FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Spencer, T Biederman, J Coffey, B Geller, D Wilens, T Faraone, S AF Spencer, T Biederman, J Coffey, B Geller, D Wilens, T Faraone, S TI The 4-year course of tic disorders in boys with attention-deficit/hyperactivity disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; LA-TOURETTES SYNDROME; OBSESSIVE-COMPULSIVE DISORDER; NERVOUS-SYSTEM STIMULANTS; BIPOLAR DISORDER; CHILDREN; METHYLPHENIDATE; FAMILY; ADHD; ADOLESCENTS AB Background: Despite long-standing clinical concerns, relatively little is known about the comorbidity between attention-deficit/hyperactivity disorder (ADHD) and tic disorders. Therefore, we examined tic disorders in an ongoing prospective follow-up study of male subjects with ADHD, a sample unselected for ally comorbid disorder. Methods: One hundred twenty-eight male children and adolescents with ADHD and 110 male controls were comprehensively evaluated at baseline and 4 years later. We characterized tic disorders along with a nide range of neuropsychiatric correlates, including other comorbid disorders and indices of psychosocial function in multiple domains (school, cognitive, social, and family). Results: Compared with controls, subjects with ADHD showed more tic disorders at baseline and more new on-sets were reported at follow-up. Attention-deficit/hyperactivity disorder and tic disorders appeared to be independent in course: in contrast to low rates of ADHD remission, tic disorders mostly remitted. The age-adjusted rate of ADHD remission was 20% and that of tic remission, 65%. Tic disorders had little effect on the psychosocial functioning of subjects with ADHD. Conclusions: These findings suggest that comorbidity with a tic disorder has a limited effect on ADI-ID outcome.. However, because of the relatively small sample of subjects with tic disorders, our conclusions should be considered preliminary until confirmed in larger studies of medicated and unmedicated children with ADHD with and without tic disorders. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC725, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. McLean Hosp, Tourettes Syndrome Clin, Belmont, MA 02178 USA. RP Spencer, T (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC725, Psychiat Serv, Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K20 MH01169-01] NR 49 TC 50 Z9 51 U1 1 U2 3 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 SEP PY 1999 VL 56 IS 9 BP 842 EP 847 DI 10.1001/archpsyc.56.9.842 PG 6 WC Psychiatry SC Psychiatry GA 232PK UT WOS:000082379000009 PM 12884890 ER PT J AU Jeste, DV Alexopoulos, GS Bartels, SJ Cummings, JL Gallo, JJ Gottlieb, GL Halpain, MC Palmer, BW Patterson, TL Reynolds, CF Lebowitz, BD AF Jeste, DV Alexopoulos, GS Bartels, SJ Cummings, JL Gallo, JJ Gottlieb, GL Halpain, MC Palmer, BW Patterson, TL Reynolds, CF Lebowitz, BD TI Consensus statement on the upcoming crisis in geriatric mental health - Research agenda for the next 2 decades SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Workshop on the Future of Mental Health and Aging CY MAR 11, 1998 CL SAN DIEGO, CALIFORNIA ID PRIMARY-CARE PATIENTS; OLDER ADULTS; COMMUNITY POPULATION; ALZHEIMERS-DISEASE; LATER LIFE; DEPRESSION; SERVICES; PREVALENCE; SCHIZOPHRENIA; DEMENTIA AB It is anticipated that the number of people older than 65 years with psychiatric disorders in the United States will increase from about 4 million in 1970 to 15 million in 2030, The current health care system serves mentally ill older adults poorly and is unprepared to meet the upcoming crisis in geriatric mental health. We recommend the formulation of a 15- to :25-year plan for research on mental disorders in elderly persons. It should include studies of prevention, translation of findings from bench to bedside, large-scale intervention trials with meaningful outcome measures, and health services research. Innovative strategies are needed to formulate new conceptualizations of psychiatric disorders, especially those given scant attention in the past. New methods of clinical and research training involving specialists, primary care clinicians, and the lay public are warranted. C1 Univ Calif San Diego, San Diego, CA 92103 USA. VA San Diego Healthcare Syst, San Diego, CA USA. Cornell Univ, Med Ctr, White Plains, NY 10605 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Johns Hopkins Univ, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NIMH, Rockville, MD 20857 USA. RP Jeste, DV (reprint author), Univ Calif San Diego, San Diego, CA 92103 USA. NR 64 TC 324 Z9 327 U1 7 U2 14 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 SEP PY 1999 VL 56 IS 9 BP 848 EP 853 DI 10.1001/archpsyc.56.9.848 PG 6 WC Psychiatry SC Psychiatry GA 232PK UT WOS:000082379000010 PM 12884891 ER PT J AU Chen, TC Walton, DS AF Chen, TC Walton, DS TI Goniosurgery for prevention of aniridic glaucoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 134th Annual Meeting of the American-Ophthalmological-Society CY MAY 19, 1998 CL HOT SPRINGS, VIRGINIA SP Amer Ophthalmol Soc AB Objective: To report the long-term success and complications of modified goniosurgery to prevent aniridic glaucoma, an entity that typically is difficult to control medically or surgically. Design: A retrospective review of the medical charts. Results: Fifty-five eyes in 33 patients who had aniridia without glaucoma and who underwent goniosurgery were identified. Ninety-one procedures were performed on the SS eyes by 1 surgeon (D.S.W.). Each eye had an average of 1.65 procedures and an average of 200 degrees of goniosurgery. Average age at time of initial goniosurgery was 36.6 months. There were no operative complications. No eye had a decrease in visual acuity at last follow-up. All eyes had a preoperative intraocular pressure (IOP) less than 21 mm Hg. At last follow-up (average, 9 years 6 months; range, 8 months to 24 years), 49 eyes (89%) had IOPs less than 22 mm Hg without medications. The remaining 6 eyes (11%) had IOPs of 22 nlm Hg or less with up to 2 types of eyedrops. Conclusions: Without prophylactic goniotomy, aniridic glaucoma may be expected in half of patients, and when it occurs, it is extremely difficult to control. Prophylactic goniosurgery in selected eyes of young patients with aniridia may be effective in preventing aniridic glaucoma. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Chen, TC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv,Dept Ophthalmol, 1st Floor,243 Charles St, Boston, MA 02114 USA. NR 16 TC 17 Z9 19 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1999 VL 117 IS 9 BP 1144 EP 1148 PG 5 WC Ophthalmology SC Ophthalmology GA 234ZE UT WOS:000082513600004 PM 10496385 ER PT J AU Miller, JW Schmidt-Erfurth, U Sickenberg, M Pournaras, CJ Laqua, H Barbazetto, I Zografos, L Piguet, B Donati, G Lane, AM Birngruber, R van den Berg, H Strong, HA Manjuris, U Gray, T Fsadni, M Bressler, NM Gragoudas, ES AF Miller, JW Schmidt-Erfurth, U Sickenberg, M Pournaras, CJ Laqua, H Barbazetto, I Zografos, L Piguet, B Donati, G Lane, AM Birngruber, R van den Berg, H Strong, HA Manjuris, U Gray, T Fsadni, M Bressler, NM Gragoudas, ES TI Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration - Results of a single treatment in a phase 1 and 2 study SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 11-17, 1997 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID LIPOPROTEIN-DELIVERED BENZOPORPHYRIN; TUMOR; MACULOPATHY; PREVALENCE AB Objective: To evaluate the safety and short-term visual and fluorescein angiographic effects of a single photodynamic therapy treatment with verteporfin with the use of different dosage regimens in patients with choroidal neovascularization (CNV) from age-related macular degeneration. Design: Nonrandomized, multicenter, open-label, clinical trial using 5 dosage regimens. Setting: Four ophthalmic centers in North America and Europe providing retinal care. Participants: Patients with subfoveal CNV caused by age-related macular degeneration. Methods: Standardized protocol refraction, visual acuity testing, ophthalmic examination, color photographs, and fluorescein angiograms were used to evaluate the effects of a single treatment of photodynamic therapy with verteporfin. Follow-up was planned through 3 months in 97 patients and for less than 3 months in 31 other patients. Results: The mean visual acuity change (and range of change) from baseline at the follow-up examination at week 12 after a single treatment with regimens 1 through 5 was -0.2 (-3 to +2), -0.9 (-9 to +5);, -1.6 (-9 to +2), +0.4 (-8 to +7), and +0.1 (-8 to +9) lines, respectively. Only the highest light dose (150J/cm(2)) in regimens 2 and 3, which produced angiographic nonperfusion of neurosensory retinal vessels, caused marked vision loss. Some cessation of fluorescein leakage from CNV was achieved without loss of vision when the light dose used was less than 150J/cm(2). Systemic adverse events were rare. Cessation of fluorescein leakage from CNV was noted in all regimens by 1 week after photodynamic therapy. Fluorescein leakage from at least a portion of the CNV reappeared by 4 to 12 weeks after treatment in almost all cases. Progression of classic CNV beyond the area of CNV identified before treatment was noted in 42 (51%) of the 83 eyes with classic CNV followed up for 3 months after a single treatment. Eyes in which the area of any CNV leakage at 12 weeks was less than at baseline had a significantly better visual acuity outcome (+0.8 line) than eyes in which CNV leakage progressed (-0.8 line). Conclusions: Photodynamic therapy with verteporfin achieved short-term cessation of fluorescein leakage from CNV without loss of vision or growth of classic CNV in some patients with age-related macular degeneration. Except for nonperfusion of neurosensory retinal vessels at a light dose of 150 J/cm(2), no other adverse events were of concern. Randomized clinical trials to investigate whether this new modality can preserve vision in patients with CNV secondary to age-related macular degeneration are justified. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Laser Res Lab, Boston, MA 02114 USA. Univ Lubeck, Hosp Eye, Retina Dept, D-2400 Lubeck, Germany. Hop Ophtalm Jules Gonin, Lausanne, Switzerland. Hop Cantonal Univ Geneva, Dept Otoneuroophthalmol, Geneva, Switzerland. Ecole Polytech Fed Lausanne, Dept Environm Engn, Lab Air Pollut Studies, Lausanne, Switzerland. QLT PhotoTherapeut Inc, Vancouver, BC, Canada. CIBA Vis Inc, Duluth, MN USA. CIBA Vis AG, Bulach, Switzerland. Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Wilmer Ophthalmol Inst, Baltimore, MD USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Laser Res Lab, 243 Charles St, Boston, MA 02114 USA. RI Birngruber, Reginald/Q-2342-2016 NR 35 TC 210 Z9 222 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1999 VL 117 IS 9 BP 1161 EP 1173 PG 13 WC Ophthalmology SC Ophthalmology GA 234ZE UT WOS:000082513600007 PM 10496388 ER PT J AU Schmidt-Erfurth, U Miller, JW Sickenberg, M Laqua, H Barbazetto, I Gragoudas, ES Zografos, L Piguet, B Pournaras, CJ Donati, G Lane, AM Birngruber, R van den Berg, H Strong, HA Manjuris, U Gray, T Fsadni, M Bressler, NM AF Schmidt-Erfurth, U Miller, JW Sickenberg, M Laqua, H Barbazetto, I Gragoudas, ES Zografos, L Piguet, B Pournaras, CJ Donati, G Lane, AM Birngruber, R van den Berg, H Strong, HA Manjuris, U Gray, T Fsadni, M Bressler, NM TI Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration - Results of retreatments in a phase 1 and 2 study SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 23-29, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Ophthalmol ID RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; BENZOPORPHYRIN; MACULOPATHY AB Objectives: To evaluate safety and short-term visual acuity and fluorescein angiographic effects of photodynamic therapy (PDT) after retreatments with verteporfin for choroidal neovascularization (CNV) in age-related macular degeneration (AMD) that demonstrated fluorescein leakage after at least 1 course of PDT, Design: Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens. Setting: Four ophthalmic centers in Europe and North America providing retinal care. Methods: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of multiple PDT treatments. Two regimens (regimens 2 and 4) for treatment and retreatment were chosen from 5 used in a single-treatment study. Both regimens used a verteporfin dose of 6 mg/m(2) infused for 10 minutes. However, regimen 2 used a light dose of 100 J/cm(2) applied 20 minutes after the start of the verteporfin infusion, whereas regimen 4 used a light dose of 50, 75, or 100 J/cm(2) applied 15 minutes after infusion commenced. Posttreatment evaluations were planned in 31 participants up to 3 months after up to 2 retreatments given at 2- or 4-week intervals after initial PDT treatment. Similar posttreatment evaluations were planned after retreatments in 5 additional participants who were reenrolled some time more than 12 weeks after an initial PDT treatment. Results: The average visual acuity change for the 31 participants who had retreatment within 2 to 4 weeks after the initial treatment and a follow-up examination 16 to 20 weeks after the initial treatment was 0.2 lines (range, -4 to 4 lines) in regimen 2 and -1.0 line (range, - 5 to 3 lines) in regimen 4. Similar outcomes were noted in the 5 reenrolled participants. Cessation of fluorescein leakage from classic CNV for at least 1 to 4 weeks could be achieved without loss of visual acuity after at least 2 treatments in 2 (6.5%) of 31 patients. Similar to single-treatment effects, the disappearance of leakage was documented regularly at 1 week after each retreatment. Fluorescein leakage reappeared by 4 to 12 weeks after a retreatment in almost all cases. However, compared with baseline, leakage activity appeared to be reduced after multiple PDT courses. For the 31 patients who had follow-up for 3 months after the last retreatment and had received retreatment 2 to 4 weeks after the initial treatment, progression of CNV beyond the area identified before the retreatment was noted in 10 (48%) of the 21 eyes with classic CNV in regimen 2 and 9 (90%) of 10 eyes in regimen 4. The rate and severity of ocular or systemic adverse events were not increased by multiple applications. Conclusions: Multiple applications of PDT with verteporfin achieve repetitive, short-term cessation of fluorescein leakage from CNV secondary to AMD, without loss of visual acuity. This strategy can be used in randomized clinical trials investigating the efficacy of verteporfin in PDT for recurrent fluorescein dye leakage from persistent or recurrent CNV, following an initial or subsequent PDT treat ment, with maintenance of visual acuity. Retreatments may achieve progressive cessation of leakage and prevent further growth of CNV and subsequent visual loss. C1 Univ Lubeck, Hosp Eye, Retina Dept, D-23538 Lubeck, Germany. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA USA. Hop Ophtalm Jules Gonin, Lausanne, Switzerland. Hop Cantonal Univ Geneva, Dept Otoneuroophthalmol, Geneva, Switzerland. Ecole Polytech Fed Lausanne, Dept Environm Engn, Lab Air Pollut Studies, Lausanne, Switzerland. QLT Phototherapeut Inc, Vancouver, BC, Canada. CIBA Vis Inc, Duluth, MN USA. CIBA Vis AG, Bulach, Switzerland. Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Wilmer Ophthalmol Inst, Baltimore, MD USA. RP Schmidt-Erfurth, U (reprint author), Univ Lubeck, Hosp Eye, Retina Dept, Ratzeburger Allee 160, D-23538 Lubeck, Germany. RI Birngruber, Reginald/Q-2342-2016 NR 25 TC 217 Z9 231 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1999 VL 117 IS 9 BP 1177 EP 1187 PG 11 WC Ophthalmology SC Ophthalmology GA 234ZE UT WOS:000082513600008 PM 10496389 ER PT J AU Pins, MR Ferrell, MA Madsen, JC Piubello, Q Dickersin, GR Fletcher, CDM AF Pins, MR Ferrell, MA Madsen, JC Piubello, Q Dickersin, GR Fletcher, CDM TI Epithelioid and spindle-celled leiomyosarcoma of the heart - Report of 2 cases and review of the literature SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PRIMARY SARCOMAS; TUMORS AB Background,-Primary cardiac leiomyosarcomas are rare. isolated reported cases and small series generally describe spindle-celled, high-grade tumors with poor shortterm survival; however, the pathologic features of many of these tumors are incompletely documented. The authors report in detail the clinicopathologic features of 2 relatively low-grade epithelioid and spindle-celled primary cardiac leiomyosarcomas. Methods.-Cases 1 and 2 were studied using standard histochemical and immunohistochemical techniques, and case 1 was examined by electron microscopy. The literature was reviewed with regard to primary cardiac leiomyosarcomas. Results.-Both tumors showed epithelioid and spindle-celled areas. The tumor in case 1 was low grade, and the tumor in case 2 was predominately low grade with a high- grade focus. A review of 28 reported cases revealed a wide age range (mean, 43 years), equal male-to-female ratio, and a predilection for the left atrium (48%). Follow-up of reported cases with fewer than 5 mitoses per 10 high-power fields showed a mean survival of 22 months compared with a 9-month mean survival for all others. Conclusions.-Short-term follow-up of reported cases of high-grade cardiac leiomyosarcoma suggests a poor prognosis. Long-term follow-up in our case 2, along with follow-up of reported cases that were histologically similar to our cases, suggests that cardiac leiomyosarcomas with lowgrade Features or mixed low- and high-grade features also have a poor overall long-term survival, with a high rate of local recurrence and systemic spread. C1 NW Mem Hosp, Dept Pathol, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Azienda Ospedaliera Verona, Dept Pathol, Verona, Italy. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Pins, MR (reprint author), NW Mem Hosp, Dept Pathol, Feinberg Pavil,7-325,251 E Huron St, Chicago, IL 60611 USA. NR 23 TC 12 Z9 13 U1 0 U2 0 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 SEP PY 1999 VL 123 IS 9 BP 782 EP 788 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 232DA UT WOS:000082349400007 PM 10458824 ER PT J AU Cooper, RA DiGiovine, CP Rentschler, A Lawrence, BM Boninger, ML AF Cooper, RA DiGiovine, CP Rentschler, A Lawrence, BM Boninger, ML TI Fatigue-life of two manual wheelchair cross-brace designs SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID UNITED-STATES; SIMULATIONS; ACCIDENTS AB Objective: To compare the durability of two designs of cross-braces for folding manual wheelchairs and to determine the nature of wheelchair cross-brace failures. Design: Fatigue testing of two folding wheelchair cross-brace designs (one with a rectangular cross-section and the other with a circular cross-section). A total of 20 cross-brace pairs were tested, Results: The cross-braces with a circular cross-section endured a mean +/- SD of 100,159 +/- 45,814 cycles before experiencing a fatigue failure, whereas the cross-braces with a rectangular cross-section endured an average of 261,254 +/- 160,741 cycles. A t test showed significant differences (p = .01) in fatigue-life between cross-braces with a circular cross-section versus cross-braces with a rectangular cross-section. All 20 cross-braces experienced similar fatigue failures that would develop at the bolt hole where the two cross-braces connect to form a hinge. Conclusion: The results suggest that the rectangular cross-brace design has a longer fatigue-life than the circular cross-brace design. People should regularly inspect the cross-brace for cracks. The area around the bolt forming the hinge should be inspected carefully. If a crack is observed, the cross-brace should be replaced immediately. (C) 1999 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151R1, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr Hlth Syst, Div Phys Med & Rehabil, Pittsburgh, PA 15260 USA. RP Cooper, RA (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151R1, 7180 Highland Dr, Pittsburgh, PA 15206 USA. RI DiGiovine, Carmen/E-2982-2011; OI Boninger, Michael/0000-0001-6966-919X NR 15 TC 3 Z9 3 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 1999 VL 80 IS 9 BP 1078 EP 1081 DI 10.1016/S0003-9993(99)90064-3 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 234ZZ UT WOS:000082515400017 PM 10489012 ER PT J AU de Virgilio, C Bui, H Donayre, C Ephraim, L Lewis, RJ Elbassir, M Stabile, BE White, R AF de Virgilio, C Bui, H Donayre, C Ephraim, L Lewis, RJ Elbassir, M Stabile, BE White, R TI Endovascular vs open abdominal aortic aneurysm repair - A comparison of cardiac morbidity and mortality SO ARCHIVES OF SURGERY LA English DT Article ID VASCULAR-SURGERY AB Hypothesis: Adverse cardiac event rates following endovascular abdominal aortic aneurysm (EAAA) and open abdominal aortic aneurysm (OAAA) repair are similar. We also hypothesized that the Eagle criteria (Q wave on electrocardiogram, diabetes, angina, congestive heart failure, age >70 years, and ventricular ectopy) are useful predictors of cardiac events in patients undergoing EAAA repair. Design: Prospective (patients undergoing EAAA repair) and retrospective (patients undergoing OAAA repair). Setting: Public teaching and Veterans Affairs medical centers. Patients: Eighty-three EAAA and 63 OAAA repairs. Main Outcome Measurer: Myocardial infarction, congestive heart failure, and cardiac death. Results: Patients with EAAA were older (73 vs 68 years, P=.003). There were no differences in the mean number of Eagle criteria (1.2 vs 1.3), cardiac event rates (6% vs 4.8%), or mortalities (3.6% vs 4.8%;,). Within the EAAA group, congestive heart failure (P = .005) and Q wave on electrocardiogram (P = .006) were the only predictors of cardiac events. Conclusions: Patients undergoing OAAA and EAAA repair had similar cardiac event rates and mortality. In patients undergoing EAAA repair, history of congestive heart failure and Q wave on electrocardiogram were predictors of cardiac events. C1 Harbor UCLA Med Ctr, Div Vasc Surg, Dept Surg, Torrance, CA 90509 USA. Harbor UCLA Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. RP de Virgilio, C (reprint author), Harbor UCLA Med Ctr, Div Vasc Surg, Dept Surg, 1000 W Carson St,Box 25, Torrance, CA 90509 USA. NR 11 TC 23 Z9 24 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD SEP PY 1999 VL 134 IS 9 BP 947 EP 950 DI 10.1001/archsurg.134.9.947 PG 4 WC Surgery SC Surgery GA 232NR UT WOS:000082377300009 PM 10487588 ER PT J AU Zhang, L Fishman, MC Huang, PL AF Zhang, L Fishman, MC Huang, PL TI Estrogen mediates the protective effects of pregnancy and chorionic gonadotropin in a mouse model of vascular injury SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE vascular endothelium; atherosclerosis; estrogen; sex; pregnancy ID NITRIC-OXIDE SYNTHASES; RABBIT CAROTID-ARTERY; BALLOON INJURY; POSTMENOPAUSAL WOMEN; NEOINTIMA FORMATION; ANTIGEN RETRIEVAL; PROLIFERATION; ESTRADIOL; ATHEROSCLEROSIS; PROGESTERONE AB To determine why pregnancy protects against intimal proliferation in a mouse model of vessel injury, we administered chorionic gonadotropin to intact and ovariectomized female mice. Chorionic gonadotropin markedly suppressed intimal proliferation in intact but not in ovariectomized female mice, indicating that the protective effects of chorionic gonadotropin require ovarian function. To test whether estrogen or progesterone might mediate the protective effects of pregnancy and chorionic gonadotropin, we administered estrogen and progesterone to ovariectomized mice. Estrogen administration to ovariectomized mice to achieve the elevated levels seen in pregnancy was sufficient to reproduce the marked suppression of intimal proliferation in response to vessel injury. Progesterone administration reduced intimal proliferation to a lesser degree and was correlated with increases in estrogen to levels seen in nonpregnant female mice. Staining for proliferating cell nuclear antigen suggested that estrogen reduced medial and intimal cell proliferation. Both the classic estrogen receptor-alpha and the recently discovered estrogen receptor-beta are present in vascular tissue as assessed by immunohistochemistry, providing a possible mechanism for the effects of estrogen. These results suggest that the protective effects of estrogen do not plateau at levels seen in normal females but increase further with estrogen levels up through levels seen during pregnancy. