safe in animals and merits investigation for alleviating urethral obstruction due to benign prostatic hyperplasia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. RP Goldberg, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Fruit St, Boston, MA 02114 USA. NR 25 TC 10 Z9 10 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 1998 VL 208 IS 2 BP 491 EP 498 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 101WP UT WOS:000074891400037 PM 9680581 ER PT J AU Riley, LE AF Riley, LE TI Herpes simplex virus SO SEMINARS IN PERINATOLOGY LA English DT Review ID RECURRENT GENITAL HERPES; POLYMERASE CHAIN-REACTION; NEONATAL HERPES; PREGNANT-WOMEN; VAGINAL TRANSMISSION; CESAREAN DELIVERY; VIRAL CULTURES; ORAL ACYCLOVIR; PROTECTS MICE; INFECTIONS C1 Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Riley, LE (reprint author), 32 Fruit St,Founders 430, Boston, MA 02114 USA. NR 75 TC 21 Z9 21 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD AUG PY 1998 VL 22 IS 4 BP 284 EP 292 DI 10.1016/S0146-0005(98)80017-7 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 115PQ UT WOS:000075674200007 PM 9738993 ER PT J AU Zelen, M Freedman, D Ashby, D Harrison, JE Korn, EL Baumrind, S AF Zelen, M Freedman, D Ashby, D Harrison, JE Korn, EL Baumrind, S TI Clinician preferences and the estimation of causal treatment differences - Comments and rejoinder SO STATISTICAL SCIENCE LA English DT Article C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. Univ London Queen Mary & Westfield Coll, St Bartholomews & Royal London Sch Med & Dent, Wolfson Inst Prevent Med, Dept Environm & Prevent Med, London EC1M 6BQ, England. Univ Liverpool, Dent Hosp, Liverpool L3 5PS, Merseyside, England. Cochrane Collaborat Oral Hlth Grp, Oxford, England. RP Zelen, M (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 1 U2 1 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 7, 3401 INVESTMENT BLVD, HAYWARD, CA 94545 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD AUG PY 1998 VL 13 IS 3 BP 228 EP 235 PG 8 WC Statistics & Probability SC Mathematics GA 141PQ UT WOS:000077152700002 ER PT J AU Bode, BP Reuter, N Conroy, JL Souba, WW AF Bode, BP Reuter, N Conroy, JL Souba, WW TI Protein kinase C regulates nutrient uptake and growth in hepatoma cells SO SURGERY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-of-University-Surgeons CY FEB 12-14, 1998 CL MILWAUKEE, WISCONSIN SP Soc Univ Surgeons ID NEUTRAL AMINO-ACIDS; GLUTAMINE-METABOLISM; PHORBOL ESTERS; HEPATOCELLULAR-CARCINOMA; TRANSPORT-SYSTEM; LIVER; HEPATOCYTES; SYNTHETASE AB Background. Human hepatoma cells extract glutamine at rates severalfold greater than normal hepatocytes through a high-affinity transporter encoded by the ATB(0) gene, which contains two putative phosphorylation sites for protein kinase C (PKC). The studies presented here were undertaken to determine whether Sq stem B-0-mediated glutamine uptake regulates hepatoma growth and whether PKC regulates the activity of this transporter. Methods. SK-Hep cells were treated with the PKC activator phorbol 12-myristate 13-acetate (PMA) and the initial-rate transport of glutamine and other nutrients measured at specific times thereafter. Growth rates were monitored during culture +/- PMA or an excess of system B-0 substrates relative to glutamine. Results. PMA treatment exerted a rapid (half-life similar to 15 minutes) concentration-dependent inhibition of glutamine uptake rates to 50% of control values via a posttranslational mechanism that decreased transporter maximum velocity. This effect persisted after 24 hours and was abrogated by the PKC inhibitor staurosporine. PMA also significantly decreased amino acid transport System y(+) and System L, activities but not System A. Chronic treatment with PMA (PKC depletion) inhibited SK-Hep growth, as did attenuation of System B-0-mediated! glutamine uptake with other. B-0 substrates. Conclusions, System B-0-mediated glutamine uptake regulates hepatoma cell growth, whereas PKC influences both processes. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Surg Oncol, Boston, MA 02114 USA. RP Bode, BP (reprint author), Massachusetts Gen Hosp, Gray Jackson 918,55 Fruit St, Boston, MA 02114 USA. OI Beauchamp, Robert Daniel/0000-0002-8446-4114 FU NCI NIH HHS [CA69505] NR 25 TC 27 Z9 27 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1998 VL 124 IS 2 BP 260 EP 267 DI 10.1067/msy.1998.90568 PG 8 WC Surgery SC Surgery GA 108EC UT WOS:000075252200036 PM 9706147 ER PT J AU Farokhzad, OC Mun, EC Sicklick, JK Smith, JA Matthews, JB AF Farokhzad, OC Mun, EC Sicklick, JK Smith, JA Matthews, JB TI Effects of bryostatin 1, a novel anticancer agent, on intestinal transport and barrier function: Role of protein kinase C SO SURGERY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-of-University-Surgeons CY FEB 12-14, 1998 CL MILWAUKEE, WISCONSIN SP Soc Univ Surgeons ID PHORBOL ESTER; ELECTROLYTE TRANSPORT; SECRETION; ISOZYMES; CELLS AB Background. Bryostatin 1 is a novel chemotherapeutic agent that activates specific members of the protein kinase C (PKC) family in a complex pattern overlapping with, but distinct from, that of tumor-promoting phorbol esters. Phorbol esters profoundly alter epithelial phenotype, abolishing both barrier function and Cl secretion (the latter due to loss of a key transport site, the Na-K-Cl cotransporter). The effects of bryostatin 1 on these parameters are unknown. Methods. Cl secretion and barrier function of T84 human intestinal epithelia were assessed as cyclic adenosine monophosphate-stimulated short-circuit current and transepithelial resistance, respectively. Na-K-Cl cotransporter function and mRNA expression were assayed by Rb-86 uptake and Northern analysis. Results. Bryostatin 1 reduced Cl secretion, Na-K-Cl cotransport, and cotransporter mRNA expression. Unlike phorbol esters, these effects were largely transient. In contrast to phorbol esters, bryostatin 1 did not decrease barrier function. Conclusions. Bryostatin 1 transiently inhibits Na-K-Cl cotransport and Cl secretion, possibly through a PKC isoform also targeted by phorbol esters. Unlike phorbol esters, bryostatin 1 does not impair barrier function. The data imply that bryostatin 1 and phorbol esters differentially affect a PKC isoform involved in junctional regulation, and that epithelial transport and barrier function may be regulated by distinct PKC isoforms. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Gen Surg, Boston, MA 02215 USA. RP Matthews, JB (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Gen Surg, East Campus,330 Brookline Ave, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK48010] NR 24 TC 11 Z9 11 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1998 VL 124 IS 2 BP 380 EP 386 DI 10.1067/msy.1998.90574 PG 7 WC Surgery SC Surgery GA 108EC UT WOS:000075252200066 PM 9706162 ER PT J AU Fussing, V Paster, BJ Dewhirst, FE Poulsen, LK AF Fussing, V Paster, BJ Dewhirst, FE Poulsen, LK TI Differentiation of Actinobacillus pleuropneumoniae strains by sequence analysis of 16S rDNA and ribosomal intergenic regions, and development of a species specific oligonucleotide for in situ detection SO SYSTEMATIC AND APPLIED MICROBIOLOGY LA English DT Article DE Actinobacillus pleuropneumoniae; ribosomal operons; ribosomal intergenic region; 16S rRNA; in situ detection ID SEROLOGICAL CHARACTERIZATION; ESCHERICHIA-COLI; HEMOPHILUS-PLEUROPNEUMONIAE; LARGE-INTESTINE; RNA OPERONS; IDENTIFICATION; HAEMOPHILUS; HYBRIDIZATION; PHYLOGENY; PROPOSAL AB The aims of this study were to characterize and determine intraspecies and interspecies relatedness of Actinobacillus pleuropneumoniae to Actinobacillus lignieresii and Actinobacillus suis by sequence analysis of the ribosomal operon and to find a species-specific area for in situ detection of A. pleuropneumoniae. Amplification and sequence analysis of the 16S-23S rDNA ribosomal intergenic sequence (RIS) from the three species showed the existence of two RIS's, differing by about 100 bp. Both sequences contained a region resembling the ribonuclease III cleavage site found in Escherichia coli. The smaller RIS contained a Glu-tRNA gene, and the larger one contained genes encoding Ile-tRNA and Ala-tRNA. These tRNA's showed a high sequence homology to the respective tRNA genes found in E. coli. Sequence analysis of the RIS's showed a high degree of genetic similarity of 24 strains of A. pleuropneumoniae. The larger RIS's were different between the 3 species tested. The sequence of the 16S ribosomal gene was determined for 8 serotypes of A. pleuropneumoniae. These sequences showed only minor base differences, indicating a close genetic relatedness of these serotypes within the species. An oligonucleotide DNA probe designed from the 16S rRNA gene sequence of A. pleuropneumoniae was specific for all strains of the target species and did not cross react with A. lignieresii, the closest known relative of A. pleuropneumoniae. This species-specific DNA probe labeled with fluorescein was used for in situ hybridization experiments to detect A. pleuropneumoniae in biopsies of diseased porcine lungs. C1 Danish Vet Lab, Dept Microbiol, Copenhagen V, Denmark. Forsyth Dent Ctr, Dept Mol Genet, Boston, MA 02115 USA. Tech Univ Denmark, Dept Microbiol, DK-2800 Lyngby, Denmark. RP Fussing, V (reprint author), Statens Serum Inst, Dept Gastrointestinal Infect, Artillerivej, DK-2300 Copenhagen S, Denmark. EM vfu@ssi.dk FU NIDCR NIH HHS [DE-10374, DE-08303] NR 43 TC 13 Z9 13 U1 0 U2 2 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0723-2020 J9 SYST APPL MICROBIOL JI Syst. Appl. Microbiol. PD AUG PY 1998 VL 21 IS 3 BP 408 EP 418 PG 11 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 121RN UT WOS:000076027900010 PM 9779607 ER PT J AU Lee, SJ Liljas, B Churchill, WH Popovsky, MA Stowell, CP Cannon, ME Johannesson, M AF Lee, SJ Liljas, B Churchill, WH Popovsky, MA Stowell, CP Cannon, ME Johannesson, M TI Perceptions and preferences of autologous blood donors SO TRANSFUSION LA English DT Article ID COST-EFFECTIVENESS; UNITED-STATES; TRANSFUSION PRACTICE; DONATION; COLLECTION; RISK AB BACKGROUND: The public's perception of autologous blood donation and transfusion as a worthwhile alternative to allogeneic blood transfusion increased dramatically with discovery of the human immunodeficiency virus. However, new concerns are being raised about the health outcomes and cost-effectiveness of the procedure. As more restrictive guidelines for autologous blood donation evolve, opposition from patients concerned about exposure to allogeneic blood may arise. Physicians' ability to reassure patients and garner their support for more restrictive policies requires an understanding of patients' concerns. The motivations, perceptions, and preferences of patients currently participating in autologous blood donation programs were investigated in this study. STUDY DESIGN AND METHODS: Results from two questionnaire studies of 647 autologous blood donors are presented. The questionnaires assessed demographics, risk perceptions, preferences, willingness to pay, and reactions to different interventions designed to decrease patient preference for autologous blood donation. RESULTS: Patients expressed a strong preference for the availability of autologous blood and indicated that they would be willing to pay substantial amounts of money even ii the procedure were not covered by insurance. Despite education about the low risks of complications from allogeneic transfusions, an aversion to allogeneic transfusion and a willingness to pay for autologous blood donation persisted. Patients were not reassured by information on better infectious disease testing or physician recommendation against autologous blood donation. CONCLUSION: Patients currently participating in autologous blood donor programs strongly prefer continued access to this procedure, primarily because they remain concerned about the complications of allogeneic transfusions. They may not be significantly reassured despite increasingly rigorous and costly improvements in donor and component screening. C1 Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Amer Red Cross, New England Reg, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Hosp, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02115 USA. Stockholm Sch Econ, S-11383 Stockholm, Sweden. Univ Lund, Dept Econ, Lund, Sweden. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, 454 Brookline Ave,Suite 23, Boston, MA 02115 USA. RI Johannesson, Magnus/E-9680-2011 OI Johannesson, Magnus/0000-0001-8759-6393 FU NCI NIH HHS [K07 CA75267-01] NR 41 TC 32 Z9 35 U1 2 U2 3 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 1998 VL 38 IS 8 BP 757 EP 763 DI 10.1046/j.1537-2995.1998.38898375515.x PG 7 WC Hematology SC Hematology GA 109GE UT WOS:000075312600009 PM 9709784 ER PT J AU Sachs, DH AF Sachs, DH TI Transplantation tolerance SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Congress on New Dimensions in Transplantation - Weaving the Future CY FEB 16-19, 1998 CL FLORENCE, ITALY SP Novartis Pharma AG ID BONE-MARROW TRANSPLANTATION; HUMAN T-CELLS; MINIATURE SWINE; RENAL-ALLOGRAFTS; CYNOMOLGUS MONKEYS; RADIATION CHIMERAS; MIXED CHIMERISM; CLASS-I; INDUCTION; ANTIGENS C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH-E,Bldg 149,13th St,Charlestown Navy Yard, Boston, MA 02129 USA. NR 23 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 1998 VL 30 IS 5 BP 1627 EP 1629 DI 10.1016/S0041-1345(98)00370-4 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 110ZM UT WOS:000075412900005 PM 9723221 ER PT J AU Tolkoff-Rubin, NE Rubin, RH AF Tolkoff-Rubin, NE Rubin, RH TI Viral infections in organ transplantation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Congress on New Dimensions in Transplantation - Weaving the Future CY FEB 16-19, 1998 CL FLORENCE, ITALY SP Novartis Pharma AG ID HEPATITIS-B; RECIPIENTS; DISEASE; VIRUS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemodialysis Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, CAPD Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, End Stage Renal Dis Program, Boston, MA 02114 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Rubin, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hemodialysis Unit, 55 Fruit St, Boston, MA 02114 USA. NR 9 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 1998 VL 30 IS 5 BP 2060 EP 2063 DI 10.1016/S0041-1345(98)00541-7 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 110ZM UT WOS:000075412900177 PM 9723393 ER PT J AU Cooper, DKC AF Cooper, DKC TI The safety of xenotransplantation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Congress on New Dimensions in Transplantation - Weaving the Future CY FEB 16-19, 1998 CL FLORENCE, ITALY SP Novartis Pharma AG ID RETROVIRUS; PIG C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 10 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 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 1998 VL 30 IS 5 BP 2461 EP 2462 DI 10.1016/S0041-1345(98)00686-1 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 110ZM UT WOS:000075412900320 PM 9723537 ER PT J AU Chin, L Pomerantz, J DePinho, RA AF Chin, L Pomerantz, J DePinho, RA TI The INK4a/ARF tumor suppressor: one gene - two products - two pathways SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID CELL-CYCLE REGULATORS; RETINOBLASTOMA PROTEIN; UNRELATED PROTEINS; IN-VIVO; P53; MUTATIONS; P16(INK4A); MELANOMA; CANCER; LOCUS AB Functional inactivation of the retinoblastoma (RB) and p53 pathways appears to be a rite of passage for all cancerous cells and results in disruption of cell-cycle regulation and deactivation of the apoptotic response that normally ensues. The INK4a/ARF locus sits at the nexus of these two growth-control pathways, by virtue of its ability to generate two distinct products: the p16(INK4a) protein, a cyclin-dependent kinase inhibitor that functions upstream of RE; and the p19(ARF) protein, which blocks MDM2 inhibition of p53 activity. This 'one gene - two products - two pathways' arrangement provides a basis for the prominence of INK4a/ARF in tumorigenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY 10461 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Chin, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM ronald_depinho@dfci.harvard.edu FU NEI NIH HHS [R01EY09300, R01EY11267]; NICHD NIH HHS [R01HD28317] NR 49 TC 225 Z9 235 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD AUG PY 1998 VL 23 IS 8 BP 291 EP 296 DI 10.1016/S0968-0004(98)01236-5 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 113QU UT WOS:000075563400009 PM 9757829 ER PT J AU Poppas, DP Pavlovich, CP Folkman, J Voest, EE Chen, XH Luster, AD O'Donnell, MA AF Poppas, DP Pavlovich, CP Folkman, J Voest, EE Chen, XH Luster, AD O'Donnell, MA TI Intravesical bacille Calmette-Guerin induces the antiangiogenic chemokine interferon-inducible protein 10 SO UROLOGY LA English DT Article ID SUPERFICIAL BLADDER-CANCER; ENDOTHELIAL-CELL PROLIFERATION; MEDIATED ANTITUMOR-ACTIVITY; TUMOR-NECROSIS-FACTOR; ANGIOGENESIS IN-VIVO; IFN-GAMMA PRODUCTION; X-C CHEMOKINE; IMMUNE-RESPONSE; URINARY CYTOKINES; RECOMBINANT IL-12 AB Objectives. Intravesical bacille Calmette-Guerin (BCG) induces a variety of cytokines into the urine of patients with superficial transitional cell carcinoma (TCC) of the bladder. Recent data have shown that some cytokines have antiangiogenic activity. We sought to determine whether the potently antiangiogenic chemokine interferon-inducible protein 10 (IP-10) and its inducing antiangiogenic cytokines, interferon-gamma (IFN-gamma) and interleukin-12 (IL-12), are increased during intravesical BCG immunotherapy of bladder TCC. Methods. Voided urine samples were collected sequentially from 8 patients before and after each weekly intravesical BCG treatment and from 4 patients receiving maintenance BCG treatments. The urinary output of IP-10, IFN-gamma, and IL-12 over 12 post-treatment hours was assessed by enzyme-linked immunosorbent assay. In vitro BCG and cytokine stimulations of human TCC and primary endothelial cell lines were also performed, and their supernatants were studied for IP-10. Results. In all cases after intravesical BCG, patient urine was found to contain significant elevations of IP-10. Urinary IFN-gamma and IL-12 levels also increased in similar patterns after intravesical BCC. The peak weekly cytokine response per patient usually occurred between the fourth and sixth treatment for IFN-gamma and IP-10, but was less predictable for IL-12. Human TCC and endothelial cell lines were able to secrete IP-10 in response to BCC or interferon stimulation in vitro. Conclusions. Our small series demonstrates that IP-10 and its inducing cytokines are elevated in response to intravesical BCG. These data suggest that, in addition to a cellular immune response, BCG may induce a cytokine-mediated antiangiogenic environment that aids in inhibiting future tumor growth and progression. UROLOGY 52: 268-276, 1998. (C) 1998, Elsevier Science Inc. All rights reserved. C1 Univ Utrecht Hosp, Dept Internal Med, Utrecht, Netherlands. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Dept Surg, Div Urol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Charlestown, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Surg, Boston, MA USA. Cornell Univ, Med Ctr, New York Hosp,James Buchanan Brady Fdn, Dept Urol,Sect Pediat Urol, New York, NY 10021 USA. RP Poppas, DP (reprint author), Cornell Univ, Med Ctr, New York Hosp,James Buchanan Brady Fdn, Dept Urol,Sect Pediat Urol, 525 E 68th St, New York, NY 10021 USA. FU NCI NIH HHS [R01-CA69212-01, R29-CA64230] NR 47 TC 40 Z9 40 U1 0 U2 2 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD AUG PY 1998 VL 52 IS 2 BP 268 EP 275 DI 10.1016/S0090-4295(98)00188-5 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 104QT UT WOS:000075025800022 PM 9697793 ER PT J AU Luo, Y Kosanke, S Mieles, L Kobayashi, T Li, SF Niekrasz, M Shimizu, A Ye, Y Colvin, RB Cooper, DKC AF Luo, Y Kosanke, S Mieles, L Kobayashi, T Li, SF Niekrasz, M Shimizu, A Ye, Y Colvin, RB Cooper, DKC TI Comparative histopathology of hepatic allografts and xenografts in the nonhuman primate SO XENOTRANSPLANTATION LA English DT Article DE liver transplantation; immunosuppressive therapy; xenografts; histopathology ID ORTHOTOPIC LIVER-TRANSPLANTATION; HYPERACUTE REJECTION; XENOTRANSPLANTATION; MONKEY; BABOON; PIG; SURVIVAL; HEART AB Liver transplantation was performed in the following groups: Group 1, baboon-to-baboon allografting (n = 8) (control group); Group 2, ABO-compatible vervet monkey-to-baboon xenografting (n = 8); Group 3, ABO-incompatible vervet monkey-to-baboon xenografting (n = 6); Group 4, pig-to-baboon xenografting (n = 2); and Group 5, pig-to-rhesus monkey xenografting (n = 6). Immunosuppressive therapy (cyclosporine, cyclophosphamide, and methylprednisolone) was begun 2-7 days before liver transplantation (LTx) and continued indefinitely after LTx. The liver grafts were biopsied pre-LTx and subsequently post-LTx at approximately 1 hr, 2-3 hr, 7-10 days, 20-30 days, 60 days, 120 days, and at euthanasia or spontaneous death. There were 19 successful LTxs with grafts functioning from one hour to 123 days. No pig liver (Groups 4 and 5) survived more than 5.5 hr, as there was an immediate severe vascular response after reperfusion, typical of hyperacute rejection (congestion and hemorrhage). Vascular rejection was not seen in allografts (Group 1), but early mild-to-moderate congestion and neutrophil infiltration were present in concordant xenografts (Groups 2 and 3), which were associated with moderate deposition of immunoglobulin, C3, and fibrinogen. Lymphoid cell infiltration, bile duct damage, and portal vein endothelialitis in the portal zones occurred later in both allografts (Group 1) and concordant xenografts (Groups 2 and 3), developing earlier in the presence of ABO-incompatibility (Group 3). In concordant xenografts it was usually followed by fibrosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Pathol, Boston, MA 02129 USA. Baptist Med Ctr, Oklahoma Transplantat Inst, Oklahoma City, OK 73112 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Pathol, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. NR 31 TC 18 Z9 19 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 1998 VL 5 IS 3 BP 197 EP 206 DI 10.1111/j.1399-3089.1998.tb00028.x PG 10 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 119FL UT WOS:000075885300005 PM 9741458 ER PT J AU Koulmanda, M Auchincloss, H AF Koulmanda, M Auchincloss, H TI Literature update 1998 - Part 1 SO XENOTRANSPLANTATION LA English DT Review C1 Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, GRB 504, Boston, MA 02114 USA. NR 102 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 1998 VL 5 IS 3 BP 226 EP 231 DI 10.1111/j.1399-3089.1998.tb00032.