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 E 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL-57818]; NINDS NIH HHS [NS-33335] NR 30 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 1999 VL 19 IS 9 BP 2059 EP 2065 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 234KE UT WOS:000082482900005 PM 10479646 ER PT J AU Heckenkamp, J Leszczynski, D Schiereck, J Kung, J LaMuraglia, GM AF Heckenkamp, J Leszczynski, D Schiereck, J Kung, J LaMuraglia, GM TI Different effects of photodynamic therapy and gamma-irradiation on vascular smooth muscle cells and matrix - Implications for inhibiting restenosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE restenosis; photodynamic therapy; ionizing irradiation ID EXPERIMENTAL INTIMAL HYPERPLASIA; FIBROBLAST GROWTH-FACTOR; EXTRACELLULAR-MATRIX; INTRAVASCULAR IRRADIATION; INTRACORONARY IRRADIATION; NEOINTIMAL HYPERPLASIA; BALLOON ANGIOPLASTY; RADIATION; INJURY; PREVENTION AB gamma-Irradiation (gamma-RT) and photodynamic therapy (PDT) are known to inhibit intimal hyperplasia. The common mechanism is that both modalities produce free radicals, but unlike gamma-RT, PDT generates them through the absorption of light by photosensitizers. The purpose of this in vitro study was to assess the differences that PDT and gamma-RT have on the fibroproliferative response after vascular injury by comparing their effects on vascular smooth muscle cells (SMCs) and on the extracellular matrix (ECM). Mitochondrial activity (tetrazolium salt), proliferation ([H-3]thymidine]thymidine incorporation), and the mechanisms of cell death (terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling [TUNEL] staining) were used to assess differences between PDT (100 J/cm(2)) and gamma-RT(10 or 20 Gy) on SMC injury. The different effects on bioregulatory molecules were investigated by quantitating the proliferation of SMCs cultured with conditioned medium and on treated ECM. PDT of SMCs reduced proliferation and mitochondrial activity (0.5 +/- 0.75% and 1.7 +/- 4.25%, respectively, P<0.0001), whereas gamma-RT of SMCs decreased cell proliferation but did not affect metabolic activity. Stimulation with calf serum of gamma-RT-treated SMCs did not affect proliferation but increased mitochondrial enzyme activity (160 +/- 11%, P<0.0005). The conditioned medium, derived from PDT- but not gamma-RT-treated SMCs, did not stimulate effector SMC proliferation compared with gamma-RT-treated SMCs(16 +/- 4.1% versus 80 +/- 16.8%, P<0.0001). Apoptosis was the principle cytotoxic mechanism after PDT, whereas gamma-RT cells were growth arrested but viable. PDT of the ECM reduced effector SMC proliferation compared with controls and gamma-RT cells (18 +/- 6.5% versus 100 +/- 17.7% and 84 +/- 8.9%, respectively, P<0.0001). These data suggest that gamma-RT and PDT may inhibit restenosis but by different mechanisms. The effects of PDT are more diverse and may result in improved outcome while avoiding the teratogenic exposure due to ionizing irradiation. C1 Harvard Univ, Massachusetts Gen Hosp, Div Vasc Surg, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, Sch Med,Gen Surg Serv, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Vasc Surg, Sch Med, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL02583] NR 45 TC 21 Z9 21 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 1999 VL 19 IS 9 BP 2154 EP 2161 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 234KE UT WOS:000082482900017 PM 10479658 ER PT J AU Schumacher, HR Gerard, HC Arayssi, TK Pando, JA Branigan, PJ Saaibi, DL Hudson, AP AF Schumacher, HR Gerard, HC Arayssi, TK Pando, JA Branigan, PJ Saaibi, DL Hudson, AP TI Lower prevalence of Chlamydia pneumoniae DNA compared with Chlamydia trachomatis DNA in synovial tissue of arthritis patients SO ARTHRITIS AND RHEUMATISM LA English DT Article ID REACTIVE ARTHRITIS; FLUID; TWAR AB Objective. To assess the presence of Chlamydia pneumoniae DNA in the joints of patients with reactive arthritis (ReA) and other arthritides. Methods. DNA was prepared from synovial tissue (ST) and several synovial fluid (SF) samples from 188 patients with either ReA, undifferentiated oligoarthritis, or other forms of arthritis, and from 24 normal (non-arthritis) individuals. Preparations were screened using polymerase chain reaction (PCR) assays that independently targeted the C pneumoniae 16S ribosomal RNA and major outer membrane protein genes. Results. Twenty-seven of 212 ST samples (12.7%) were PCR positive for C pneumoniae DNA; 10 SF samples from these 27 patients were similarly positive. Among the PCR-positive patients, 3 had ReA, 2 had Reiter's syndrome, 7 had undifferentiated oligoarthritis, 4 had undifferentiated monarthritis, 6 had rheumatoid arthritis, and 5 had other forms of arthritis. No samples from normal control individuals were PCR positive. Conclusion. DNA of C pneumoniae is present in synovial specimens from some arthritis patients. The prevalence of this organism in the joints was lower than that of C trachomatis, and synovial presence of the organism was not associated with any distinct clinical syndrome. Widely disseminated nucleic acids such as those of C pneumoniae might have some role in the pathogenesis of several arthritides, since the organism was not found in the ST from normal control individuals. C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Detroit, MI USA. RP Schumacher, HR (reprint author), Dept Vet Affairs Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. OI Arayssi, Thurayya/0000-0003-2469-0272 FU NIAMS NIH HHS [AR-42541] NR 14 TC 60 Z9 63 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1999 VL 42 IS 9 BP 1889 EP 1893 DI 10.1002/1529-0131(199909)42:9<1889::AID-ANR13>3.0.CO;2-W PG 5 WC Rheumatology SC Rheumatology GA 241YC UT WOS:000082910600013 PM 10513803 ER PT J AU Moser, KL Gray-McGuire, C Kelly, J Asundi, N Yu, H Bruner, GR Mange, M Hogue, R Neas, BR Harley, JB AF Moser, KL Gray-McGuire, C Kelly, J Asundi, N Yu, H Bruner, GR Mange, M Hogue, R Neas, BR Harley, JB TI Confirmation of genetic linkage between human systemic lupus erythematosus and chromosome 1q41 SO ARTHRITIS AND RHEUMATISM LA English DT Article ID LOCI AB Objective. Genetic susceptibility to systemic lupus erythematosus (SLE) is undoubtedly complex and, presumably, involves multiple loci. Linkage of SLE to D1S229 at chromosome 1q41 has been previously reported in a cohort of 52 affected sibpairs. The present study sought to confirm this reported linkage in an independent cohort of 127 extended multiplex SLE pedigrees containing 107 affected sibpairs. Methods. Genotype data were collected for D1S229 and 18 flanking microsatellite markers spanning chromosome 1q32-1q42. Analyses of genotype data included a model-based logarithm of odds (LOD) score approach, affected sibpair analyses, and transmission disequilibrium tests. Results. A maximum LOD score of 1.46 was found with D1S229 in a subgroup of 78 European American pedigrees, with additional support from multiple markers clustered around D1S229. Increased allele sharing in affected siblings was most significant at D1S2616, particularly in European Americans (P = 0.0005), followed by D1S229 (P = 0.002), D1S490 (P = 0.028), and D1S1605 (P = 0.037). Although linkage in a subgroup of 40 African American pedigrees was not suggested by the analyses of any marker tested in the chromosomal region surrounding D1S229, a maximum LOD score of 3.03 was found with D1S3462, mapped 15 centimorgans distal to D1S229. Conclusion. Our linkage analysis results in European Americans at D1S229 are remarkably similar to those previously reported. That at least 1 genetic effect near this locus is important for susceptibility to lupus should now be generally accepted, and efforts to identify the gene are thereby justified. C1 Univ Oklahoma, Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Harley, JB (reprint author), Univ Oklahoma, Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NIAMS NIH HHS [AR-38889, AR-45231, AR-42460] NR 15 TC 47 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1999 VL 42 IS 9 BP 1902 EP 1907 DI 10.1002/1529-0131(199909)42:9<1902::AID-ANR16>3.0.CO;2-G PG 6 WC Rheumatology SC Rheumatology GA 241YC UT WOS:000082910600016 PM 10513806 ER PT J AU Cacciola, JS Alterman, AI Rutherford, MJ McKay, JR May, DJ AF Cacciola, JS Alterman, AI Rutherford, MJ McKay, JR May, DJ TI Comparability of telephone and in-person structured clinical interview for DSM-III-R (SCID) diagnoses SO ASSESSMENT LA English DT Article DE SCID; diagnosis; reliability; telephone interviews; depression ID FACE-TO-FACE; PSYCHIATRIC-DIAGNOSIS; SCHEDULE; AGREEMENT; RELIABILITY; DEPRESSION; STRATEGIES; COMMUNITY; DISORDERS; HISTORY AB The SCID was administered twice, once by telephone and once in person (1 week later) to 41 college age men. For major depression (lifetime kappa = .64, current kappa = .66), results indicated good agreement. The lifetime occurrence estimate based on the telephone SCID diagnosis was lower than the in-person SCID estimate. Kappas for specific diagnoses were calculable for simple phobia (lifetime kappa = .47, current kappa = -.03) and social phobia (lifetime kappa = .29). Base rates were less than 10% for all individual diagnoses except lifetime major depression; therefore, the kappas may be unstable. For all diagnoses where there were any positive cases, percentages of negative agreement and specificity were high, whereas percentages of positive agreement and sensitivity were lower. Overall agreement was fair for specific lifetime diagnoses but poor for current diagnoses. These results suggest caution in assuming comparability of in-person and telephone SCID diagnoses. Circumstances under which a telephone SCID may be useful and ways to improve reliability are discussed. C1 Univ Penn, Sch Med, Treatment Res Ctr, Philadelphia, PA 19104 USA. Philadelphia Dept Vet Affairs Med Ctr, Philadelphia, PA USA. RP Cacciola, JS (reprint author), Univ Penn, Sch Med, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. NR 24 TC 53 Z9 53 U1 0 U2 4 PU PSYCHOLOGICAL ASSESSMENT RESOURCES INC PI ODESSA PA PO BOX 998, ODESSA, FL 33556 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD SEP PY 1999 VL 6 IS 3 BP 235 EP 242 DI 10.1177/107319119900600304 PG 8 WC Psychology, Clinical SC Psychology GA 237TU UT WOS:000082672800004 PM 10445961 ER PT J AU Harris, JT Eisenstein, EM AF Harris, JT Eisenstein, EM TI Transfer of learned information between ganglia in the insect ventral nerve cord SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE cockroach; avoidance learning; memory; transfer of learning; ganglion; coding; learned helplessness; insect; arthropod; invertebrate ID HELPLESSNESS; MODEL AB A yoked control training procedure was used on the decapitated cockroach, L. maderae. The right prothoracic leg was trained to lift in order to avoid a shock. It was found that this information transferred via the two interganglionic connectives from the first or prothoracic ganglion (T1) to the second or mesothoracic ganglion (T2) so that now the right mesothoracic leg lifted to avoid shock even though it was not directly trained. If both connectives were cut before training T1, no transfer to T2 was seen, i.e. the mesothoracic leg did not lift and avoid shock. However, if both connectives were cut immediately after training TI, the information had already transferred and was available for use by T2. There was redundancy in the transfer in that either connective alone could carry the same information from T1 to T2. Either mesothoracic leg could tap into this information. Using a reversible cold block on the connectives, it was found that if it was applied before training T1 it did not interfere with T1 learning but no transfer to T2 was seen after the cold block wore off. That the block was transitory and did not permanently impair the connectives was shown by the fact that if it was applied and then allowed to wear off before training began there was normal learning in T1 and transfer to T2. The transection and cold-block studies were consistent in demonstrating that the transfer of the information was 'on-line' and only occurred during T1 learning. If transfer was blocked during T1 learning the information could not be transferred or tapped into by T2 at a later time even though it was stored in T1 and available for later use by TI. The transfer occurred so quickly it most likely occurred via nerve impulses. Because no primary sensory or motor neurons are in the connectives, the information must have been coded onto interneurones for transfer from the first (T1) to the second (T2) ganglion. (C) 1999 Elsevier Science B.V. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Eisenstein, EM (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 14 TC 2 Z9 2 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD SEP PY 1999 VL 103 IS 2 BP 211 EP 217 DI 10.1016/S0166-4328(99)00039-X PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 242JH UT WOS:000082936400009 PM 10513589 ER PT J AU Tung, CH Bredow, S Mahmood, U Weissleder, R AF Tung, CH Bredow, S Mahmood, U Weissleder, R TI Preparation of a cathepsin D sensitive near-infrared fluorescence probe for imaging SO BIOCONJUGATE CHEMISTRY LA English DT Article ID BREAST-CANCER; PROGRESSION; CELLS AB A variety of proteases are overexpressed or activated during pathogenesis and represent important targets for therapeutic drugs. We have previously shown that optical imaging probes sensitive in the near-infrared fluorescence (NIRF) spectrum can be used for in vivo imaging of enzyme activity. In the current study, me show that these probes can be designed with specificity for specific enzymes, for example, cathepsin D which is known to be overexpressed in many tumors. A NIR cyanine fluorochrome served as the optical reporter and was attached to the amino terminal of an 11 amino acid peptide sequence with specificity for cathepsin D. The peptides were subsequently attached to a synthetic graft copolymer for efficient tumoral delivery. The close spatial proximity of the multiple fluorochromes resulted in quenching of fluorescence in the bound state. A 350-fold signal amplification was observed post cleavage during in vitro testing. Cell culture experiments using a rodent tumor cell line stably transfected with human cathepsin D confirmed enzyme specific activation within cells. This sequence but not a scrambled control sequence showed enzyme specificity in vitro. We conclude that activatable NIRF optical probes can be synthesized to potentially probe for specific enzymes in living organisms. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149,13th St,Room 5406, Boston, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NINDS NIH HHS [R01 NS35258] NR 17 TC 162 Z9 164 U1 1 U2 36 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 1999 VL 10 IS 5 BP 892 EP 896 DI 10.1021/bc990052h PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 239RA UT WOS:000082782400025 PM 10502358 ER PT J AU Freedman, R AF Freedman, R TI Schizophrenia as a neuronal illness SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 Denver VA Med Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver VA Med Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. RP Freedman, R (reprint author), Denver VA Med Ctr, Dept Psychiat, Campus Box C-268-71,4200 E 9th Ave, Denver, CO 80262 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 1999 VL 46 IS 5 BP 587 EP 588 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 230PZ UT WOS:000082260700001 PM 10472412 ER PT J AU Epner, DE Sawa, A Isaacs, JT AF Epner, DE Sawa, A Isaacs, JT TI Glyceraldehyde-3-phosphate dehydrogenase expression during apoptosis and proliferation of rat ventral prostate SO BIOLOGY OF REPRODUCTION LA English DT Article ID AGE-INDUCED APOPTOSIS; CELL-PROLIFERATION; CEREBELLAR NEURONS; GLYCOLYTIC PROTEIN; ANDROGEN ABLATION; DEATH; CASTRATION; INDUCTION; GLUCOSE; CULTURE AB Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme known to play a critical role in neuronal apoptosis. We undertook the current studies to determine whether GAPDH also plays a role in prostate epithelial cell apoptosis in response to androgen deprivation. To do so, we analyzed GAPDH staining by immunohistochemistry during castration-induced involution and androgen-induced regeneration of rat ventral prostate. We found that GAPDH was undetectable in secretory epithelial cells at baseline and that staining did not increase in the epithelium during the period of peak apoptosis from 1 to 3 days after castration. However, GAPDH levels did increase within nuclei of some basal epithelial cells 5 days after castration and within the cytoplasm of all secretory epithelial cells 7 days after castration. GAPDH was also abundant within the cytoplasm of secretory epithelial cells during the period of maximal cell proliferation from 2 to 3 days after androgen replacement and was clearly apparent within nuclei of some epithelial cells 4 days after androgen replacement. Our studies suggest that GAPDH plays multiple roles during prostate epithelial cell apoptosis and proliferation. C1 Va Med Ctr, Med Serv 111H, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA. RP Epner, DE (reprint author), Va Med Ctr, Med Serv 111H, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [1 R29CA78355-01] NR 26 TC 20 Z9 20 U1 1 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD SEP PY 1999 VL 61 IS 3 BP 687 EP 691 DI 10.1095/biolreprod61.3.687 PG 5 WC Reproductive Biology SC Reproductive Biology GA 229JE UT WOS:000082190000019 PM 10456846 ER PT J AU Kurtz, SM Muratoglu, OK Evans, M Edidin, AA AF Kurtz, SM Muratoglu, OK Evans, M Edidin, AA TI Advances in the processing, sterilization, and crosslinking of ultra-high molecular weight polyethylene for total joint arthroplasty SO BIOMATERIALS LA English DT Review DE UHMWPE; ultra-high molecular weight polyethylene; resin; processing; manufacturing; morphology; conversion; sterilization; degradation; oxidation; wear; mechanical behavior; crosslinking; carbon-fiber reinforced UHMWPE; poly II (TM); Hylamer (TM); total joint; arthroplasty; replacement ID CROSS-LINKED POLYETHYLENE; GAS PLASMA STERILIZATION; MECHANICAL-PROPERTIES; ACETABULAR COMPONENTS; INFRARED SPECTROMETRY; LINEAR POLYETHYLENE; GAMMA-RADIATION; WEAR; BEHAVIOR; UHMWPE AB Despite the recognized success and worldwide acceptance of total joint arthroplasty, wear is a major obstacle limiting the longevity of implanted UHMWPE components. Efforts to solve the wear problem in UHMWPE have spurred numerous detailed studies into the structure, morphology, and mechanical properties of the polymer at every stage of its production from original resin into stock material and final fabricated form. Scientific developments in this field are occurring at an accelerating rate, and periodic review of UHMWPE technology is therefore increasingly necessary. The present article provides a four-part comprehensive review of technological advancements in the processing, manufacture, sterilization, and crosslinking of UHMWPE for total joint replacements. The first part of this article describes the recently updated nomenclature of UHMWPE, including the process of resin production and conversion to stock material. The second part outlines the methods of manufacturing UHMWPE into joint replacement components and provides overviews of alternate forms of UHMWPE, namely carbon-fiber reinforced UHMWPE (Poly II(TM)) and UHMWPE recrystallized under high temperature and pressure (Hylamer(TM)). The third part summarizes the sterilization and degradation of UHMWPE. Newly developed methods for accelerating the oxidation of UHMWPE after sterilization (for preconditioning of test specimens), as well as methods for quantifying the oxidation of UHMWPE, are also discussed. Finally, the fourth part reviews the development and properties of crosslinked UHMWPE, a promising alternate biomaterial for total joint replacements. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Exponent Failure Anal Associates, Philadelphia, PA 19103 USA. Harvard Univ, Sch Med, Orthopaed Biomech Lab, Massachusetts Gen Hosp, Boston, MA 02114 USA. Poly Hi Solidur MediTech, Ft Wayne, IN 46809 USA. Stryker Howmedica Osteon, Allendale, NJ 07401 USA. RP Exponent Failure Anal Associates, 2300 Chestnut St,Suite 150, Philadelphia, PA 19103 USA. EM skurtz@exponent.com NR 201 TC 467 Z9 477 U1 15 U2 158 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD SEP PY 1999 VL 20 IS 18 BP 1659 EP 1688 DI 10.1016/S0142-9612(99)00053-8 PG 30 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 232AP UT WOS:000082343800003 PM 10503968 ER PT J AU Regan, MM Catalano, PJ AF Regan, MM Catalano, PJ TI Likelihood models for clustered binary and continuous outcomes: Application to developmental toxicology SO BIOMETRICS LA English DT Article DE dose-response modeling; exchangeability; maximum likelihood; probit model; risk assessment ID FETAL WEIGHT; MALFORMATION; TOXICITY; DISCRETE; RISK AB In developmental toxicology, methods based on dose-response modeling and quantitative risk assessment are being actively pursued. Among live fetuses, the presence of malformations and reduction in fetal weight are of primary interest, but ordinarily, the dose-response relationships are characterized in each of the outcomes separately while appropriately accounting for clustering within litters. Jointly modeling the outcomes, allowing different relationships with dose while incorporating the correlation between the fetuses and the outcomes. may be more appropriate. We propose a likelihood-based model that is an extension of a correlated probit model to incorporate continuous outcomes. Our model maintains a marginal dose-response interpretation for the individual outcomes while taking into account both the correlations between outcomes on an individual fetus and those due to clustering. The joint risk of malformation and low birth weight can then be estimated directly. This approach is particularly well suited to estimating safe dose levels as part of quantitative risk assessment. C1 Beth Israel Deaconess Med Ctr, Biometr Ctr EGZ800, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Regan, MM (reprint author), Beth Israel Deaconess Med Ctr, Biometr Ctr EGZ800, 330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [CA09337]; NIEHS NIH HHS [ES06900] NR 18 TC 50 Z9 50 U1 1 U2 6 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1999 VL 55 IS 3 BP 760 EP 768 DI 10.1111/j.0006-341X.1999.00760.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 237XZ UT WOS:000082683000013 PM 11315004 ER PT J AU Michiels, B Molenberghs, G Lipsitz, SR AF Michiels, B Molenberghs, G Lipsitz, SR TI Selection models and pattern-mixture models for incomplete data with covariates SO BIOMETRICS LA English DT Article DE categorical data; maximum likelihood estimation; missing data; multiple imputation; sensitivity analysis ID MISSING DATA; MULTIVARIATE AB Most models for incomplete data are formulated within the selection model framework. This paper studies similarities and differences of modeling incomplete data within both selection and pattern-mixture settings. The focus is on missing at random mechanisms and on categorical data. Paint and interval estimation is discussed. A comparison of both approaches is done on side effects in a psychiatric study. C1 Limburgs Univ Ctr, B-3590 Diepenbeek, Belgium. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. RP Michiels, B (reprint author), Limburgs Univ Ctr, Univ Campus, B-3590 Diepenbeek, Belgium. NR 11 TC 21 Z9 21 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1999 VL 55 IS 3 BP 978 EP 983 DI 10.1111/j.0006-341X.1999.00978.x PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 237XZ UT WOS:000082683000047 PM 11315038 ER PT J AU Shen, Y Zelen, M AF Shen, Y Zelen, M TI Parametric estimation procedures for screening programmes: Stable and nonstable disease models for multimodality case finding SO BIOMETRIKA LA English DT Article DE conditional likelihood; multiple screening examination; nonstable disease model; sensitivity; sojourn time; stable disease model ID BREAST-CANCER DETECTION; LEAD TIME; DEATH RATES; INFERENCE AB This paper develops methods for estimating the parameters associated with early detection programmes. Disease is considered to have three states: a disease-free state or a state in which the disease cannot be detected, a preclinical state and a clinical state. The natural history of the disease is assumed to be progressive. The parameters to be estimated, are the sensitivity of one or two disease detection modalities and the characteristics of the preclinical sojourn time distribution under both the stable disease and nonstable disease models. The stable-disease model assumes that the incidence or prevalence of a disease is independent of age or chronological time, while the nonstable disease model allows these quantities to depend on time. With the nonstable disease model, the relevant parameters can be jointly estimated by a two-step iteration procedure from the likelihood function. For the stable disease model, the sensitivity and the parameters of the sojourn time distribution of the preclinical state can be obtained directly from a conditional likelihood function. Applications are made to recent clinical trials for the early detection of breast cancer. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shen, Y (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. OI Shen, Yu/0000-0002-3899-7868 NR 26 TC 30 Z9 30 U1 1 U2 2 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD SEP PY 1999 VL 86 IS 3 BP 503 EP 515 DI 10.1093/biomet/86.3.503 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 241NY UT WOS:000082890500002 ER PT J AU Lieberman, E Lang, JM Frigoletto, F Cohen, A AF Lieberman, E Lang, JM Frigoletto, F Cohen, A TI Epidurals and cesareans: The jury is still out. SO BIRTH-ISSUES IN PERINATAL CARE LA English DT Editorial Material ID RANDOMIZED TRIAL; ANALGESIA; LABOR; DELIVERY C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Cambridge, MA 02138 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Lieberman, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Cambridge, MA 02138 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0730-7659 J9 BIRTH-ISS PERINAT C JI Birth-Issue Perinat. Care PD SEP PY 1999 VL 26 IS 3 BP 196 EP 198 DI 10.1046/j.1523-536x.1999.00196.x PG 3 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 231YD UT WOS:000082338200010 PM 10655821 ER PT J AU Bover, J Jara, A Trinidad, P Rodriguez, M Felsenfeld, AJ AF Bover, J Jara, A Trinidad, P Rodriguez, M Felsenfeld, AJ TI Dynamics of skeletal resistance to parathyroid hormone in the rat: Effect of renal failure and dietary phosphorus SO BONE LA English DT Article DE calcium; parathyroid hormone (PTH); phosphorus; skeletal resistance; uremia ID CALCEMIC RESPONSE; IN-VITRO; SECONDARY HYPERPARATHYROIDISM; PTH SECRETION; CALCIUM; CALCITRIOL; PHOSPHATE; UREMIA; PATHOGENESIS; HEMODIALYSIS AB Secondary hyperparathyroidism develops in renal failure and is generally ascribed to factors directly affecting parathyroid hormone (PTH) production and/or secretion, These include hypocalcemia, phosphorus retention, and a calcitriol deficiency. However, not often emphasized is that skeletal resistance to PTH is an important factor. Our study evaluated: (1) the relative effects of uremia and dietary phosphorus on the skeletal resistance to PTH; and (2) how, during a PTH infusion, the dynamics of skeletal resistance to PTH were affected by renal failure. Renal failure was surgically induced and, based on serum creatinine, rats were divided into normal, moderate renal failure, and advanced renal failure, In each group, three diets with the same calcium (0.6%) but different phosphorus contents were used: high (1.2%, HPD); moderate (0.6%, MPD); and low (0.2, LPD) phosphorus. The study diet was given for 14-16 days followed by a 48 h infusion of rat PTH(1-34) (0.11 mu g/100 g per hour), a dose five times greater than the normal replacement dose. During the PTH infusion, rats received a calcium-free, low phosphorus (0.2%) diet. In both moderate and advanced renal failure, the PTH level was greatest in the HPD group (p < 0.05) and, despite normal serum calcium values, PTH was greater in the MPD than the LPD group (p < 0.05), Despite phosphorus restriction and normal serum calcium and calcitriol levels in the azotemic LPD groups, the PTH level was greater (p < 0.05) in the LPD group with advanced rather than moderate renal failure. During PTH infusion, the increase in serum calcium was progressively less (p < 0.05) in all groups as renal function declined, Furthermore, despite normal and similar serum phosphorus values at the end of PTH infusion, the serum calcium concentration was less (p < 0.05) in the HPD group than the other two groups and similar in the LPD and MPD groups. In conclusion: (1) uremia and phosphorus each had separate and major effects on skeletal resistance to PTH; (2) skeletal resistance to PTH was an important cause of secondary hyperparathyroidism, even in moderate renal failure; (3) during PTH infusion, the dynamics of skeletal resistance to PTH changed because all groups received a low phosphorus diet, and the adaptation to a new steady state was delayed by the degree of renal failure and the previous dietary phosphorus burden; and (4) normal serum phosphorus may not be indicative of body phosphorus stores during states of disequilibrium. (C) 1999 by Elsevier Science Inc. All rights reserved. C1 W Los Angeles VA Med Ctr, Nephrol Sect 111L, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Hosp Univ Reina Sofia, Unit Investigat, Cordoba, Spain. Hosp Univ Reina Sofia, Dept Nephrol, Cordoba, Spain. RP Felsenfeld, AJ (reprint author), W Los Angeles VA Med Ctr, Nephrol Sect 111L, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Rodriguez, teresa/H-5452-2011 NR 28 TC 29 Z9 29 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD SEP PY 1999 VL 25 IS 3 BP 279 EP 285 DI 10.1016/S8756-3282(99)00169-6 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 234GR UT WOS:000082476600004 PM 10495131 ER PT J AU Thomson, B Hawkins, D Felgenhauer, J Radich, JP AF Thomson, B Hawkins, D Felgenhauer, J Radich, JP TI RT-PCR evaluation of peripheral blood, bone marrow and peripheral blood stem cells in children and adolescents undergoing VACIME chemotherapy for Ewing's sarcoma and alveolar rhabdomyosarcoma SO BONE MARROW TRANSPLANTATION LA English DT Article DE Ewing's sarcoma; alveolar rhabdomyosarcoma; PBSC transplant; in vivo purging ID POLYMERASE CHAIN-REACTION; HEMATOPOIETIC PROGENITOR CELLS; SOFT-TISSUE SARCOMAS; SOLID TUMORS; TRANSPLANTATION; TRANSLOCATION; NEUROBLASTOMA; MALIGNANCIES; TRANSCRIPTS; SUPPORT AB Peripheral blood stem cell support allows dose intensification of multiple cycle chemotherapy for metastatic tumors, including pediatric sarcomas, The VACIME protocol (vincristine, adriamycin, cyclophosphamide, ifosfamide, mesna and etoposide) utilizes peripheral blood stem cells (PBSC) collected following the treatment cycle as support for subsequent dose- and time-intensive chemotherapy, A critical assumption is that PBSC collected in this manner will be purged of residual tumor cells in vivo. We tested this assumption using sensitive reverse-transcriptase polymerase chain reaction (RT-PCR) to assess the presence of the characteristic translocations of the Ewing's sarcoma family of tumors (ESFT) and alveolar rhabdomyosarcoma (ARMS), t(11;22), and t(2;13), respectively. We used RT-PCR to evaluate 122 samples of peripheral blood (PB), bone marrow (BM) and PBSC collected from 12 pediatric patients with metastatic ESFT and ARMS. The samples included pre-therapy BM and PB, as well as BM, PB, and PBSC collections at various times in the VACIME treatment course. Molecular evidence of tumor contamination was detected in 1/40 PBSC collections from 12 patients. In all patients, we documented clearance of disease by RT-PCR in peripheral blood and bone marrow by week 9 of the VACIME protocol. In vivo purging in combination with the intensive VACIME regime appears to be effective in removing tumor cells from PBSC, bone marrow, and peripheral blood as detected by RT-PCR. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Deaconess Med Ctr, Spokane, WA USA. RP Thomson, B (reprint author), Indiana Univ, James Whitcomb Riley Hosp Children, 702 Barnhill Dr,Room 2720, Indianapolis, IN 46202 USA. NR 26 TC 28 Z9 30 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD SEP PY 1999 VL 24 IS 5 BP 527 EP 533 DI 10.1038/sj.bmt.1701939 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 234KV UT WOS:000082484600012 PM 10482938 ER PT J AU Harris, GJ Codori, AM Lewis, RF Schmidt, E Bedi, A Brandt, J AF Harris, GJ Codori, AM Lewis, RF Schmidt, E Bedi, A Brandt, J TI Reduced basal ganglia blood flow and volume in pre-symptomatic, gene-tested persons at-risk for Huntington's disease SO BRAIN LA English DT Article DE MRI; single photon emission computed tomography (SPECT); Huntington's disease; pre-symptomatic; gene-testing ID STRIATAL GLUCOSE CONSUMPTION; POSITRON EMISSION TOMOGRAPHY; SCAN INVESTIGATIONS; EARLY DIAGNOSIS; METABOLISM; ATROPHY; CHOREA; BRAIN; PET; FEATURES AB The aim of this study was to examine basal ganglia volumes and regional cerebral blood flow in asymptomatic subjects at-risk for Huntington's disease who had undergone genetic testing, We determined which measures were the best 'markers' for the presence of the mutation and for the onset of symptoms, Twenty subjects who were Huntington's disease gene mutation-positive and 24 Huntington's disease gene mutation-negative participants, all of whom had a parent with genetically confirmed Huntington's disease, and were therefore 50% at-risk for inheriting the Huntington's disease gene mutation, were included in the study, To evaluate basal ganglia structure and function, MRI and single photon emission computed tomography (SPECT) were used. Quantitative measures of regional volumes and relative measures of regional perfusion were calculated. SPECT and MRI scans were co-registered so that MRI anatomy could be used accurately to place SPECT regions, Estimated years-to-onset in the mutation-positive subjects was calculated based on a regression formula that included gene (CAG)(n) repeat length and parental age of onset, Changes in imaging measures in relation to estimated years-to-onset were assessed. The imaging measure that was most affected in mutation-positive subjects was putamen volume, This was also the measure that correlated most strongly with approaching onset. In subjects greater than or equal to 7 years from estimated onset age, the putamen volume measures n ere similar to those of the mutation-negative subjects, However, in subjects 56 years from estimated onset age, there were dramatic reductions in putamen volume, resulting in >90% discrimination from both the far-from-onset and the mutation-negative subjects. Caudate volume and bicaudate ratio also showed a significant decline in the close-to-onset subjects, although to a lesser degree than putamen volume reductions. Furthermore, SPECT basal ganglia perfusion deficits were observed in mutation-positive subjects. Imaging markers of neuropathological decline preceding clinical onset are important for assessing the effects of treatments aimed at slowing the course of Huntington's disease. The current study suggests that quantitative assessment of basal ganglia may provide a means to track early signs of decline in individuals with the Huntington's disease gene mutation prior to clinical onset. C1 Massachusetts Gen Hosp, Radiol Comp Aided Diagnost Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Dept Psychiat, Boston, MA 02111 USA. Johns Hopkins Med Inst, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Harris, GJ (reprint author), Massachusetts Gen Hosp, Radiol Comp Aided Diagnost Lab, Gray 2 Room B-285,55 Fruit St, Boston, MA 02114 USA. OI Brandt, Jason/0000-0001-7381-6244 FU NIMH NIH HHS [MH-46034]; NINDS NIH HHS [NS-16375, NS-33398] NR 53 TC 85 Z9 85 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 1999 VL 122 BP 1667 EP 1678 DI 10.1093/brain/122.9.1667 PN 9 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 239RB UT WOS:000082782500006 PM 10468506 ER PT J AU Gomez-Isla, T Growdon, WB McNamara, MJ Nochlin, D Bird, TD Arango, JC Lopera, F Kosik, KS Lantos, PL Cairns, NJ Hyman, BT AF Gomez-Isla, T Growdon, WB McNamara, MJ Nochlin, D Bird, TD Arango, JC Lopera, F Kosik, KS Lantos, PL Cairns, NJ Hyman, BT TI The impact of different presenilin 1 and presenilin 2 mutations on amyloid deposition, neurofibrillary changes and neuronal loss in the familial Alzheimer's disease brain - Evidence for other phenotype-modifying factors SO BRAIN LA English DT Article DE A beta plaques; neurofibrillary tangles; neuronal loss; presenilin; familial Alzheimer's disease ID PRECURSOR PROTEIN GENE; VOLGA GERMAN FAMILIES; A-BETA DEPOSITION; CEREBRAL-HEMORRHAGE; A-BETA-42; APOPTOSIS; KINDREDS; FEATURES; PEDIGREE AB To assess the influence of the presenilin 1 (PS1) and 2 (PS2) mutations on amyloid deposition, neurofibrillary tangle (NFT) formation and neuronal loss, we performed stereologically based counts in a high-order association cortex, the superior temporal sulcus, of 30 familial Alzheimer's disease cases carrying 10 different PSI and PSZ mutations, 51 sporadic Alzheimer's disease cases and 33 non-demented control subjects. All the PS1 and PS2 mutations assessed in this series led to enhanced deposition of total A beta and A beta(x-42/43) but not A beta(x-40) senile plaques in the superior temporal sulcus when compared with brains from sporadic Alzheimer's disease patients. Some of the PS1 mutations studied (M139V, I143F, G209V, R269H, E280A), but not others, were also associated with faster rates of NFT formation and accelerated neuronal loss in the majority of the patients who harboured them when compared with sporadic Alzheimer's disease patients. In addition, our analysis showed that dramatic quantitative differences in clinical and neuropathological features can exist even among family members with the identical PS mutation, This suggests that further individual or pedigree genetic or epigenetic factors are likely to modulate PS phenotypes strongly. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Neurol Serv, Boston, MA 02114 USA. Univ Washington, Sch Med, Dept Pathol Neuropathol, Seattle, WA 98195 USA. Vet Adm Med Ctr, Neurol Serv, Seattle, WA 98108 USA. Univ Antioquia, Dept Pathol, Medellin, Colombia. Inst Psychiat, Dept Neuropathol, London SE5 8AF, England. RP Gomez-Isla, T (reprint author), Univ Minnesota, Dept Neurol, 420 Delaware St SE,Box 295 FUMC, Minneapolis, MN 55455 USA. FU NIA NIH HHS [AG06786, AG08031, AG05134] NR 39 TC 75 Z9 75 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 1999 VL 122 BP 1709 EP 1719 DI 10.1093/brain/122.9.1709 PN 9 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 239RB UT WOS:000082782500010 PM 10468510 ER PT J AU Hamblin, MR Rajadhyaksha, M Momma, T Soukos, NS Hasan, T AF Hamblin, MR Rajadhyaksha, M Momma, T Soukos, NS Hasan, T TI In vivo fluorescence imaging of the transport of charged chlorin e6 conjugates in a rat orthotopic prostate tumour SO BRITISH JOURNAL OF CANCER LA English DT Article DE photosensitizer; pharmacokinetics; photodynamic therapy; tumour vasculature; polymer conjugate ID PHOTODYNAMIC THERAPY; MICROVASCULAR PERMEABILITY; VASCULAR-PERMEABILITY; BLOOD-VESSELS; SOLID TUMORS; CELL-SURFACE; DRUG; CANCER; PHARMACOKINETICS; BIODISTRIBUTION AB Polymeric drug conjugates are used in cancer therapy and, varying their molecular size and charge, will affect their in vivo transport and extravasation in tumours. Partitioning between tumour vasculature and tumour tissue will be of particular significance in the case of photosensitizer conjugates used in photodynamic therapy, where this partitioning can lead to different therapeutic effects. Poly-l-lysine chlorin e6 conjugates (derived from polymers of average M-r 5000 and 25 000) were prepared both in a cationic state and by poly-succinylation in an anionic state. A fluorescence scanning laser microscope was used to follow the pharmacokinetics of these conjugates in vivo in an orthotopic rat prostate cancer model obtained with MatLyLu cells. Fluorescence was excited with the 454-528 nm group of lines of an argon laser and a 570 nm long pass filter used to isolate the emission. Results showed that the conjugates initially bound to the walls of the vasculature, before extravasating into the tissue, and eventually increasing in fluorescence. The anionic conjugates produced tissue fluorescence faster-than the cationic ones, and surprisingly, the larger M-r conjugates produced tissue fluorescence faster than the smaller ones with the same charge. These results are consistent with differences in aggregation state between conjugates. (C) 1999 Cancer Research Campaign. C1 Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, WEL 224, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 FU NIAMS NIH HHS [R01 AR40352] NR 62 TC 28 Z9 33 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP PY 1999 VL 81 IS 2 BP 261 EP 268 DI 10.1038/sj.bjc.6690686 PG 8 WC Oncology SC Oncology GA 235JW UT WOS:000082539400012 PM 10496351 ER PT J AU Anstey, AV Ryan, A Rhodes, LE Charman, CR Arlett, CF Tyrrell, RM Taylor, CR Pearse, AD AF Anstey, AV Ryan, A Rhodes, LE Charman, CR Arlett, CF Tyrrell, RM Taylor, CR Pearse, AD TI Characterization of photosensitivity in the Smith-Lemli-Opitz syndrome: a new congenital photosensitivity syndrome SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE 7-dehydrocholesterol; monochromator light testing; photosensitivity; Smith-Lemli-Opitz syndrome ID DEFECTIVE CHOLESTEROL-BIOSYNTHESIS; 7-DEHYDROCHOLESTEROL; IDENTIFICATION; SKIN; SUPPLEMENTATION; METABOLISM; MUTATIONS; GENE AB Photosensitivity has recently been reported as a feature of the Smith-Lemli-Opitz syndrome (SLO), The aim of this study was to establish the photobiological features of this disorder and to examine the hypothesis that the photosensitivity is caused by the high levels of 7-dehydrocholesterol found in SLO. All known cases of SLO in the U.K. were reviewed and clinical details of photosensitivity were recorded in detail. The action spectrum of the photosensitive eruption was defined by monochromator light testing, Thirteen of the 23 subjects (57%) had severe photosensitivity, and in 10 there was no photosensitivity. No correlation was identified between levels of 7-dehydrocholesterol and severity of photosensitivity, suggesting that the photosensitivity in SLO is not caused by a direct phototoxic effect mediated by 7-dehydrocholesterol A novel pattern of photosensitivity was observed, with onset of a sunburn-like erythema on sun-exposed skin within minutes of sun exposure, which persisted in most cases for up to 24-48 h before fading, Monochromator light testing in three subjects showed an ultraviolet (UV) A-mediated photosensitivity eruption with greatest photosensitivity at 350 nm, Photosensitivity is a common and prominent feature of SLO and appears to be UVA-mediated. Elucidation of its biochemical basis may provide insight into normal cutaneous protective mechanisms against UVA-induced photodamage, and also sun sensitivity in general. C1 Univ Wales Hosp, Coll Med, Photodermatol Unit, Cardiff CF4 4XN, S Glam, Wales. Univ Newcastle Upon Tyne, No Genet Serv, Royal Victoria Infirm, Newcastle Upon Tyne NE2 4AA, Tyne & Wear, England. Univ Liverpool, Dept Dermatol, Photobiol Unit, Liverpool L69 3GA, Merseyside, England. Univ Sussex, MRC, Cell Mutat Unit, Brighton BN1 9RR, E Sussex, England. Univ Bath, Sch Pharm & Pharmacol, Bath BA2 7AY, Avon, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Gange Ctr,Wellman Labs Photomed, Boston, MA 02114 USA. RP Anstey, AV (reprint author), Univ Wales Hosp, Coll Med, Photodermatol Unit, Cardiff CF4 4XN, S Glam, Wales. RI Rhodes, Lesley/H-5324-2015 OI Rhodes, Lesley/0000-0002-9107-6654 NR 34 TC 27 Z9 27 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD SEP PY 1999 VL 141 IS 3 BP 406 EP 414 PG 9 WC Dermatology SC Dermatology GA 240PM UT WOS:000082834400004 PM 10583043 ER PT J AU Shcherbina, A Rosen, FS Remold-O'Donnell, E AF Shcherbina, A Rosen, FS Remold-O'Donnell, E TI Pathological events in platelets of Wiskott-Aldrich syndrome patients SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Wiskott-Aldrich syndrome; platelets; Ca2+ regulation; phosphatidylserine exposure; microparticles ID GLYCOPROTEIN-IIB-IIIA; SYNDROME PROTEIN; SCOTT SYNDROME; AMINOPHOSPHOLIPID EXPOSURE; MICROPARTICLE FORMATION; PROCOAGULANT ACTIVITY; CALPAIN ACTIVATION; COAGULANT ACTIVITY; PLASMA-MEMBRANE; BLOOD-CELLS AB The Wiskott-Aldrich syndrome (WAS) is a severe X-linked platelet/immunological disorder arising from mutations of the gene WASP. At the clinical level, the major platelet abnormalities are small size and low number, both partially correctable by splenectomy, To identify underlying pathological events, we examined WAS platelets at various stages of their lifetime. In spleen sections from WAS patients, fluorescence microscopy showed dramatic co-localization of markers of platelets (CD41) and macrophages (CD68) compared to non-thrombocytopenic controls, suggesting that WAS splenic macrophages are involved in platelet removal. Study of isolated WAS blood platelets by flow cytometry showed substantial enhancement of surface exposure of phosphatidylserine (PS), a signal for engulfment by macrophages. Isolated resting WAS platelets were also aberrantly susceptible to microparticle release, and plasma samples of WAS patients contained >5 times normal numbers of platelet-derived microparticles which may explain the small size of circulating platelets. Measurements with the Ca2+ sensitive dye fluo-3 revealed significantly increased Ca2+ levels, 310 +/- 13 nmol/l for WAS platelets versus 106 +/- 12 nmol/l for normal platelets, and also prolongation of agonist-induced Ca2+ flux. Cumulatively, these studies identify abnormal events occurring in WAS platelets: increased Ca2+ levels and enhancement of two Ca2+ dependent processes, PS exposure and microparticle release; these abnormal events may contribute to the in vivo decrease of platelet number and reduction of platelet size in this disease. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Remold-O'Donnell, E (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL059561, HL59561]; NIAID NIH HHS [R01 AI039574, AI39574] NR 51 TC 27 Z9 27 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 1999 VL 106 IS 4 BP 875 EP 883 DI 10.1046/j.1365-2141.1999.01637.x PG 9 WC Hematology SC Hematology GA 240VR UT WOS:000082848200006 PM 10519987 ER PT J AU Baile, WF Kudelka, AP Beale, EA Glober, GA Myers, EG Greisinger, AJ Bast, RC Goldstein, MG Novack, D Lenzi, R AF Baile, WF Kudelka, AP Beale, EA Glober, GA Myers, EG Greisinger, AJ Bast, RC Goldstein, MG Novack, D Lenzi, R TI Communication skills training in oncology - Description and preliminary outcomes of workshops on breaking bad news and managing patient reactions to illness SO CANCER LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Association-for-Cancer-Education CY NOV 05-08, 1998 CL PORTLAND, OREGON SP Amer Assoc Canc Educ DE communication; training; cancer; outcomes ID CANCER-PATIENTS; HEALTH-PROFESSIONALS; DECISION-MAKING; INFORMATION; CARE; PREFERENCES; DIAGNOSIS; EDUCATION; EFFICACY; DOCTORS AB BACKGROUND. Cancer clinicians do not receive routine training in the psychosocial aspects of patient care such as how to communicate bad news or respond to patients who have unrealistic expectations of cure. Postgraduate workshops may be an effective way to increase interpersonal skills in managing these stressful patient encounters. METHODS. The authors conducted 2 half-day workshops for oncology faculty, one on breaking bad news and one on dealing with "problem situations." Participants met in a large group for didactic presentations and then small groups in which they used role-play and discussion to problem-solve difficult cases from their practices. The small groups were assisted in their work by trained physician facilitators. The workshops were evaluated by means of a follow-up satisfaction questionnaire as well as a self-efficacy measure, which was administered before and after the workshops. RESULTS. Twenty-seven faculty and 2 oncology fellows participated in the training programs. Satisfaction questionnaires showed that the programs met the educational objectives and were considered to be useful and relevant by the participants. Self-efficacy questionnaires revealed an increase in confidence in communicating bad news and managing problem situation cases from before to after the workshop. The majority of attendees welcomed the opportunity to discuss their difficult cases with colleagues. A number resolved to implement newly learned approaches to common patient problems they encountered frequently. CONCLUSIONS. Communication skills workshops may be a useful modality to provide training to oncologists in stressful aspects of the physician-patient relationship. Further research is needed to assess whether long term benefits accrue to the participants. (C) 1999 American Cancer Society. C1 Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Sect Psychiat, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Med Specialties, Sect Gynecol Med Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol & Digest Dis, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Dept Med, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Med, Houston, TX 77030 USA. Bayer Inst Hlth Care Commun, W Haven, CT USA. Med Coll Penn & Hahnemann Univ, Dept Med, Div Med Educ, Philadelphia, PA USA. RP Baile, WF (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Sect Psychiat, 1515 Holcombe Blvd,Box 100, Houston, TX 77030 USA. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 50 TC 150 Z9 152 U1 5 U2 10 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 SEP 1 PY 1999 VL 86 IS 5 BP 887 EP 897 DI 10.1002/(SICI)1097-0142(19990901)86:5<887::AID-CNCR27>3.0.CO;2-X PG 11 WC Oncology SC Oncology GA 228JK UT WOS:000082133200027 PM 10463990 ER PT J AU Tikoo, A Cutler, H Lo, SH Chen, LB Maruta, H AF Tikoo, A Cutler, H Lo, SH Chen, LB Maruta, H TI Treatment of Ras-induced cancers by the F-actin cappers tensin and chaetoglobosin K, in combination with the caspase-1 inhibitor N1445 SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE Ras; tumor suppressors; F-actin capping; tensin; cytochalasins ID PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; CELL-LINE; GROWTH; PROTEINS; GELSOLIN; CDNA; TUMORIGENICITY; TRANSFORMATION; FIBROBLASTS; APOPTOSIS AB BACKGROUND For transforming normal fibroblasts to malignant cells, oncogenic Ras mutants such as v-Ha-ras require Rho family GTPases (Rho, Pac, and CDC42) that are responsible for controlling actin-cytoskeleton organization. Pas activates Rac through a PI-3 kinase-mediated pathway. Pac causes uncapping of actin filaments (F-actin) at the plus-ends, through phosphatidylinositol 4,5 bisphosphate (PIP2), and eventually induces membrane ruffling. Several distinct F-actin/PIP2-binding proteins, such as gelsolin, which severs and caps the plus-ends of actin filaments, or HS1, which cross-links actin filaments, have been shown to suppress v-Ha-Ras-induced malignant transformation when they are overexpressed. Interestingly an F-actin cross-linking drug (photosensitizer) called MKT-077 suppresses Ras transformation. Thus, an F-actin capping/severing drug might also have an anticancer potential. PURPOSE This study was conducted to determine first whether Pas-induced malignant phenotype (anchorage-independent growth) is suppressed by overexpression of the gene encoding a large plus-end F-actin capping protein called tensin and second to test the anti-pas potential of a unique fungal antibiotic (small compound) called chaetoglobosin K (CK) that also caps the plus-ends of actin filaments. METHODS AND RESULTS DNA transfection with a retroviral vector carrying the tensin cDNA was used to overexpress tensin in v-Ha-Ras-transformed NIH 3T3 cells. All stable tensin transfectants rarely formed colonies in soft agar, indicating that tensin suppresses the anchorage-independent growth. The anti-Ras action of CK was determined by incubating the Ras-transformants in the presence of CK in soft agar, Two mu M CK almost completely inhibited their colony formation, indicating that CK also suppresses the malignant phenotype. However, unlike tensin, CK causes an apoptosis of Ras-transformed NIH 3T3 cells and, less effectively, of normal NIH 3T3 cells, indicating that CK has an F-actin capping-independent side effect(s). CK-induced apoptosis is at least in part caused by CK-induced inhibition of the kinase PKB/AKT. However, a specific ICE/caspase-1 inhibitor called N1445 completely abolished the CK-induced apoptosis by reactivating PKB, but without affecting the CK-induced suppression of Ras transformation. CONCLUSIONS Like the F-actin cross-linking drug MKT-077, the F-actin capping drug CK may be useful for the treatment of Ras-associated cancers if it is combined with the ICE inhibitor N1445, which abolishes the side effect of CK. Our observations that two distinct F-actin capping molecules (i.e., tensin and CK) suppress Ras-induced malignant phenotype strongly suggest, if not prove, that capping of actin filaments at the plus-ends alone is sufficient to block one of the Pas signaling pathways essential for its oncogenicity, This notion is compatible with the fact that Ras induces the uncapping of actin filaments at the plus-ends through the Rac/PIP2 pathway. C1 Royal Melbourne Hosp, Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia. Mercer Univ, So Sch Pharm, Dept Pharmaceut Sci, Atlanta, GA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Maruta, H (reprint author), Royal Melbourne Hosp, Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia. NR 37 TC 21 Z9 21 U1 0 U2 1 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD SEP-OCT PY 1999 VL 5 IS 5 BP 293 EP 300 PG 8 WC Oncology SC Oncology GA 247CL UT WOS:000083203000008 PM 10526670 ER PT J AU McMenamin, ME Soung, P Perera, S Kaplan, I Loda, M Sellers, WR AF McMenamin, ME Soung, P Perera, S Kaplan, I Loda, M Sellers, WR TI Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high gleason score and advanced stage SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol ID TUMOR-SUPPRESSOR GENE; COWDEN-DISEASE; GERMLINE MUTATIONS; PTEN/MMAC1 GENE; GLIOMA-CELLS; FREQUENT INACTIVATION; PHOSPHATASE-ACTIVITY; HOMOZYGOUS DELETION; GLIOBLASTOMA CELLS; MMAC1/PTEN GENE AB The tumor suppressor gene PTEN/MMAC-1/TEP-1 (referred to hereafter as PTEN) maps to chromosome 10q23 and encodes a dual specificity phosphatase, The PTEN protein negatively regulates cell migration and cell survival and induces a G(1) cell cycle black via negative regulation of the phosphatidylinositol 3'-kinase/protein kinase B/Akt signaling pathway, PTEN is frequently mutated or deleted in both prostate cancer cell lines and primary prostate cancers. A marine polyclonal antiserum was raised against a glutathione S-transferase fusion polypeptide of the COOH terminus of PTEN, Archival paraffin tissue sections from 109 cases of resected prostate cancer were immunostained with the antiserum, using DU145 and PC-3 cells as positive and negative controls, respectively. PTEN expression was seen in the secretory cells, Cases were considered positive when granular cytoplasmic staining was seen in all tumor cells, mixed when areas of both positive and negative tumor cell clones were seen, and negative when adjacent benign prostate tissue but not tumor tissue shelved positive staining, Seventeen cases (15.6%) of prostate cancer were positive, 70 cases (64.2%) were mixed, and 22 cases (20.2%) were negative. Total absence of PTEN expression correlated with the Gleason score (P = 0.0081) and correlated more significantly with a Gleason score of 7 or higher (P = 0.0004) and with advanced pathological stage (American Joint Committee on Cancer stages T3b and T4; P = 0.0078). Thus, loss of PTEN protein is correlated with pathological markers of poor prognosis in prostate cancer. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Loda, M (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 59 TC 436 Z9 461 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1999 VL 59 IS 17 BP 4291 EP 4296 PG 6 WC Oncology SC Oncology GA 232PY UT WOS:000082380200030 PM 10485474 ER PT J AU Heijn, M Roberge, S Jain, RK AF Heijn, M Roberge, S Jain, RK TI Cellular membrane permeability of anthracyclines does not correlate with their delivery in a tissue-isolated tumor SO CANCER RESEARCH LA English DT Article ID RESISTANT K562 CELLS; BLOOD-FLOW; SOLID TUMORS; DRUG-DELIVERY; PHARMACOKINETICS; DOXORUBICIN; DAUNORUBICIN; KINETICS; HETEROGENEITY; IDARUBICIN AB The clearance of anthracyclines from the vasculature was studied in perfused tissue-isolated tumors. Human tumor lines MCF-7, U87, and LS174T were implanted in the ovarian fat pad of immune-deficient mice and grown isolated from the surrounding tissue. The initial and continuous tissue uptakes of doxorubicin, daunorubicin, and idarubicin were measured. The clearance of these anthracyclines from the perfused vasculature of the tissue-isolated tumor was calculated using BSA as an intravascular marker. The measured clearances ranged from 50-200 mu l/min/g tumor tissue, and the fractional clearances were between 0.30 and 0.70. On the basis of the in vitro cellular uptake rates of the anthracyclines, we expected a higher clearance of idarubicin than of doxorubicin. No significant differences were found among the clearances of the anthracyclines or among the tumor lines. The observed similarities in clearance of the anthracyclines was largely explained by differences in their protein binding and tissue diffusion gradients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, 100 Blossom St,Cox 7, Boston, MA 02114 USA. FU NCI NIH HHS [R35-CA-56591] NR 31 TC 15 Z9 16 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 SEP 1 PY 1999 VL 59 IS 17 BP 4458 EP 4463 PG 6 WC Oncology SC Oncology GA 232PY UT WOS:000082380200054 PM 10485498 ER PT J AU Kim, CS Matsumori, A Goldberg, L Doye, AA McCoy, Q Gwathmey, JK AF Kim, CS Matsumori, A Goldberg, L Doye, AA McCoy, Q Gwathmey, JK TI Effects of pranidipine, a calcium channel antagonist, in an avian model of heart failure SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Article DE Broad-Breasted White turkey poults; Ca2- channel antagonist; cardiomyopathy; dihydropyridines; furazolidone; turkeys ID LEFT-VENTRICULAR MASS; DILATED CARDIOMYOPATHY; CONTRACTILE PERFORMANCE; SARCOPLASMIC-RETICULUM; MYOCARDIAL-INFARCTION; STAGE; FORCE; PATHOPHYSIOLOGY; DYSFUNCTION; HYPERTROPHY AB We have previously demonstrated that turkey poults fed furazolidone (Fz) in high concentrations (700 ppm) develop dilated cardiomyopathy (DCM) which approximates the human condition [1-3]. We wanted to study the effects of a calcium channel blocker in an animal model with a documented decrease in beta-receptor density, increased levels of circulating catecholamines, and abnormal calcium metabolism. The effects of a third generation calcium channel blocker has not been studied in our model. We hypothesized that the model would be predictive of the human condition and provide additional insights into the potential use of Ca2+ channel blockers in the setting of DCM. In the present study, we examined the effect of pranidipine, a new dihydropyridine calcium antagonist, in the setting of DCM on the gross and microscopic morphology of the heart and the overall contractile performance of the myocardium. A state of symptomatic to mild cardiomyopathy was induced in Broad-Breasted White turkey poults by administration of Fz for three weeks. Blood pressure, heart rate, fractional shortening, and body weight were monitored and compared in DCM animals treated with pranidipine and those given a placebo. After four weeks of treatment or no treatment with pranidipine, animals were euthanized and heart weight, cardiac dimensions, and microscopic morphology were compared. Progressive left ventricular (LV) dilatation and wall thinning was prevented with pranidipine treatment. In addition, microscopic examination demonstrated myocyte hypertrophy regression in DCM animals treated with pranidipine. In DCM animals, treatment with pranidipine resulted in significantly smaller left ventricular dimensions. We conclude that the calcium channel blocker pranidipine was not detrimental to global cardiac function in animals with dilated cardiomyopathy. C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Inst Cardiovasc Dis & Muscle Res Inc, Robnette F Turpin Res Ctr, Cambridge, MA USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Kyoto Univ, Fac Med, Dept Internal Med, Div 3, Kyoto 606, Japan. Medifare Drug & Hlth Educ Ctr, Blacksburg, SC USA. RP Gwathmey, JK (reprint author), 763 Bldg E Concord Ave, Cambridge, MA 02138 USA. FU NHLBI NIH HHS [2RO1 HL49574, R44-HL60323] NR 41 TC 6 Z9 7 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD SEP PY 1999 VL 13 IS 5 BP 455 EP 463 DI 10.1023/A:1007816309841 PG 9 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 231QY UT WOS:000082322600010 PM 10547227 ER PT J AU Kiesz, RS Rozek, MM Ebersole, DG Mego, DM Chang, CW Chilton, RL AF Kiesz, RS Rozek, MM Ebersole, DG Mego, DM Chang, CW Chilton, RL TI Novel approach to rotational atherectomy results in low restenosis rates in long, calcified lesions: Long-term results of the San Antonio Rotablator Study (SARS) SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE atherectomy; restenosis; complex lesions ID ADJUNCTIVE BALLOON ANGIOPLASTY; CORONARY-ARTERY DISEASE; PLATELET-AGGREGATION; SINGLE-CENTER; FOLLOW-UP; EXPERIENCE; INTERVENTION; ABLATION; REGISTRY; INJURY AB Ablation technique and adjunctive strategy may affect restenosis after rotational atherectomy To minimize trauma to the vascular wall, we changed the technique of rotablation as follows: the RPM range was decreased to 140,000-160,000 RPM, the ablation was performed using a repetitive pecking motion, avoiding a decrease in the rotational speed of the burr greater than 3,000 RPM, long lesions were divided into segments and each segment was separately ablated, and the burr-to-artery ratio was intended to be approximately 0.75. To prevent coronary spasm, before and after each pass, 100-200 mu g nitroglycerin and 100-200 mu g verapamil i.c. boluses were administered. Adjunctive PTCA was performed using a closely sized 1.1:1 balloon-to-artery ratio with a noncompliant balloon at low pressures for 120 sec. The study incorporated 111 patients with a combined total of 146 calcified lesions. Results. A total of 31.5% of patients underwent a multivessel procedure. No deaths occurred. CI-wave MI and/or creatine kinase elevation greater than three times baseline levels occurred in 4.5% of patients. By quantitative coronary angiography (QCA), the reference vessel diameter was 3.13+/-0.59 mm, mean lesion length was 33.41+/-18.58 mm. Percent stenosis and mean luminal diameter were as follows: at baseline 75.7%+/-10.8%, or 0.76+/-0.41 mm, Post-rotational atherectomy 41.5%+/-3.6%, or 1.83+/-0.43 mm, Post-PTCA 18.2%+/-11.9%, or 2.56+/-0.50 mm. Six-month angiographic follow-up was available in 64 (57.7%) pts. Net luminal gain was 1.15+/-0.76 mm, with a late luminal loss of 0.65+/-0.84 mm. The mean diameter stenosis at follow-up was 37.6%+/-28.5%, with MLD 1.91 +/- 1.21 mm. The binary restenosis rate was 28.1%. Therefore, modification of rotational atherectomy technique with adjunctive PTCA resulted in a favorable restenosis rate in long, calcified lesions. (C) 1999 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Div Cardiol, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Cardiac Catheterizat Labs, Audie Murphy Div, San Antonio, TX USA. Brooke Army Med Ctr, San Antonio, TX USA. RP Kiesz, RS (reprint author), Univ Texas, Hlth Sci Ctr, Div Cardiol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 26 TC 17 Z9 18 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD SEP PY 1999 VL 48 IS 1 BP 48 EP 53 DI 10.1002/(SICI)1522-726X(199909)48:1<48::AID-CCD9>3.0.CO;2-Y PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 231ZH UT WOS:000082340900009 PM 10467070 ER PT J AU Schmidt, T Korner, K Karsunky, H Korsmeyer, S Muller, R Moroy, T AF Schmidt, T Korner, K Karsunky, H Korsmeyer, S Muller, R Moroy, T TI The activity of the murine Bax promoter is regulated by Sp1/3 and E-box binding proteins but not by p53 SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE bax; p53; in vivo footprinting; apoptosis ID CELL-DEATH; REPRESSOR ELEMENT; T-CELLS; IN-VIVO; APOPTOSIS; GENE; FAMILY; CYCLE; MICE; P21 AB In human cells the expression of the pro-apoptotic protein Bax appears to be regulated through p53-dependent transcriptional activation. However, in the mouse, p53 deficiency does not affect Bax expression. To shed more light on the transcriptional regulation of the bax gene we have analyzed the murine bax promoter. We find several E-box and Sp1/Sp3 binding sites as well as three putative p53 binding sites that are conserved in the human promoter sequence. We can show that both the Spl and the E-box binding sites are necessary for proper regulation of bax transcription and show by genomic DMS footprinting that all these sites are occupied in vivo. In contrast, the putative p53 binding sites were not occupied by protein in vivo in primary murine thymocytes either before or after induction of p53 by DNA damage. Moreover, p53 was unable to regulate the transcription of bax promoter fragments up to 6.5 kb in length. Further, steady state levels of bax mRNA did not correlate with Bax protein expression levels in DNA damage-induced cell death. Our findings exclude a direct transcriptional transactivation of the bax gene by p53 in murine cells suggesting a dominance of p53 independent mechanisms for the regulation of Bax protein expression. C1 Univ Klinikum Essen, Inst Zellbiol Tumorforsch, IFZ, D-45122 Essen, Germany. Dana Farber Canc Inst, Dept Canc Immunol & AIDS 1, Boston, MA 02115 USA. Univ Marburg, Inst Mol Biol & Tumorforsch, D-35033 Marburg, Germany. RP Moroy, T (reprint author), Univ Klinikum Essen, Inst Zellbiol Tumorforsch, IFZ, Virchowstr 173, D-45122 Essen, Germany. RI Moroy, Tarik/D-9923-2011; Muller, Rolf/L-4997-2016 OI Muller, Rolf/0000-0003-3339-4248 NR 38 TC 38 Z9 38 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD SEP PY 1999 VL 6 IS 9 BP 873 EP 882 DI 