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 119FL UT WOS:000075885300009 PM 9741462 ER PT J AU Yu, GS Lu, YC Gulick, T AF Yu, GS Lu, YC Gulick, T TI Rat carnitine palmitoyltransferase I beta mRNA splicing isoforms SO BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM LA English DT Article DE carnitine palmitoyltransferase; fatty acid oxidation; mRNA splicing; mitochondrion ID MALONYL-COA SENSITIVITY; CHROMOSOMAL LOCALIZATION; SINGLE POLYPEPTIDE; CPT-I; LIVER; CDNA; HEART; EXPRESSION; CLONING; ENZYME AB Carnitine palmitoyltransferase I (CPT-I) catalyzes the rate-determining step in mitochondrial fatty acid beta-oxidation. The enzyme has two cognate structural genes (alpha and beta) that are differentially expressed in tissues. We show multiple mature mRNAs in rat heart derived from alternative splicing of CPT-I beta transcripts. Two novel messages are deleted for regions of the previously described mRNA that encode membrane-spanning and regulatory domains, suggesting that the cognate isozymes will exhibit unique kinetic characteristics. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Gulick, T (reprint author), Massachusetts Gen Hosp, Diabet Unit, 149 13th St,MGH E,CNY 149 8218, Boston, MA 02129 USA. EM gulick@helix.mgh.harvard.edu FU NICHD NIH HHS [HD35685]; NIDDK NIH HHS [K02-DK02461, P30-DK40561] NR 29 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2760 J9 BBA-LIPID LIPID MET JI Biochim. Biophys. Acta-Lipids Lipid Metab. PD JUL 31 PY 1998 VL 1393 IS 1 BP 166 EP 172 DI 10.1016/S0005-2760(98)00075-7 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 112MJ UT WOS:000075498100019 PM 9714790 ER PT J AU Aberdam, E Bertolotto, C Sviderskaya, EV de Thillot, V Hemesath, TJ Fisher, DE Bennett, DC Ortonne, JP Ballotti, R AF Aberdam, E Bertolotto, C Sviderskaya, EV de Thillot, V Hemesath, TJ Fisher, DE Bennett, DC Ortonne, JP Ballotti, R TI Involvement of microphthalmia in the inhibition of melanocyte lineage differentiation and of melanogenesis by agouti signal protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATING-HORMONE-RECEPTOR; TRANSCRIPTION FACTOR; HUMAN HOMOLOG; MELANOCORTIN RECEPTORS; INVERSE AGONISTS; TYROSINASE GENE; IN-VITRO; MOUSE; LOCUS; MICE AB In mouse follicular melanocytes, production of eumelanins (brown-black pigments) and pheomelanins (yellow-brownish pigments) is under the control of two intercellular signaling molecules that exert opposite actions, alpha-melanocyte-stimulating hormone (alpha MSH) which preferentially increases the synthesis of eumelanins, and agouti signal protein (ASP) whose expression favors the production of hair containing pheomelanins. In this study, we report that ASP does not only affect mature melanocytes but can also inhibit the differentiation of melanoblasts. We show that both alpha MSH and forskolin promote the differentiation of murine melanoblasts into mature melanocytes and that ASP inhibits this process. We present evidence that the expression of a specific melanogenic transcription factor, microphthalmia, and its binding to an M box regulatory element, is inhibited by ASP. We also show that, in B16 murine melanoma cells, ASP inhibits alpha MSH-stimulated expression of tyrosinase, tyrosine-related proteins 1 and 2 through an inhibition of the transcription activity of their respective promoters. Further, ASP inhibits alpha MSH-induced expression of the microphthalmia gene and reduces the level of microphthalmia in the cells. Our data demonstrate that ASP can regulate both melanoblast differentiation and melanogenesis, pointing out the key role of microphthalmia in the control of these processes. C1 Fac Med, INSERM, U385, F-06107 Nice 2, France. Harvard Univ, Sch Med, Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. RP Ballotti, R (reprint author), Fac Med, INSERM, U385, Ave Valombrose, F-06107 Nice 2, France. RI Bennett, Dorothy/C-2418-2008; Sviderskaya, Elena/D-2419-2009; Bertolotto-Ballotti, Corine/O-2155-2016; BALLOTTI, Robert/F-8825-2013 OI Bennett, Dorothy/0000-0002-3639-7527; NR 43 TC 54 Z9 58 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 JUL 31 PY 1998 VL 273 IS 31 BP 19560 EP 19565 DI 10.1074/jbc.273.31.19560 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106JB UT WOS:000075125200032 PM 9677380 ER PT J AU Andersson, L Freeman, MW AF Andersson, L Freeman, MW TI Functional changes in scavenger receptor binding conformation are induced by charge mutants spanning the entire collagen domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; HELICAL PEPTIDE MODEL; HAMSTER OVARY CELLS; ALZHEIMERS-DISEASE; LIGAND-BINDING; IN-VITRO; EXPRESSION; PROTEINS; SITE; DEGRADATION AB Macrophage scavenger receptors are trimeric integral membrane proteins that bind a diverse array of negatively charged ligands, They have been shown to play a role in the pathogenesis of atherosclerosis and in host responses to microbial infections. Earlier mutational studies demonstrated that the distal segment of the collagen domain of the receptor was critically important for high affinity ligand binding activity. In this study, mutations spanning the entire collagen domain were generated and binding was assayed in transfected cells, as well as in assays employing a secreted, receptor fusion protein, Many of the distal, positively charged C-terminal residues in the type II collagen domain of the receptor, previously reported to be essential for binding at 37 degrees C, were found not to be critical for binding at 4 degrees C, Conversely, more proximally charged residues of the collagen receptor that have not been previously mutated were shown to have substantial effects on binding that were also temperature-dependent. These data suggest that scavenger receptor ligand recognition depends on more complex conformational interactions, involving charged residues throughout the entire collagen domain, than was previously recognized. C1 Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Nessel Gene Therapy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Lipid Metab Unit, GRJ 1328, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 45098]; NIDDK NIH HHS [DK50305] NR 33 TC 42 Z9 42 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 JUL 31 PY 1998 VL 273 IS 31 BP 19592 EP 19601 DI 10.1074/jbc.273.31.19592 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106JB UT WOS:000075125200037 PM 9677385 ER PT J AU Chandra, NC Spiro, MJ Spiro, RG AF Chandra, NC Spiro, MJ Spiro, RG TI Identification of a glycoprotein from rat liver mitochondrial inner membrane and demonstration of its origin in the endoplasmic reticulum SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-D-MANNOSIDASE; N-LINKED OLIGOSACCHARIDES; FRACTION; PROTEINS; PATHWAY; CELLS; GRADIENT; PHOSPHATIDYLETHANOLAMINE; PHOSPHATIDYLSERINE; LOCALIZATION AB Employing antisera against various subfractions of rat liver mitochondria (mitoplast, inner membrane, intermembrane, and matrix) as well as metabolically radiolabeled BRL-3A rat liver cells, we undertook a search for the presence of glycoproteins in this major cellular compartment for which little information in regard to glycoconjugates was available. Subsequent to [S-35]methionine labeling of BRL-3A cells, a peptide:N-glycosidase-sensitive protein (45 kDa) was observed by SDS-polyacrylamide gel electrophoresis of the inner membrane immunoprecipitate, which was reduced to a molecular mass of 42 kDa by this enzyme. The 45-kDa protein was readily labeled with [2-H-3]mannose, and indeed the radioactivity of the inner membrane immunoprecipitate was almost exclusively present in this component. Moreover, antisera directed against mitochondrial NADH-ubiquinone oxidoreductase (complex I) or F1F0-ATPase (complex V) also precipitated a 45-kDa protein from BRL-3A cell lysates as the predominant mannose-radiolabeled constituent. Endo-beta-N-acetylglu-cosaminidase completely removed the radiolabel hom this glycoprotein, and the released oligosaccharides were of the partially trimmed polymannose type (Glc(1)Man(9)GlcNAc to Man(8)GlcNAc). Cycloheximide as well as tunicamycin resulted in total inhibition of radiolabeling of the inner membrane glycoprotein and moreover, pulse-chase studies employing metrizamide density gradient centrifugation demonstrated that the glycoprotein was initially present in the endoplasmic reticulum (ER) and subsequently appeared in a mitochondrial location. Early movement of the glycoprotein to the mitochondria after synthesis in the;ER was also evident from the limited processing undergone by its N-linked oligosaccharides; this stood in contrast to lysosomal glycoproteins in which we noted extensive conversion to complex oligosaccharides. Our findings suggest that the 45-kDa glycoprotein migrates from ER to mitochondria by the previously observed contact sites between the two organelles. Furthermore, the presence of this glycoprotein in at least two major mitochondrial multienzyme complexes would be consistent with a role in mitochondrial translocations. C1 Joslin Diabet Ctr, Elliott P Joslin Res Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Spiro, RG (reprint author), Joslin Diabet Ctr, Elliott P Joslin Res Lab, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK17325, DK17477] NR 58 TC 48 Z9 49 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 31 PY 1998 VL 273 IS 31 BP 19715 EP 19721 DI 10.1074/jbc.273.31.19715 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106JB UT WOS:000075125200053 PM 9677401 ER PT J AU Lin, HM Hutchcroft, JE Andoniou, CE Kamoun, M Band, H Bierer, BE AF Lin, HM Hutchcroft, JE Andoniou, CE Kamoun, M Band, H Bierer, BE TI Association of p59(fyn) with the T lymphocyte costimulatory receptor CD2 - Binding of the Fyn Src homology (SH) 3 domain is regulated by the Fyn SH2 domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; PROTEIN-TYROSINE KINASE; NATURAL-KILLER-CELLS; CYTOPLASMIC DOMAIN; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; ALTERNATIVE PATHWAY; PHOSPHATASE CD45; LIGAND AVIDITY; SURFACE LIGAND AB Human CD2 is a 50-55-kDa cell surface receptor specifically expressed on the surface of T lymphocytes and NK cells. Stimulation of human peripheral blood T cells with mitogenic pairs of anti-CD2 monoclonal antibodies (mAbs) is sufficient to induce interleukin-a production and T cell proliferation in the absence of an antigen-specific signal through the T cell receptor. CD2 has been shown previously to associate physically with the Src family protein-tyrosine kinases p56(lck) and p59(fyn). We now report that stimulation of T cells with mitogenic pairs of anti-CD2 mAbs enhanced the association of the Fyn polypeptide with the CD2 complex, whereas stimulation with single anti-CD2 mAb had minimal effect. Using glutathione S-transferase (GST) fusion proteins, we found that CD2 bound to the Src homology (SH) 3 domain of Fyn. Interestingly, the CD2-Fyn association was negatively regulated by the Fyn SH2 domain; CD2 bound poorly to GST fusion proteins expressing both the SH2 and SH3 domains of Fyn. However, the inhibitory effect of the Fyn SH2 domain on binding of the Fyn SH3 domain to CD2 was relieved by peptides containing a phosphorylated YEEI sequence that bound directly to the Fyn SH2 domain. In addition, we found that the ability of the Fyn SH2 domain to precipitate tyrosine-phosphorylated proteins, including the CD3 zeta chain, was enhanced after T cell stimulation with mitogenic pairs of CD2 mAbs. Finally, overexpression of a mutated Fyn molecule, in which the ability of the Fyn SH2 domain to bind phosphotyrosine-containing proteins was abrogated, inhibited CD2-induced transcriptional activation of the nuclear factor of activated T cells (NFAT), suggesting a functional involvement of the Fyn SH2 domain in CD2-induced T cell signaling. We thus propose that stimulation through the CD2 receptor leads to the tyrosine phosphorylation of intracellular proteins, including CD3 zeta itself, which in turn bind to the Fyn-SH2 domain, allowing the direct association of the Fyn SH3 domain with CD2 and the initiation of downstream signaling events. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Sci, Comm Immunol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Rheumatol & Immunol, Lymphocyte Biol Sect, Boston, MA 02115 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, NIH, Bldg 10,Rm 5D49,10 Ctr Dr, Bethesda, MD 20892 USA. EM biererb@nih.gov RI Andoniou, Christopher/B-6296-2013 NR 65 TC 28 Z9 30 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 JUL 31 PY 1998 VL 273 IS 31 BP 19914 EP 19921 DI 10.1074/jbc.273.31.19914 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106JB UT WOS:000075125200082 PM 9677430 ER PT J AU Francklyn, C Adams, J Augustine, J AF Francklyn, C Adams, J Augustine, J TI Catalytic defects in mutants of class II histidyl-tRNA synthetase from Salmonella typhimurium previously linked to decreased control of histidine biosynthesis regulation SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE histidine biosynthesis; class II aminoacyl-tRNA synthetases; tRNA recognition; enzyme mechanisms ID TRANSFER-RNA-SYNTHETASE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; THERMUS-THERMOPHILUS; ACTIVE-SITE; SERYL-ADENYLATE; AMINOACYLATION; IDENTITY; RECOGNITION; RESOLUTION AB The expression of histidine biosynthetic genes in enteric bacteria is regulated by an attenuation mechanism in which the level of histidyl-tRNA serves as a key sensor of the intracellular histidine pool. Among the early observations that led to the formation of this model for Salmonella typhimurium were the identification of mutants in the gene (hisS) encoding histidyl-tRNA synthetase. We report here the detailed biochemical characterization of five of these S. typhimurium bradytrophic mutants isolated by selection for resistance to histidine analogs, including identification of the deduced amino acid substitutions and determination of the resulting effects on the kinetics of adenylation and aminoacylation. Using the crystal structure of the closely related Escherichia coli histidyl-tRNA synthetase (HisRS) as a guide, two mutants were mapped to a highly conserved proline residue in motif 2 (P117S, P117Q), and were correlated with a fivefold decrease in the k(cat) for the pyrophosphate exchange reaction, as well as a tenfold increase in the K-m for tRNA in the aminoacylation reaction. Another mutant substitution (A302T) mapped to a residue adjacent to the histidine binding pocket, leading to a tenfold increase in K-m for histidine in the pyrophosphate exchange reaction. The remaining two mutants (S167F, N254T) substitute residues in or directly adjacent to the hinge region, which joins the insertion domain between motif 2 and motif 3 to the catalytic core, and cause the K-m for tRNA to increase four- to tenfold. The kinetic analysis of these mutants establishes a direct link between critical interactions within the active site of HisRS and regulation of histidine biosynthesis, and provides further evidence for the importance of local conformational changes during the catalytic cycle. (C) 1998 Academic Press. C1 Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. Kern Med Ctr, Bakersfield, CA 93309 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Francklyn, C (reprint author), Univ Vermont, Coll Med, Dept Biochem, Hlth Sci Complex, Burlington, VT 05405 USA. EM franck@emba/uvm.edu FU NIGMS NIH HHS [GM 48146, R01 GM054899] NR 58 TC 15 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 31 PY 1998 VL 280 IS 5 BP 847 EP 858 DI 10.1006/jmbi.1998.1902 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 106XY UT WOS:000075177600008 PM 9671554 ER PT J AU Krause, WL Kazemi, H Burton, MD AF Krause, WL Kazemi, H Burton, MD TI Potential role for imidazole in the rhythmic respiratory activity of the in vitro neonatal rat brainstem SO NEUROSCIENCE LETTERS LA English DT Article DE alphastat hypothesis; imidazole-histidine; diethylpyrocarbonate; control of breathing ID SPINAL-CORD PREPARATION; ACID-BASE-BALANCE; DIETHYL PYROCARBONATE; BODY-TEMPERATURE; ACETYLCHOLINE; STEM; IDENTIFICATION; PERTURBATIONS; SENSITIVITY; INVITRO AB We used the imidazole-binding agent, diethylpyrocarbonate (DEPC), to test the hypothesis that rhythmic respiratory activity of the in vitro neonatal rat brainstem-spinal cord preparation was functionally dependent on imidazole. Neural activity was recorded from spinal nerves (C1-C4) during superfusion with 95%O-2/5%CO2 buffer at pH 7.3 and T = 26 degrees C. Superfusate containing DEPC (40 mM) caused cessation of rhythmic activity within minutes. In eight of 33 preparations, microinjection of DEPC (32 nmol) onto the ventral medullary surface (VMS) reduced burst amplitude by at least 50% within 10 min, and in 12 of 33 preparations, microinjection of DEPC produced neural apnea. Therefore, we conclude that proteins containing imidazole near the VMS are critically important for the maintenance of rhythmic respiratory activity in vitro. Furthermore, alphastat regulation of respiration may be an essential trait of this preparation. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Krause, WL (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Med Serv, Bulfinch 148,32 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-07674] NR 23 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 31 PY 1998 VL 251 IS 3 BP 153 EP 156 DI 10.1016/S0304-3940(98)00502-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 111QB UT WOS:000075448200003 PM 9726366 ER PT J AU Carmeliet, P Dor, Y Herbert, JM Fukumura, D Brusselmans, K Dewerchin, M Neeman, M Bono, F Abramovitch, R Maxwell, P Koch, CJ Ratcliffe, P Moons, L Jain, RK Collen, D Keshet, E AF Carmeliet, P Dor, Y Herbert, JM Fukumura, D Brusselmans, K Dewerchin, M Neeman, M Bono, F Abramovitch, R Maxwell, P Koch, CJ Ratcliffe, P Moons, L Jain, RK Collen, D Keshet, E TI Role of HIF-1 alpha or in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis SO NATURE LA English DT Article ID GLUCOSE-REGULATED PROTEINS; INDUCIBLE FACTOR-1; ARREST; P21 AB As a result of deprivation of oxygen (hypoxia) and nutrients, the growth and viability of cells is reduced(1). Hypoxia-inducible factor (KIF)-1 alpha helps to restore oxygen homeostasis by inducing glycolysis, erythropoiesis and angiogenesis(2-4). Here we show that hypoxia and hypoglycaemia reduce proliferation and increase apoptosis in wild-type (HIF-1 alpha(+/+)) embryonic stem (ES) cells, but not in ES cells with inactivated HIF-1 alpha. genes (HIF-1 alpha(-/-)); however, a deficiency of HIF-1 alpha does not affect apoptosis induced by cytokines. We find that hypoxia/hypoglycaemia-regulated genes involved in controlling the cell cycle are either HIF-1 alpha-dependent (those encoding the proteins p53, p21, Bcl-2) or HLF-1 alpha-independent (p27, GADD153), suggesting that there are at least two different adaptive responses to being deprived of oxygen and nutrients, Loss of HIF-1 alpha. reduces hypoxia-induced expression of vascular endothelial growth factor, prevents formation of large vessels in ES-derived tumours, and impairs vascular function, resulting in hypoxic microenvironments within the tumour mass, However, growth of HIF-1 alpha. tumours was not retarded but was accelerated, owing to decreased hypoxia-induced apoptosis and increased stress-induced proliferation. As hypoxic stress contributes to many (patho)biological disorders(1,5), this new role for HIF-1 alpha in hypoxic control of cell growth and death may be of general pathophysiological importance. C1 Catholic Univ Louvain VIB, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Biol, IL-91120 Jerusalem, Israel. Sanofi Rech, Haemobiol Res Dept, F-31036 Toulouse, France. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. John Radcliffe Hosp, Welcome Trust Ctr Human Genet, Inst Mol Med, Oxford OX3 7BN, England. Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Carmeliet, P (reprint author), Catholic Univ Louvain VIB, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium. EM Peter.Carmeliet@med.kuleuven.ac.be RI Dor, Yuval/C-2405-2011; Maxwell, Patrick/C-5557-2008; Neeman, Michal/A-8264-2008; OI Maxwell, Patrick/0000-0002-0338-2679; Neeman, Michal/0000-0002-6296-816X; Ratcliffe, Peter/0000-0002-2853-806X FU Wellcome Trust NR 30 TC 1659 Z9 1751 U1 18 U2 156 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 30 PY 1998 VL 394 IS 6692 BP 485 EP 490 DI 10.1038/28867 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 105NT UT WOS:000075080400054 PM 9697772 ER PT J AU Zeng, CX Toole, BP Kinney, SD Kuo, JW Stamenkovic, I AF Zeng, CX Toole, BP Kinney, SD Kuo, JW Stamenkovic, I TI Inhibition of tumor growth in vivo by hyaluronan oligomers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CARCINOMA-CELLS; BINDING-PROTEINS; RECEPTOR RHAMM; T-CELLS; CD44; VARIANT; MACROPHAGES; EXPRESSION; ADHESION; ISOFORMS AB One of the critical events in tumor growth and metastasis is the interaction between tumor cells and host tissue stroma, mediated by different adhesion receptor repertoires in different tumor cell types. Several lines of evidence indicate that interaction between the hyaluronan receptor CD44, expressed on tumor cells, and host tissue stromal hyaluronan can enhance growth and invasiveness of certain tumors. Disruption of CD44-hyaluronan interaction by soluble recombinant CD44 has been shown to inhibit tumor formation by lymphoma and melanoma cells transfected with CD44. Since hyaluronan is a ubiquitous glycosaminoglycan polymer from which oligosaccharides of defined size can be readily purified, we tested the ability of hyaluronan oligomers to inhibit tumor formation by subcutaneously (s.c.) injected B16F10 melanoma cells. Our results indicate that hyaluronan oligomers injected at concentrations as low as 1 mg/ml can markedly inhibit B16F10 melanoma growth, providing a potentially attractive reagent for the control of local tumor development. (C) 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Pathol Res Labs, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Tufts Univ, Med Ctr, Dept Anat & Cellular Biol, Boston, MA 02111 USA. Anika Therapeut Inc, Woburn, MA USA. RP Stamenkovic, I (reprint author), Massachusetts Gen Hosp, Pathol Res Labs, 149 13th St,Charlestown Navy Yard, Boston, MA 02129 USA. FU NCI NIH HHS [CA05838, CA55735]; NICHD NIH HHS [HD23681] NR 41 TC 161 Z9 168 U1 1 U2 16 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 29 PY 1998 VL 77 IS 3 BP 396 EP 401 PG 6 WC Oncology SC Oncology GA ZW531 UT WOS:000074420300015 PM 9663602 ER PT J AU Williamson, PTF Grobner, G Spooner, PJR Miller, KW Watts, A AF Williamson, PTF Grobner, G Spooner, PJR Miller, KW Watts, A TI Probing the agonist binding pocket in the nicotinic acetylcholine receptor: A high-resolution solid-state NMR approach SO BIOCHEMISTRY LA English DT Article ID POSTSYNAPTIC MEMBRANES; PROTEIN-STRUCTURE; CHEMICAL-SHIFTS; TORPEDO; SITE AB Acetylcholine, the agonist for the nicotinic acetylcholine receptor, has been observed directly when bound specifically to its binding site in the fully functional receptor-enriched membranes from Torpedo nobiliana. High-resolution solid-state, magic angle spinning C-13 NMR methods have been used to observe selectively N+((CH3)-C-13)(3) acetylcholine bound in as few as 20 nmol of receptor binding sites, against a background of natural abundance membrane resonances and excess acetylcholine in free solution. The specificity of the binding has been demonstrated to be pharmacologically significant through the use of the competitive inhibitor alpha-bungarotoxin which selectively displaces and prevents binding of acetylcholine to the membrane-bound receptor. The chemical shift assigned to N+((CH3)-C-13)(3) acetylcholine in solution and crystalline solid is 53.9 +/- 0.04 ppm, and it changes by 1.6 ppm (p < 0.05) for agonist when bound specifically in the receptor binding site. Through the use of computer simulations of chemical shifts carried out on acetylcholine bound to the acetylcholinesterase, we propose that the cause for this change is the presence of aromatic side chains lining the receptor binding site. It is suggested that the binding of acetylcholine to the nicotinic acetylcholine receptor is mediated primarily through the interaction of the quaternary ammonium group of the acetylcholine with the pi bonded systems in the aromatic side chains. Longitudinal relaxation time measurements show that the residency time for the acetylcholine observed in DDCP experiments is long (>200 ms) with respect to the longitudinal relaxation time of other assignable resonances within the spectrum from the lipid and protein and confirms that the acetylcholine is protein-associated, and not free in solution or nonspecifically bound. C1 Univ Oxford, Dept Biochem, Biomembrane Struct Unit, Oxford OX1 3QU, England. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Watts, A (reprint author), Univ Oxford, Dept Biochem, Biomembrane Struct Unit, S Parks Rd, Oxford OX1 3QU, England. EM awatts@bioch.ox.ac.uk RI Williamson, Philip/A-3362-2008 OI Williamson, Philip/0000-0002-0231-8640 FU NIAAA NIH HHS [NIAAA07040] NR 28 TC 27 Z9 28 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 28 PY 1998 VL 37 IS 30 BP 10854 EP 10859 DI 10.1021/bi980390q PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108RZ UT WOS:000075280400034 PM 9692976 ER PT J AU Durante, W Liao, L Peyton, KJ Schafer, AI AF Durante, W Liao, L Peyton, KJ Schafer, AI TI Thrombin stimulates vascular smooth muscle cell polyamine synthesis by inducing cationic amino acid transporter and ornithine decarboxylase gene expression SO CIRCULATION RESEARCH LA English DT Article DE thrombin; L-ornithine; polyamine; proliferation ID ECOTROPIC RETROVIRUS RECEPTOR; GROWTH-FACTOR; PROLIFERATION; INDUCTION; PROTEIN; IDENTIFICATION; MITOGENESIS; MEMBRANE; HEPARIN; DOMAIN AB Thrombin, a serine protease, is a potent mitogen for vascular smooth muscle cells (SMCs), but its mechanism of action is not known. Since L-ornithine is metabolized to growth-stimulatory polyamines, we examined whether thrombin regulates the transcellular transport and metabolism of L-ornithine by vascular SMCs. Treatment of SMCs with thrombin initially (0 to 2 hours) decreased L-ornithine uptake, whereas longer exposures (6 to 24 hours) progressively increased transport. Kinetic studies indicated that thrombin-induced inhibition was associated with a decrease in affinity for L-ornithine, whereas stimulation was mediated by an increase in transport capacity. Thrombin induced the expression of both cationic amino acid transporter (CAT)-1 and CAT-2 mRNA. Furthermore, thrombin stimulated L-ornithine metabolism by inducing ornithine decarboxylase (ODC) mRNA expression and activity. The stimulatory effect of thrombin on both L-ornithine transport and ODC activity was reversed by hirudin, a thrombin inhibitor, and was mimicked by a 14-amino acid thrombin receptor-activating peptide. Thrombin also markedly increased the capacity of SMCs to generate putrescine, a polyamine, from extracellular L-ornithine. The thrombin-mediated increase in putrescine production was reversed by N-G-methyl-L-arginine, a competitive inhibitor of cationic amino acid transport, or by cu-difluoromethylornithine (DFMO), an ODC inhibitor. DFMO also inhibited thrombin-induced SMC proliferation. These results demonstrate that thrombin stimulates polyamine synthesis by inducing CAT and ODC gene expression and that thrombin-stimulated SMC proliferation is dependent on polyamine formation. The ability of thrombin to upregulate L-ornithine transport and direct its metabolism to growth-stimulatory polyamines may contribute to postangioplasty restenosis and atherosclerotic lesion formation. C1 Houston VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. RP Durante, W (reprint author), Houston VA Med Ctr, Bldg 109,Room 128,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL-36045] NR 42 TC 29 Z9 30 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL 27 PY 1998 VL 83 IS 2 BP 217 EP 223 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 103HP UT WOS:000075152100012 PM 9686762 ER PT J AU Dominov, JA Dunn, JJ Miller, JB AF Dominov, JA Dunn, JJ Miller, JB TI Bcl-2 expression identifies an early stage of myogenesis and promotes clonal expansion of muscle cells SO JOURNAL OF CELL BIOLOGY LA English DT Article DE apoptosis; Bcl-2; myoblast; myogenin; skeletal muscle ID DYSTROPHIN-DEFICIENT MUSCLE; REGULATORY FACTOR PROTEINS; MOUSE MUSCLE; IMMUNOHISTOCHEMICAL ANALYSIS; POLYCYSTIC KIDNEY; SATELLITE CELLS; CHICK-EMBRYO; IN-VIVO; APOPTOSIS; DEATH AB We show that Bcl-2 expression in skeletal muscle cells identifies an early stage of the myogenic pathway, inhibits apoptosis, and promotes clonal expansion. Bcl-2 expression was limited to a small proportion of the mononucleate cells in muscle cell cultures, ranging from similar to 1-4% of neonatal and adult mouse muscle cells to similar to 5-15% of the cells from the C2C12 muscle cell line. In rapidly growing cultures, some of the Bcl-2-positive cells coexpressed markers of early stages of myogenesis, including desmin, MyoD, and Myf-5. In contrast, Bcl-2 was not expressed in multinucleate myotubes or in those mononucleate myoblasts that expressed markers of middle or late stages of myogenesis, such as myogenin, muscle regulatory factor 4 (MRF4), and myosin. The small subset of Bcl-2-positive C2C12 cells appeared to resist staurosporine-induced apoptosis. Furthermore, though myogenic cells from genetically Bcl-2-null mice formed myotubes normally, the muscle colonies produced by cloned Bcl-2-null cells contained only about half as many cells as the colonies produced by cells from wild-type mice. This result suggests that, during clonal expansion from a muscle progenitor cell, the number of progeny obtained is greater when Bcl-2 is expressed. C1 Massachusetts Gen Hosp, Myogenesis Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Miller, JB (reprint author), Massachusetts Gen Hosp, Myogenesis Res Lab, 149 13th St, Charlestown, MA 02129 USA. EM Miller@helix.mgh.harvard.edu NR 53 TC 68 Z9 75 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL 27 PY 1998 VL 142 IS 2 BP 537 EP 544 DI 10.1083/jcb.142.2.537 PG 8 WC Cell Biology SC Cell Biology GA 106CC UT WOS:000075111300019 PM 9679150 ER PT J AU Yao, JK Reddy, R van Kammen, DP AF Yao, JK Reddy, R van Kammen, DP TI Reduced level of plasma antioxidant uric acid in schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE haloperidol; antioxidant defense system; plasma uric acid; psychosis ID CELL MEMBRANE DYNAMICS; DRUG-FREE PATIENTS; LIPID-PEROXIDATION; ARACHIDONIC-ACID; BLOOD; URATE; INHIBITION; DISMUTASE; ASCORBATE; PSYCHOSIS AB There is evidence of dysregulation of the antioxidant defense system in schizophrenia. The purpose of the present study was to examine whether uric acid, a potent antioxidant, is reduced in the plasma of patients with schizophrenia. To this end, a within-subject, repeated measures, on-off-on haloperidol treatment design was utilized. Male schizophrenic patients with either a haloperidol treatment (n = 47) or a drug-free condition (n = 35) had significantly lower levels of plasma uric acid than the age- and sex-matched normal control subjects (n = 34). Following haloperidol withdrawal, plasma uric acid levels were further reduced in schizophrenic patients (P = 0.018; paired t-test, n = 35). However, no relationship was found between uric acid levels and the length of the drug-free period (<5 or > 5 weeks) or days drug free. In addition, the plasma levels of uric acid in patient groups were significantly and inversely correlated with psychosis. There was a trend for lower uric acid levels in relapsed patients relative to clinically stable patients. Smoking, which can modify plasma antioxidant capacity, was not found to have prominent effects on uric acid levels. The present finding of a significant decrease of a selective antioxidant provides additional support to the hypothesis that oxidative stress in schizophrenia may be due to a defect in the antioxidant defense system. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Yao, JK (reprint author), Dept Vet Affairs Med Ctr, 113A,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM jkyao@vms.cis.pitt.edu NR 42 TC 69 Z9 72 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL 27 PY 1998 VL 80 IS 1 BP 29 EP 39 DI 10.1016/S0165-1781(98)00051-1 PG 11 WC Psychiatry SC Psychiatry GA 110KG UT WOS:000075379500003 PM 9727961 ER PT J AU Kozlowski, T Monroy, R Xu, YX Glaser, R Awwad, M Cooper, DKC Sachs, DH AF Kozlowski, T Monroy, R Xu, YX Glaser, R Awwad, M Cooper, DKC Sachs, DH TI Anti-Gal alpha 1-3Gal antibody response to porcine bone marrow in unmodified baboons and baboons conditioned for tolerance induction SO TRANSPLANTATION LA English DT Article ID HUMAN T-CELLS; NONLETHAL PREPARATIVE REGIMEN; CYNOMOLGUS MONKEY; XENOTRANSPLANTATION; TRANSPLANTATION; PIG; COSTIMULATION; RECOGNITION; CHIMERISM; BARRIERS AB Background Mixed lymphohematopoietic chimerism can provide an effective means of inducing longterm immunological tolerance and has been documented in a monkey allograft model, A conditioning regimen including nonmyeloablative or myeloablative irradiation and splenectomy has been used to induce chimerism in a pig-to-primate transplantation model. Since the presence of anti-Gal alpha 1-3Gal (alpha Gal) natural antibodies leads to the hyperacute rejection of pig organs transplanted into primates, extracorporeal immunoaffinity adsorption (EIA) of anti-alpha Gal antibodies is also included in the regimen. The effect of the tolerance induction protocol on the anti-alpha Gal antibody response has been assessed. Methods. Anti-alpha Gal antibody was measured after the EIA of plasma through an alpha Gal immunoaffinity column in baseline studies involving two unmodified baboons, one splenectomized baboon, and one baboon that received a challenge with porcine bone marrow (BM), and in three groups of baboons (n=2 in each group) that received different conditioning regimens for tolerance induction. Group 1 received a nonmyeloablative conditioning regimen without porcine BM transplantation, Group 2 received nonmyeloablative conditioning with pig BM transplantation and pig cytokine therapy. Group 3 received myeloablative conditioning, an autologous BM transplant (with BM depleted of CD2(+) or CD2(+)/CD20(+) cells), and pig BM transplantation, Results. In the baseline studies, a single EIA of anti-alpha Gal antibodies in an unmodified animal initially depleted anti-alpha Gal antibody, followed by a mild rebound. Nonmyeloablative conditioning (group 1) in the absence of pig cell exposure reduced the rate of anti-alpha Gal antibody return. Pig BM cells markedly stimulated anti-alpha Gal antibody production in an unmodified baboon (alpha Gal IgM and IgG levels increased 40- and 220-fold, respectively). This response was significantly reduced (to an only 2- to 5.5-fold increase of IgM and IgG) in baboons undergoing nonmyeloablative conditioning (group 2). A myeloablative conditioning regimen (group 3) prevented the antibody response to pig BM, with the reduction in response being greater in the baboon that received autologous BM depleted of both CD2(+) and CD20(+) cells. No new antibody directed against pig non-alpha Gal antigens was detected ill any baboon during the 1 month follow-up period. Conclusions. (i) EIA of anti-alpha Gal antibody in unmodified baboons results in a transient depletion followed by a mild rebound of antibody; (ii) exposure to pig BM cells results in a substantial increase in anti-alpha Gal antibody production; (iii) a nonmyeloablative conditioning regimen reduces the rate of antibody return and (iv) markedly reduces the response to pig BM cells; (v) the anti-alpha Gal response is completely suppressed by a myeloablative regimen if CD2(+) and CD20(+) cells are eliminated from the autologous BM inoculum. Furthermore, (vi) challenge with pig BM cells appears to stimulate only an anti-alpha Gal antibody response without the development of other (non-alpha Gal) anti-pig antibodies. We conclude that regimens used for T-cell tolerance induction can be beneficial in reducing the anti-alpha Gal antibody response to porcine BM. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. BioTransplant Inc, Charlestown, MA USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 39 TC 65 Z9 68 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 27 PY 1998 VL 66 IS 2 BP 176 EP 182 DI 10.1097/00007890-199807270-00006 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 106RW UT WOS:000075165100006 PM 9701260 ER PT J AU Warrens, AN Simon, AR Theodore, PR Sachs, DH Sykes, M AF Warrens, AN Simon, AR Theodore, PR Sachs, DH Sykes, M TI Function of porcine adhesion molecules in a human marrow microenvironment SO TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; MONOCLONAL-ANTIBODIES; LYMPHO-HEMATOPOIESIS; MIXED CHIMERISM; CELLS; TOLERANCE; FIBRONECTIN; MICE; TRANSPLANTATION; CULTURES AB Background. One way to circumvent the need for chronic immunosuppression in solid organ xenografting may be to induce donor-specific tolerance using bone marrow transplantation, If this approach is to succeed in the pig-to-human species combination, pig marrow must be capable of maturing into relevant tolerance-inducing cells and replenishing itself in host human marrow. One possible barrier is adhesion molecule incompatibility, We have studied the compatibility across the pig human species barrier of two well-characterized ligands known to be important in hematopoiesis, CD44 and very late antigen (VLA)-4, Methods. In vitro long-term bone marrow cultures were studied in which the effects of blocking antibodies were assessed by measuring cell numbers and colony-forming units. Results, The blocking of CD44 had a comparable inhibitory effect on the hematopoiesis of human and pig marrow, even if the latter was maintained on a human stromal layer. Both cellular proliferation and colony-forming activity were inhibited by anti-CD44 monoclonal antibody, By contrast, a significant difference was observed in VLA-4 usage by hematopoietic cells of the two species. Blocking VLA-4 markedly inhibited human hematopoietic cellular proliferation but had no effect on pig hematopoiesis, on either porcine or human stroma, Conclusion. The data suggest that the incompatibility of either CD44 or VLA-4 is unlikely to Limit the efficiency of porcine hematopoiesis in a human marrow environment, However, the difference in VLA-4 utilization between these species raises the possibility that other interactions may be important for effective porcine hematopoiesis and that their failure to function between species may contribute to the poor function of porcine hematopoietic cells in primate marrow microenvironments. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL54038] NR 40 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 27 PY 1998 VL 66 IS 2 BP 252 EP 259 DI 10.1097/00007890-199807270-00020 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 106RW UT WOS:000075165100020 PM 9701274 ER PT J AU Mulrow, CD AF Mulrow, CD TI Evidence based case report - Helping an obese patient make informed choices SO BRITISH MEDICAL JOURNAL LA English DT Review ID WEIGHT-LOSS; WOMEN; MORTALITY C1 Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Mulrow, CD (reprint author), Audie L Murphy Mem Vet Hosp, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM mulrowc@uthscsa.edu NR 16 TC 3 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD JUL 25 PY 1998 VL 317 IS 7153 BP 266 EP 267 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 105PG UT WOS:000075081900029 PM 9677222 ER PT J AU Pivniouk, V Tsitsikov, E Swinton, P Rathbun, G Alt, FW Geha, RS AF Pivniouk, V Tsitsikov, E Swinton, P Rathbun, G Alt, FW Geha, RS TI Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76 SO CELL LA English DT Article ID T-CELL DEVELOPMENT; TYROSINE KINASE; MUTANT MICE; ALPHA-BETA; LYMPHOCYTE DEVELOPMENT; THYMIC SELECTION; TCR-BETA; B-CELLS; GENE; DIFFERENTIATION AB The adaptor protein SLP-76 is expressed in T lymphocytes and myeloid cells and is a substrate for ZAP-70 and Syk. We generated a SLP-76 null mutation in mice by homologous recombination in embryonic stem cells to evaluate the role of SLP-76 in T cell development and activation. SLP-76-deficient mice exhibited subcutaneous and intraperitoneal hemorrhaging and impaired viability. Analysis of lymphoid cells revealed a profound block in thymic development with absence of double-positive CD4(+)8(+) thymocytes and of peripheral T cells. This block could not be overcome by in vivo treatment with anti-CD3. V-D-J rearrangement of the TCR beta locus was not obviously affected. B cell development was normal. These results indicate that SLP-76 collects all pre-TCR signals that drive the development and expansion of double-positive thymocytes. C1 Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. RP Geha, RS (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI-35714] NR 53 TC 297 Z9 301 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 24 PY 1998 VL 94 IS 2 BP 229 EP 238 DI 10.1016/S0092-8674(00)81422-1 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 104NF UT WOS:000075020100011 PM 9695951 ER PT J AU Sturm, NR Fleischmann, J Campbell, DA AF Sturm, NR Fleischmann, J Campbell, DA TI Efficient trans-splicing of mutated spliced leader exons in Leishmania tarentolae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MINI-EXON; TRYPANOSOMA-BRUCEI; IN-VIVO; LEPTOMONAS-COLLOSOMA; MESSENGER-RNAS; GENE; EXPRESSION; ELEMENTS; TRANSCRIPTION; METHYLATIONS AB Every kinetoplastid mRNA receives a common, conserved leader sequence via the process of trans-splicing. In Leishmania tarentolae the precursor spliced leader RNA is 96 nucleotides, with a 39-nucleotide exon that is 7meG-capped and methylated on the first 4 nucleotides. trans-Splicing was inferred from the presence of tagged leader in the high molecular weight RNA population and confirmed for accuracy by cDNA cloning. Linker scan substitutions within the exon between positions 10 and 39 did not affect trans-splicing. The trans-splicing efficiency for three of the scan exons was proportional to the tagged:wild type ratio in the spliced leader precursor population. Two scan leader RNAs that were efficiently spliced showed reduced methylation. Longer exons showed reduced splicing, whereas 10- or 20-base pair deletions abolished splicing. These results indicate that size, but not content, of the exon is a constraint on the splicing process. These results, in combination with previous data eliminating a role in transcription initiation, suggest that translation may be the selective pressure on the leader content. C1 Univ Calif Los Angeles, Sch Med, Dept Immunol & Microbiol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. RP Campbell, DA (reprint author), Univ Calif Los Angeles, Sch Med, Dept Immunol & Microbiol, Los Angeles, CA 90095 USA. FU NIAID NIH HHS [2-T32-AI-07323, AI34536] NR 29 TC 29 Z9 30 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 JUL 24 PY 1998 VL 273 IS 30 BP 18689 EP 18692 DI 10.1074/jbc.273.30.18689 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103TV UT WOS:000074974700004 PM 9668037 ER PT J AU Phelan, SA Loeken, MR AF Phelan, SA Loeken, MR TI Identification of a new binding motif for the paired domain of Pax-3 and unusual characteristics of spacing of bipartite recognition elements on binding and transcription activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR ALVEOLAR RHABDOMYOSARCOMA; DNA-BINDING; WAARDENBURG SYNDROME; BOX GENE; PROTEIN; SEQUENCES; DROSOPHILA; FUSION; EXPRESSION; MUTATIONS AB Pax-3, a transcription factor that is required for development of the embryonic neural tube, neural crest, and semitic derivatives, contains two DNA-binding domains, a paired domain, and a paired-type homeodomain. Although Pax-3 binds to sequences related to the e5 element of the Drosophila even-skipped gene, the sequence requirements of an optimal Pax-3 response element have not been well characterized. Using both DNA-binding domains and a pool of random oligonucleotides, we identified a new paired box consensus motif, "GT-TAT," which was located 1, 4, 5, 8, or 13 base pairs downstream of the homeobox binding motif, "ATTA." Binding analysis of these sequences demonstrated that the distance between recognition elements for the homeodomain and the paired domain affects affinity. Specifically, spacing elements 1 or 13 base pairs apart from each other conferred low affinity Pax-3 binding, whereas intermediate spacing (5 or 8 bass pairs) conferred high affinity binding. Contrary to previous reports, oligonucleotides deleted for either the ATTA or the GTTAT could also be bound by Pax-5, although both sites were necessary for maximal affinity. Finally, transient transfections demonstrated that Pax-3 trans-activation correlated with binding affinity. Because the Pax-3-responsive genes identified to date contain almost exclusively low affinity binding sequences, our analysis indicates that they may be responsive to Pax-3 only when cellular levels are high. C1 Joslin Diabet Ctr, Mol Biol Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Med Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Mol Biol Sect, 1 Joslin Pl, Boston, MA 02215 USA. FU NCI NIH HHS [CA50599]; NIDDK NIH HHS [T32 DK07260, DK36836] NR 44 TC 33 Z9 33 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 JUL 24 PY 1998 VL 273 IS 30 BP 19153 EP 19159 DI 10.1074/jbc.273.30.19153 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103TV UT WOS:000074974700068 PM 9668101 ER PT J AU Shirra, MK Hansen, U AF Shirra, MK Hansen, U TI LSF and NTF-1 share a conserved DNA recognition motif yet require different oligomerization states to form a stable protein-DNA complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR CP2; CRYSTAL-STRUCTURE; VIRUS TYPE-1; OPERATOR COMPLEX; BINDING-PROTEINS; B/HLH/Z DOMAIN; ACTIVATION; REGION; DIMER; RESOLUTION AB The mammalian transcription factor LSF (also known as CP2 and LBP-1c) binds as a homo-oligomer to directly repeated elements in viral and cellular promoters. LSF and the Drosophila transcription factor NTF-1 (also known as Elf-1 and Grainyhead) share a similar DNA binding region, which is unlike any established DNA binding motifs. However, we demonstrate that dimeric NTF-1 can bind an LSF half-site, whereas LSF cannot. To characterize further the DNA binding and oligomerization characteristics of LSF, truncation mutants were used to demonstrate that between 234 and 320 amino acids of LSF are required for high affinity DNA binding. Mixing of a truncation mutant with full-length LSF in a DNA binding assay established that the form of LSF that binds DNA is larger than a dimer. Unexpectedly, one C-terminal deletion derivative, partially defective in oligomerization properties, could occupy odd numbers of adjacent, tandem LSF half-sites, unlike full-length LSF. The numbers of DNA-protein complexes formed on multiple half-sites with this mutant indicated that LSF binds DNA as a tetramer, although cross-linking experiments confirmed a previous report concluding that LSF is primarily dimeric in solution. The DNA binding and oligomerization properties of LSF support models depicting novel mechanisms to prevent continual, adjacent binding by a protein that recognizes directly repeated DNA sequences. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Mol Genet, Boston, MA 02115 USA. RP Hansen, U (reprint author), Boston Univ, Dept Biol, 5 Cummington St, Boston, MA 02215 USA. FU NCI NIH HHS [CA38038, T32 CA09361] NR 47 TC 42 Z9 42 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 JUL 24 PY 1998 VL 273 IS 30 BP 19260 EP 19268 DI 10.1074/jbc.273.30.19260 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103TV UT WOS:000074974700082 PM 9668115 ER PT J AU Hata, Y Duh, E Zhang, K Robinson, GS Aiello, LP AF Hata, Y Duh, E Zhang, K Robinson, GS Aiello, LP TI Transcription factors Sp1 and Sp3 alter vascular endothelial growth factor receptor expression through a novel recognition sequence SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCIBLE ENHANCER ELEMENTS; BOVINE RETINAL PERICYTES; PERMEABILITY FACTOR; IN-VIVO; FACTOR VEGF; GENE-EXPRESSION; TYROSINE KINASE; DEVELOPMENTAL EXPRESSION; DIABETIC-RETINOPATHY; SIGNAL-TRANSDUCTION AB Kinase domain receptor (KDR) is a high affinity, endothelial cell-specific, autophosphorylating tyrosine kinase receptor for vascular endothelial growth factor, This transcriptionally regulated receptor is a critical mediator of endothelial cell (EC) growth and vascular development. In this study, we identify a DNA element modulating KDR promoter activity and evaluate the nuclear binding proteins accounting for a portion of the cell-type specificity of the region. KDR promoter luciferase activity was retained within -85/+296 and was 10-30-fold higher in EC than non-EC, Electrophoretic mobility shift assays demonstrated specific nuclear protein binding to -85/-64, and single point mutations suggested important binding nucleotides between -79/-68 with five critical bases between -74/-70 (5'-CTCCT-3'). DNA-protein complexes were displaced by Spl consensus sequence oligodeoxynucleotides and supershifted by Sp1- and Sp3-specific antibodies. Spl and Sp3 protein in EC nuclear extracts bound the -79/-68 region even when all surrounding classic Spl recognition sites were removed. Spl protein in nuclear extracts was 4-24-fold higher in EC than non-EC, whereas Sp3 was 3-7-fold higher. Sp1/Sp3 ratios in EC were 2-10-fold higher. Overexpression of Spl protein increased KDR promoter activity 3-fold in both EC and non-EC, whereas simultaneous co-expression of Sp3 attenuated this response. An Spl consensus sequence cis element "decoy" reduced EC KDR promoter activity and mRNA expression by 85 and 69%, respectively. An antisense phosphorothioate oligodeoxynucleotide to Spl inhibited Spl and KDR protein expression by 66 and 68%, respectively, without changing Sp3 protein expression. These data illustrate that Spl and Sp3 modulate KDR promoter activity through a novel recognition binding sequence. However, since Spl-mediated promoter activation is attenuated by Sp3, endothelial selective KDR promoter activity may be partially regulated by variations in the Sp1/Sp3 ratio. C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. Hybridon Inc, Cambridge, MA 02139 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [EY-10827] NR 76 TC 112 Z9 113 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 JUL 24 PY 1998 VL 273 IS 30 BP 19294 EP 19303 DI 10.1074/jbc.273.30.19294 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103TV UT WOS:000074974700086 PM 9668119 ER PT J AU Gordon, LK Levin, LA AF Gordon, LK Levin, LA TI Visual loss in giant cell arteritis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TEMPORAL ARTERITIS; POLYMYALGIA-RHEUMATICA; BIOPSY FINDINGS; PROGNOSIS; DIAGNOSIS C1 Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI 53792 USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Hosp, Los Angeles, CA USA. RP Levin, LA (reprint author), Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, 600 Highland Ave, Madison, WI 53792 USA. NR 25 TC 33 Z9 34 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 22 PY 1998 VL 280 IS 4 BP 385 EP 386 DI 10.1001/jama.280.4.385 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 100FC UT WOS:000074804200044 PM 9686559 ER PT J AU Bonadonna, RC Saccomani, MP Del Prato, S Bonora, E DeFronzo, RA Cobelli, C AF Bonadonna, RC Saccomani, MP Del Prato, S Bonora, E DeFronzo, RA Cobelli, C TI Role of tissue-specific blood flow and tissue recruitment in insulin-mediated glucose uptake of human skeletal muscle SO CIRCULATION LA English DT Article DE blood flow; insulin; glucose; muscles ID NITRIC-OXIDE RELEASE; ESSENTIAL-HYPERTENSION; ORAL GLUCOSE; RESISTANCE; TRANSPORT; VASODILATION; MECHANISM; HYPERINSULINEMIA; GLYCOLYSIS; OXIDATION AB Background-Conflicting evidence exist concerning whether insulin-induced vasodilation plays a mechanistic role in the regulation of limb glucose uptake. It can be predicted that if insulin augments blood flow by causing tissue recruitment, this mechanism would enhance limb glucose uptake. Methods and Results-Twenty healthy subjects were studied with the forearm perfusion technique in combination with the euglycemic insulin clamp technique. Ten subjects were studied at physiological insulin concentrations (approximate to 400 pmol/L) and the other 10 at supraphysiological insulin concentrations (approximate to 5600 pmoI/L). Four additional subjects underwent a saline control study. Pulse injections of a nonmetabolizable extracellular marker (1-[H-3]-L-glucose) were administered into the brachial artery, and its washout curves were measured in one ipsilateral deep forearm Vein and used to estimate the extracellular volume of distribution and hence the amount of muscle tissue drained by the deep forearm vein. Both during saline infusion and at physiological levels of hyperinsulinemia we observed no changes in blood flow and/or muscle tissue drained by the deep forearm vein. However, supraphysiological hyperinsulinemia accelerated total forearm blood flow (45.0+/-1.8 versus 36.5+/-1.3 mL.min(-1).kg(-1), P<0.01) and increased the amount of muscle tissue drained by the deep forearm vein (305+/-46 versus 229+/-32 g, P<0.05). The amount of tissue newly recruited by insulin was strongly correlated to the concomitant increase in tissue glucose uptake (r=0.789, P<0.01). Conclusions-Acceleration of forearm blood flow mediated by supraphysiological hyperinsulinemia is accompanied by tissue recruitment, which may be a relevant determinant of forearm (muscle) glucose uptake. C1 Univ Verona, Div Endocrinol & Metab Dis, I-37100 Verona, Italy. Azienda Osped Verona, Verona, Italy. Univ Padua, Dept Elect & Informat, I-35100 Padua, Italy. Univ Padua, Div Metab Dis, I-35100 Padua, Italy. Univ Texas, Hlth Sci Ctr, Div Diabet, San Antonio, TX USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Bonadonna, RC (reprint author), Osped Civile Maggiore, Div Endocrinol & Metab Dis, Piazzale Stefani 1, I-37126 Verona, Italy. EM malmetab@borgotrento.univr.it RI Del Prato, Stefano/K-3405-2016; OI Del Prato, Stefano/0000-0002-5388-0270; BONORA, Enzo/0000-0003-1074-5164 FU NCRR NIH HHS [RRMO1RR1346]; NIDDK NIH HHS [DK 24092] NR 48 TC 83 Z9 87 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 21 PY 1998 VL 98 IS 3 BP 234 EP 241 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 108YD UT WOS:000075293300008 PM 9697823 ER PT J AU Liu, J Kang, H Raab, M da Silva, AJ Kraeft, SK Rudd, CE AF Liu, J Kang, H Raab, M da Silva, AJ Kraeft, SK Rudd, CE TI FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYROSINE KINASES; PHOSPHATIDYLINOSITOL 3-KINASE; DIFFERENTIAL REGULATION; RECEPTOR FUNCTION; ZAP-70 KINASE; SH3 DOMAINS; ZETA-CHAIN; CD5 ACTS; SLP-76; P56(LCK) AB TcR zeta/CD3 ligation initiates a signaling cascade involving CD4/CD8-p56(lck), p59(fyn), and ZAP-70, as well as lymphoid downstream proteins VAV, SLP-76, and FYB/SLAP, A current question concerns the nature of the downstream binding partner(s) of FYB in T cells. In this study, using a two-hybrid screen with FYB as bait, we have identified eight clones, four of which correspond to the recently published lymphoid protein SKAP55, and two which correspond to a related protein with some 44% homology to SKAP55 (termed SKAP55-related protein, SKAP55R), The SKAP55 clones showed only minor differences (two substitutions and one residue deletion) from SKAP55. SKAP55R has the same overall structure as SKAP55 except for the presence of a unique N terminus with a well-defined coiled-coil domain, Both SKAP55 and SKAP55R were found to bind FYB through their SH3 domains and to act as substrates for the FYN kinase in T cells, Furthermore, immunofluorescence confocal microscopy showed that FYB and SKAP55 colocalize in the perinuclear region of cells. SKAP55 also colocalizes with another FYB binding protein, SLP-76, Taken together, these observations demonstrate that FYB is part of an interactive matrix with SKAP55 and a SKAP55-related protein. C1 Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. EM christopher_rudd@dfci.harvard.edu FU NCI NIH HHS [CA51887] NR 41 TC 94 Z9 99 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 JUL 21 PY 1998 VL 95 IS 15 BP 8779 EP 8784 DI 10.1073/pnas.95.15.8779 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900066 PM 9671755 ER PT J AU Endres, M Laufs, U Huang, ZH Nakamura, T Huang, P Moskowitz, MA Liao, JK AF Endres, M Laufs, U Huang, ZH Nakamura, T Huang, P Moskowitz, MA Liao, JK TI Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cerebral blood flow; cerebral ischemia ID CORONARY HEART-DISEASE; MEVALONATE PATHWAY; BLOOD-FLOW; HYPERCHOLESTEROLEMIA; HYPERTENSION; PRAVASTATIN; EXPRESSION; MUSCLE; MODEL; CELLS AB The treatment of ischemic strokes is limited to prophylactic agents that block the coagulation cascade. Here, we show that cholesterol-lowering agents, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, protect against cerebral injury by a previously unidentified mechanism involving the selective up-regulation of endothelial NO synthase (eNOS). Prophylactic treatment with HMG-CoA reductase inhibitors augments cerebral blood flow, reduces cerebral infarct size, and improves neurological function in normocholesterolemic mice. The up-regulation of eNOS by HMG-CoA reductase inhibitors is not associated with changes in serum cholesterol levels, but is reversed by cotreatment with L-mevalonate and by the downstream isoprenoid, geranylgeranyl pyrophosphate and not by.farnesyl pyrophosphate. The blood flow and neuroprotective effects of HMG-CoA reductase inhibitors are completely absent in eNOS-deficient mice, indicating that enhanced eNOS activity by HMG-CoA reductase inhibitors is the predominant if not the only mechanism by which these agents protect against cerebral injury. Our results suggest that HMG-CoA reductase inhibitors provide a prophylactic treatment strategy for increasing blood flow and reducing brain injury during cerebral ischemia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM Moskowitz@helix.mgh.harvard.edu RI Moskowitz, Michael/D-9916-2011 FU NHLBI NIH HHS [R01 HL052233, HL52233]; NINDS NIH HHS [F32 NS010828, NS10828, P01 NS010828, P50 NS010828] NR 44 TC 728 Z9 749 U1 1 U2 15 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 JUL 21 PY 1998 VL 95 IS 15 BP 8880 EP 8885 DI 10.1073/pnas.95.15.8880 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900084 PM 9671773 ER PT J AU Matthews, RT Yang, LC Browne, S Baik, M Beal, MF AF Matthews, RT Yang, LC Browne, S Baik, M Beal, MF TI Coenzyme Q(10) administration increases brain mitochondrial concentrations and exerts neuroprotective effects SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; INDUCED DEGENERATION; ENERGY-METABOLISM; ELECTRON-TRANSFER; OXIDATIVE STRESS; RAT-LIVER; UBIQUINONE; THERAPY; ENCEPHALOMYOPATHY; NEUROTOXICITY AB Coenzyme Q(10) is an essential cofactor of the electron transport chain as well as a potent free radical scavenger in lipid and mitochondrial membranes. Feeding with coenzyme Q(10) increased cerebral cortex concentrations in 12- and 24-month-old rats. In 12-month-old rats administration of coenzyme Q(10) resulted in significant increases in cerebral cortex mitochondrial concentrations of coenzyme Q(10) Oral administration of coenzyme Q(10) markedly attenuated striatal lesions produced by systemic administration of 3-nitropropionic acid and significantly increased life span in a transgenic mouse model of familial amyotrophic lateral sclerosis. These results show that oral administration of coenzgme Q(10) increases both brain and brain mitochondrial concentrations. They provide further evidence that coenzyme Q(10) can exert neuroprotective effects that might be useful in the treatment of neurodegenerative diseases. C1 Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, WRN 408,32 Fruit St, Boston, MA 02114 USA. EM beal@helix.harvard.mgh.edu FU NIA NIH HHS [P01 AG012992, P01 AG12992]; NINDS NIH HHS [NS16367, NS31579, P50 NS016367] NR 48 TC 334 Z9 346 U1 2 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 21 PY 1998 VL 95 IS 15 BP 8892 EP 8897 DI 10.1073/pnas.95.15.8892 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900086 PM 9671775 ER PT J AU Liu, AK Belliveau, JW Dale, AM AF Liu, AK Belliveau, JW Dale, AM TI Spatiotemporal imaging of human brain activity using functional MRI constrained magnetoencephalography data: Monte Carlo simulations SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE electroencephalography; brain mapping; inverse problem; biomagnetic ID ELECTRICAL POTENTIALS; SENSORY STIMULATION; MAGNETIC-FIELDS; LOCALIZATION; RESOLUTION; CORTEX; MODEL; MEG AB The goal of our research is to develop an experimental and analytical framework for spatiotemporal imaging of human brain function. Preliminary studies suggest that noninvasive spatiotemporal maps of cerebral activity can be produced by combining the high spatial resolution (millimeters) of functional MRI (fMRI) with the high temporal resolution (milliseconds) of electroencephalography (EEG) and magnetoencephalography (MEG), Although MEG and EEG are sensitive to millisecond changes in mental activity, the ability to resolve source localization and timing is limited by the ill-posed "inverse" problem. We conducted Monte Carlo simulations to evaluate the use of MRI constraints in a linear estimation inverse procedure, where fMRI weighting, cortical location and orientation, and sensor noise statistics were realistically incorporated. An error metric was computed to quantify the effects of fMRI invisible ("missing") sources, "extra" fMRI sources, and cortical orientation errors. Our simulation results demonstrate that prior anatomical and functional information from MRI can be used to regularize the EEG/MEG inverse problem, giving an improved solution with high spatial and temporal resolution. An fh IRI weighting of approximately 90%; was determined to provide the best compromise between separation of activity from correctly localized sources and minimization of error caused by missing sources. The accuracy of the estimate was relatively independent of the number and extent of the sources, allowing for incorporation of physiologically realistic multiple distributed sources. This linear estimation method provides an operator-independent approach for combining information from fMRI, MEG, and EEG and represents a significant advance over traditional dipole modeling. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Dale, AM (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. EM dale@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010 NR 49 TC 250 Z9 250 U1 0 U2 4 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 JUL 21 PY 1998 VL 95 IS 15 BP 8945 EP 8950 DI 10.1073/pnas.95.15.8945 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103EA UT WOS:000075143900095 PM 9671784 ER PT J AU Morita, R Miyazaki, E Fong, CYG Chen, XN Korenberg, JR Delgado-Escueta, AV Yamakawa, K AF Morita, R Miyazaki, E Fong, CYG Chen, XN Korenberg, JR Delgado-Escueta, AV Yamakawa, K TI JH8, a gene highly homologous to the mouse jerky gene, maps to the region for childhood absence epilepsy on 8q24 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID FAMILIAL NEONATAL CONVULSIONS; CENP-B; SEIZURES; MICE; MUTANT; IDENTIFICATION; RECEPTOR; PROTEIN; LOCUS; CDNA AB Insertional inactivation of the jerky gene in transgenic mice resulted epileptic seizures, suggesting that the jerky gene was responsible for mouse epilepsy. To isolate a human homologue of the jerky gene, we screened an Expressed Sequence Tag (EST) database using the cDNA sequence of the mouse jerky gene and identified several EST clones which contained homologous sequences to mouse jerky gene. Using a clone which showed highest homology as a probe, we isolated cDNA clones from a human fetal brain cDNA library. Sequence analysis of these clones named JH8 (jerky homologue of Human on chromosome 8) indicated that it encoded a putative protein with 520 amino acid residues. The JH8 gene has 77% identity to the mouse jerky gene at the DNA level, and its protein has 76% identity and 84% similarity to the mouse protein at the amino acid level. Northern blot analysis showed that the JH8 gene is expressed ubiquitously with a major transcript of about 9.5 kb in size, Fluorescence in situ Hybridization (FISH) analysis and radiation hybrid panel mapping revealed that the JH8 gene was located on chromosome band 8q24.3 in a region that was syntenic to mouse chromosome 15, the mapping site of the mouse jerky gene. Childhood Absence Epilepsy (CAE), one type of Idiopathic Generalized Epilepsy (IGE), has been mapped to chromosome 8q24,3 by linkage analysis. These results suggest that JH8 is a strong candidate gene for CAE. (C) 1998 Academic Press. C1 Inst Phys & Chem Res, Brain Sci Inst, Neurogenet Lab, Wako, Saitama 3510198, Japan. Univ Calif Los Angeles, Sch Med, Comprehens Epilepsy Program, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Cedars Sinai Res Inst, Div Med Genet, Los Angeles, CA 90048 USA. RP Yamakawa, K (reprint author), Inst Phys & Chem Res, Brain Sci Inst, Neurogenet Lab, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. RI Yamakawa, Kazuhiro/N-5050-2015 FU NICHD NIH HHS [P01 HD17449]; NINDS NIH HHS [5PO1-NS21908] NR 37 TC 14 Z9 15 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 20 PY 1998 VL 248 IS 2 BP 307 EP 314 DI 10.1006/bbrc.1998.8947 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 103HG UT WOS:000075151500019 PM 9675132 ER PT J AU Schellingerhout, D Bogdanov, A Marecos, E Spear, M Breakefield, X Weissleder, R AF Schellingerhout, D Bogdanov, A Marecos, E Spear, M Breakefield, X Weissleder, R TI Mapping the in vivo distribution of herpes simplex virions SO HUMAN GENE THERAPY LA English DT Article ID BRAIN-BARRIER DISRUPTION; GENE-TRANSFER; SOLID TUMORS; RAT-BRAIN; DELIVERY; PARTICLES; CELLS; EXPRESSION; ADENOVIRUS; PROTEINS AB We describe a method for labeling enveloped viral particles with a radiotracer, indium-lll, allowing labeled viruses to be traced in viveo by nuclear imaging. After initial optimization experiments, a labeling efficiency of 83% (incorporation yield) was achieved for herpes simplex virus (HSV), resulting in a specific activity of 30 mu Ci/10(9) PFU, The labeling procedure did not significantly reduce the infectivity of the labeled virus and the virus did not release any significant amounts of the radionuclide within 12 hr after labeling. Sequential imaging of animals after intravenous administration of the labeled virus showed fast accumulation in the liver and redistribution from the blood pool (immediately after injection) to liver and spleen (12-24 hr after injection). At 12 hr after injection 7% of the virus-associated In-111 had been eliminated from the body and the remaining organ distribution of the virus was as follows: spleen 28.7 +/- 5.4% ID/g; liver, 26.0 +/- 5.1% ID/g; kidney, 9.8 +/- 3.1% ID/g; lung, 5.7 +/- 1.0% ID/g; and lower amounts in other organs, Our results indicate that the described method allows qualitative and quantitative assessment of viral biodistribution in vivo by nuclear imaging. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, 149 13th St,Room 5403, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01 NS 35258-01] NR 29 TC 47 Z9 52 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL 20 PY 1998 VL 9 IS 11 BP 1543 EP 1549 DI 10.1089/hum.1998.9.11-1543 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 103LP UT WOS:000075157700004 PM 9694153 ER PT J AU Marasco, WA Chen, SY Richardson, JH Ramstedt, U Jones, SD AF Marasco, WA Chen, SY Richardson, JH Ramstedt, U Jones, SD TI Intracellular antibodies against HIV-1 envelope protein for AIDS gene therapy SO HUMAN GENE THERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; TUMOR-INFILTRATING LYMPHOCYTES; HTLV-III/LAV ENVELOPE; T-CELL RECEPTOR; REVERSE-TRANSCRIPTASE; CD4-PSEUDOMONAS EXOTOXIN; HOMOSEXUAL MEN; BRAIN-TUMORS; INFECTION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 99 TC 30 Z9 31 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL 20 PY 1998 VL 9 IS 11 BP 1627 EP 1642 DI 10.1089/hum.1998.9.11-1627 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 103LP UT WOS:000075157700012 PM 9694161 ER PT J AU Shekelle, PG Roland, M AF Shekelle, PG Roland, M TI Measuring quality in the NHS: lessons from across the Atlantic SO LANCET LA English DT Editorial Material C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Manchester, Natl Primary Care Res & Dev Ctr, Manchester, Lancs, England. RP Shekelle, PG (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 18 PY 1998 VL 352 IS 9123 BP 163 EP 164 DI 10.1016/S0140-6736(05)77801-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 101FW UT WOS:000074859800004 PM 9683200 ER PT J AU Hoeting, JA Ibrahim, JG AF Hoeting, JA Ibrahim, JG TI Bayesian predictive simultaneous variable and transformation selection in the linear model SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE Bayesian criterion; box-cox transformation; calibration number; comparison score; backwards selection ID REGRESSION AB Variable selection and transformation selection are two commonly encountered problems in the linear model. It is often of interest to combine these two procedures in an analysis. Due to recent developments in computing technology, such a procedure is now feasible. In this paper, we propose two variable and transformation selection procedures on the predictor variables in the linear model. The first procedure is a simultaneous variable and transformation selection procedure. For data sets with many predictors, a backward elimination procedure for variables and transformations is also presented. The procedures are based on Bayesian model selection criteria introduced by Ibrahim and Laud (1994) and Laud and Ibrahim (1995). Several examples are given to illustrate the methodology. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Colorado State Univ, Dept Stat, Ft Collins, CO 80523 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 29 TC 6 Z9 6 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD JUL 17 PY 1998 VL 28 IS 1 BP 87 EP 103 DI 10.1016/S0167-9473(98)00028-0 PG 17 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 110FR UT WOS:000075370000005 ER PT J AU Ohtsuki, T Hosono, O Kobayashi, H Munakata, Y Souta, A Shioda, T Morimoto, C AF Ohtsuki, T Hosono, O Kobayashi, H Munakata, Y Souta, A Shioda, T Morimoto, C TI Negative regulation of the anti-human immunodeficiency virus and chemotactic activity of human stromal cell-derived factor 1 alpha by CD26/dipeptidyl peptidase IV SO FEBS LETTERS LA English DT Article DE anti-human immunodeficiency virus and chemotactic activity; CD26/dipeptidyl peptidase IV; human immunodeficiency virus infection; N-terminal cleavage; stromal cell-derived factor 1 alpha ID T-CELLS; ACTIVATION ANTIGEN; HIV-1 ENTRY; ADENOSINE-DEAMINASE; CD26; RECEPTORS; SURFACE; IDENTIFICATION; MIP-1-ALPHA; LESTR/FUSIN AB Stromal cell-derived factor 1 alpha (SDF-1 alpha) is a chemokine that has been shown to prevent infection of T-tropic HIV strains and is a possible substrate of CD26/dipeptidyl peptidase IV (DPPIV). In this studg, we show that SDF-1 alpha was cleaved at the N-terminal region by CD26/DPPIV and as a result the inhibitory activity of SDF-1 alpha against HIV infection disappeared, Moreover, the chemotactic activity of SDF-1 alpha also disappeared specifically by DPPIV activity of recombinant soluble CD26, These results suggested that dissemination of T-tropic HIV strains in vivo may be facilitated by CD26/DPPIV via inactivation of functional SDF-1 alpha. (C) 1998 Federation of European Biochemical Societies. C1 Univ Tokyo, Inst Med Sci, Dept Clin Immunol, Minato Ku, Tokyo 1080071, Japan. Univ Tokyo, Inst Med Sci, AIDS Res Ctr, Minato Ku, Tokyo 1080071, Japan. Univ Tokyo, Inst Med Sci, Dept Infect Dis, Minato Ku, Tokyo 1080071, Japan. Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. RP Morimoto, C (reprint author), Univ Tokyo, Inst Med Sci, Dept Clin Immunol, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1080071, Japan. FU NIAID NIH HHS [AI29530]; NIAMS NIH HHS [AR33713] NR 32 TC 48 Z9 48 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 17 PY 1998 VL 431 IS 2 BP 236 EP 240 DI 10.1016/S0014-5793(98)00763-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 104HT UT WOS:000075009200023 PM 9708910 ER PT J AU Price, ER Ding, HF Badalian, T Bhattacharya, S Takemoto, C Yao, TP Hemesath, TJ Fisher, DE AF Price, ER Ding, HF Badalian, T Bhattacharya, S Takemoto, C Yao, TP Hemesath, TJ Fisher, DE TI Lineage-specific signaling in melanocytes - c-Kit stimulation recruits p300/CBP to microphthalmia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RUBINSTEIN-TAYBI-SYNDROME; RECEPTOR TYROSINE KINASE; NUCLEAR-PROTEIN CBP; TRANSCRIPTION FACTOR; GENE-PRODUCT; IN-VIVO; HISTONE ACETYLTRANSFERASE; CONSERVED FAMILY; PHOSPHATASE SHP1; MAST-CELLS AB During melanocyte development, the cytokine Steel factor activates its receptor c-Kit, initiating a signal transduction cascade, which is vital for lineage determination via unknown downstream nuclear targets. c-Kit has recently been found to trigger mitogen-activated protein kinase-mediated phosphorylation of Microphthalmia (Mi), a lineage-restricted transcription factor, which, like Steel factor and c-Kit, is essential for melanocyte development. This cascade results in increased Mi-dependent transcriptional reporter activity, Here we examine the mechanism by which Mi is activated by this pathway. Phosphorylation does not significantly alter Mi's nuclear localization, DNA binding, or dimerization, However, the transcriptional coactivator p300/CBP selectively associates with mitogen-activated protein kinase-phosphorylated Mi, even under conditions in which non-MAPK phospho-Mi is more abundant. Moreover, p300/CBP coactivates Mi transcriptional activity in a manner dependent upon this phosphorylation, Mi thus joins CREB as a transcription factor whose signal-responsive phosphorylation regulates coactivator recruitment, in this case modulating lineage development in melanocytes. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Bhattacharya, Shoumo/F-4127-2010 NR 50 TC 123 Z9 123 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 17 PY 1998 VL 273 IS 29 BP 17983 EP 17986 DI 10.1074/jbc.273.29.17983 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100RE UT WOS:000074828500002 PM 9660747 ER PT J AU Druey, KM Sullivan, BM Brown, D Fischer, ER Watson, N Blumer, KJ Gerfen, CR Scheschonka, A Kehrl, JH AF Druey, KM Sullivan, BM Brown, D Fischer, ER Watson, N Blumer, KJ Gerfen, CR Scheschonka, A Kehrl, JH TI Expression of GTPase-deficient G(i alpha 2) results in translocation of cytoplasmic RGS4 to the plasma membrane SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID G-PROTEIN; RECEPTORS; FAMILY; DOMAIN; CELLS; GAIP AB The members of a recently identified protein family termed regulators of G-protein signaling (RGS) act as GTPase activating proteins for certain G(alpha) subunits in vitro, but their physiological effects in cells are uncertain in the face of similar biochemical activity and overlapping patterns of tissue expression. Consistent with its activity in in vitro GTPase-activating protein assays, RGS4 interacts efficiently with endogenous proteins of the G(i) and G(q) subclasses of G(alpha) subunits but not with G(12 alpha) or G(s alpha). Unlike other RGS proteins such as RGS9, RGS-GAIP, and Sst2p, which have been reported to be largely membrane-associated, a majority of cellular RGS4 is found as a soluble protein in the cytoplasm, However, the expression of a GTPase-deficient G(i alpha) subunit (G(i alpha 2)-Q204L) resulted in the translocation of both wild type RGS4 and a non-G(1 alpha)-binding mutant (L159F) to the plasma membrane. These data suggest that RGS4 may be recruited to the plasma membrane indirectly by G-protein activation and that multiple RGS proteins within a given cell might be differentially localized to determine a physiologic response to a G-protein-linked stimulus. C1 NIAID, Immunoregulat Lab, Rocky Mt Labs, NIH, Bethesda, MD 20892 USA. NIAID, Mol Biol Lab, Rocky Mt Labs, NIH, Bethesda, MD 20892 USA. NIMH, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, Rocky Mt Labs, NIH, Bldg 10,Rm 11B-13,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. RI Blumer, Kendall/C-5268-2012 FU NIDDK NIH HHS [DK38452] NR 26 TC 68 Z9 70 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 JUL 17 PY 1998 VL 273 IS 29 BP 18405 EP 18410 DI 10.1074/jbc.273.29.18405 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100RE UT WOS:000074828500063 PM 9660808 ER PT J AU Chu, BY Zhong, R Soncin, F Stevenson, MA Calderwood, SK AF Chu, BY Zhong, R Soncin, F Stevenson, MA Calderwood, SK TI Transcriptional activity of heat shock factor 1 at 37 degrees C is repressed through phosphorylation on two distinct serine residues by glycogen synthase kinase 3 alpha and protein kinases C alpha, and C zeta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING; GENE-EXPRESSION; MAP KINASE; BETA-CATENIN; HSP70 GENE; FACTOR-I; ACTIVATION; CELLS; STRESS; YEAST AB Heat shock factor 1 (HSF1) is the key transcriptional regulator of the heat shock genes that protect cells from environmental stress. However, because heat shock gene expression is deleterious to growth and development, we have examined mechanisms for HSF1 repression at growth temperatures, focusing on the role of phosphorylation. Mitogen-activated protein kinases (MAPKs) of the ERR family phosphorylate HSF1 and represses transcriptional function. The mechanism of repression involves initial phosphorylation by MAP kinase on serine 307, which primes HSF1 for secondary phosphorylation by glycogen synthase kinase 3 on a key residue in repression (serine 303). In vivo expression of glycogen synthase kinase 3 (alpha or beta) thus represses HSF1 through phosphorylation of serine 303. HSF1 is also phosphorylated by MAPK in vitro on a second residue (serine 363) adjacent to activation domain 1, and this residue is additionally phosphorylated by protein kinase C. In vivo, HSF1 is repressed through phosphorylation of this residue by protein kinase C alpha or -zeta but not MAPK. Regulation at 37 degrees C, therefore, involves the action of three protein kinase cascades that repress HSF1 through phosphorylation of serine residues 303, 307, and 363 and may promote growth by suppressing the heat shock response. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Dept Adult Oncol, Boston, MA 02115 USA. Inst Pasteur Lille, CNRS, EP 560, F-59021 Lille, France. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM stuart_calderwood@dfci.harvard.edu RI SONCIN, Fabrice/A-1475-2009 FU NCI NIH HHS [CA31303, CA4707, CA50642] NR 51 TC 121 Z9 131 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 17 PY 1998 VL 273 IS 29 BP 18640 EP 18646 DI 10.1074/jbc.273.29.18640 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100RE UT WOS:000074828500093 PM 9660838 ER PT J AU Daggett, DA Oberley, TD Nelson, SA Wright, LS Kornguth, SE Siegel, FL AF Daggett, DA Oberley, TD Nelson, SA Wright, LS Kornguth, SE Siegel, FL TI Effects of lead on rat kidney and liver: GST expression and oxidative stress SO TOXICOLOGY LA English DT Article DE glutathione S-transferase; glutathione; lead; oxidative stress; antioxidant response element ID GLUTATHIONE-S-TRANSFERASE; PROTEIN-KINASE-C; YA SUBUNIT GENE; CONTROLLING INDUCIBLE EXPRESSION; RESPONSIVE ELEMENT; LIPID-PEROXIDATION; ANTIOXIDANT ENZYMES; CATALYTIC ACTIVITY; CHEMICAL-AGENTS; CELL-NUCLEUS AB The effect of acute exposure to lead acetate on the expression of glutathione S-transferase (GST) subunits and the levels of reduced and oxidized glutathione (GSH) and malondialdehyde (MDA) in rat kidney and liver was determined. The purpose of this study was to determine if GSH depletion and/or oxidative stress were responsible for changes in the expression of some or all GSTs that followed lead exposure. In kidney, all GST subunits increased following injection of lead. The level of kidney GSH was not changed at either 0.5 or 1 h after lead exposure, but increased 3, 6, 12 and 24 h after a single injection of lead. MDA levels (a marker of lipid peroxidation) did not change in kidney following lead injection. Immunohistochemical markers of oxidative stress and nitric oxide production were also unchanged by lead administration. Therefore, we conclude that the increases in GST levels in kidney following lead exposure were not dependent on oxidative stress. In liver, lead injection caused GSH depletion (61% of control 12 h after lead treatment) and increased MDA production (2.5-fold increase 6 h after lead exposure), while GSTA1, GSTA2, GSTM1 and GSTM2 did not increase. Analysis of the effects of lead on GST mRNA and GST cellular localization were performed by Northern blot and immunohistochemical techniques. Immunoperoxidase light microscopy and immunogold electron microscopy revealed that the increase in kidney GSTM1 and GSTP1 occurred in nuclei: cytoplasm and microvilli of proximal tubules, Northern blot analysis of GSTA2 and GSTP1 mRNAs showed that their increase following lead exposure was inhibited by actinomycin D, suggesting transcriptional induction. This study demonstrates that acute lead exposure causes dramatic changes in the subcellular distribution and expression of rat kidney GSTs, and that these changes are not a result of oxidative stress. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Wisconsin, Ctr Environm Toxicol, Madison, WI 53705 USA. Univ Wisconsin, Waisman Ctr 655, Mol & Genet Sci Unit, Madison, WI 53705 USA. Univ Wisconsin, Dept Pathol, Madison, WI 53703 USA. Univ Wisconsin, Dept Pediat, Madison, WI 53703 USA. Univ Wisconsin, Dept Neurol, Madison, WI 53703 USA. Univ Wisconsin, Dept Biomol Chem, Madison, WI 53703 USA. William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. RP Siegel, FL (reprint author), Univ Wisconsin, Ctr Environm Toxicol, Madison, WI 53705 USA. FU NICHD NIH HHS [HD03352]; NIEHS NIH HHS [T32 ES07015]; NINDS NIH HHS [NS24669] NR 58 TC 67 Z9 77 U1 1 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 17 PY 1998 VL 128 IS 3 BP 191 EP 206 DI 10.1016/S0300-483X(98)00080-8 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 120CQ UT WOS:000075937500003 PM 9750042 ER PT J AU Mauceri, HJ Hanna, NN Beckett, MA Gorski, DH Staba, MJ Stellato, KA Bigelow, K Heimann, R Gately, S Dhanabal, M Soff, GA Sukhatme, VP Kufe, DW Weichselbaum, RR AF Mauceri, HJ Hanna, NN Beckett, MA Gorski, DH Staba, MJ Stellato, KA Bigelow, K Heimann, R Gately, S Dhanabal, M Soff, GA Sukhatme, VP Kufe, DW Weichselbaum, RR TI Combined effects of angiostatin and ionizing radiation in antitumour therapy SO NATURE LA English DT Article ID ANGIOGENESIS; CANCER; SUPPRESSION; CARCINOMA; DISEASE; AGENTS AB Angiogenesis, the formation of new capillaries from pre-existing vessels, is essential for tumour progression(1-5). Angiostatin, a proteolytic fragment of plasminogen(6) that was first isolated from the serum and urine of tumour-bearing mice(7), inhibits angiogenesis and thereby growth of primary(8) and metastatic(7,9,10) tumours. Radiotherapy is important in the treatment of many human cancers, but is often unsuccessful because of tumour cell radiation resistance(11,12). Here we combine radiation with angiostatin to target tumour vasculature that is genetically stable and therefore less likely to develop resistance(13-15). The results show an antitumour interaction between ionizing radiation and angiostatin for four distinct tumour types, at doses of radiation that are used in radiotherapy. The combination produced no increase in toxicity towards normal tissue. In vitro studies show that radiation and angiostatin have combined cytotoxic effects on endothelial cells, but not tumour cells. In vivo studies show that these agents, in combination, target the tumour vasculature. Our results provide support for combining ionizing radiation with angiostatin to improve tumour eradication without increasing deleterious effects. C1 Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Northwestern Univ, Sch Med, Dept Med, Div Hematol Oncol, Chicago, IL 60611 USA. Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. EM rrw@rover.uchicago.edu NR 15 TC 485 Z9 504 U1 2 U2 15 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 16 PY 1998 VL 394 IS 6690 BP 287 EP 291 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 101CK UT WOS:000074851900051 PM 9685160 ER PT J AU Emanuel, EJ Battin, MP AF Emanuel, EJ Battin, MP TI What are the potential cost savings from legalizing physician-assisted suicide SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TERMINAL CANCER-PATIENTS; ACTIVE EUTHANASIA; MEDICAL DECISIONS; MANAGED DEATH; DATA SHOW; LAST YEAR; CARE; LIFE; END; ATTITUDES C1 Dana Farber Canc Inst, Div Canc Epidemiol & Control, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Med Eth, Boston, MA USA. Univ Utah, Dept Philosophy, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Internal Med, Div Med Eth, Salt Lake City, UT USA. RP Emanuel, EJ (reprint author), Dana Farber Canc Inst, Div Canc Epidemiol & Control, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. NR 42 TC 39 Z9 39 U1 3 U2 5 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 16 PY 1998 VL 339 IS 3 BP 167 EP 172 DI 10.1056/NEJM199807163390306 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZZ922 UT WOS:000074782900006 PM 9664094 ER PT J AU Rosenbaum, JF Fava, M Hoog, SL Ascroft, RC Krebs, WB AF Rosenbaum, JF Fava, M Hoog, SL Ascroft, RC Krebs, WB TI Selective serotonin reuptake inhibitor discontinuation syndrome: A randomized clinical trial SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Neuroscience Discussion Forum A Decade of Serotonin Research CY NOV, 1997 CL AMELIA ISLAND, FLORIDA SP Soc Biol Psychiat, Eli Lilly & Co DE discontinuation-emergent events; selective serotonin reuptake inhibitors; withdrawal events; treatment interruption; fluoxetine ID ANTIDEPRESSANT WITHDRAWAL; SERTRALINE DISCONTINUATION; PAROXETINE; SYMPTOMS; FLUOXETINE; DISORDER; DRUGS AB Background: Recent reports describe discontinuation-emergent adverse events upon cessation of selective serotonin reuptake inhibitors including dizziness, insomnia, nervousness, nausea, and agitation. We hypothesized that interruption of fluoxetine treatment would be associated with fewer discontinuation-emergent adverse events than interruption of sertraline or paroxetine treatment, based on fluoxetine's longer half-life. Methods: In this 4-week study, 242 patients with remitted depression receiving maintenance therapy with open-label fluoxetine, sertraline, or paroxetine for 4-24 months had their maintenance therapy interrupted with double-blind placebo substitution for 5-8 days. The Symptom Questionnaire (Se), the Discontinuation-Emergent Signs and Symptoms checklist, the 28-item Hamilton Depression Rating Scale, and the Montgomery-Asberg Depression Rating Scale were used to assess somatic.distress and stability of antidepressant response. Results: Two hundred twenty patients (91%) completed the study. Following interruption of therapy, fluoxetine-treated patients experienced fewer discontinuation-emergent events than either sertraline-treated or paroxetine-treated patients (p <.001). The mean Se somatic symptom scale score in fluoxetine-treated patients was significantly lower than that in sertraline-treated and paroxetine-treated patients (p <.001). Fluoxetine-treated patients also experienced less reemergence of depressive symptoms than sertraline-treated or paroxetine-treated patients (p <.001). Conclusions: Abrupt interruption of antidepressant therapy for 5-8 days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline, with few symptoms seen with fluoxetine. Biol Psychiatry 1998;44:77-87 (C) 1998 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Rosenbaum, JF (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, 15 Parkman St, Boston, MA 02114 USA. NR 38 TC 298 Z9 304 U1 5 U2 15 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 JUL 15 PY 1998 VL 44 IS 2 BP 77 EP 87 DI 10.1016/S0006-3223(98)00126-7 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZV316 UT WOS:000074292400002 PM 9646889 ER PT J AU Guadagnoli, E Shapiro, CL Weeks, JC Gurwitz, JH Borbas, C Soumerai, SB AF Guadagnoli, E Shapiro, CL Weeks, JC Gurwitz, JH Borbas, C Soumerai, SB TI The quality of care for treatment of early stage breast carcinoma - Is it consistent with national guidelines? SO CANCER LA English DT Article DE quality of care; early stage breast carcinoma; axillary lymph node dissection; radiation therapy; adjuvant therapy; health services research ID LYMPH-NODE DISSECTION; RADIATION-THERAPY; CANCER PATIENTS; GEOGRAPHIC-VARIATION; AXILLARY DISSECTION; CONSERVING SURGERY; RADIOTHERAPY; LUMPECTOMY; WOMEN; IRRADIATION AB BACKGROUND, In response to the importance of early stage breast carcinoma as a public health concern and to the complexity of the clinical literature devoted to treatment of the disease, the National Institutes of Health has held a series of Consensus Development Conferences on the treatment of early stage breast carcinoma. The authors assessed compliance with standards of care for women treated in two states. METHODS. The authors identified patients diagnosed at 18 randomly selected hospitals (N = 1514) in Massachusetts and at 30 hospitals (N = 1061) in Minnesota. They collected data from medical records, patients, and their surgeons to assess compliance with four indicators of quality of care: radiation therapy after breast-conserving surgery, axillary lymph node dissection, chemotherapy for premenopausal women with positive lymph nodes, and hormonal therapy for postmenopausal women with positive lymph nodes and positive estrogen receptor status. RESULTS. Rates of compliance for 3 of the 4 standards of care were > 80% in both states. Only the rate for hormonal therapy for postmenopausal women was low (< 64%). However, the proportion of these women who received either chemotherapy or hormonal therapy was > 90% in both states. CONCLUSIONS. In the states studied, practice appears to be consistent with the results of national consensus conferences and clinical trials regarding the treatment of early stage breast carcinoma. For practices demonstrated to be associated definitively with better outcomes (for example, chemotherapy for premenopausal women with positive lymph nodes) or to be important with respect to prognosis (axillary lymph node dissection) high rates of compliance were observed. (C) 1998 American Cancer Society. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Meyers Primary Care Inst, Worcester, MA USA. Healthcare Educ Res Fdn, St Paul, MN USA. Harvard Pilgrim Hlth Ctr, Dept Ambulatory Care & Prevent, Boston, MA USA. RP Guadagnoli, E (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA57755, CA59408]; NIA NIH HHS [K08 AG00510] NR 35 TC 61 Z9 61 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 JUL 15 PY 1998 VL 83 IS 2 BP 302 EP 309 DI 10.1002/(SICI)1097-0142(19980715)83:2<302::AID-CNCR14>3.0.CO;2-X PG 8 WC Oncology SC Oncology GA ZY706 UT WOS:000074651200014 PM 9669813 ER PT J AU Fornzler, D Her, H Knapik, EW Clark, M Lehrach, H Postlethwait, JH Zon, LI Beier, DR AF Fornzler, D Her, H Knapik, EW Clark, M Lehrach, H Postlethwait, JH Zon, LI Beier, DR TI Gene mapping in zebrafish using single-strand conformation polymorphism analysis SO GENOMICS LA English DT Article ID DANIO-RERIO; MUTATIONS; DNA; VERTEBRATE; CENTROMERE; MAP AB To exploit fully the power of the zebrafish system as a model for vertebrate development, it will be necessary to develop efficient tools for genomic analysis. In this report we have tested whether single-strand conformation polymorphism analysis (SSCP) can be utilized for gene mapping in zebrafish. Over 100 primer pairs derived from noncoding regions of known genes and partially characterized cDNAs were analyzed, and a polymorphism frequency of approximately 50% was detected in zebrafish strains used for genetic mapping studies. A subset of these polymorphic cDNAs was localized on the zebrafish map. SSCP thus represents an efficient strategy for mapping transcribed sequences with a high resolution in the zebrafish genome, which will facilitate the integration of existing zebrafish framework maps, the generation of a zebrafish EST map, and the application of alternative gene localization strategies such as comparative mapping. (C) 1998 Academic Press. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02114 USA. Max Planck Inst Mol Genet, Berlin, Germany. Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. Harvard Univ, Childrens Hosp, Sch Med, HHMI, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Beier, DR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, 20 Shattuck St, Boston, MA 02115 USA. RI Knapik, Ela/J-6172-2014 NR 19 TC 16 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 15 PY 1998 VL 51 IS 2 BP 216 EP 222 DI 10.1006/geno.1998.5386 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 111WK UT WOS:000075461300007 PM 9722944 ER PT J AU Bourdette, DN Chou, YK Whitham, RH Buckner, J Kwon, HJ Nepom, GT Buenafe, A Cooper, SA Allegretta, M Hashim, GA Offner, H Vandenbark, AA AF Bourdette, DN Chou, YK Whitham, RH Buckner, J Kwon, HJ Nepom, GT Buenafe, A Cooper, SA Allegretta, M Hashim, GA Offner, H Vandenbark, AA TI Immunity to T cell receptor peptides in multiple sclerosis. III. Preferential immunogenicity of complementarity-determining region 2 peptides from disease-associated T cell receptor BV genes SO JOURNAL OF IMMUNOLOGY LA English DT Article; Proceedings Paper CT 4th International Congress of the International-Society-of-Neuroimmunology CY OCT, 1994 CL AMSTERDAM, NETHERLANDS SP Int Soc Neuroimmunol ID MYELIN BASIC-PROTEIN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; V-BETA-6.1 CDR2 PEPTIDES; PROTEOLIPID PROTEIN; CEREBROSPINAL-FLUID; TCR PEPTIDES; CHAIN; SELECTION; LINES; IDENTIFICATION AB Vaccination with synthetic TCR peptides from the BV5S2 complementarity-determining region 2 (CDR2) can boost significantly the frequency of circulating CD4(+) peptide-specific Th2 cells in multiple sclerosis (MS) patients, with an associated decrease in the frequency of myelin basic protein (MBP)-reactive Th1 cells and possible clinical benefit. To evaluate the immunogenicity of CDR2 vs other regions of the TCR, vee vaccinated seven MS patients with overlapping BV5S2 peptides spanning amino acids 1-94. Six patients responded to at least one of three overlapping or substituted CDR2 peptides possessing a core epitope of residues 44-52, and one patient also responded to a CDR1 peptide. Of the CDR2 peptides, the substituted (Y49T)BV5S2-38-58 peptide was the most immunogenic but cross-reacted with the native sequence and had the strongest binding affinity for MS-associated HLA-DR2 alleles, suggesting that position 49 is an MHC rather than a TCR contact residue. Two MS patients who did not respond to BV5S2 peptides were immunized successfully with CDR2 peptides from different BV gene families overexpressed by their MBP-specific T cells. Taken together, these results suggest that a widely active vaccine for MS might well involve a limited set of slightly modified CDR2 peptides from BV genes involved in T cell recognition of MBP. C1 Vet Affairs Med Ctr, Neurol Serv, Portland, OR 97207 USA. Vet Affairs Med Ctr, Res Serv, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Virginia Mason Res Ctr, Seattle, WA 98101 USA. Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Univ Washington, Dept Rheumatol, Seattle, WA 98195 USA. St Pauls Hosp, Dept Clin Pathol, Seoul, South Korea. Connet Corp, Palo Alto, CA 94303 USA. Council Tobacco Res, New York, NY 10022 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Vandenbark, AA (reprint author), Portland VA Med Ctr, Neuroimmunol Res R&D-31,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NINDS NIH HHS [NS21466, NS23221, NS23444] NR 49 TC 23 Z9 23 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1998 VL 161 IS 2 BP 1034 EP 1044 PG 11 WC Immunology SC Immunology GA ZZ428 UT WOS:000074728400062 PM 9670985 ER PT J AU Kamiguchi, H Long, KE Pendergast, M Schaefer, AW Rapoport, I Kirchhausen, T Lemmon, V AF Kamiguchi, H Long, KE Pendergast, M Schaefer, AW Rapoport, I Kirchhausen, T Lemmon, V TI The neural cell adhesion molecule L1 interacts with the AP-2 adaptor and is endocytosed via the clathrin-mediated pathway SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neural cell adhesion molecule; L1; tyrosine-based sorting signal; clathrin-mediated endocytosis; AP-2 adaptor; axonal growth cone ID COATED VESICLE FORMATION; TRANS-GOLGI NETWORK; CYTOPLASMIC DOMAIN; IMMUNOGLOBULIN SUPERFAMILY; SYNAPTIC PLASTICITY; SORTING SIGNALS; PROTEIN; RECEPTOR; TRANSFERRIN; SEQUENCE AB Cell-cell interactions mediated via cell adhesion molecules (CAMs) are dynamically regulated during nervous system development. One mechanism to control the amount of cell surface CAMs is to regulate their recycling from the plasma membrane. The L1 subfamily of CAMs has a highly conserved cytoplasmic domain that contains a tyrosine, followed by the alternatively spliced RSLE (Arg-Ser-Leu-Glu) sequence. The resulting sequence of (Y) under bar RS (L) under bar. conforms to a tyrosine-based sorting signal that mediates clathrin-dependent endocytosis of signal-bearing proteins. The present study shows that L1 associates in rat brain with AP-2, a clathrin adaptor that captures plasma membrane proteins with tyrosine-based signals for endocytosis by coated pits. In vitro assays demonstrate that this interaction occurs via the YRSL sequence of L1 and the mu 2 chain of AP-2. In L1-transfected 3T3 cells, L1 endocytosis is blocked by dominant-negative dynamin that specifically disrupts clathrin-mediated internalization. Furthermore, endocytosed L1 colocalizes with the transferrin receptor (TfR), a marker for clathrin-mediated internalization. Mutant forms of LI that lack the YRSL do not colocalize with TfR, indicating that the YRSL mediates endocytosis of L1. In neurons, L1 is endocytosed preferentially at the rear of axonal growth cones, colocalizing with Eps15, another marker for the clathrin endocytic pathway. These results establish a mechanism by which L1 can be internalized from the cell surface and suggest that an active region of LI endocytosis at the rear of growth cones is important in L1-dependent axon growth. C1 Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Lemmon, V (reprint author), Case Western Reserve Univ, Dept Neurosci, 2109 Adelbert Rd, Cleveland, OH 44106 USA. RI Lemmon, Vance/A-2565-2008; Kamiguchi, Hiroyuki/N-5409-2015; Lemmon, Vance/A-7410-2010 OI Lemmon, Vance/0000-0003-3550-7576 FU NEI NIH HHS [EY-5285, P30 EY011373, P30 EY11373, R01 EY005285]; NIGMS NIH HHS [R01 GM036548]; NINDS NIH HHS [NS-34352] NR 63 TC 146 Z9 147 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1998 VL 18 IS 14 BP 5311 EP 5321 PG 11 WC Neurosciences SC Neurosciences & Neurology GA ZY294 UT WOS:000074605700022 PM 9651214 ER PT J AU Banner, LR Patterson, PH Allchorne, A Poole, S Woolf, CJ AF Banner, LR Patterson, PH Allchorne, A Poole, S Woolf, CJ TI Leukemia inhibitory factor is an anti-inflammatory and analgesic cytokine SO JOURNAL OF NEUROSCIENCE LA English DT Article DE pain; inflammation; edema; hyperalgesia; primary sensory neuron; analgesia ID NERVE GROWTH-FACTOR; PRIMARY SENSORY NEURONS; PAIN HYPERSENSITIVITY; INDUCED HYPERALGESIA; FACTOR CONTRIBUTES; MESSENGER-RNAS; SCIATIC-NERVE; UP-REGULATION; INTERLEUKIN-6; NOCICEPTORS AB The mRNA for leukemia inhibitory factor (LIF), a neuroimmune signaling molecule, is elevated during skin inflammation produced by intraplantar injection of complete Freund's adjuvant (CFA). Moreover, although LIF knock-out mice display normal sensitivity to cutaneous mechanical and thermal stimulation compared with wild-type mice, the degree of CFA-induced inflammation in mice lacking LIF is enhanced in spatial extent, amplitude, cellular infiltrate, and interleukin (IL)-1 beta and nerve growth factor (NGF) expression. Conversely, local injection of low doses of recombinant LIF diminishes mechanical and thermal hypersensitivity as well as the IL-1 beta and NGF expression induced by CFA. These data show that upregulation of LIF during peripheral inflammation serves a key, early antiinflammatory role and that exogenous LIF can reduce inflammatory hyperalgesia. C1 Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. Univ London Univ Coll, Dept Anat & Dev Biol, London WC1E 6BT, England. Natl Inst Biol Stand & Controls, Div Endocrinol, Potters Bar EN6 3QG, Herts, England. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Neural Plast Res Grp, Bldg 149,13th St, Charlestown, MA 02129 USA. FU Wellcome Trust NR 51 TC 52 Z9 53 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1998 VL 18 IS 14 BP 5456 EP 5462 PG 7 WC Neurosciences SC Neurosciences & Neurology GA ZY294 UT WOS:000074605700034 PM 9651226 ER PT J AU Elgadi, KM Labow, BI Abcouwer, SF Souba, WW AF Elgadi, KM Labow, BI Abcouwer, SF Souba, WW TI Sepsis increases lung glutamine synthetase expression in the tumor-bearing host SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 06-08, 1997 CL DALLAS, TEXAS SP Assoc Acad Surg DE lung; muscle; cachexia; glutamine ID SKELETAL-MUSCLE CELLS; CANCER CACHEXIA; SEPTIC RATS; METABOLISM; CULTURE; GENE AB Acute stresses such as trauma or endotoxemia augment GLN demand and are associated with increased release of this amino acid from skeletal muscle and lung as well as increased expression of glutamine synthetase (GS, the principal enzyme of GLN synthesis) in these tissues. Muscle GLN release is also increased during chronic catabolic states which are associated with depletion of lean body mass, such as starvation or malignancy. We hypothesized that the expression of GS in response to an acute stress would be altered in tumor-bearing rats (TBR) experiencing severe cachexia and therefore a previously heightened GLN demand. Male Fischer 344 rats were implanted with methylcholanthrene-induced fibrosarcoma tumors or underwent sham operations and pair-feeding (sham) with TBR partners. When tumor burden reached approximately 15% of carcass weight, animals received injections of either Escherichia coli lipopolysaccharide (LPS, 1 mg/kg body wt) or saline vehicle. Rats were sacrificed 8 h after injection and lung and muscle tissue were analyzed for GS mRNA and protein via Northern and Western blot techniques, respectively. LPS injection caused an equivalent 4- to B-fold increase in lung and muscle GS mRNA in both TBR and sham rats (P < 0.01). LPS did not produce a significant increase in GS protein level in muscle tissue of either group or in lung tissue of sham rats. In contrast, endotoxin did lead to a 3.5-fold increase in GS protein levels in lung tissue of TBRs (P < 0.05). This increase in lung GS protein may signify the importance of the lung in maintaining GLN homeostasis during chronic catabolic states where muscle mass is diminished. (C) 1998 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Elgadi, KM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NCI NIH HHS [CA57690] NR 35 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL 15 PY 1998 VL 78 IS 1 BP 18 EP 22 DI 10.1006/jsre.1998.5384 PG 5 WC Surgery SC Surgery GA 116UC UT WOS:000075742400004 PM 9733611 ER PT J AU Suzuki, K Bonner-Weir, S Trivedi, N Yoon, KH Hollister-Lock, J Colton, CK Weir, GC AF Suzuki, K Bonner-Weir, S Trivedi, N Yoon, KH Hollister-Lock, J Colton, CK Weir, GC TI Function and survival of macroencapsulated syngeneic islets transplanted into streptozocin-diabetic mice SO TRANSPLANTATION LA English DT Article ID MEMBRANE MICROARCHITECTURE; MASS; XENOGRAFTS; IMMUNOSUPPRESSION; NEOVASCULARIZATION; REPLICATION; PANCREAS; PORCINE; GROWTH; RATS AB Background. Macroencapsulation is a strategy to protect transplanted islets from rejection and autoimmune attack. This study addresses questions about the survival and function of macroencapsulated syngeneic islets. Methods. Planar immunobarrier membrane diffusion devices were used for syngeneic islet transplantation. After being mixed with a 1% alginate solution, a total of 250, 500, 750 or 1000 islets were loaded into the devices, which were implanted into the epididymal fat pad(s) of streptozocin diabetic mice. Results. The success rate for restoration of normoglycemia at week 4 was highest for the recipients receiving two devices, each with 500 islets. Loading 750 or 1000 islets provided no improvement over loading 500 islets in a single device, Devices containing 250 islets were rarely successful. There was a striking tendency of transplants to either bring glucose levels into the near normal range or to fail with marked hyperglycemia, After an overnight fast at 1 and 4 weeks, but not at 12 weeks, hypoglycemia was found. The insulin content of devices from animals with normalized glucose values was higher than the insulin content in failed devices. Islet volume was maintained for 12 weeks, and fibrosis did not increase. Conclusions. A relatively small mass of macroencapsulated islet tissue can survive and function well enough to normalize glucose levels for at least 12 weeks. Maintenance of glucose levels in the near-normal range seems to have a beneficial influence on graft success. The finding of fasting hypoglycemia raises important clinical questions about islet dysfunction. Important limitations in the requirements for islet packing density in macroencapsulation have been defined. New approaches for improving islet packing density must be developed to make diffusion-dependent macroencapsulation more practical. C1 Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-35449, DK-36836, DK-50657] NR 29 TC 43 Z9 44 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 1998 VL 66 IS 1 BP 21 EP 28 DI 10.1097/00007890-199807150-00004 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 101VR UT WOS:000074889300004 PM 9679817 ER PT J AU Yang, YG deGoma, E Barth, R Sergio, JJ Sykes, M AF Yang, YG deGoma, E Barth, R Sergio, JJ Sykes, M TI B-cell reconstitution and xenoreactive anti-pig natural antibody production in severe combined immunodeficient mice reconstituted with immunocompetent B cells from varying sources SO TRANSPLANTATION LA English DT Article ID PORCINE ENDOTHELIAL-CELLS; BONE-MARROW; DISCORDANT XENOGRAFTS; MONOCLONAL-ANTIBODY; B-1 CELLS; HYPERACUTE REJECTION; CARDIAC XENOGRAFTS; MINIATURE SWINE; SCID MICE; IMMUNOGLOBULIN AB Background. Little is known about the B-cell subsets that produce xenoreactive natural antibodies (NAb). This study was undertaken to investigate the potential role of varying B-cell populations in anti-pig NAb production in mice. Methods. Severe combined immunodeficient (scid) mice were reconstituted with bone marrow or splenic or peritoneal B cells from immunocompetent mice. B-cell reconstitution and anti-pig NAb were evaluated by flow cytometric analysis. Results. Adult marrow failed to reconstitute normal numbers of CD5(+) Bla cells, but fully reconstituted CD5(-) Mac1(-) B2 and CD5(-) Mac1(+) Bib cell populations in scid mice. Recipients of peritoneal B cells showed poor reconstitution of B2 cells, and an overshoot of B1 cells in the peritoneal cavity, Although B2 cells predominate in the adult spleen, splenic B cells from immunocompetent mice preferentially reconstituted B cells, including B1 cells, in the peritoneal cavity, but did not reconstitute splenic B2 cells. Therefore, neither adult marrow, splenocytes nor peritoneal cells can fully reconstitute scid mice with all B-cell subpopulations. Nevertheless, serum anti-pig NAb in mar row-reconstituted mice recovered to normal levels by 3 weeks, and were maintained for at least 30 weeks. Serum NAb in scid mice receiving peritoneal B cells reached normal levels by 4-7 weeks after transfer. However, NAb in sera of acid mice receiving splenic B cells took longer (>25 weeks) to reach normal levels. Conclusions. These results indicate that adult marrow-derived B cells can efficiently produce anti-pig NAb, and that peritoneal B cells have greater NAb-producing ability than splenic B cells or their immediate progeny. C1 Harvard Univ, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Surg Serv,Massachusetts Gen Hosp,Sch Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Surg Serv,Massachusetts Gen Hosp,Sch Med, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL49915] NR 52 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 1998 VL 66 IS 1 BP 89 EP 95 DI 10.1097/00007890-199807150-00014 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 101VR UT WOS:000074889300014 PM 9679827 ER PT J AU Manilay, JO Pearson, DA Sergio, JJ Swenson, KG Sykes, M AF Manilay, JO Pearson, DA Sergio, JJ Swenson, KG Sykes, M TI Intrathymic deletion of alloreactive T cells in mixed bone marrow chimeras prepared with a nonmyeloablative conditioning: Regimen SO TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; TRANSPLANTATION TOLERANCE; XENOGENEIC BARRIER; ANTIGEN RECEPTOR; TRANSGENIC MICE; LYMPHOCYTES-T; GRAFT; EXPRESSION; SELECTION; ANTIBODY AB Background. Mixed hematopoietic chimerism induced with a nonmyeloablative conditioning regimen leads to donor-specific transplantation tolerance. Analyses of specific Vp bearing T-cell families that recognize endogenous superantigens demonstrated that donor-specific tolerance is due mainly to an intrathymic deletional mechanism in these mixed chimeras. However, superantigens are not known to behave as classical transplantation antigens, We therefore used T-cell receptor (TCR) transgenic (Tg) recipients expressing a clonotypic TCR specific for an allogeneic major histocompatibility complex antigen to further assess deletional tolerance. Methods. 2C TCR Tg mice (H2(b)), whose Tg TCR recognizes major histocompatibility complex class I Ld, were used as recipients of Ld+ bone marrow cells after conditioning with depleting anti-CD4 and CD8 monoclonal antibodies, 3 Gy whole-body irradiation, and 7 Gy thymic irradiation. Chimerism and deletion of CD8(+) 2C recipient T cells was evaluated by flow cytometry and by immunohistochemical staining. Tolerance was tested with in vitro cell-mediated lympholysis assays and in vivo by grafting with donor skin. Results. Intrathymic and peripheral deletion of 2C(+) CD8-single-positive T cells was evident in mixed chimeras, and deletion correlated with the presence of donor-type cells with dendritic morphology in the thymus, and with chimerism in lymphohematopoietic tissues. Chimeras showed tolerance to the donor in cell-mediated lympholysis assays and specifically accepted donor skin grafts, Conclusions, Tolerance to transplantation antigens is achieved through intrathymic deletion of donor-reactive T cells in mixed chimeras prepared with a nonmyeloablative conditioning regimen and allogeneic bone marrow transplantation. C1 Harvard Univ, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Massachusetts Gen Hosp,Sch Med,Surg Serv, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Massachusetts Gen Hosp,Sch Med,Surg Serv, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [T32 HL 07623-11A1, R01 HL49915] NR 24 TC 115 Z9 118 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 1998 VL 66 IS 1 BP 96 EP 102 DI 10.1097/00007890-199807150-00015 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 101VR UT WOS:000074889300015 PM 9679828 ER PT J AU Suga, H Cowan, JA Szostak, JW AF Suga, H Cowan, JA Szostak, JW TI Unusual metal ion catalysis in an acyl-transferase ribozyme SO BIOCHEMISTRY LA English DT Article ID TETRAHYMENA RIBOZYME; HAMMERHEAD RIBOZYME; PH DEPENDENCIES; BINDING SITES; RNA; CLEAVAGE; MECHANISM; MAGNESIUM; PROTEIN; PHOSPHOROTHIOATE AB Most studies Of the roles of catalytic metal ions in ribozymes have focused on inner-sphere coordination of the divalent metal ions to the substrate or ribozyme. However, divalent metal ions are strongly hydrated in water, and some proteinenzymes, such as Escherichia coli RNase H and exonuclease III, are known to use metal cofactors in their fully hydrated form [Duffy, T. H., and Nowak, T. (1985) Biochemistry 24, 1152-1160; Jou, R., and Cowan, J. A. (1991) J. Am. Chem. Sec. 113, 6685-6686]. It is therefore important to consider the possibility of outer-sphere coordination of catalytic metal ions in ribozymes. We have used an exchange-inert metal complex, cobalt hexaammine, to show that the catalytic metal ion in an acyl-transferase ribozyme acts through outer-sphere coordination. Our studies provide an example of a fully hydrated Mg2+ ion that plays an essential role in ribozyme catalysis. Kinetic studies of wild-type and mutant ribozymes suggest that a pair of tandem G:U wobble base pairs adjacent to the reactive center constitute the metal-binding site. This result is consistent with recent crystallographic studies [Cate, J. H., and Doudna, J. A. (1996) Structure 4, 1221-1229; Gate, J. H., Gooding, A. R., Podell, E., Zhou, K., Golden, B. L., Kundrot, C. E., Cech, T. R., and Doudna, J. A. (1996) Science 273, 1678-1685; Gate, J. H., Hanna, R. L., and Doudna, J. A. (1997) Nat. Struct. Biol. 4, 553-558] showing that tandem wobble base pairs are good binding sites for metal hexaammines. We propose a model in which the catalytic metal ion is bound in the major groove of the tandem wobble base pairs, is precisely positioned by the ribozyme within the active site, and stabilizes the developing oxyanion in the transition state. Our results may have significant implications for understanding the mechanism of protein synthesis [Noller, H. F., Hoffarth, V., and Zimniak, L. (1992) Science 256, 1416-1419]. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA. Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. RP Suga, H (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM53936] NR 43 TC 58 Z9 59 U1 1 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 JUL 14 PY 1998 VL 37 IS 28 BP 10118 EP 10125 DI 10.1021/bi980432a PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 101XQ UT WOS:000074893800028 PM 9665717 ER PT J AU Hsueh, YP Yang, FC Kharazia, V Naisbitt, S Cohen, AR Weinberg, RJ Sheng, M AF Hsueh, YP Yang, FC Kharazia, V Naisbitt, S Cohen, AR Weinberg, RJ Sheng, M TI Direct interaction of CASK/LIN-2 and syndecan heparan sulfate proteoglycan and their overlapping distribution in neuronal synapses SO JOURNAL OF CELL BIOLOGY LA English DT Article DE CASK; LIN-2; syndecan; heparan sulfate proteoglycan; PDZ domain ID TUMOR-SUPPRESSOR PROTEIN; ELEGANS VULVAR INDUCTION; NMDA RECEPTOR SUBUNITS; GUANYLATE KINASES; SIGNAL-TRANSDUCTION; PSD-95 FAMILY; PDZ DOMAINS; K+ CHANNELS; RAT-BRAIN; CELL AB CASK, the rat homolog of a gene (LIN-2) required for vulval differentiation in Caenorhabditis elegans, is expressed in mammalian brain, but its function in neurons is unknown. CASK is distributed in a punctate somatodendritic pattern in neurons. By immunogold EM, CASK protein is concentrated in synapses, but is also present at nonsynaptic membranes and in intracellular compartments. This immunolocalization is consistent with biochemical studies showing the presence of CASK in soluble and synaptosomal membrane fractions and its enrichment in postsynaptic density fractions of rat brain. By yeast two-hybrid screening, a specific interaction was identified between the PDZ domain of CASK and the COOH terminal tail of syndecan-2, a cell surface heparan sulfate proteoglycan (HSPG). The interaction was confirmed by coimmunoprecipitation from heterologous cells. In brain, syndecan-2 localizes specifically at synaptic junctions where it shows overlapping distribution with CASK, consistent with an interaction between these proteins in synapses. Cell surface HSPGs can bind to extracellular matrix proteins, and are required for the action of various heparin-binding polypeptide growth/differentiation factors. The synaptic localization of CASK and syndecan suggests a potential role for these proteins in adhesion and signaling at neuronal synapses. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. Yale Univ, Sch Med, Dept Cell Biol & Internal Med, New Haven, CT 06520 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wel 423,50 Blossom St, Boston, MA 02114 USA. OI Hsueh, Yi-Ping/0000-0002-0866-6275 FU NINDS NIH HHS [NS29879] NR 46 TC 238 Z9 243 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL 13 PY 1998 VL 142 IS 1 BP 139 EP 151 DI 10.1083/jcb.142.1.139 PG 13 WC Cell Biology SC Cell Biology GA 102VB UT WOS:000074945000012 PM 9660869 ER PT J AU Faraone, SV Matise, T Svrakic, D Pepple, J Malaspina, D Suarez, B Hampe, C Zambuto, CT Schmitt, K Meyer, J Markel, P Lee, H Harkavy-Friedman, J Kaufmann, C Cloninger, CR Tsuang, MT AF Faraone, SV Matise, T Svrakic, D Pepple, J Malaspina, D Suarez, B Hampe, C Zambuto, CT Schmitt, K Meyer, J Markel, P Lee, H Harkavy-Friedman, J Kaufmann, C Cloninger, CR Tsuang, MT TI Genome scan of European-American schizophrenia pedigrees: Results of the NIMH Genetics Initiative and Millennium Consortium SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE schizophrenia; linkage; NIMH Genetics Initiative ID GLUTAMIC-ACID DECARBOXYLASE; LINKAGE ANALYSIS; SUPRACHIASMATIC NUCLEUS; CHROMOSOME 22Q12-Q13.1; SUSCEPTIBILITY GENES; VULNERABILITY LOCUS; POTENTIAL LINKAGE; BRAIN; EXPRESSION; PSYCHOSIS AB The Genetics Initiative of the National Institute of Mental Health (NIMH) was a multisite study that created a national repository of DNA from families informative for genetic linkage studies of schizophrenia, bipolar disorder, and Alzheimer's disease. The schizophrenia families were collected by three sites: Washington University, Harvard University, and Columbia University. This article, one in a series that describes the data collected for linkage analysis by the schizophrenia consortium, presents the results for the European-American sample. The European-American sample comprised 43 nuclear families and 146 subjects. Ninety-six of the family members were considered affected by virtue of having received a DSM-III-R diagnosis of schizophrenia (N = 82) or schizoaffective disorder, depressed (N = 14). The families contained a total of 50 independent sib-pairs, Using the significance threshold criteria suggested by Lander and Kruglyak [(1995): Nat Genet 241-247], no region showed statistically significant evidence for linkage; two markers on chromosome 10p showed statistical evidence suggestive of linkage using the criteria of Lander and Kruglyak [(1995): Nat Genet 241-247]: D10S1423 (nonparametric linkage (NPL) Z = 3.4, P =.0004) and its neighbor, D10S582 (NPL Z = 3.2, P = .0006), Am, J, Med, Genet. (Neuropsychiatr. G;enet.) 81:290-295, 1998, (C) 1998 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Faraone, SV (reprint author), Harvard Univ, Sch Med, 750 Washington St,Suite 255, S Easton, MA 02375 USA. RI Cloninger, Claude/F-5357-2012; OI Cloninger, Claude/0000-0003-3096-4807; Harkavy-Friedman, Jill/0000-0002-1449-0667; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [1 R01MH41874-01, 1 R37MH43518, 5 UO1MH46318] NR 43 TC 230 Z9 233 U1 5 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 10 PY 1998 VL 81 IS 4 BP 290 EP 295 DI 10.1002/(SICI)1096-8628(19980710)81:4<290::AID-AJMG3>3.0.CO;2-Y PG 6 WC Genetics & Heredity SC Genetics & Heredity GA ZX390 UT WOS:000074511000003 PM 9674973 ER PT J AU Tsuang, D DiGiacomo, L Lipe, H Bird, TD AF Tsuang, D DiGiacomo, L Lipe, H Bird, TD TI Familial aggregation of schizophrenia-like symptoms in Huntington's disease SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Huntington's disease; genetics; schizophrenia AB An increased incidence of schizophrenia-like symptoms in Huntington's disease (HD) has been well-documented in the past, The reasons for this association, however, have never been explained. At the University of Washington Medical Genetics Clinic, we had the opportunity to evaluate a unique juvenile-onset HD proband who had schizophrenia-like symptoms. This patient was referred to our clinic because of new onset of somatic delusions and command auditory hallucinations early in the course of her illness. Since we had already evaluated other affected individuals in her family, we selected another family with a nonpsychotic juvenile-onset proband for comparison. Using these two families in a small case-control study, we investigated the following hypotheses which could explain the association between schizophrenia-like symptoms and HD: first, schizophrenia-like symptoms may be related to the number of CAG repeats in the HD gene; second, schizophrenia-like symptoms may segregate in certain HD families, for unknown reasons; and third, there may coincidentally be an unrelated gene for schizophrenia in certain HD families, Comparisons of clinical characteristics and the HD genotype showed that family history of schizophrenia-like symptoms segregated with the HD gene; however, age of onset of HD, size of CAG; repeat, and sex of the transmitting parent were not associated with psychotic symptoms. Further genetic and neurobiological studies are necessary to investigate the potential mechanism underlying this association, Am. J, Med, Genet, (Neuropsychiatr. Genet.) 81:323-327, 1998. (C) 1998 Wiley-Liss, Inc. C1 VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Med Ctr, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Dept Internal Med, Div Med Genet, Seattle, WA 98195 USA. RP Tsuang, D (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [5K12 AG00503-07] NR 12 TC 13 Z9 13 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 10 PY 1998 VL 81 IS 4 BP 323 EP 327 DI 10.1002/(SICI)1096-8628(19980710)81:4<323::AID-AJMG9>3.0.CO;2-U PG 5 WC Genetics & Heredity SC Genetics & Heredity GA ZX390 UT WOS:000074511000009 PM 9674979 ER PT J AU Schnitzler, G Sif, S Kingston, RE AF Schnitzler, G Sif, S Kingston, RE TI Human SWI/SNF interconverts a nucleosome between its base state and a stable remodeled state SO CELL LA English DT Article ID TRANSCRIPTIONAL ACTIVATORS; RETINOBLASTOMA PROTEIN; CHROMATIN STRUCTURE; COMPLEX; DNA; BINDING; DISRUPTION; SEQUENCES; RECEPTOR; FAMILY AB The human SWI/SNF complex remodels nucleosome structure in an ATP-dependent manner, although the nature of this change has not been determined. Here we show that hSWI/SNF and ATP generate an altered nucleosomal structure that is stable in the absence of SWI/SNF. This product has an altered sensitivity to digestion by DNAse, restriction enzymes, and micrococcal nuclease, and an increased affinity for GAL4. It has the same protein composition but is approximately twice the size of a normal nucleosome. Incubation of the altered nucleosome with hSWI/SNF converts this structure back to a standard nucleosome in an ATP-dependent process. These results suggest that hSWI/SNF acts by facilitating an exchange between normal and altered, more accessible, nucleosome conformations. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. NR 36 TC 236 Z9 236 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 10 PY 1998 VL 94 IS 1 BP 17 EP 27 DI 10.1016/S0092-8674(00)81217-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 100AB UT WOS:000074790800005 PM 9674423 ER PT J AU Hugl, SR White, MF Rhodes, CJ AF Hugl, SR White, MF Rhodes, CJ TI Insulin-like growth factor I (IGF-I)-stimulated pancreatic beta-cell growth is glucose-dependent - Synergistic activation of insulin receptor substrate-mediated signal transduction pathways by glucose and IGF-I in INS-1 CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FETAL-RAT ISLETS; PROTEIN-KINASE; TISSUE-CULTURE; HORMONE; PROLIFERATION; BIOSYNTHESIS; PROLACTIN; REPLICATION; MECHANISMS; SECRETION AB Nutrients and certain growth factors stimulate pancreatic beta-cell mitogenesis, however, the appropriate mitogenic signal transduction pathways have not been defined, In the glucose sensitive pancreatic beta-cell line, INS-I, it was found that glucose (6-18 mM) independently increased INS-1 cell proliferation (>20-fold at 15 mM glucose). Insulin-like growth factor I (IGF-I)-induced INS-1 cell proliferation was glucose-dependent only in the physiologically relevant concentration range (6-18 mm glucose), The combination of IGF-I and glucose was synergistic, increasing INS-1 cell-proliferation >20-fold at 15 mM glucose + 10 nM IGF-I, Glucose metabolism and phosphatidylinositol S'-kinase (PI 3'-kinase) activation were necessary for both glucose and IGF-I-stimulated INS-1 cell proliferation, IGF-I and 15 mM glucose increased tyrosine phosphorylation mediated recruitment of Grb2/mSOS and PI 3'-kinase to IRS-2 and pp60, Glucose and IGF-I also induced Shc association with Grb2/ mSOS, Glucose (3-18 mM) and IGF-I, independently of glucose, activated mitogen-activated protein kinase but this did not correlate with IGF-I-induced beta-cell proliferation, In contrast, p70(S6K) was activated with increasing glucose concentration (between 6 and 18 mM), and potentiated by IGF I in the same glucose concentration range which correlated with INS-1 cell proliferation rate. Thus, glucose and IGF-I-induced beta-cell proliferation were mediated via a signaling mechanism that was facilitated by mitogen-activated protein kinase but de pendent on IRS-mediated induction of PI 3'-kinase activity and downstream activation of p70S6K. The glucose dependence of IGF-I mediated INS-1 cell proliferation emphasizes beta-cell signaling mechanisms are rather unique in being tightly linked to glycolytic metabolic flux. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Gifford Labs Diabet Res, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Gifford Labs Diabet Res, Dallas, TX 75235 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Rhodes, CJ (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Gifford Labs Diabet Res, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. EM rhodes02@utsw.swmed.edu FU NIDDK NIH HHS [DK 50610] NR 46 TC 184 Z9 189 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 10 PY 1998 VL 273 IS 28 BP 17771 EP 17779 DI 10.1074/jbc.273.28.17771 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KW UT WOS:000074816100071 PM 9651378 ER PT J AU Poon, B Grovit-Ferbas, K Stewart, SA Chen, ISY AF Poon, B Grovit-Ferbas, K Stewart, SA Chen, ISY TI Cell cycle arrest by Vpr in HIV-1 virions and insensitivity to antiretroviral agents SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; OPEN READING FRAME; PRODUCTIVE INFECTION; MUTATIONAL ANALYSIS; RHESUS-MONKEYS; TYPE-1; GENE; PROTEIN; MACROPHAGES; LYMPHOCYTES AB Expression of human immunodeficiency virus-type 1 (HIV-1) Vpr after productive infection of T cells induces cell cycle arrest in the G(2) phase of the cell cycle. In the absence of de novo expression, HIV-1 Vpr packaged into virions still induced cell cycle arrest. Naturally noninfectious virus or virus rendered defective for infection by reverse transcriptase or protease inhibitors were capable of inducing Vpr-mediated cell cycle arrest. These results suggest a model whereby both infectious and noninfectious virions in vivo, such as those surrounding follicular dendritic cells, participate in immune suppression. C1 Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol & Med, AIDS Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Med, AIDS Inst, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90095 USA. RP Chen, ISY (reprint author), Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol & Med, AIDS Inst, Los Angeles, CA 90095 USA. RI Stewart, Sheila/C-5213-2012 FU NCI NIH HHS [CA70018]; NIAID NIH HHS [AI28697]; PHS HHS [T32/A107388] NR 50 TC 153 Z9 154 U1 0 U2 3 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 JUL 10 PY 1998 VL 281 IS 5374 BP 266 EP 269 DI 10.1126/science.281.5374.266 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZZ286 UT WOS:000074714200052 PM 9657723 ER PT J AU Basgoz, N Frosch, MP AF Basgoz, N Frosch, MP TI A 32-year-old woman with pharyngeal spasms and paresthesias after a dog bite - Rabies, involving the central and peripheral nervous systems, salivary glands, and heart (epicardium) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID VIRUS-INFECTION; PATHOPHYSIOLOGY; ENCEPHALITIS; PATHOGENESIS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Basgoz, N (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 25 TC 21 Z9 23 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 9 PY 1998 VL 339 IS 2 BP 105 EP 112 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZY828 UT WOS:000074665300008 ER PT J AU Bradley, KA Boyd-Wickizer, J Powell, SH Burman, ML AF Bradley, KA Boyd-Wickizer, J Powell, SH Burman, ML TI Alcohol screening questionnaires in women - A critical review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID PRIMARY-CARE PATIENTS; RISK-DRINKING; INTERVIEW SCHEDULE; LABORATORY TESTS; EMERGENCY ROOM; DSM-IV; ABUSE; CONSUMPTION; DEPENDENCE; POPULATION AB Objective.-To describe the performance of alcohol screening questionnaires in female patients. Data Sources.-We searched MEDLINE from 1966 to July 1997 for alcoholism or alcohol-drinking and for CAGE, AUDIT, BMAST, TWEAK, T-ACE, MAST, SMAST, or SAAST; Citations Indexes for newer screening questionnaires and those without acronyms; and MEDLINE from 1996 to July 1997 for alcoholism or alcohol-drinking and screening. Study Selection and Data Extraction.-Reviewed studies presented data for women comparing brief alcohol screening questionnaires with valid criterion standards for heavy drinking (greater than or equal to 2 drinks per day) or alcohol abuse or dependence in US general clinical populations. Sensitivities, specificities, and areas under receiver operating characteristic curves (AUROCs) were extracted. Data Synthesis.-Thirteen articles (9 studies) were reviewed. The CAGE questionnaire had AUROCs of 0.84 to 0.92 for alcohol abuse and dependence in predominantly black populations of women, but using the traditional cut point of 2 or more resulted in low sensitivities (38%-50%) in predominantly white female populations. The TWEAK and Alcohol Use Disorders Identification Test (AUDIT) questionnaires had high AUROCs (0.87-0.93) for past-year alcohol abuse or dependence in black or white women, but had sensitivities less than 80% at traditional cut points. For detecting heavy drinking, the AUDIT questionnaire had AUROCs of at least 0.87 in female primary care patients. The TWEAK and T-ACE questionnaires had higher AUROCs (0.84-0.87) than the CAGE questionnaire (0.76-0.78) for detecting heavy drinking before pregnancy was recognized in black obstetric patients. Conclusions.-The CAGE questionnaire was relatively insensitive in predominantly white female populations. The TWEAK and AUDIT questionnaires have performed adequately in black or white women, using lower cut points than usual. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Hlth Serv Res & Dev, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle Div, Med Serv, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Bradley, KA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Hlth Serv Res & Dev, 1660 S Columbian Way,Mail Stop 152, Seattle, WA 98108 USA. EM bradley.katharine_a@seattle.va.gov NR 54 TC 237 Z9 241 U1 4 U2 11 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 JUL 8 PY 1998 VL 280 IS 2 BP 166 EP 171 DI 10.1001/jama.280.2.166 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZY321 UT WOS:000074608400033 PM 9669791 ER PT J AU Ebrahimi, S Wang, E Udar, N Arnold, E Burbee, D Small, K Sawicki, MP AF Ebrahimi, S Wang, E Udar, N Arnold, E Burbee, D Small, K Sawicki, MP TI Genomic organization and cloning of the human homologue of murine Sipa-1 SO GENE LA English DT Article DE GTPase activating protein; chromosome 11q13; tumor suppressor gene; multiple endocrine neoplasia type 1 ID GTPASE-ACTIVATING PROTEIN; BUD-SITE-SELECTION; MOLECULAR-CLONING; GENE-PRODUCT; RAN; DOMAIN; YEAST; P21 AB Murine Sipa-1 (signal-induced proliferation associated protein) is a mitogen induced GTPase activating protein (GAP). While mapping candidate genes for multiple endocrine neoplasia type 1 (MEN1) at 11q13, we cloned the human homologue of Sipa-1. Herein, we report the complete cDNA sequence, expression, and genomic organization of SIPA-1. SIPA-1 consists of 16 exons with highly conserved exon-intron boundaries. The predicted SIPA-1 protein is highly homologous to the mouse protein, particularly in the region of the GAP-related domain at the amino terminus and the leucine zipper at the carboxy terminus. It is widely expressed, including in fetal tissues, but is most highly expressed in lymphoid organs. During the course of cloning SIPA-1, the MEN1 gene was identified, thus excluding human SIPA-1 as a candidate for this disease. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Core Mol Biol Unit, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Univ Texas, Hammond Ctr Therapeut Oncol Res, Dallas, TX 75235 USA. RP Sawicki, MP (reprint author), Univ Calif Los Angeles, Sch Med, 10833 LeConte Ave,72-215 CHS, Los Angeles, CA 90095 USA. EM msawicki@ucla.edu FU NEI NIH HHS [EY-02134] NR 21 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 3 PY 1998 VL 214 IS 1-2 BP 215 EP 221 DI 10.1016/S0378-1119(98)00212-1 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 109JL UT WOS:000075318400025 PM 9651531 ER PT J AU Kojima, H Endo, K Moriyama, H Tanaka, Y Alnemri, ES Slapak, CA Teicher, B Kufe, D Datta, R AF Kojima, H Endo, K Moriyama, H Tanaka, Y Alnemri, ES Slapak, CA Teicher, B Kufe, D Datta, R TI Abrogation of mitochondrial cytochrome c release and caspase-3 activation in acquired multidrug resistance SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-LINE; OVEREXPRESSION; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; CIS-DIAMMINEDICHLOROPLATINUM(II); INDUCTION; BCL-X(L); DRUGS AB Acquired multidrug resistance to anti-cancer agents has been associated with overexpression of the P-glycoprotein and other members of the ATP-binding cassette superfamily. The present studies demonstrate that SCC-25 cells selected for resistance to the alkylating agent cisplatin (CDDP) overexpress the anti-apoptotic Bcl-x(L) protein. In contrast to parental cells, the SCC-25/CDDP-resistant variant failed to exhibit activation of caspase-3, cleavage of protein kinase C delta, and other characteristics of apoptosis in response to CDDP. Similar results were obtained when SCC-25/CDDP cells were exposed to the structurally and functionally unrelated antimetabolite l-beta-D-arabinofuranosyl-cytosine (ara-C). Other cells selected for resistance to doxorubicin or vincristine also exhibited overexpression of Bcl-x(L) and failed to respond to CDDP and ara-C with activation of caspase-3. The results further demonstrate that multidrug-resistant cells exhibit a block in the release of mitochondrial cytochrome c into the cytosol and that this effect is dependent on overexpression of Bcl-x(L). The demonstration that lysates from the resistant cells respond to the addition of cytochrome c with activation of caspase-3 confirms that the block in apoptosis is because of inhibition of mitochondrial cytochrome c release, These findings demonstrate that cells respond to diverse classes of anti-cancer drugs with overexpression of Bcl-x(L) and that this response represents another mechanism of acquired multidrug resistance. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Jikei Univ, Sch Med, Dept Otolaryngol, Tokyo 105, Japan. Kimmel Canc Inst, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Datta, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM Rakesh_Datta@dfci.harvard.edu FU NCI NIH HHS [CA29431] NR 30 TC 111 Z9 119 U1 0 U2 4 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 JUL 3 PY 1998 VL 273 IS 27 BP 16647 EP 16650 DI 10.1074/jbc.273.27.16647 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZX700 UT WOS:000074545200005 PM 9642215 ER PT J AU Mannstadt, M Luck, MD Gardella, TJ Juppner, H AF Mannstadt, M Luck, MD Gardella, TJ Juppner, H TI Evidence for a ligand interaction site at the amino-terminus of the parathyroid hormone (PTH)/PTH-related protein receptor from cross-linking and mutational studies SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OSTEO-SARCOMA CELLS; PEPTIDE RECEPTOR; PLASMA-MEMBRANE; BINDING; AGONIST; DETERMINANTS; MUTAGENESIS; EXPRESSION; PTH-(1-34); CALCITONIN AB Low resolution mutational studies have indicated that the amino-terminal extracellular domain of the rat parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor (rP1R) interacts with the carboxyl-terminal portion of PTH-(1-34) or PTHrP-(1-36), To further define ligand-receptor interactions, we prepared a fully functional photoreactive analog of PTHrP, [Ile(5),Bpa(23),Tyr(36)] PTHrP-(1-36)-amide ([Bpa(23)]PTHrP, where Bpa is p-benzoyl-L-phenylalanine), Upon photolysis, radioiodinated [Bpa23]PTHrP covalently and specifically bound to the rP1R, CNBr cleavage of the broad approximate to 80-kDa complex yielded a radiolabeled approximate to 9-kDa nonglycosylated protein band that could potentially be assigned to rP1R residues 23-63, Tyr(23) being the presumed amino-terminus of the receptor. This assignment was confirmed using a mutant rP1R (rP1R-M63I) that yielded, upon photoligand binding and CNBr digestion, a broad protein band of approximate to 46 kDa, which was reduced to a sharp band of approximate to 20 kDa upon deglycosylation, CNBr digestion of complexes formed with two additional rP1R double mutants (rP1R-M63I/L40M and rP1R-M63I/L41M) yielded non-glycosylated protein bands that were approximate to 6 kDa in size, indicating that [Bpa23]PTHrP cross-links to amino acids 23-40 of the rP1R, This segment overlaps a receptor region previously identified by deletion mapping to be important for ligand binding. Alanine scanning of this region revealed two residues, Thr(33) and Gln(37), as being functionally involved in ligand binding. Thus, the convergence of photoaffinity cross-linking and mutational data demonstrates that the extreme amino-terminus of the rP1R participates in ligand binding. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Childrens Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Wellman 503,50 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-11794] NR 33 TC 88 Z9 88 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 JUL 3 PY 1998 VL 273 IS 27 BP 16890 EP 16896 DI 10.1074/jbc.273.27.16890 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZX700 UT WOS:000074545200040 PM 9642250 ER PT J AU Conrad, C Amano, N Andreadis, A Xia, Y Namekataf, K Oyama, F Ikeda, K Wakabayashi, K Takahashi, H Thal, LJ Katzman, R Shackelford, DA Matsushita, M Masliah, E Sawa, A AF Conrad, C Amano, N Andreadis, A Xia, Y Namekataf, K Oyama, F Ikeda, K Wakabayashi, K Takahashi, H Thal, LJ Katzman, R Shackelford, DA Matsushita, M Masliah, E Sawa, A TI Differences in a dinucleotide repeat polymorphism in the tau gene between Caucasian and Japanese populations: implication for progressive supranuclear palsy SO NEUROSCIENCE LETTERS LA English DT Article DE tau; dinucleotide repeat; chromosome 17; intron; exon 10; progressive supranuclear palsy; Alzheimer's disease; Japanese; Caucasian ID PROTEINS; EXONS AB Previous studies of a tau polymorphism in Caucasian subjects with progressive supranuclear palsy (PSP) showed an overrepresentation of one genotype, A0/A0, versus normal control subjects. This result suggested that tau may be playing a genetic role in the progression of PSP. This study examines whether the over-representation of A0/A0 is Caucasian-specific or universal to PSP. Unfortunately, we found this dinucleotide repeat was relatively non-polymorphic in Japanese subjects. As a result, the genotypes were virtually the same, A0/A0, between Japanese PSP and control subjects. However, this outcome, albeit negative, does suggest two possible roles of the tau gene in PSP pathogenesis: (1) the role of this dinucleotide repeat in PSP may be different between Caucasian and Japanese populations or (2) this repeat may not be causal for PSP but represents a marker for other molecular genetic risk factors within or close to the tau gene on chromosome 17. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. Univ Tokyo, Fac Med, Dept Neuropsychiat, Tokyo 113, Japan. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Dept Biomed Sci, Waltham, MA 02116 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02116 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02116 USA. Univ Tokyo, Fac Med, Dept Neuropathol, Tokyo 113, Japan. Tokyo Inst Psychiat, Dept Neuropathol, Tokyo 157, Japan. Niigata Univ, Brain Res Inst, Brain Dis Res Ctr, Niigata 951, Japan. Niigata Univ, Brain Res Inst, Dept Pathol, Niigata 951, Japan. RP Sawa, A (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, 725 N Wolfe St, Baltimore, MD 21205 USA. OI Oyama, Fumitaka/0000-0002-1095-8306 FU NIA NIH HHS [P50-AG05131]; NINDS NIH HHS [NS28121] NR 20 TC 37 Z9 38 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 3 PY 1998 VL 250 IS 2 BP 135 EP 137 DI 10.1016/S0304-3940(98)00417-0 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 106AY UT WOS:000075108600016 PM 9697937 ER PT J AU Kaelin, WG AF Kaelin, WG TI Carcinogenesis - Another p53 Doppelganger? SO SCIENCE LA English DT Editorial Material C1 Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 11 TC 29 Z9 29 U1 0 U2 1 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 JUL 3 PY 1998 VL 281 IS 5373 BP 57 EP 58 DI 10.1126/science.281.5373.57 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZZ009 UT WOS:000074685800034 PM 9679018 ER PT J AU Weaver, DT AF Weaver, DT TI Telomeres: Moonlighting by DNA repair proteins SO CURRENT BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; V(D)J RECOMBINATION; BINDING PROTEIN; YEAST TELOMERE; RAP1 AB Chromosome ends, or telomeres, are dynamic DNA structures maintained by a multisubunit telomerase and other proteins. New evidence indicates that proteins previously implicated in the repair of DNA double-strand breaks also play an important role in the control of telomere organization and length. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Weaver, DT (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 24 TC 16 Z9 16 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 2 PY 1998 VL 8 IS 14 BP R492 EP R494 DI 10.1016/S0960-9822(98)70315-X PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZY173 UT WOS:000074593600010 PM 9663383 ER PT J AU Tzivion, G Luo, ZJ Avruch, J AF Tzivion, G Luo, ZJ Avruch, J TI A dimeric 14-3-3 protein is an essential cofactor for Raf kinase activity SO NATURE LA English DT Article ID 14-3-3-PROTEINS; ACTIVATION; C-RAF-1; IDENTIFICATION; PATHWAY; BINDING AB cRaf-1 is a mitogen-activated protein kinase that is the main effector recruited by GTP-bound Ras in order to activate the MAP kinase pathway(1). Inactive Raf is found in the cytosol in a complex with Hsp90, Hsp50 (Cdc37)(2,3) and the 14-3-3 proteins(4). GTP-bound Ras binds Raf and is necessary but not sufficient for the stable activation of Raf that occurs in response to serum, epidermal growth factor, platelet-derived growth factor or insulin(5-8). These agents cause a two- to threefold increase in overall phosphorylation of Raf on serine/threonine residues(8,9), and treatment of cRaf-1 with protein (serine/threonine) phosphatases can deactivate it, at least partially(10). The role of 14-3-3 proteins in the regulation of Raf's kinase activity is uncertain(4,11) and is investigated here. Active Raf can be almost completely deactivated in vitro by displacement of 14-3-3 using synthetic phosphopeptides. Deactivation can be substantially reversed by addition of purified recombinant bacterial 14-3-3; however, Raf must have been previously activated in vivo to be reactivated by 14-3-3 in vitro. The ability of 14-3-3 to support Raf activity is dependent on phosphorylation of serine residues on Raf and on the integrity of the 14-3-3 dimer; mutant monomeric forms of 14-3-3, although able to bind Raf in vivo, do not enable Raf to be activated in vivo or restore Raf activity after displacement of 14-3-3 in vitro. The 14-3-3 protein is not required to induce dimerization of Raf, We propose that dimeric 14-3-3 is needed both to maintain Raf in an inactive state in the absence of GTP-bound Ras and to stabilize an active conformation of Raf produced during activation in vivo. C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. EM avruch@helix.mgh.harvard.edu RI Tzivion, Guri/D-8954-2011 NR 28 TC 332 Z9 336 U1 0 U2 8 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 2 PY 1998 VL 394 IS 6688 BP 88 EP 92 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZY030 UT WOS:000074579600055 PM 9665134 ER PT J AU Kahn, JO Walker, BD AF Kahn, JO Walker, BD TI Acute human immunodeficiency virus type 1 infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID PRIMARY HIV-1 INFECTION; T-LYMPHOCYTE ACTIVITY; ORAL INTERCOURSE; DISEASE; SEROCONVERSION; VIREMIA; PLASMA; RESPONSES; RECEPTOR; CELLS C1 San Francisco Gen Hosp, AIDS Program, San Francisco, CA 94110 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [P30 AI 27763, R37 AI28568]; PHS HHS [UO1 41531] NR 81 TC 373 Z9 387 U1 1 U2 13 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 2 PY 1998 VL 339 IS 1 BP 33 EP 39 DI 10.1056/NEJM199807023390107 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZX285 UT WOS:000074500000007 PM 9647878 ER PT J AU Tsuji, T Todd, R Meyer, C McBride, J Liao, PH Huang, MF Chou, MY Donoff, RB Wong, DTW AF Tsuji, T Todd, R Meyer, C McBride, J Liao, PH Huang, MF Chou, MY Donoff, RB Wong, DTW TI Reduction of ornithine decarboxylase antizyme (ODC-Az) level in the 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis model SO ONCOGENE LA English DT Article DE oral cancer; hamster; ornithine decarboxylase antizyme; proliferation; subtractive hybridization ID POLYAMINE LEVELS; NECK-CANCER; GENE; EXPRESSION; HEAD; DEGRADATION; CARCINOMA; LESIONS; TUMORS; TISSUE AB Ornithine decarboxylase (ODC) activity is elevated in and necessary for oral carcinogenesis, but the mechanism for its deregulation is unclear. Using subtractive hybridization, a 1029 bp full-length cDNA encoding a 222 amino acid open reading frame has been isolated from normal hamster oral keratinocytes. The hamster cDNA is homologous to the human, mouse and rat ornithine decarboxylase antizyme gene (ODC-Az). The hamster ODC-Az gene demonstrated a restriction fragment length polymorphism (RFLP) upon Southern blot analysis comparing normal and tumor hamster genomic DNA. Northern blot analysis revealed that normal hamster oral keratinocytes express readily detectable level of ODC-Az mRNA. Malignant oral keratinocytes demonstrate reduced expression of the ODC-Az mRNA, In contrast, malignant hamster oral keratinocytes have elevated ODC mRNA levels and lengthened ODC protein half-life when compared to the normal counterparts, This mas corroborated by direct measurement of ODC enzymatic activity. These data support the hypothesis that the reduced and/or loss of expression and function of the ODC-Az gene is an important event for the early de-regulation of cellular proliferation during oral tumor development. C1 Harvard Univ, Sch Dent Med, Div Oral Pathol, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Harvard Univ, Sch Dent Med, Div Oral Pathol, Dept Oral Med & Diagnost Sci, 188 Longwood Ave, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-00318, DE-08680, P01 DE-12467] NR 41 TC 23 Z9 27 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JUL 2 PY 1998 VL 16 IS 26 BP 3379 EP 3385 DI 10.1038/sj.onc.1201887 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZX689 UT WOS:000074544100004 PM 9692545 ER PT J AU Tsao, HS Zhang, X Benoit, E Haluska, FG AF Tsao, HS Zhang, X Benoit, E Haluska, FG TI Identification of PTEN/MMAC1 alterations in uncultured melanomas and melanoma cell lines SO ONCOGENE LA English DT Article DE cancer; genetics; mutation; PTEN/MMAC1; melanoma ID PRIMARY CUTANEOUS MELANOMA; FAMILIAL MELANOMA; HETEROZYGOSITY; DELETIONS; MUTATIONS; GLIOMAS; NEVI; P16 AB A novel tumor suppressor gene, PTEN/MMAC1, has been recently shown to be mutated in gliomas, breast, prostate, kidney cancers and melanomas, Loss-of-heterozygosity studies in melanoma have suggested the presence of at least one chromosome 10q locus lost early in tumor progression. In this study, we screened 45 melanoma cell lines and 17 paired uncultured metastatic melanoma and peripheral blood specimens for PTEN/MMAC1 alterations using PCR-SSCP and direct sequencing. We found nine melanoma cell lines with homozygous deletions (five with intragenic loss) and four cell lines with mutations (one nonsense and one frameshift; two intronic); from among our uncultured melanoma specimens, me found one tumor with a somatic 17 bp duplication in exon 7 leading to a premature stop codon and one tumor with a possible homozygous deletion. Furthermore, we ha ce identified a novel intragenic polymorphism within intron 4 of PTEN/MMAC1. Taken together, these data suggest that PTEN/MMAC1 may be a chromosome 10q tumor suppressor important in melanoma turner formation or progression. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Dana Farber Partners Canc Care, Boston, MA 02114 USA. RP Haluska, FG (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [5T32AR07098-23] NR 30 TC 164 Z9 164 U1 0 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 2 PY 1998 VL 16 IS 26 BP 3397 EP 3402 DI 10.1038/sj.onc.1201881 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZX689 UT WOS:000074544100006 PM 9692547 ER PT J AU Nagurney, JT Borczuk, P Thomas, SH AF Nagurney, JT Borczuk, P Thomas, SH TI Elder patients with closed head trauma: A comparison with nonelder patients SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 19-22, 1997 CL WASHINGTON, D.C. SP Soc Acad Emergency Med DE geriatrics; aged; accidents; neurosurgery; head injuries, closed; trauma ID COMPUTED-TOMOGRAPHY; BRAIN INJURY AB Objective: Little is known about the circumstances surrounding closed head trauma (CHT) in elders, and how they differ from nonelders. The study objective was to compare the 2 populations for outcome (positive cranial CT scan depicting traumatic injury, or the need for neurosurgery), mechanism of injury, and the value of the neurologic examination to predict a CT scan positive for traumatic injury or the need for neurosurgical intervention. Methods: A retrospective study was conducted by collecting a case series of patients with blunt head trauma who underwent CT scanning, and comparing elder (aged greater than or equal to 60 years) with nonelder patients. The setting was the ED of a university-affiliated Level-1 trauma center. Results: Twenty percent of the elders and 13% of the nonelders had CT scans positive for traumatic injury, which conferred a risk ratio of 1.58 (95% CI 1.21-2.05). Older women were more at risk for the need for neurosurgery than were younger ones (3.1 vs 0.3%, RR 10.66, 95% CI 1.26-90.46). Among the elders, falls were the dominant mechanism of closed head trauma, followed by motor vehicle collisions (MVCs), then being struck as a pedestrian. In the nonelders, MVCs, falls, and assaults were the most important mechanisms of injury. A focally abnormal neurologic examination imparted an increased risk for both a CT scan positive for traumatic injury (elder 4.39, 95% CI 2.91-6.62; nonelder 7.75, 95% CI 5.53-10.72) and the need for neurosurgery (elder 35.68, 95% CI 4.58-275.89; nonelder 142.58, 95% CI 19.11-1064.22) in both age groups. Conclusions: Significant differences exist between elder and nonelder victims of CHT with respect to mechanisms of trauma and outcomes (CT scan positive for traumatic injury, or the need for neurosurgery). C1 Massachusetts Gen Hosp, Clin 117, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Clin 117, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA. EM nagurney.john@mgh.harvard.edu NR 17 TC 22 Z9 22 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUL PY 1998 VL 5 IS 7 BP 678 EP 684 PG 7 WC Emergency Medicine SC Emergency Medicine GA 100KJ UT WOS:000074815100006 PM 9678391 ER PT J AU Woodruff, PG Emond, SD Singh, AK Camargo, CA AF Woodruff, PG Emond, SD Singh, AK Camargo, CA TI Sudden-onset severe acute asthma: Clinical features and response to therapy SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE asthma; status asthmaticus; peak expiratory flow rate; time factors ID PRECIPITATING FACTOR AB Objectives: To characterize patients with sudden onset of severe acute asthma (SAA) and to examine whether this presentation is associated with rapid recovery. Methods: Retrospective cohort study of ED visits to a teaching hospital. Subjects were aged 18-64 years, with SAA (n = 225), defined as initial peak expiratory flow rate (PEFR) less than or equal to 40% of predicted. Visits for sudden-onset SAA (less than or equal to 3 hours of symptoms) were characterized and multivariate logistic regression was used to examine the association between sudden onset and rapid recovery. Results: Patient visits for sudden-onset SAA had different triggers as compared with those for the slower-onset group (p = 0.006). The sudden-onset patients were less likely to report an upper-respiratory-tract infection (17% vs 40%) and more likely to have an unidentifiable trigger (40% vs 19%). In the multivariate logistic regression model, sudden onset was a strong independent predictor of rapid response [odds ratio (OR) 4.3, 95% confidence interval (CI) 1.6-11.6]. Sudden-onset visits were less likely to lead to admission (23% vs 43%, p = 0.03). Conclusions: These data suggest that different triggers may be involved in sudden-onset SAA and that sudden onset of symptoms is independently associated with rapid recovery. In their rapid deterioration and rapid response, these subjects share certain characteristics with "sudden asphyxic asthmatics" and may constitute a population suitable for further study of factors contributing to that condition. While these visits led to admission less frequently, prospective studies are necessary to provide information on duration of response and risk for relapse. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. Columbia Univ, St Lukes Roosevelt Hosp Ctr, Dept Emergency Med, New York, NY USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin Bldg 116, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-03533, HL-07427] NR 18 TC 22 Z9 22 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUL PY 1998 VL 5 IS 7 BP 695 EP 701 PG 7 WC Emergency Medicine SC Emergency Medicine GA 100KJ UT WOS:000074815100009 PM 9678394 ER PT J AU Magnusson, AR Hedges, JR Ashley, P Harper, RJ AF Magnusson, AR Hedges, JR Ashley, P Harper, RJ TI Resident educational time study: A tale of three specialties SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 19-22, 1997 CL WASHINGTON, D.C. SP Soc Acad Emergency Med DE graduate medical education; resident; training; clinical practice; time study ID INTERNAL-MEDICINE; WORKING HOURS; CALL AB Objective: To compare amounts of in-hospital time use by PGY1 residents during rotations in emergency medicine (EM), internal medicine (IM), and surgery. This article reports the general study methodology and focuses on the educational aspects of residency time use. Methods: A cross-sectional, observational study of the activities of Ehl PGY1 residents was performed while the residents were on duty during the 3 specialty rotations. The activities were recorded by an observer using a log with predetermined categories for clinical/service, educational, and personal areas. A time-blocked, convenience sample of resident shifts was observed for each service rotation. The sample was proportional Do the total number of hours for which a PGY1 resident was expected to be in the hospital during a rotation on that service. No attempt was made to sample the same resident at all time periods or on all rotations. Results: Twelve PGY1 residents were observed for a total of 166 hours on surgery, 156 hours on IM, and 120 hours on EM. These hourly amounts were representative of a typical 2-week span of service on each rotation for the residents. On average, the residents spent 57% of their time on clinical or service-oriented activities, 24% on educational activities, and 19% on personal activities. The proportions of time devoted to the 3 major areas were similar for the 3 rotations. In all 3 rotations, the largest proportion of time was spent on patient-focused education (81% to 92% of total educational time). Only 2% to 11% of educational time was devoted to self-education. Within the patient-focused education category, proportionately less resident time with faculty occurred on the surgery rotation than on the EM and IM rotations (18% vs 30% and 27%, respectively). Conclusion: The general breakdowns of clinical/service, educational, and personal time use by PGY1 residents are proportionately similar for the 3 service rotations. Patient-focused education is the primary mode of education for all services. In-hospital, self-education time is limited. Clinical teaching is largely by nonfaculty. The educational implications of these findings are discussed. C1 Oregon Hlth Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Sch Med, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Emergency Care Unit, Portland, OR USA. RP Hedges, JR (reprint author), Oregon Hlth Sci Univ, Dept Emergency Med, 3181 SW Jackson Pk Rd,UHN 52, Portland, OR 97201 USA. NR 14 TC 7 Z9 7 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUL PY 1998 VL 5 IS 7 BP 718 EP 725 PG 8 WC Emergency Medicine SC Emergency Medicine GA 100KJ UT WOS:000074815100012 PM 9678397 ER PT J AU Block, S Billings, JA AF Block, S Billings, JA TI Nurturing humanism through teaching palliative care SO ACADEMIC MEDICINE LA English DT Article AB After many years of neglect by the medical establishment, the discipline of palliative medicine is finally moving into academic health centers (AHCs). While hospice programs have cared for dying patients in the community for years with little input from mainstream medicine, palliative care is gaining a foothold in: AHCs, challenging these centers to integrate the hospice approach with biomedicine. The discipline of palliative care promises to be a rich source of learning and growth for physicians-in-training. Teaching about palliative care affirms two essential but vulnerable dimensions of the practice of medicine-the importance of relationship-centered care and the value of doctoring as a source of meaning and growth for physicians. In addition to fostering fundamental humanistic learning, palliative medicine is an excellent vehicle for teaching basic but often neglected clinical competencies, including pain and Symptom control, communication, and working as part of a health care team. Because palliative care settings offer extraordinary learning opportunities, the authors recommend that clinical experiences in palliative care be integrated into the core curricula of all medical schools as well as appropriate residency programs. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Med Serv, Gen Internal Med Unit, Palliat Care Serv, Boston, MA 02114 USA. RP Block, S (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 126 Brookline Ave, Boston, MA 02215 USA. EM sblock@warren.med.harvard.edu FU NCI NIH HHS [R25CA 66818-01] NR 12 TC 25 Z9 25 U1 2 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 1998 VL 73 IS 7 BP 763 EP 765 DI 10.1097/00001888-199807000-00012 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 101MW UT WOS:000074873600015 PM 9679465 ER PT J AU Sox, CM Burstin, HR Orav, EJ Conn, A Setnik, G Rucker, DW Dasse, P Brennan, TA AF Sox, CM Burstin, HR Orav, EJ Conn, A Setnik, G Rucker, DW Dasse, P Brennan, TA TI The effect of supervision of residents on quality of care in five university-affiliated emergency departments SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT 19th Annual National Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 1996 CL WASHINGTON, D.C. SP Soc Gen Internal Med AB Purpose. To assess the impact of direct supervision of resident physicians by attending physicians on quality of care in emergency departments. Method. In 1993, compliance with process-of-care guidelines was measured for 3,667 patients cared for by residents in five emergency departments in Boston and Cambridge, Massachusetts. Those patients presented with abdominal pain, asthma/COPD, chest pain, hand laceration, head trauma, or vaginal bleeding. A follow-up survey to assess patient satisfaction and reported problems with care was completed by 1,094 randomly sampled patients. Results. In multivariate analysis, residents directly supervised by attending physicians had significantly (p < .0001) higher adjusted mean percentage compliance with guidelines (64%) than did residents alone (55%). Better compliance was also associated with higher level of training of the resident and greater patient urgency. There was no significant difference between supervised and unsupervised residents in either adjusted patient satisfaction or reported problems with care. Conclusions. Direct supervision of residents in emergency departments is significantly associated with better compliance with guidelines, regardless of level of training. However, direct supervision was not shown to influence patients' experience with care. C1 Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA. Univ Calif San Francisco Hosp, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Auburn Hosp, Cambridge, MA 02138 USA. Beth Israel Hosp, Div Emergency Med, Boston, MA 02215 USA. Brigham & Womens Phys Hosp Org, Boston, MA 02115 USA. RP Brennan, TA (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. EM tabrennen@bics.bwh.harvard.edu NR 13 TC 50 Z9 51 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 1998 VL 73 IS 7 BP 776 EP 782 DI 10.1097/00001888-199807000-00017 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 101MW UT WOS:000074873600019 PM 9679467 ER EF