10.1038/sj.cdd.4400562 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 242UC UT WOS:000082959200008 PM 10510469 ER PT J AU Dearolf, CR AF Dearolf, CR TI JAKs and STATs in invertebrate model organisms SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Drosophila; Dictyostelium; JAK kinase; STAT; genetics; signaling; transcription ID DICTYOSTELIUM-DISCOIDEUM; DROSOPHILA-MELANOGASTER; HEMATOPOIETIC ONCOGENE; 2 DISTINCT; STALK CELL; KINASE; PROTEIN; MUTATION; GENE; ACTIVATION AB Invertebrate organisms provide systems to elucidate the developmental roles of Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathways, thereby complementing research conducted with mammalian cells and animals. Components of the JAK/STAT protein pathway have been identified and characterized in the fruit fly Drosophila melanogaster and the cellular slime mold Dictyostelium discoideum. This review summa rites the molecular and genetic data obtained from these model organisms. In particular, a Drosophila JAK/STAT pathway regulates normal segmentation, cell proliferation, and differentiation, and hyperactivation of the pathway leads to tumor formation and leukemia-like defects. A Dictyostelium STAT regulates the development of stalk cells during the multicellular part of the life cycle. Future research utilizing these organisms should continue to provide insights into the roles and regulation of these proteins and their signaling pathways. C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Dearolf, CR (reprint author), Massachusetts Gen Hosp, Dept Pediat, Jackson 1402,55 Fruit St, Boston, MA 02114 USA. NR 36 TC 44 Z9 45 U1 1 U2 7 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD SEP PY 1999 VL 55 IS 12 BP 1578 EP 1584 DI 10.1007/s000180050397 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 242YV UT WOS:000082971200008 PM 10526575 ER PT J AU Thurer, RL AF Thurer, RL TI The definition of survival SO CHEST LA English DT Editorial Material C1 Beth Israel Deaconee Med Ctr, Boston, MA 02212 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Thurer, RL (reprint author), Beth Israel Deaconee Med Ctr, 330 Brookline Ave, Boston, MA 02212 USA. NR 2 TC 0 Z9 0 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 SEP PY 1999 VL 116 IS 3 BP 593 EP 594 DI 10.1378/chest.116.3.593 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 234GJ UT WOS:000082475900004 PM 10492258 ER PT J AU Munakata, Y Umezawa, Y Iwata, S Dong, RP Yoshida, S Ishii, T Morimoto, C AF Munakata, Y Umezawa, Y Iwata, S Dong, RP Yoshida, S Ishii, T Morimoto, C TI Specific inhibition of TH2-type cytokine production from human peripheral T cells by terfenadine in vitro SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE terfenadine; CD26; CD28; CD3; costimulation; interferon-gamma; interleukin-2; interleukin4; interleukin-5; T cell ID ACTIVATION; RECEPTOR; BLOOD; ANTIGEN; INTERLEUKIN-4; LYMPHOCYTES; EXPRESSION; RESPONSES; MICE AB Background Cytokine imbalance is thought to be one of the causes for allergic diseases. The effect of anti-allergic drugs on cytokine production from T cells should be examined in a convenient way. Objectives To study the in vitro effect of terfenadine, a prototype non-sedating H1 receptor antagonist, on cytokine production from activated T cells. Methods T cells were cultured in the presence of terfenadine on anti-CD3 mAb and anti-CD26 mAb-coated wells, anti-CD3 mAb and anti-CD28 mAb-coated wells, and anti-CD3 mAb wells with PMA. T-cell proliferation, along with the concentrations of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-5 were measured. Results Terfenadine inhibited T-cell proliferation and IL-4 and IL-5 production under each costimulatory condition tested, whereas it had no effect on IL-2 and IFN-gamma production. Conclusions These results indicate that terfenadine has a specific inhibitory effect on TH2-type cytokine production induced by several ways of costimulatory activation. C1 Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Juntendo Univ, Sch Med, Dept Pathol 2, Tokyo 113, Japan. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Morimoto, C (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. RI Iwata, Satoshi/A-8819-2011 FU NIAID NIH HHS [AI-29530]; NIAMS NIH HHS [AR-33713] NR 26 TC 23 Z9 24 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD SEP PY 1999 VL 29 IS 9 BP 1281 EP 1286 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 235KN UT WOS:000082541000020 PM 10469039 ER PT J AU Grossbard, ML Multani, PS Freedman, AS O'Day, S Gribben, JG Rhuda, C Neuberg, D Nadler, LM AF Grossbard, ML Multani, PS Freedman, AS O'Day, S Gribben, JG Rhuda, C Neuberg, D Nadler, LM TI A phase II study of adjuvant therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with relapsed B-cell non-Hodgkin's lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID A CHAIN IMMUNOTOXIN; HEMATOLOGIC MALIGNANCIES; CONTINUOUS-INFUSION; BOLUS INFUSION; BLOCKED RICIN; TRIAL; INTERLEUKIN-2; NEOPLASMS; TOXICITY; MARKING AB This Phase II trial was undertaken to determine the safety, toxicity, and potential efficacy of the B-cell restricted immunotoxin anti-B4-blocked ricin (Anti-B4-bR) when administered as adjuvant therapy to patients in complete remission (CR) after autologous bone marrow transplantation (ABMT) for B-cell non-Hodgkin's lymphoma (NHL), Forty-nine patients with B-cell NHL in CR 46-202 days (median, 112 days) post-ABMT received Anti-B4-bR at a dose of 30 mu g/kg lean body weight/day for 7 days by continuous i.v. infusion. Patients were eligible for up to two additional courses of therapy at 14-day intervals. A total of 83 courses of Anti B4-bR were administered, with 31 patients receiving two or more courses of therapy. The mean serum level on day 7 of the first course was 0.77 +/- 0.41 nM. Reversible toxicities included hepatic transaminase elevations, thrombocytopenia, myalgias, fatigue, nausea, hypoalbuminemia, and dyspnea, Human antimouse antibody (HAMA) and/or human antiricin antibody (HARA) responses occurred in 23 patients at a median of 22 days from the initiation of Anti-B4-bR therapy (range, 11-100 days). The l-year disease-free survival and overall survival are estimated at 56 and 72%, respectively, Twenty-six patients remain in CR after a median follow-up of 54.5 months. This study demonstrates that Anti-B4-bR can be administered safely to patients as adjuvant therapy early after ABMT for B-cell NHL, The toxicities are tolerable and reversible. Although the early estimate of disease-free survival was very encouraging in this single-armed trial, the 4-year follow-up data demonstrate continued relapse. C1 Massachusetts Gen Hosp, Hematol Oncol Unit Cox 2, Boston, MA 02114 USA. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Grossbard, ML (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit Cox 2, 100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [1K12CA01730, CA55207, CA66996] NR 26 TC 36 Z9 39 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1999 VL 5 IS 9 BP 2392 EP 2398 PG 7 WC Oncology SC Oncology GA 236DN UT WOS:000082583100017 PM 10499609 ER PT J AU Teicher, BA Ara, G Herbst, R Palombella, VJ Adams, J AF Teicher, BA Ara, G Herbst, R Palombella, VJ Adams, J TI The proteasome inhibitor PS-341 in cancer therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; NF-KAPPA-B; ALKYLATING-AGENTS; DEGRADATION; ACID; LACTACYSTIN; PATHWAY; RESISTANCE; PROTEIN; ACTIVATION AB The anticancer activity of the boronic acid dipeptide proteasome inhibitor PS-341 was examined in vitro and in vivo. PS-341 was a potent cytotoxic agent toward MCF-7 human breast carcinoma cells in culture, producing an IC90 of 0.05 mu M on 24 h of exposure to the drug. In the EMT-6 tumor cell survival assay, PS-341 was equally cytotoxic administered p.o. or by i.p. injection up to a dose of 2 mg/kg. PS-341 was also toxic to the bone marrow colony-forming unit-granulocyte macrophage. PS 341 increased the tumor cell killing of radiation therapy, cyclophosphamide, and cisplatin in the EMT-6/Parent tumor, but was not able to overcome the in vivo resistance of the EMT-6/CTX and EMT-6/CDDP tumors. In the tumor grow th delay assay, PS-341 administered p.o. had antitumor activity against the Le,vis lung carcinoma, both primary and metastatic disease, In combination, regimens with 5-fluorouracil, cisplatin, Taxol and adriamycin, PS-341 seemed to produce primarily additive tumor growth delays against the s.c. tumor and was highly effective against disease metastatic to the lungs. The proteasome is an interesting new target for cancer therapy, and the proteasome inhibitor PS-341 warrants continued investigation in cancer therapy. C1 ProScript Inc, Cambridge, MA 02139 USA. 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. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 41 TC 347 Z9 359 U1 1 U2 18 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1999 VL 5 IS 9 BP 2638 EP 2645 PG 8 WC Oncology SC Oncology GA 236DN UT WOS:000082583100051 PM 10499643 ER PT J AU Zusman, RM Chesebro, JH Comerota, A Hartmann, JR Massin, EK Raps, E Wolf, PA AF Zusman, RM Chesebro, JH Comerota, A Hartmann, JR Massin, EK Raps, E Wolf, PA TI Antiplatelet therapy in the prevention of ischemic vascular events: Literature review and evidence-based guidelines for drug selection SO CLINICAL CARDIOLOGY LA English DT Article DE antiplatelet; atherosclerosis; evidence-based; peripheral arterial disease; myocardial infarction; ischemic stroke ID CORONARY-ARTERY DISEASE; HUMAN ATHEROSCLEROTIC PLAQUES; DOUBLE-BLIND TRIAL; LOW-DOSE ASPIRIN; MYOCARDIAL-INFARCTION; INTERMITTENT CLAUDICATION; CARDIOVASCULAR-DISEASE; ANTITHROMBOTIC THERAPY; ACETYLSALICYLIC-ACID; SECONDARY PREVENTION AB Background: New antiplatelet drugs are being developed and many clinical trials evaluating the benefits of antiplatelet drugs for the secondary prevention of ischemic events in patients with atherosclerotic vascular disease have been performed. Hypothesis: An updated systematic review and evidence-based guidelines for the appropriate selection of antiplatelet drugs may be beneficial to physicians and healthcare organizations attempting to create or update current clinical practice guidelines or clinical pathways aimed at caring for these patients. Methods: (1) A systematic review of the recent literature on the relative efficacy and safety of aspirin, ticlopidine, and clopidogrel was undertaken; (2) an evidence-based, expert panel approach using a modified Delphi technique to create explicit guidelines for prescribing antiplatelet therapy was instituted; and (3) the recommendations of an expert panel were summarized. Results: Consensus guidelines were developed for the utilization of aspirin, ticlopidine, or clopidogrel for the prevention of ischemic events in patients with manifestations of atherosclerotic vascular disease (prior myocardial infarction, prior ischemic stroke, or established peripheral arterial disease) who are at increased risk for recurrent ischemic events. Based on efficacy and safety, clopidogrel was recommended as the drug of choice for patients with established peripheral arterial disease; aspirin or clopidogrel should be considered in patients with prior myocardial infarction (with clopidogrel favored for patients who have had a recurrent event while on aspirin or in whom aspirin is contraindicated); aspirin or clopidogrel should be considered as first-line treatment in patients with prior ischemic (nonhemorrhagic) stroke-however, clopidogrel is the favored drug in patients in whom other antiplatelet drugs are either contraindicated or who have had recurrent events while on therapy. Conclusions: Myocardial infarction, ischemic stroke, and peripheral arterial disease are all clinical manifestations of the same underlying disease process (atherosclerosis), with thrombus formation on the disrupted atherosclerotic plaque (atherothrombosis) being a common precipitating factor of ischemic events in patients suffering from these disorders. An evidence-based approach was used to develop a practice guideline, based on available published evidence, for the appropriate utilization of antiplatelet agents (aspirin, ticlopidine, or clopidogrel). These guidelines may be of use to multidisciplinary teams wishing to create or update clinical guidelines or clinical pathways which address the care of patients with atherosclerotic vascular disease. New antiplatelet agents such as clopidogrel may be more effective and associated with lower risk of selected adverse effects (such as gastrointestinal distress, gastrointestinal hemorrhage, and neutropenia) than those previously used to prevent thrombus formation in the setting of atherosclerotic arterial disease. Combination antiplatelet therapy is being evaluated as an option for those patients who experience recurrent events on a single antiplatelet agent. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hypertens & Vasc Med,Cardiac Unit, Boston, MA 02114 USA. Mt Sinai Med Ctr, Mt Sinai Sch Med, Cardiovasc Inst, New York, NY 10029 USA. Temple Univ, Temple Univ Hosp, Sch Med, Ctr Vasc Dis, Philadelphia, PA 19140 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Univ Penn, Med Ctr, Dept Neurol, Philadelphia, PA 19104 USA. Boston Univ, Med Ctr, Sch Med, Boston, MA 02118 USA. RP Zusman, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hypertens & Vasc Med,Cardiac Unit, 15 Parkman St, Boston, MA 02114 USA. NR 86 TC 21 Z9 22 U1 1 U2 2 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 SEP PY 1999 VL 22 IS 9 BP 559 EP 573 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 231WZ UT WOS:000082335500004 PM 10486695 ER PT J AU Plaschke, J Bulitta, C Saeger, HD Schackert, HK AF Plaschke, J Bulitta, C Saeger, HD Schackert, HK TI Quantitative differences between aberrant transcripts which occur as common isoforms and due to mutation-based exon skipping of the mismatch repair gene hMLH1 SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article DE aberrant transcripts; cDNA; hMLH1; HNPCC; RT-PCR ID NONPOLYPOSIS COLORECTAL-CANCER; MESSENGER-RNA; MSH2 MUTATIONS; MLH1 MUTATIONS; SPECTRUM; CELLS; LOCUS; HMSH2 AB About one-third of hereditary non-polyposis colorectal cancer-related mutations in the mismatch repair gene hMLH1 result in the loss of entire exons from the wild type transcripts. Here we describe quantitative differences of hMLH1 transcripts without exon 15, exon 16 or exon 17 in several members of a family with hereditary non-polyposis colorectal cancer. The transcript lacking exon 15 is caused by a G to A transition affecting the last nucleotide of the respective exon and results in a truncated protein. The transcripts lacking exon 16 or exon 17, which are in-frame deletions, were also found in all tested samples of a normal population and represent common isoforms. Reverse transcription-polymerase chain reaction-based relative quantification revealed about 50 % signal intensity for the mutation-based transcript, but less than 10 % for the common isoforms, if compared to the wild type. All aberrant transcripts were detected from blood-derived cDNAs but not from samples of normal colon epithelium. Although the biological significance of the common isoforms is unknown, they might lead to false risk assessment in hereditary non-polyposis colorectal cancer cases. C1 Tech Univ Dresden, Carl Gustav Carus Klinikum, Dept Surg Res, D-01307 Dresden, Germany. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Tech Univ Dresden, Carl Gustav Carus Klinikum, Dept Surg, Dresden, Germany. RP Plaschke, J (reprint author), Tech Univ Dresden, Carl Gustav Carus Klinikum, Dept Surg Res, Fetscherstr 74, D-01307 Dresden, Germany. NR 21 TC 3 Z9 3 U1 0 U2 0 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD SEP PY 1999 VL 37 IS 9 BP 883 EP 887 DI 10.1515/CCLM.1999.131 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 266WD UT WOS:000084322500004 PM 10596954 ER PT J AU Filley, CM AF Filley, CM TI Toxic leukoencephalopathy SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE leukoencephalopathy; white matter; white matter dementia; neurotoxicology ID CENTRAL-NERVOUS-SYSTEM; CEREBRAL WHITE-MATTER; MULTIFOCAL INFLAMMATORY LEUKOENCEPHALOPATHY; BONE-MARROW TRANSPLANT; HIGH-DOSE CHEMOTHERAPY; BRAIN IRRADIATION; PROPHYLACTIC TREATMENT; PROTON SPECTROSCOPY; CHRONIC-ALCOHOLICS; TOLUENE ABUSE AB The white matter of the brain is vulnerable to a wide variety of toxins. Leukoencephalopathy is being increasingly recognized in a number of different patient populations. The detection of early and subtle toxin effects has been facilitated by the advent of magnetic resonance imaging, which offers better resolution of white matter than other neuroimaging methods. Neuropathologic features of leukoencephalopathy are also becoming more completely elucidated. Injury to white matter has been described from cranial irradiation and cancer chemotherapeutic drugs, and from a number of other therapeutic agents, drugs of abuse, and environmental toxins. Many patients have reversible leukoencephalopathy, whereas others experience a progressive and irreversible course. Leukoencephalopathy is associated with neurobehavioral manifestations that may be subtle or devastating, and the syndrome of white matter dementia may result. The pathogenesis of toxic leukoencephalopathy remains largely unknown, and treatment is limited in most cases to prevention by avoidance or minimization of the toxin exposure. However, the prognosis for this syndrome may be relatively favorable because of the frequent sparing of axons even when myelin is affected. Toxic leukoencephalopathy is an emerging clinical disorder that presents the opportunity for improving clinical outcomes in a number of patient groups and for achieving a deeper understanding of the role of white matter in cognitive and emotional function. C1 Univ Colorado, Sch Med, Dept Neurol, Denver, CO USA. Univ Colorado, Sch Med, Dept Psychiat, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Filley, CM (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, Behav Neurol Sect, B-183,4200 E 9th Ave, Denver, CO 80262 USA. NR 73 TC 26 Z9 27 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD SEP-OCT PY 1999 VL 22 IS 5 BP 249 EP 260 PG 12 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 241FN UT WOS:000082872200001 PM 10516874 ER PT J AU Thadhani, R Stampfer, MJ Chasan-Taber, L Willett, WC Curhan, GC AF Thadhani, R Stampfer, MJ Chasan-Taber, L Willett, WC Curhan, GC TI A prospective study of pregravid oral contraceptive use and risk of hypertensive disorders of pregnancy SO CONTRACEPTION LA English DT Article DE oral contraceptives; gestational hypertension; preeclampsia; prospective cohort study ID HEALTHY NULLIPAROUS WOMEN; CARDIOVASCULAR-DISEASE; UNITED-STATES; PREECLAMPSIA; EPIDEMIOLOGY; LIPOPROTEINS; LIPIDS AB Oral contraceptive use is associated with hypertension, dyslipidemias, and insulin resistance, all of which also characterize hypertensive disorders of pregnancy. In this prospective cohort study, the association of oval contraceptive use before pregnancy and the risk of gestational hypertension and preeclampsia was assessed. Between 1991 and 1995, 3973 nulliparous women who reported their first pregnancy lasting greater than or equal to 6 months were studied. Pregravid exposures were collected by biennial mailed questionnaires, and cases were confirmed by medical record review Recent oral contraceptive use was defined as use within 2 years of pregnancy. Proportional hazards analysis as used to adjust for potential confounding variables. During the 4 years of follow-up, 133 (3.3%) women with gestational hypertension and 62 (1.6%) with preeclampsia were identified. Twenty-five percent of women who did not develop these disorders were recent users of oral contraceptives, compared with 19% (p = 0.12) of women who developed gestational hypertension and 30% (p = 0.38) who developed preeclampsia. Mean duration of prior oral contraceptive use was similar for cases and noncases. Compared with never and past users, the multivariate relative risk among recent users for developing gestational hypertension was 0.7 (95% confidence interval (CI), 0.4-1.0) and for preeclampsia was 1.3 (95% CI, 0.8-2.4). Among recent users who had used oral contraceptives for greater than or equal to 8 years, the relative risk for gestational hypertension was 0.6 (95% CI, 0.3-1.2) and for preeclampsia was 2.1 (95% CI, 1.1-4.2). When the analysis was restricted to women who had never smoked, the risk for gestational hypertension was 0.2 (95% CI, 0.1-0.9) and for preeclampsia was 4.1 (95% CI, 1.9-8.7). Thus, recent use of oral contraceptives was associated with a reduced risk for developing gestational hypertension. In contrast, there was a suggestion that recent use was associated with an increased risk of developing preeclampsia, but only among women who had used these agents for greater than or equal to 8 years. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. RP Thadhani, R (reprint author), Founders 036,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA50385]; NHLBI NIH HHS [K08HL03804] NR 36 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 0010-7824 J9 CONTRACEPTION JI Contraception PD SEP PY 1999 VL 60 IS 3 BP 145 EP 150 DI 10.1016/S0010-7824(99)00079-7 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 267HR UT WOS:000084352900003 PM 10640157 ER PT J AU Bigatello, LM Hurford, WE AF Bigatello, LM Hurford, WE TI Inhaled nitric oxide and pulmonary vascular resistance SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE nitric oxide; septic shock; endotoxin; pulmonary vascular resistance; pulmonary hypertension; vasodilators; inhalation therapy ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; ISCHEMIA-REPERFUSION; INHALATION; HYPERTENSION; OXYGENATION; PRESSURE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bigatello, LM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 20 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1999 VL 27 IS 9 BP 2060 EP 2061 DI 10.1097/00003246-199909000-00075 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 238VZ UT WOS:000082736300075 PM 10507659 ER PT J AU Artinger, KB Chitnis, AB Mercola, M Driever, W AF Artinger, KB Chitnis, AB Mercola, M Driever, W TI Zebrafish narrowminded suggests a genetic link between formation of neural crest and primary sensory neurons SO DEVELOPMENT LA English DT Article DE narrowminded; neural crest; sensory neurons; cell signalling; zebrafish ID XENOPUS-EMBRYOS; WILD-TYPE; NO TAIL; PRIMARY NEUROGENESIS; BRACHYDANIO-RERIO; MUTANT EMBRYOS; DANIO-RERIO; CELL FATE; EXPRESSION; MUTATIONS AB In the developing vertebrate nervous system, both neural crest and sensory neurons form at the boundary between non-neural ectoderm and the neural plate. From an in situ hybridization based expression analysis screen, we have identified a novel zebrafish mutation, narrowminded (nrd), which reduces the number of early neural crest cells and eliminates Rohon-Beard (RB) sensory neurons. Mosaic analysis has shown that the mutation acts cell autonomously suggesting that nrd is involved in either the reception or interpretation of signals at the lateral neural plate boundary. Characterization of the mutant phenotype indicates that nrd is required for a primary wave of neural crest cell formation during which progenitors generate both RE sensory neurons and neural crest cells. Moreover, the early deficit in neural crest cells in nrd homozygotes is compensated later in development. Thus, we propose that a later wave can compensate for the loss of early neural crest cells but, interestingly, not the RE sensory neurons, We discuss the implications of these findings for the possibility that RE sensory neurons and neural crest cells share a common evolutionary origin. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Artinger, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NICHD NIH HHS [HD29761, F32 HD008209-04, HD08209, F32 HD008209]; NIMH NIH HHS [MH56552] NR 64 TC 72 Z9 74 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP PY 1999 VL 126 IS 18 BP 3969 EP 3979 PG 11 WC Developmental Biology SC Developmental Biology GA 242WY UT WOS:000082965700001 PM 10457007 ER PT J AU Morita, Y Tilly, JL AF Morita, Y Tilly, JL TI Oocyte apoptosis: Like sand through an hourglass SO DEVELOPMENTAL BIOLOGY LA English DT Review DE germ cell; oocyte; apoptosis; cell death; Bcl-2; Bax; caspase; ovary; menopause ID PRIMORDIAL GERM-CELLS; LEUKEMIA INHIBITORY FACTOR; DAUNORUBICIN-INDUCED APOPTOSIS; BCL-2 GENE FAMILY; CYTOCHROME-C; DEFICIENT MICE; IN-VITRO; PHOSPHATIDYLINOSITOL 3-KINASE; CHROMOSOMAL BREAKPOINT; CAENORHABDITIS-ELEGANS AB Although the study of germ cell death is arguably still in its infancy as a held, several recent breakthroughs have provided the fodder for a story, replete with episodes of apparent mass cellular suicide if not murder, that will undoubtedly serve as a research base for many laboratories over the next several years. Death is known to strike the male and female germlines with roughly equal intensity, but the innate feature of male germ cells being self-renewing while those of the female are not places the death of oocytes in a completely different light. Indeed, the functional life span of the female gonads is defined in most species, including humans, by the size and rate of depletion of the precious endowment of oocytes enclosed within follicles in the ovaries at birth. This continuous loss of oocytes throughout life, referred to by many as the female biological clock, appears to be driven by a genetic program of cell death that is composed of players and pathways conserved from worms to humans. It is on this genetic pathway, and the role of its constituent molecules in regulating female germ cell fate, that this review will focus. Emphasis will be placed on those studies using genetic-null or transgenic models to explore the functional requirement of proteins, such as Bcl-2 family members, Apaf-1, and caspases in vertebrates to CED-9, CED-4, and CED-3 in Caenorhabditis elegans, in oocyte survival and death. Furthermore, hypotheses regarding the potential impact of translating what is now known of the oocyte death pathway into new approaches for the clinical diagnosis and management of female infertility and the menopause will be offered as a means to stimulate further research in this new and exciting field, (C) 1999 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG1279]; NICHD NIH HHS [R01-HD34226]; NIEHS NIH HHS [R01-ES08430] NR 158 TC 235 Z9 254 U1 1 U2 7 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 SEP 1 PY 1999 VL 213 IS 1 BP 1 EP 17 DI 10.1006/dbio.1999.9344 PG 17 WC Developmental Biology SC Developmental Biology GA 233HR UT WOS:000082421900001 PM 10452843 ER PT J AU Song, JW Oh, SP Schrewe, H Nomura, M Lei, H Okano, M Gridley, T Li, E AF Song, JW Oh, SP Schrewe, H Nomura, M Lei, H Okano, M Gridley, T Li, E TI The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice SO DEVELOPMENTAL BIOLOGY LA English DT Article DE activin receptor; nodal/BMP; gastrulation; mesoderm formation; cyclopia; mouse development ID NODAL-RELATED SIGNALS; PRIMITIVE STREAK; MOUSE EMBRYO; MESODERM FORMATION; TRUNCATED ACTIVIN; AXIAL STRUCTURES; SONIC-HEDGEHOG; EXPRESSION; GENE; INDUCTION AB The type II activin receptors, ActRIIA and ActRIIB, have been shown to play critical roles in axial patterning and organ development in mice. To investigate whether their function is required for mesoderm formation and gastrulation as implicated in Xenopus studies, we generated mice carrying both receptor mutations by interbreeding the ActRIIA and ActRIIB knockout mutants. We found that embryos homozygous for both receptor mutations were growth arrested at the egg cylinder stage and did not form mesoderm. further analyses revealed that ActRIIA(-/-)ActRIIB(+/-) and about 15% of the ActRIIA(-/-) embryos failed to form an elongated primitive streak, resulting in severe disruption of mesoderm formation in the embryo proper. Interestingly, we observed similar gastrulation defects in ActRIIA(-/-)nodal(+/-) double mutants, which, if they developed beyond the gastrulation stage, displayed rostral head defects and cyclopia. These results provide genetic evidence that type II activin receptors are required for egg cylinder growth, primitive streak formation, and rostral head development in mice. (C) 1999 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Max Planck Inst Immunbiol, Dept Dev Biol, D-7800 Freiburg, Germany. Jackson Lab, Bar Harbor, ME 04609 USA. RP Li, E (reprint author), Massachusetts Gen Hosp E, Room 4217,13th St, Charlestown, MA 02129 USA. FU NIGMS NIH HHS [GM52106] NR 69 TC 137 Z9 141 U1 1 U2 4 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 SEP 1 PY 1999 VL 213 IS 1 BP 157 EP 169 DI 10.1006/dbio.1999.9370 PG 13 WC Developmental Biology SC Developmental Biology GA 233HR UT WOS:000082421900011 PM 10452853 ER PT J AU Caballero, AE Arora, S Saouaf, R Lim, SC Smakowski, P Park, JY King, GL LoGerfo, FW Horton, ES Veves, A AF Caballero, AE Arora, S Saouaf, R Lim, SC Smakowski, P Park, JY King, GL LoGerfo, FW Horton, ES Veves, A TI Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes SO DIABETES LA English DT Article ID ENDOTHELIUM-DEPENDENT VASODILATION; MULTIPLE METABOLIC ABNORMALITIES; INSULIN-RESISTANCE; ESSENTIAL-HYPERTENSION; MEDIATED VASODILATION; ADHESION MOLECULE-1; HEALTHY-MEN; DYSFUNCTION; CORONARY; NIDDM AB Abnormalities in vascular reactivity in the micro- and macrocirculation are well established in type 2 diabetes. However, little is known about changes in vascular reactivity in those at risk for developing type 2 diabetes. To address this situation the vascular reactivity in both the micro- and macrocirculation was studied in four age and sex comparable groups: 30 healthy normoglycemic subjects with no history of type 2 diabetes in a first-degree relative (controls), 39 healthy normoglycemic subjects with a history of type 2 diabetes in one or both parents (relatives), 32 subjects with impaired glucose tolerance (IGT), and 42 patients with type 2 diabetes without vascular complications (diabetes). Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to ioatophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent) and 1% sodium nitroprusside (SNP) (endothelium-independent), whereas high-resolution ultrasound images were used to measure brachial artery diameter changes during reactive hyperemia. Plasma concentrations of endothelin-1 (ET-1), vonWillebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The vasodilatory responses to Ach, expressed as percent increase of blood flow over baseline, were reduced in relatives (98 +/- 48, mean +/- SD), IGT (94 +/- 52), and diabetes (74 +/- 45) compared with controls (126 +/- 67) (P < 0.001 controls versus relatives, IGT, and diabetes). The responses to SNP were similarly reduced: controls (123 +/- 46), relatives (85 +/- 46), IGT (83 +/- 48), and diabetes (65 +/- 31) (P < 0.001 controls versus relatives, IGT, and diabetes) as were the responses in the brachial artery diameter during reactive hyperemia: controls (13.7 +/- 6.1), relatives (10.5 +/- 6.7), IGT (9.8 +/- 4.5), and diabetes (8.4 +/- 5.0) (P < 0.01 controls versus relatives, IGT, and diabetes). Women had greater responses than men in both the micro- and macrovascular circulatory tests, but a similar progressive reduction was observed in both sexes with increasing degrees of glucose intolerance. A significant inverse correlation was found between microvascular reactivity and systolic blood pressure fasting plasma glucose, HDL cholesterol, fasting plasma insulin, and homeostasis model assessment (HOMA) values, an index of insulin resistance. BMI and diastolic blood pressure had a significant inverse correlation only with endothelium-dependent; vasodilation. In the macrocirculation, systolic blood pressure, HbA(1c), HDL cholesterol, and HOMA had significant correlation with brachial artery diameter changes. Compared with control subjects, ET-1 was significantly higher in all groups, vWF was higher only in the diabetic group, sICAM levels were higher in the IGT and diabetic groups, while sVCAM concentrations were higher in the relatives and those with diabetes (P < 0.05). On stepwise multivariate analysis, age, sex, fasting plasma glucose and BMI were the most important; contributing factors to the variation of vascular reactivity. Addition of all clinical and biochemical measures explained only 32-37% of the variation in vascular reactivity. These results suggest that abnormalities in vascular reactivity and biochemical markers of endothelial cell activation are present early in individuals at risk of developing type 2 diabetes, even at; a stage when normal glucose tolerance exists, and that factors in addition to insulin resistance may be operative. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Vasc Surg, Boston, MA 02215 USA. Columbia Univ, Columbia Presbyterian Med Ctr, Sch Med, Dept Radiol, New York, NY 10032 USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Palmer 317,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. NR 38 TC 413 Z9 435 U1 1 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1999 VL 48 IS 9 BP 1856 EP 1862 DI 10.2337/diabetes.48.9.1856 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 230HC UT WOS:000082244900026 PM 10480619 ER PT J AU Bursell, SE King, GL AF Bursell, SE King, GL TI Can protein kinase C inhibition and vitamin E prevent the development of diabetic vascular complications? SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article; Proceedings Paper CT 1st International Symposium on Free Radicals and Vascular Biology of Diabetes CY SEP 20-21, 1997 CL SEOUL, SOUTH KOREA DE protein kinase C; vitamin E; diabetic vascular complications ID GLOMERULAR MESANGIAL CELLS; SMOOTH-MUSCLE CELLS; RETINAL BLOOD-FLOW; GROWTH-FACTOR-BETA; ELEVATED GLUCOSE-LEVELS; ALDOSE REDUCTASE INHIBITORS; SODIUM-POTASSIUM-ATPASE; GLYCATION END-PRODUCTS; NITRIC-OXIDE SYNTHASE; EXTRACELLULAR-MATRIX AB Hyperglycemia causes vascular complications of diabetes possible by the activation of protein kinase C (PKC). We have provided substantial evidence that activation of PKC can lead to a whole host of vascular dysfunction in diabetes. The activation of PKC induced by hyperglycemia appears to be due to an increase in diacylglycerol (DAG) levels, a physiological activator of PKC. Studies involving cultural cells, animal models of diabetes and patients have shown that inhibition of PKC by specific PKC-up down arrow inhibitor was able to reverse many of the vascular dysfucntions in the retina, kidney and cardiovascular systems induced by either hyoperglycemia or diabetes. In addition high doses of vitamin E were shown to decrease the level of DAG and PKC induced by diabetes or hyperglycemia. Thus animal and clinical studies have shown that high doses of vitamin E treatment can apparently reverse some of the changes in the retinal and renal vessels. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beetham Eye Inst Eye Res, Boston, MA USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. NR 127 TC 53 Z9 53 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD SEP PY 1999 VL 45 IS 2-3 BP 169 EP 182 DI 10.1016/S0168-8227(99)00047-9 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240KY UT WOS:000082826200013 PM 10588370 ER PT J AU Lee, IK Koya, D Ishi, H Kanoh, H King, GL AF Lee, IK Koya, D Ishi, H Kanoh, H King, GL TI d-alpha-tocopherol prevents the hyperglycemia induced activation of diacylglycerol (DAG)-protein kinase C (PKC) pathway in vascular smooth muscle cell by an increase of DAG kinase activity SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article; Proceedings Paper CT 1st International Symposium on Free Radicals and Vascular Biology of Diabetes CY SEP 20-21, 1997 CL SEOUL, SOUTH KOREA DE vascular smooth muscle; diacylglycerol (DAG)-protein kinase C (PKC) pathway; DAG kinase; vitamin E ID VITAMIN-E; DIABETIC RATS; ENDOTHELIAL-CELLS; INHIBITION; EXPRESSION; CLONING; GLUCOSE; AORTA AB We have reported that d-alpha-tocopherol can prevent hyperglycemia-induced activation of DAG and PKC levels in vascular tissues as well as normalizing retinal blood flow and renal hyperfiltration. The mechanism of this effect, however, is not clear. Aside from alpha-tocopherol's principal role as an antioxidant agent, it has also been shown to act as a membrane stabilizer. Another possibility is that the effect of alpha-tocopherol is focused on the activation of DAG kinase, which is a key enzyme in the metabolism of DAG. Therefore, in this study, we examined the effect of alpha-tocopherol on the DAG kinase activity in vascular smooth muscle cell. We have also examined the effect of alpha-tocopherol, its analogues, and probucol on DAG kinase activities and expression. The present study showed that d-alpha-tocopherol's inhibitory effect on DAG-PKC pathway is by increasing DAG kinase activity in rat and human vascular smooth muscle cell (VSMC). Total DAG level was increased by 40 +/- 10% (mean +/- S.E.) (P < 0.05) in human VSMC, after exposure to 22 vs 5 mM glucose. This increase was normalized by d-alpha-tocopherol treatment in a concentration-dependent manner. In parallel, DAG kinase activation by d-alpha-tocopherol was also induced in a time- and dose-dependent manner. DAG kinase activity was increased by 57 +/- 19% (P < 0.05) in human VSMC and 112 +/- 35% (P < 0.05) in rat VSMC after 24 h of incubation with d-alpha-tocopherol (100 mu g/ml). Another lipophilic antioxidant, probucol, also increased DAG kinase activity by 124 +/- 34%, but other vitamin E analogues with much less antioxidant potencies were ineffective. Western blots of various DAG kinase isoforms were not changed by d-alpha-tocopherol treatment. These results provide strong and detailed evidence that d-alpha-tocopherol can prevent hyperglycemia induced DAG-PKC activation by enhancing DAG kinase activity, probably through an antioxidant effect. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP King, GL (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Koya, Daisuke /J-3257-2014 NR 24 TC 47 Z9 50 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD SEP PY 1999 VL 45 IS 2-3 BP 183 EP 190 DI 10.1016/S0168-8227(99)00048-0 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240KY UT WOS:000082826200014 PM 10588371 ER PT J AU Ge, YG MacDonald, D Henry, MM Halt, HI Nelson, KA Lipsky, BA Zasloff, MA Holroyd, KJ AF Ge, YG MacDonald, D Henry, MM Halt, HI Nelson, KA Lipsky, BA Zasloff, MA Holroyd, KJ TI In vitro susceptibility to pexiganan of bacteria isolated from infected diabetic foot ulcers SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID PEPTIDE ANTIBIOTICS AB During two clinical trials involving the treatment of 835 out patients with infected diabetic foot ulcers, 2515 bacterial isolates, including 2337 aerobes and 178 anaerobes, were grown from cultures of the ulcers. The in vitro susceptibility of these isolates was determined to pexiganan, a peptide anti-infective evaluated in these clinical trials, and to other classes of antibiotics. Pexiganan demonstrated broad spectrum antimicrobial activity against Gram-positive and Guam-negative aerobes and anaerobes. The MIC90 values for the most common species among 1735 Gram-positive aerobes isolated, such as Staphylococcus aureus, coagulase-negative staphylococci, Group A streptococci, and Group B streptococci, were 16 mu g/mL or less. Of 602 Gram-negative aerobes tested, the MIC90 values for pexiganan were 16 mu g/mL ou less for Acinetobacter, Pseudomonas, Stenotrophomonas, Citrobacter, Enterobacter, Escherichia, Klebsiella, and Flavobacterium species. Pexiganan had a MIC90 of 4 to 16 mu g/mL against the anaerobic isolates of Bacteroides, Peptostreptococcus, Clostridium, and Prevotella species. Importantly pexiganan did not exhibit cross-resistance with other commonly used antibiotics, including beta-lactams, quinolones, macrolides, and lincosamides. The broad spectrum in vitro antimicrobial activity of pexiganan against clinical isolates from infected diabetic foot ulcers supports its potential as a local therapy for infected diabetic foot ulcers. (C) 1999 Elsevier Science Inc. C1 Magainin Pharmaceut Inc, Dept Microbiol, Plymouth Meeting, PA 19462 USA. Covance Cent Lab Serv Inc, Indianapolis, IN USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Med Serv, Seattle, WA USA. RP Ge, YG (reprint author), Magainin Pharmaceut Inc, Dept Microbiol, Plymouth Meeting, PA 19462 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 19 TC 65 Z9 67 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD SEP PY 1999 VL 35 IS 1 BP 45 EP 53 DI 10.1016/S0732-8893(99)00056-5 PG 9 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 240LA UT WOS:000082826400008 PM 10529881 ER PT J AU Simons, M Laham, RJ AF Simons, M Laham, RJ TI Chronic myocardial ischemia: Contemporary management strategies SO DRUGS OF TODAY LA English DT Review ID CORONARY-ARTERY DISEASE; FIBROBLAST GROWTH-FACTOR; CHRONIC STABLE ANGINA; TRANSMYOCARDIAL LASER REVASCULARIZATION; CONVERTING ENZYME-INHIBITORS; CONGESTIVE HEART-FAILURE; EUROPEAN TRIAL TIBET; TERM FOLLOW-UP; NITRATE TOLERANCE; CALCIUM-ANTAGONISTS AB The presence of chronic myocardial ischemia signifies an imbalance between myocardial oxygen supply and demand that usually reflects the existence of advanced atherosclerotis coronary disease. Standard therapies for this condition that have evolved over the past 40 years include drugs primarily designed to reduce myocardial oxygen demand or improve flow through the existing vessels. In a select group of patients this approach is supplemented by coronary bypass grafting or coronary angioplasty. A new and currently evolving approach relies on stimulation of growth of new coronary vessels to improve myocardial perfusion that can be achieved either by the application of growth factors or mechanical means. (C) 1999 Prous Science. All rights reserved. C1 Harvard Univ, Sch Med, BIDMC, Angiogenesis Res Ctr,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Intervent Cardiol Sect, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Simons, M (reprint author), Harvard Univ, Sch Med, BIDMC, Angiogenesis Res Ctr,Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. RI yilmaz, huseyin/G-1211-2011; Simons, Michael/G-8553-2014 OI Simons, Michael/0000-0003-0348-7734 NR 110 TC 0 Z9 0 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0025-7656 J9 DRUGS TODAY JI Drugs Today PD SEP PY 1999 VL 35 IS 9 BP 667 EP 684 DI 10.1358/dot.1999.35.9.553214 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 253DQ UT WOS:000083541700002 PM 12973465 ER PT J AU Robbins, J Coyle, J Rosenbek, J Roecker, E Wood, J AF Robbins, J Coyle, J Rosenbek, J Roecker, E Wood, J TI Differentiation of normal and abnormal airway protection during swallowing using the penetration-aspiration scale SO DYSPHAGIA LA English DT Article DE penetration-aspiration scale; airway invasion; stroke; deglutition; deglutition disorders AB Accidental loss of food or liquids into the airway while eating or drinking is perhaps the most clinically significant consequence of dysphagia. Although videofluoroscopic recording of swallowing is the current gold standard for identifying and determining remediation for aspiration, results are generally described in descriptive terms, thus limiting information and lending to errors of interpretation. We previously published an 8-point scale to quantitate selected aspects of penetration and aspiration conveying depth of airway invasion and whether or not material entering the airway is expelled (Rosenbek et al., 1996, Dysphagia 11:93-98). The present study defines the distribution of the Penetration-Aspiration Scale scores in healthy normal subjects of different genders and ages. The scale was also used with two groups of patients known to have significant dysphagia relative to stroke or head and neck cancer. Significant differences found among groups are discussed. C1 William S Middleton Mem Vet Hosp, GRECC 11G, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Biostat, Madison, WI USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Hosp, GRECC 11G, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NINDS NIH HHS [NS24427] NR 8 TC 103 Z9 113 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD FAL PY 1999 VL 14 IS 4 BP 228 EP 232 DI 10.1007/PL00009610 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 231NJ UT WOS:000082316400006 PM 10467048 ER PT J AU Hsu, DW Hedley-Whyte, ET AF Hsu, DW Hedley-Whyte, ET TI Clinical interpretation of special pathologic procedures applied to pituitary adenoma biopsies: Immunocytochemistry, electron microscopy, and cell proliferative studies SO ENDOCRINOLOGIST LA English DT Article ID ANALOG SMS 201-995; GROWTH-HORMONE; GLYCOPROTEIN HORMONE; ALPHA-SUBUNIT; MONOCLONAL-ANTIBODIES; ACROMEGALIC PATIENTS; KI-67 ANTIGEN; PROLACTIN; MIB-1; MACROADENOMAS AB Pituitary adenomas are an important group of intracranial tumors. Modern methods available to pathologists and their laboratories can provide information regarding the secretory activities and growth potential of these tumors that are useful to clinicians in making management decisions and determining prognosis for individual patients. Among these methods are immunocytochemistry, electron microscopy, and tumor cell proliferation studies. Immunocytochemistry is an indispensable tool for revealing the cell type and hormone production of a pituitary adenoma. Ultrastructural study provides more morphologic detail than routine histopathology can for the classification of pituitary adenomas. Antibodies to cell cycle specific proteins are used as markers for tumor cell proliferation whose indices may be useful prognostically. C1 Massachusetts Gen Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02114 USA. Harvard Med Sch, Dept Pathol, Boston, MA USA. RP Hedley-Whyte, ET (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Neuropathol, Warren 3, Boston, MA 02114 USA. NR 66 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD SEP-OCT PY 1999 VL 9 IS 5 BP 350 EP 357 DI 10.1097/00019616-199909000-00005 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240PY UT WOS:000082835400005 ER PT J AU Kearns, AE Goto, K Gianakakos, G Lippmann, W Demay, MB AF Kearns, AE Goto, K Gianakakos, G Lippmann, W Demay, MB TI Transcriptional repression of the rat osteocalcin gene: Role of two intronic CCTCCT motifs SO ENDOCRINOLOGY LA English DT Article ID PROMOTER; RECEPTOR; RESPONSIVENESS; EXPRESSION; ELEMENT; SEQUENCES; SILENCER; CELL; 1,25-DIHYDROXYVITAMIN-D3; DIFFERENTIATION AB The regulation of osteocalcin gene transcription is complex, involving multiple positive and negative regulators. Previous studies have demonstrated that an intronic sequence, TTTCTTT (+118 to +124) is capable of mediating transcriptional repression of osteocalcin-CAT fusion genes in cells of the osteoblast lineage, by interacting with a specific nuclear protein. Further analyses of intronic sequences have identified a second silencer motif in this region. Two copies of a CCTCCT motif are present within the first intron of the rat osteocalcin gene (+106 to +111 and +135 to +140) and are capable of mediating transcriptional repression of osteocalcin-CAT fusion genes in rat osteosarcoma cells. Transient gene expression assays of wildtype and mutant osteocalcin-CAT fusion genes into ROS 17/2.8 cells demonstrate that mutagenesis of either of these CCTCCT motifs in isolation results in a 1.6-fold increase in CAT activity relative to the parent fusion gene. Moreover, a 5-fold increase in reporter gene activity is observed when both motifs are mutated together. These sequences are also capable of suppressing osteocalcin promoter activity when placed upstream to the osteocalcin promoter. Gel retardation and southwestern analyses demonstrate that the CCTCCT motifs interact with specific proteins present in nuclear extracts from ROS 17/2.8 and UMR 106 osteosarcoma cells but not COS-7 kidney cells. Mutations that abolish suppressor function of this motif markedly impair interactions with this specific nuclear protein. These data demonstrate that at least two different silencer motifs (TTTCTTT and CCTCCT) in the first intron of the rat osteocalcin gene contribute to its transcriptional repression. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 501,50 Blossom St, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu NR 25 TC 6 Z9 7 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 SEP PY 1999 VL 140 IS 9 BP 4120 EP 4126 DI 10.1210/en.140.9.4120 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228UC UT WOS:000082153200030 PM 10465284 ER PT J AU Demetri, GD AF Demetri, GD CA PODCRIT Study Grp TI Equivalent effects on functional status and hematologic indicators of epoetin alfa in patients (PTS) treated with platinum (P) or non-platinum (NP) chemotherapy(CT) regimens independent of disease response SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 Dana Farber Canc Inst, PODCRIT Study Grp, Boston, MA 02115 USA. 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1999 VL 35 SU 4 MA 1530 BP S376 EP S376 DI 10.1016/S0959-8049(99)81944-3 PG 1 WC Oncology SC Oncology GA 244UC UT WOS:000083068301509 ER PT J AU Maass, N Zhang, M Sager, R Astner, A Jonat, W AF Maass, N Zhang, M Sager, R Astner, A Jonat, W TI Regulation of protease-inhibitor maspin in prostate epithelial- and prostate carcinoma-cells SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 Univ Kiel, Dept Gynecol Oncol, D-24098 Kiel, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Jonat, Walter/E-3024-2010; Maass, Nicolai/F-2639-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1999 VL 35 SU 4 MA 1380 BP S342 EP S342 DI 10.1016/S0959-8049(99)81796-1 PG 1 WC Oncology SC Oncology GA 244UC UT WOS:000083068301361 ER PT J AU Penson, RT Kronish, K Duan, Z Feller, A Stark, P Cook, SE Duska, LR Puller, AF Goodman, AK Nikrui, N MacNeill, KM Matulonis, UA Preffer, FI Seiden, MV AF Penson, RT Kronish, K Duan, Z Feller, A Stark, P Cook, SE Duska, LR Puller, AF Goodman, AK Nikrui, N MacNeill, KM Matulonis, UA Preffer, FI Seiden, MV TI Cytokines IL-lb, IL-2, IL-6, IL-8, MCP-1, GM-CSF and TNFa in patients with epithelial ovarian cancer and their relationship to treatment with paclitaxel SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 MGH, Boston, MA USA. DFCI, Boston, MA USA. NR 0 TC 0 Z9 0 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 SEP PY 1999 VL 35 SU 4 MA 942 BP S239 EP S239 DI 10.1016/S0959-8049(99)81362-8 PG 1 WC Oncology SC Oncology GA 244UC UT WOS:000083068300927 ER PT J AU Herz, U Kammertoens, T Rosenbaum, J da Palma, JC Rimm, I Renz, H AF Herz, U Kammertoens, T Rosenbaum, J da Palma, JC Rimm, I Renz, H TI Impact of V beta 8(+/+) T cells on the development of increased airway reactivity and IgE production in SJL mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE SJL mice; allergic sensitization; TCR; V beta 8 T cell; airway hyperresponsiveness ID TRANSGENIC MICE; PHENOTYPE DEVELOPMENT; OVALBUMIN PEPTIDE; INTERFERON-GAMMA; GENE-EXPRESSION; B-CELLS; INTERLEUKIN-4; ANTIGEN; CD4(+); INHIBITION AB SJL mice have been extensively characterized as "low-responder" animals in terms of IgE-dependent immediate-type hypersensitivity responses. Since these mice are genetically deficient in certain TCR V beta gene segments, we asked whether this might be the reason for the "low-responder" status. Specifically in H-2(d) mice the TCR-V beta 8.2 gene element has been shown to play an important role in Th2 immune responses to ovalbumin (OVA). Utilizing a TCR V beta 8.2-transgenic SJL (SJL V beta 8(+/+)) mouse, we examined whether the H-2(s)-bearing "low-responder" mouse could be converted into a "high-responder" animal. Remarkably, non-sensitized SJL V beta 8(+/+) mice demonstrated strongly elevated levels of total IgE antibody. Mitogen-stimulated T cells from these mice released high amounts of IL-4 as compared to SJL wild-type (wt) mice. In addition, sensitization to OVA via the airways resulted in the development of increased airway responsiveness in SJL V beta 8(+/+) mice, but not in SJL wt animals. The results indicate that the capacity to produce IgE and IL-4 and to develop increased airway responsiveness can be restored in SJL wt mice by introducing the V beta 8.2 gene segment into the TCR repertoire. C1 Inst Lab Med & Pathobiochem, Charite, D-13353 Berlin, Germany. Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. RP Herz, U (reprint author), Inst Lab Med & Pathobiochem, Charite, Campus Virchow Clin,Augustenburger Pl 1, D-13353 Berlin, Germany. NR 33 TC 5 Z9 5 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 1999 VL 29 IS 9 BP 3028 EP 3034 DI 10.1002/(SICI)1521-4141(199909)29:09<3028::AID-IMMU3028>3.0.CO;2-J PG 7 WC Immunology SC Immunology GA 237RM UT WOS:000082669900039 PM 10508277 ER PT J AU Fischmann, AJ Meltzer, P Hillier, S Barrow, SA Callahan, RJ Bonab, AA Madras, BK AF Fischmann, AJ Meltzer, P Hillier, S Barrow, SA Callahan, RJ Bonab, AA Madras, BK TI Evaluation of a new and highly selective 99mTc labeled ligand for SPECT of dopamine transporter (DAT) sites SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD SEP PY 1999 VL 26 IS 9 MA OS87 BP 982 EP 982 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 236TF UT WOS:000082614100089 ER PT J AU Barrow, SA Ryu, JS Choi, NC Fischman, AJ AF Barrow, SA Ryu, JS Choi, NC Fischman, AJ TI Increased accumulation of FDG in the esophageal region of lung cancer patients after treatment with neoadjuvant chemoradiotherapy SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 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 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD SEP PY 1999 VL 26 IS 9 MA OS250 BP 1023 EP 1023 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 236TF UT WOS:000082614100252 ER PT J AU Barrow, SA Bonab, AA Lanser, M Fischman, AJ AF Barrow, SA Bonab, AA Lanser, M Fischman, AJ TI Detection of early Parkinson's disease with 123I-AL tropane SPECT: Comparison with 18F DOPA PET SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 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 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD SEP PY 1999 VL 26 IS 9 MA PS340 BP 1137 EP 1137 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 236TF UT WOS:000082614100710 ER PT J AU Bruning, R Seelos, K Yousry, T Scheidler, J Exner, H Porn, U Reiser, M Rosen, BR AF Bruning, R Seelos, K Yousry, T Scheidler, J Exner, H Porn, U Reiser, M Rosen, BR TI Echo-planar magnetic resonance imaging (EPI) with high-resolution matrix in intra-axial brain tumors SO EUROPEAN RADIOLOGY LA English DT Article DE magnetic resonance; brain; brain tumors; echo planar imaging ID PERFUSION; ISCHEMIA; GLIOMAS; GRADE; FLOW; MRI AB The aim of this study was to assess the potential of high-speed interleaved echo-planar imaging (EPI) to achieve diagnostic image quality comparable to T2-weighted imaging in patients with brain tumors. Seventeen patients wit intra-axial, supratentorial tumors (10 untreated gliomas, 7 radiated gliomas) were investigated on a 1.5-T scanner. The conventional scan (SE, TR/TE = 2200/80 ms, 18 slices) was acquired in 8 min, 4 s, and EPI (TR/TE = 3000/80 ms, 18 slices) was completed in 25 s. The films were compared in a blinded trail by three radiologists. On the general impression and anatomic display, both sequences were rated to be similar quality. Artifacts were slightly more pronounced at the skull base and around surgical clips using EPI. Tumor delineation was nearly equivalent using EPI, compared with the T2-weighted sequence. Echo-planar imaging reached diagnostic quality in all patients. Interleaved high-resolution EPI yielded sufficient quality to depict intra-axial, supratentorial brain tumors. Since EPI can bo obtained in a small fraction of the time needed for conventional spin echo, in addition to other indications it could be considered to study patients unable to cooperate. C1 Univ Munich, Klinikum Grosshadern, Inst Diagnost Radiol, D-81366 Munich, Germany. Univ Munich, Klinikum Grosshadern, Inst Diagnost Radiol, Dept Neuroradiol, D-81366 Munich, Germany. Univ Munich, Klinikum Grosshadern, Inst Med Epidemiol, D-81366 Munich, Germany. Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02129 USA. RP Bruning, R (reprint author), Univ Munich, Klinikum Grosshadern, Inst Diagnost Radiol, D-81366 Munich, Germany. RI Yousry, Tarek/B-3417-2009 FU NCI NIH HHS [CA 40303]; NHLBI NIH HHS [HL 39810] NR 27 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD SEP PY 1999 VL 9 IS 7 BP 1392 EP 1396 DI 10.1007/s003300050854 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 233LR UT WOS:000082428800025 PM 10460380 ER PT J AU Gudmundsson, A Goodman, B Lent, S Barczi, S Grace, A Boyle, L Ershler, WB Carnes, M AF Gudmundsson, A Goodman, B Lent, S Barczi, S Grace, A Boyle, L Ershler, WB Carnes, M TI Effects of estrogen replacement therapy on the circadian rhythms of serum cortisol and body temperature in postmenopausal women SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE circadian rhythm; hydrocortisone; body temperature; estrogen replacement therapy; post-menopausal ID CORTICOSTEROID-BINDING GLOBULIN; RHESUS-MONKEYS; HORMONE; ADRENOCORTICOTROPIN; MODULATION; DEPRESSION; SECRETION; ESTRADIOL; FREQUENCY; INCREASE AB Estrogen replacement therapy (ERT) seems to enhance longevity in women. Both gender and aging have been shown to influence the regulation of circadian rhythms, yet little is known about the effect of ERT on circadian regulation. The aim of this study was to determine the effects of ERT (oral conjugated estrogen: Premarin(R), 0.625 mg) for 6-8 weeks on circadian serum cortisol by continuous blood sampling every 15 min for 24 h with simultaneous measurements of body temperature in six healthy postmenopausal women (range, 54-61 years). The results are presented as median values (range in quartiles). The circadian amplitude of cortisol increased during ERT from 20.20 (18.35, 23.61) to 25.97 (24.94, 27.74) mu g/dL (p = 0.016), whereas the timing of nocturnal nadir and morning acrophase did not differ significantly. ERT lowered the 24-h body temperature from 37.03 degrees C (36.95 degrees C, 37.07 degrees C) to 36.90 degrees C (36.77 degrees C, 36.97 degrees C) (p = 0.038), but did not alter the peak and trough body temperatures significantly. These findings are noteworthy because the increased circadian amplitude of serum cortisol during ERT contrasts with the reduction in circadian amplitude seen with normal aging. The reduction in body temperature confirms the regulatory effect of ERT in thermoregulation and has implications regarding the correlation between basal metabolic rate and life span. (C) 1999 Elsevier Science Inc. AII rights reserved. C1 William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. RP Gudmundsson, A (reprint author), William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. FU NCRR NIH HHS [RR29-DK40759, RR03186]; NIA NIH HHS [R01 AG-1071] NR 37 TC 24 Z9 25 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD SEP PY 1999 VL 34 IS 6 BP 809 EP 818 DI 10.1016/S0531-5565(99)00044-3 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 243UR UT WOS:000083016100008 PM 10579640 ER PT J AU Isacson, O Sladek, JR AF Isacson, O Sladek, JR TI Cellular and molecular treatments of neurological diseases SO EXPERIMENTAL NEUROLOGY LA English DT Editorial Material ID NERVE GROWTH-FACTOR; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; STRIATAL NEURONS; RODENT MODEL; DEGENERATION; PREVENTS; CNTF; IMPLANTATION; CELLS C1 Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, Belmont, MA 02478 USA. Harvard Univ, McLean Hosp, Sch Med, Neurosci Program, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Finch Univ Hlth Sci Chicago Med Sch, Dept Pathol, Chicago, IL USA. RP Isacson, O (reprint author), Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, Belmont, MA 02478 USA. NR 16 TC 5 Z9 5 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 1999 VL 159 IS 1 BP 1 EP 3 DI 10.1006/exnr.1999.7155 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 237FM UT WOS:000082644700001 PM 10486170 ER PT J AU Bogdanov, MB Beal, MF McCabe, DR Griffin, RM Matson, WR AF Bogdanov, MB Beal, MF McCabe, DR Griffin, RM Matson, WR TI A carbon column-based liquid chromatography electrochemical approach to routine 8-hydroxy-2 '-deoxyguanosine measurements in urine and other biologic matrices: A one-year evaluation of methods SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE 8-hydroxy-2 '-deoxyguanosine; carbon columns; chromatography; high-pressure liquid; urine; plasma; cerebrospinal fluid; DNA; free radicals ID OXIDATIVE DNA-DAMAGE; DIABETES-MELLITUS; ASCORBIC-ACID; MARKER; ASSAY; 8-HYDROXYDEOXYGUANOSINE; EXCRETION; 8-OXO-7,8-DIHYDRO-2'-DEOXYGUANOSINE; CARCINOGENESIS; BIOMARKER AB 8-Hydroxy-2'-deoxyguanosine (80H2'dG) is a principal stable marker of hydroxyl radical damage to DNA. It has been related to a wide variety of disorders and environmental insults, and has been proposed as a useful systematic marker of oxidative stress. Analytic procedures for 80H2'dG in DNA digests are well established; however, routine measurement of free 8OH2'dG in other body fluids such as urine or plasma has been problematic. This has hindered its evaluation as a general clinical, therapeutic monitoring, or environmental assessment tool. Therefore, we developed a liquid chromatography electrochemical column-switching system based on the use of the unique purine selectivity of porous carbon columns that allows routine accurate measurement of 80H2'dG in a variety of biologic matrices. This paper describes the rationale of the system design and the protocols developed for 80H2'dG in urine, plasma, cerebrospinal fluid, tissue, DNA, saliva, sweat, kidney dialysis fluid, foods, feces, culture matrix, and microdialysates. Concentrations in both human and animal body fluids and tissues are reported. The system performance is discussed in the context of a 1-year evaluation of the methods applied to approximately 3600 samples, using internal quality control and external blind testing to determine long-term accuracy. The methods are reliable and accurate, and therefore should prove useful in assessing the role and utility of oxidative DNA damage in aging and human illness. (C) 1999 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Neurochem Lab, Serv Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Cornell Univ, Coll Med, Dept Neurol & Neurosci, New York, NY USA. ESA Inc, Chelmsford, MA USA. RP Bogdanov, MB (reprint author), Massachusetts Gen Hosp, Neurochem Lab, Serv Neurol, Boston, MA 02114 USA. RI Bell, Tiffany/F-4403-2010 FU NIMH NIH HHS [2R44MH53810-02] NR 39 TC 141 Z9 147 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 1999 VL 27 IS 5-6 BP 647 EP 666 DI 10.1016/S0891-5849(99)00113-6 PG 20 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 234RK UT WOS:000082498000020 PM 10490286 ER PT J AU Oberley, TD Toyokuni, S Szweda, LI AF Oberley, TD Toyokuni, S Szweda, LI TI Localization of hydroxynonenal protein adducts in normal human kidney and selected human kidney cancers SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE 4-hydroxy-2-nonenal; oxidative damage; kidney cancer; nucleus; mitochondria; free radicals ID GLUTATHIONE-S-TRANSFERASE; RENAL-CELL CARCINOMA; ANTIOXIDANT ENZYMES; LIPID-PEROXIDATION; IMMUNOGOLD ANALYSIS; DIFFERENTIATION; 8-HYDROXY-2'-DEOXYGUANOSINE; IMMUNOLOCALIZATION; CARCINOGENESIS; MITOCHONDRIA AB Both polyclonal and monoclonal antibodies to 4-hydroxy-2-nonenal (HNE) protein adducts were used to identify lipid peroxidation products in normal human kidney and in selected human kidney cancers using immunoperoxidase techniques at the light microscopic level and immunogold techniques at the ultrastructural level. HNE protein adducts were detected in most cell types in normal kidney, although in highly variable amounts. All six morphologic types of renal tumors examined showed some staining with antibodies to HNE protein adducts, although the intensity of staining Varied considerably depending on tumor type. Renal oncocytoma and the granular cell variant of renal adenocarcinoma both showed greater cytoplasmic staining for HNE protein adducts than the other tumors examined; these tumors both contain high numbers of mitochondria and suggest that mitochondria are a major source of lipid peroxidation products. To test this possibility, immunogold ultrastructural analysis was performed. HNE protein adducts were identified in nuclei and mitochondria in both normal proximal tubule and three types of renal carcinoma examined; these results localize oxidative damage at the subcellular level in both benign and malignant epithelium to nuclei and mitochondria. In conclusion, HNE protein adducts occur in kidneys in both normal and tumor cells, although immunomorphologic analyses suggest less HNE protein adducts in tumor cells. (C) 1999 Elsevier Science Inc. C1 William S Middleton Mem Vet Adm Hosp, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI USA. Kyoto Univ, Grad Sch Med, Dept Pathol & Biol Dis, Sakyo Ku, Kyoto 606, Japan. Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Adm Hosp, Pathol & Lab Med Serv, Room A-35,2500 Overlook Terrace, Madison, WI 53705 USA. RI Toyokuni, Shinya/C-1358-2010 OI Toyokuni, Shinya/0000-0002-5757-1109 NR 36 TC 29 Z9 30 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 1999 VL 27 IS 5-6 BP 695 EP 703 DI 10.1016/S0891-5849(99)00117-3 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 234RK UT WOS:000082498000024 PM 10490290 ER PT J AU Scarborough, DM Krebs, DE Harris, BA AF Scarborough, DM Krebs, DE Harris, BA TI Quadriceps muscle strength and dynamic stability in elderly persons SO GAIT & POSTURE LA English DT Article DE quadriceps muscle strength; dynamic stability; chair rise; strategies; gait; elderly ID SIT-TO-STAND; CHAIR RISE; BALANCE; MOMENTUM; ADULTS; FALLS AB Several measures of dynamic stability during two functional activities correlated to quadriceps femoris muscle strength. A total of 34 disabled elders (aged 60-88) living in the Boston area consented to maximum isometric quadriceps muscle strength testing, chair rise and gait analysis. During chair rise, quadriceps strength significantly correlated with maximum upper body vertical linear momentum, r = 0.53, P < 0.005, anterior posterior linear momentum, r = 0.38, P < 0.05, and the time to complete the chair rise, r = -0.48, P < 0.05, n = 29. Stride length and gait velocity correlated (r = 0.56, P < 0.001 and r = 0.51, P < 0.002, n = 34) with quadriceps muscle strength. The maximum range of whole body anteroposterior (A/P) linear momentum during gait also correlated with quadriceps strength (r = 0.47, P = 0.004, n = 31). Dynamic stability during chair rise and gait, at preferred speed, correlates directly with quadriceps femoris muscle strength in functionally limited elderly individuals. In our sample, elders performed one of three movement strategies to arise from a chair, and quadriceps strength did not statistically differ between the chair rise strategy groups. However, persons with the greatest quadriceps strength values were more stable regardless of which chair I ise strategy they performed. Our data indicate that clinicians should not suggest that patients use compensatory momentum inducing locomotor strategics unless the patient has sufficient strength to control these induced forces. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Scarborough, DM (reprint author), Massachusetts Gen Hosp, Biomot Lab, Ruth Sleeper Hall,Room 010,40 Parkman St, Boston, MA 02114 USA. EM dscarborough@partners.org FU NIA NIH HHS [P50 AG11669-03, R01AG12561] NR 31 TC 93 Z9 95 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 EI 1879-2219 J9 GAIT POSTURE JI Gait Posture PD SEP PY 1999 VL 10 IS 1 BP 10 EP 20 PG 11 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 237WW UT WOS:000082680400002 PM 10469937 ER PT J AU Pandol, SJ Periskic, S Gukovsky, I Zaninovic, V Jung, Y Zong, YM Solomon, TE Gukovskaya, AS Tsukamoto, H AF Pandol, SJ Periskic, S Gukovsky, I Zaninovic, V Jung, Y Zong, YM Solomon, TE Gukovskaya, AS Tsukamoto, H TI Ethanol diet increases the sensitivity of rats to pancreatitis induced by cholecystokinin octapeptide SO GASTROENTEROLOGY LA English DT Article ID CERULEIN-INDUCED PANCREATITIS; PLATELET-ACTIVATING-FACTOR; ALCOHOLIC LIVER-DISEASE; KUPFFER CELLS; NITRIC-OXIDE; KAPPA-B; INJURY; CONSUMPTION; INFUSION; NECROSIS AB Background & Aims: Although alcoholism is a major cause of pancreatitis, the pathogenesis of this disorder remains obscure. Failure to produce experimental alcoholic pancreatitis suggests that ethanol may only increase predisposition to pancreatitis. This study sought to develop a model of ethanol pancreatitis by determining if an ethanol diet sensitizes rats to pancreatitis caused by cholecystokinin octapeptide (CCK-8). Methods: Rats were fed intragastrically either control or ethanol diet for 2 or 6 weeks. The animals were then infused for 6 hours-with either saline or CCK-8 at a dose of 3000 pmol . kg(-1) . h(-1), which by itself did not induce pancreatitis. The following parameters were measured: serum amylase and lipase levels, pancreatic weight, inflammatory infiltration, number of apoptotic acinar cells, pancreatic messenger RNA (mRNA) expression of cytokines and chemokines, and nuclear factor (NF)-kappa B activity. Results: All measures of pancreatitis, as well as NF-kappa B activity and mRNA expression for tumor necrosis factor alpha, interleukin 6, monocyte chemotactic protein 1, macrophage inflammatory protein 2, and inducible nitric oxide synthase, were significantly increased only in rats treated with ethanol plus CCK-8. Conclusions: An ethanol diet sensitizes rats to pancreatitis caused by CCK-8. The combined action of ethanol and CCK-8 results in NF-kappa B activation and up-regulation of proinflammatory cytokines and chemokines in the pancreas. These mechanisms may contribute to the development of alcoholic pancreatitis. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, CURE Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ So Calif, Sch Med, Div Gastroenterol & Liver Dis, Los Angeles, CA USA. RP Gukovskaya, AS (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIAAA NIH HHS [1 P50 AA11999-01] NR 48 TC 128 Z9 130 U1 1 U2 5 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 SEP PY 1999 VL 117 IS 3 BP 706 EP 716 DI 10.1016/S0016-5085(99)70465-8 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 230QF UT WOS:000082261300030 PM 10464148 ER PT J AU Hartwig, W Jimenez, RE Werner, J Lewandrowski, KB Warshaw, AL Fernandez-Del Castillo, C AF Hartwig, W Jimenez, RE Werner, J Lewandrowski, KB Warshaw, AL Fernandez-Del Castillo, C TI Interstitial trypsinogen release and its relevance to the transformation of mild into necrotizing pancreatitis in rats SO GASTROENTEROLOGY LA English DT Article ID LYSOSOMAL-ENZYMES; ACINAR-CELLS; ACTIVATION; ASSAY AB Background & Aims: Intracellular activation of trypsinogen is currently believed to initiate pancreatitis. Factors responsible for the progression of mild to necrotizing pancreatitis are poorly understood. This study evaluated the significance of interstitial protease release and activation in this process. Methods: in rats with cerulein-induced pancreatitis, concentrations of trypsinogen and its activation peptide TAP were measured in lymph and blood, and pancreatic injury was determined. Activation of extracellular trypsinogen was induced by intravenous infusion of enterokinase, which does not enter the acinar cell. Gabexate mesilate (acinar cell permeable) or soybean trypsin inhibitor (acinar cell nonpermeable) was administered to distinguish the effects of intracellular or extracellular protease activation. Results: In cerulein pancreatitis, trypsinogen levels increased prominently and were highest in lymph and portal vein blood, whereas TAP increments were modest. Combined cerulein/enterokinase infusions resulted in marked TAP increases in lymph and brood and in severe necrohemorrhagic pancreatitis, Gabexate mesilate as well as soybean trypsin inhibitor significantly decreased IAP levels in both lymph and blood and reduced pancreatic injury, with no significant differences between groups. Conclusions: In secretagogue-induced pancreatitis, large amounts of trypsinogen are present in the interstitium and drain via the portal and lymphatic circulation. Activation of this extracellular trypsinogen induces hemorrhagic necrosis in a setting of mild edematous pancreatitis. This phenomenon may be the central event in the progression to fulminant necrotizing pancreatitis. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fernandez-Del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, WACC 336,15 Parkman St, Boston, MA 02114 USA. NR 31 TC 44 Z9 45 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 SEP PY 1999 VL 117 IS 3 BP 717 EP 725 DI 10.1016/S0016-5085(99)70466-X PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 230QF UT WOS:000082261300031 PM 10464149 ER PT J AU Whitcomb, DC AF Whitcomb, DC TI The spectrum of complications of hereditary pancreatitis - Is this a model for future gene therapy? SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID CATIONIC TRYPSINOGEN GENE; MEDICAL PROGRESS; ACINAR-CELLS; ACTIVATION; RISK; CANCER; MICE; MUTATIONS; ZYMOGENS; PROTEIN AB Hereditary pancreatitis is an unusual form of pancreatitis that runs in families. Clinical features include recurrent episodes of acute pancreatitis in 80% of family members and eventual chronic pancreatitis in about 20% to 30% of family members. In addition, a subset of individuals with prolonged chronic pancreatitis have a high incidence of pancreatic cancer. Two mutations in the cationic trypsinogen gene were identified (R117H and N211) that appear to allow prematurely activated trypsinogen to cause acinar cell autodigestion and acute pancreatitis. Because much is known about the biochemistry and molecular biology of trypsinogen, careful consideration of gene therapy is warranted. Although gene therapy for hereditary pancreatitis is beyond current technology, new approaches probably will emerge that can allow for identification of individuals at risk for pancreatitis. Early detection will lead to early treatment with effective measures, such as gene therapies, that may prevent the development of pancreatitis. C1 Univ Pittsburgh, Div Gastroenterol & Hepatol, Dept Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Ctr Genom Sci, Pittsburgh, PA 15261 USA. Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Whitcomb, DC (reprint author), Univ Pittsburgh, Div Gastroenterol & Hepatol, Dept Med, 571 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. FU NIDDK NIH HHS [R03DK51954, R01DK50236] NR 93 TC 13 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 1999 VL 28 IS 3 BP 525 EP + DI 10.1016/S0889-8553(05)70071-6 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 257WB UT WOS:000083804500002 PM 10503134 ER PT J AU Goldberg, SN Mallery, S Gazelle, GS Brugge, WR AF Goldberg, SN Mallery, S Gazelle, GS Brugge, WR TI EUS-guided radiofrequency ablation in the pancreas: results in a porcine model SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID TISSUE ABLATION; HEPATIC METASTASES; THERMAL ABLATION; ELECTRODE; TUMORS; SIZE; TEMPERATURE; EXPERIENCE; VOLUME; RAT AB Background: Our aim in this study was to investigate the feasibility and safety of performing radiofrequency (RF) ablation in the pancreas with endoscopic ultrasound (EUS). Methods: RF was applied to normal pancreatic tissue in 13 anesthetized Yorkshire pigs with specially modified 19-gauge needle electrodes (1.0 to 1.5 cm tip). The pancreas was localized with EUS and punctured through a transgastric approach. RF current (285 +/- 120 mA) was delivered for 6 minutes. Diagnostic imaging (EUS and CT) and serum amylase and lipase levels were obtained at baseline, immediately after ablation, and 1 to 14 days after the procedure. Pigs were killed immediately (n = 5), 1 to 2 days after ablation (n = 2), and 2 weeks after the procedure (n = 6). Pathologic examination was performed. Results: Sixteen ablations were performed. During ablation, round hyperechoic foci (diameter to 1.0 cm) gradually surrounded the tip of the electrode. Immediately after the procedure CT demonstrated 1 cm hypodense foci that did not enhance with iodinated contrast. In pigs killed immediately and 1 to 2 days after ablation, pathologic examination showed discrete, well-demarcated spherical foci of coagulation necrosis measuring 8 to 12 mm in diameter surrounded by a I to 2 mm rim of hemorrhage. Radiologic-pathologic correlation was within 2 mm. In 4 of 6 (67%) pigs kilted on day 14, retraction of the coagulated focus was observed. A 1 to 3 mm fibrotic capsule surrounded the coagulated tissue in the remaining 2 pigs. One pig had mild hyperlipasemia, a focal zone of pancreatitis (<1 cm), and later a pancreatic fluid collection. Biochemical parameters were normal in the remaining pigs. Other complications included three gastric and one intestinal burn caused by improper electrode placement. Conclusions: EUS-guided RF ablation can be used safely to produce discrete zones of coagulation necrosis in the porcine pancreas. potential clinical uses of this technology include management of small neuroendocrine tumors and possibly palliation of unresectable pancreatic adenocarcinoma. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA USA. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02115 USA. NR 21 TC 122 Z9 128 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD SEP PY 1999 VL 50 IS 3 BP 392 EP 401 DI 10.1053/ge.1999.v50.98847 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 233AX UT WOS:000082404300017 PM 10462663 ER PT J AU Clifford, SC Walsh, S Hewson, K Green, EK Brinke, A Green, PM Gianelli, F Eng, C Maher, ER AF Clifford, SC Walsh, S Hewson, K Green, EK Brinke, A Green, PM Gianelli, F Eng, C Maher, ER TI Genomic organization and chromosomal localization of the human CUL2 gene and the role of von Hippel-Lindau tumor suppressor-binding protein (CUL2 and VBPI) mutation and loss in renal-cell carcinoma development SO GENES CHROMOSOMES & CANCER LA English DT Article ID SOMATIC MUTATIONS; DNA METHYLATION; ALLELIC LOSSES; HUMAN HOMOLOG; BETA-CATENIN; CYCLE EXIT; CANCER; 10P; DISEASE; ARM AB Germline mutations in the von Hippel-Lindau (VHL) disease tumor suppressor gene (TSG) convey a high risk of clear-cell renal-cell carcinoma (CC-RCC) and most sporadic CC-RCCs demonstrate somatic inactivation of the VHL TSG, However, the existence of further CC-RCC gatekeeper genes is implied by CC-RCC kindreds not linked to the VHL gene and the absence of somatic VHL inactivation in similar to 30% of sporadic CC-RCC, Genes that encode proteins which interact with the VHL gene product (VHL) provide candidate gatekeeper RCC genes. VHL forms a multimeric complex with two subunits (B and C) of the SIII (elongin) transcriptional elongation complex and CUL2, a member of the cullin family. Most pathogenic VHL mutations inhibit formation of the VHL/elonginB+C/CUL2 complex. A further VHL-binding protein of unknown function, VBPI, fails to bind to truncated forms of VHL. We have investigated the possible roles of CUL2 and VBPI in renal tumorigenesis by analyzing sporadic RCC of known VHL mutation or hypermethylation status, including CC-RCC without VHL inactivation (n = 40); CC-RCC with VHL inactivation (n = 35); and non-CC-RCC (n = 14). No VBPI mutations were identified in 89 sporadic RCCs, suggesting that VBPI is not an RCC gatekeeper gene. To investigate CUL2, we mapped the CUL2 gene to chromosome band 10p 11.1-p11.2, a region reported to show loss of heterozygosity (LOH) in several human cancers (including non-CC-RCC); determined the genomic organization; and performed mutation analysis of the 21 exons identified, Using novel intragenic polymorphisms, we detected LOH in 6/25 informative RCCs; however, no pathogenic CUL2 mutations were identified in the 89 RCCs analyzed. These findings suggest that unless CUL2 is inactivated by epigenetic events, it is not a major RCC TSG, However, CUL2 remains a candidate TSG for other tumor types demonstrating 10p LOH. (C) 1999 Wiley-Liss, Inc. C1 Univ Birmingham, Div Med & Mol Genet, Dept Paediat & Child Hlth, Sch Med,Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England. United Med & Dent Sch Guys & St Thomas Hosp, Guys Hosp, Dept Med & Mol Genet, London SE1 9RT, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. RP Maher, ER (reprint author), Univ Birmingham, Div Med & Mol Genet, Dept Paediat & Child Hlth, Sch Med,Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England. RI MAHER, EAMONN/A-9507-2008; OI MAHER, EAMONN/0000-0002-6226-6918; Eng, Charis/0000-0002-3693-5145 NR 38 TC 10 Z9 10 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 1999 VL 26 IS 1 BP 20 EP 28 DI 10.1002/(SICI)1098-2264(199909)26:1<20::AID-GCC3>3.3.CO;2-Y PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 223RE UT WOS:000081853400003 PM 10441001 ER PT J AU Staehling-Hampton, K Ciampa, PJ Brook, A Dyson, N AF Staehling-Hampton, K Ciampa, PJ Brook, A Dyson, N TI A genetic screen for modifiers of E2F in Drosophila melanogaster SO GENETICS LA English DT Article ID DEPENDENT KINASE INHIBITOR; SWI-SNF COMPLEX; RETINOBLASTOMA PROTEIN; CELL-CYCLE; TRANSCRIPTION FACTOR; HISTONE DEACETYLASE; S-PHASE; REPRESS TRANSCRIPTION; FAMILY PROTEINS; EYE DEVELOPMENT AB The activity of the E2F transcription factor is regulated in part by pRB, the protein product of the retinoblastoma tumor suppressor gene. Studies of tumor cells show that the pi 6(ink4a)/cdk4/cyclin D/pRB pathway is mutated in most forms of cancer, suggesting that the deregulation of E2F, and hence the cell cycle, is a common event in tumorigenesis. Extragenic mutations that enhance or suppress E2F activity are likely to alter cell-cycle control and may, play a role in tumorigenesis. We used an E2F overexpression phenotype in the Drosophila eye to screen for modifiers of E2F activity. Coexpression of dE2F and its heterodimeric partner dDP in the fly eye induces S phases and cell death. We isolated 33 enhancer mutations of this phenotype by EMS and X-ray mutagenesis and by screening a deficiency library collection. The majority of these mutations sorted into six complementation groups, five of which have been identified as alleles of brahma (brm), moira (mor) osa, pointed (pnt), and polycephalon (poc). osa, brm, and mor encode proteins with homology to SWI1, SWI2, and SWI3, respectively, suggesting that the activity of a SWI/SNF chromatin-remodeling complex has an important impact on E2F-dependent phenotypes. Mutations in poc also suppress phenotypes caused by p21(CiP1) expression, indicating an important role for polycephalon in cell-cycle control. C1 Massachusetts Gen Hosp, Ctr Canc, Dept Mol Oncol, Charlestown, MA 02129 USA. RP Dyson, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Mol Oncol, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIGMS NIH HHS [GM-53203] NR 73 TC 69 Z9 69 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 1999 VL 153 IS 1 BP 275 EP 287 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 233HN UT WOS:000082421600019 PM 10471712 ER PT J AU Rehm, HL Morton, CC AF Rehm, HL Morton, CC TI A new age in the genetics of deafness SO GENETICS IN MEDICINE LA English DT Review ID HEARING IMPAIRMENT; NONSYNDROMIC DEAFNESS; MUTATIONS C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. RP Rehm, HL (reprint author), Massachusetts Gen Hosp, Wellman 415,50 Blossom St, Boston, MA 02114 USA. NR 33 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD SEP-OCT PY 1999 VL 1 IS 6 BP 295 EP 302 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 271JN UT WOS:000084590600010 PM 11258632 ER PT J AU Bevan, S Woodford-Richens, K Rozen, P Eng, C Young, J Dunlop, M Neale, K Phillips, R Markie, D Rodriguez-Bigas, M Leggett, B Sheridan, E Hodgson, S Iwama, T Eccles, D Bodmer, W Houlston, R Tomlinson, I AF Bevan, S Woodford-Richens, K Rozen, P Eng, C Young, J Dunlop, M Neale, K Phillips, R Markie, D Rodriguez-Bigas, M Leggett, B Sheridan, E Hodgson, S Iwama, T Eccles, D Bodmer, W Houlston, R Tomlinson, I TI Screening SMAD1, SMAD2, SMAD3, and SMAD5 for germline mutations in juvenile polyposis syndrome SO GUT LA English DT Article DE juvenile polyposis; SMAD ID BETA; GENE; CANCERS AB Background and aims-Juvenile polyps occur in several Mendelian disorders, whether in association with gastrointestinal cancer alone (juvenile polyposis syndrome, JPS) or as part of known syndromes (Cowden, Gorlin, and Bannayan-Zonana) in association with developmental abnormalities, dysmorphic features, or extraintestinal tumours. Recently, some JPS families were shown to harbour germline mutations in the SMAD4 (DPC4) gene, providing further evidence for the importance of the TGF beta signalling pathway in colorectal cancer. There remains, however, considerable, unexplained genetic heterogeneity in JPS. Other members of the SMAD family are excellent candidates for JPS, especially SMAD2 (which, like SMAD4, is mutated somatically in colorectal cancers), SMAD3 (which causes colorectal cancer when "knocked out" in mice), SMAD5, and SMAD1. Methods-SMAD1, SMAD2, SMAD3, and SMAD5 were screened for germline mutations in 30 patients with JPS and without SMAD4 mutations. Results-No mutations were found in any of these genes. A G-A C89Y polymorphism with possible effects on protein function was found in SMAD3, but the frequencies of the G and A alleles did not differ between patients with JPS and controls. Conclusions-It remains to be determined whether or not this polymorphism is involved in a minor predisposition to colorectal or other carcinomas. SMAD4 may be the only member of the SMAD family which causes JPS when mutant in the germline. The other genes underlying JPS remain to be identified. C1 Imperial Canc Res Fund, Mol Populat Genet Lab, London WC2A 3PX, England. Inst Canc Res, Haddow Labs, Sect Canc Genet, Sutton, Surrey, England. Tel Aviv Med Ctr & Sch Med, Dept Gastroenterol, IL-64239 Tel Aviv, Israel. Harvard Univ, Sch Med, Dana Farber Canc Inst, Translat Res Lab, Boston, MA 02115 USA. Royal Brisbane Hosp Fdn, Conjoint Gastroenterol Lab, Clin Res Ctr, Brisbane, Qld, Australia. Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. St Marks Hosp, Harrow HA1 3UJ, Middx, England. Dunedin Sch med, Mol Genet Lab, Dunedin, New Zealand. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Royal Childrens Hosp, Dept Clin Genet, Bristol, Avon, England. Guys Hosp, Dept Clin Genet, London SE1 9RT, England. Ctr Polyposis & Intestinal Dis, Bunkyo Ku, Tokyo, Japan. Princess Anne Hosp, Wessex Reg Genet Serv, Southampton SO16 5YA, Hants, England. Imperial Canc Res Fund, Inst Mol Med, Can Immunogenet Lab, Oxford OX3 9DS, England. RP Houlston, R (reprint author), Imperial Canc Res Fund, Mol Populat Genet Lab, 4th Floor, London WC2A 3PX, England. RI Leggett, Barbara/D-3579-2011; Dunlop, Malcolm/F-1973-2011; OI Dunlop, Malcolm/0000-0002-3033-5851; Eng, Charis/0000-0002-3693-5145; Bodmer, Walter/0000-0001-6244-9792; Houlston, Richard/0000-0002-5268-0242 NR 15 TC 45 Z9 47 U1 0 U2 4 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 SEP PY 1999 VL 45 IS 3 BP 406 EP 408 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 229PP UT WOS:000082203200022 PM 10446110 ER PT J AU Li, L Kim, JG Gutierrez, O Graham, D Go, MF AF Li, L Kim, JG Gutierrez, O Graham, D Go, MF TI Geographic variation in cagA structural heterogeneity in HP isolates from duodenal ulcer (DU) and gastric cancer (GC) patients SO GUT LA English DT Meeting Abstract C1 Baylor Coll, VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 1999 VL 45 SU 3 BP A28 EP A28 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 234DN UT WOS:000082469400093 ER PT J AU Pena, JR Fox, JG Ferraro, MJ Versalovic, J AF Pena, JR Fox, JG Ferraro, MJ Versalovic, J TI Combination rapid urease and molecular susceptibility testing of Helicobacter pylori from gastric biopsies SO GUT LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 SEP PY 1999 VL 45 SU 3 BP A21 EP A21 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 234DN UT WOS:000082469400072 ER PT J AU Kavirajan, H AF Kavirajan, H TI The amobarbital interview revisited: A review of the literature since 1966 SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID AMYTAL INTERVIEW; CATATONIC MUTISM; MANAGEMENT AB The amobarbital interview has been a diagnostic and therapeutic tool for almost 70 years. Because safer alternatives, namely benzodiazepines, have become available over the past 30 years, its clinical use merits reexamination. Toward this end, the! psychiatric literature on the amobarbital interview is reviewed. A Medline search using the key words "amobarbital interview" generated papers published in English since 1966. Most of the literature demonstrating utility of the amobarbital interview consists of uncontrolled case series or case reports on a variety of clinical applications. One controlled study in patients with catatonia demonstrated clear superiority of amobarbital over placebo in promoting verbalization and alertness, but six other controlled studies using various doses in heterogeneous patient groups failed to find differences between this drug and placebo. Additional rigorous, controlled studies comparing amobarbital with placebo and with possible alternatives such as benzodiazepines in specific patient populations are! needed to define the place of this agent in the psychiatric armamentarium. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Kavirajan, H (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. NR 63 TC 9 Z9 9 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 1999 VL 7 IS 3 BP 153 EP 165 DI 10.1093/hrp/7.3.153 PG 13 WC Psychiatry SC Psychiatry GA 232CP UT WOS:000082348400003 PM 10483934 ER PT J AU Lynn, MM Achtmeyer, C Chavez, C Zicafoose, B Therien, J AF Lynn, MM Achtmeyer, C Chavez, C Zicafoose, B Therien, J TI The evolving role of advanced practice nursing within the new Veteran's Health Administration SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article DE advanced practice nurses (APNs); best practice model; evolving role; patient-centered care ID PRIMARY-CARE; PRACTITIONERS; SATISFACTION; PHYSICIANS; QUALITY AB The Veteran's Health Administration (VHA) is experiencing profound change in focus and organization of service delivery. The focus of the evolving VHA system includes improvements in performance outcomes, such as actual costs, better access, higher levels of customer satisfaction, and improved functional status of patients. Given the changing nature of service delivery in the VHA system and the contributions of the Advanced Practices Nurses (APNs), this article explores the expanding role of the APN within the VHA and presents a best practice model for achieving the full potential of advanced nursing practice. C1 Denver VAMC, Denver, CO USA. Univ Phoenix, Phoenix, AZ USA. Vet Affairs Puget Sound Med Ctr, Seattle, WA USA. Tucson VAMC, Tucson, AZ USA. Salem VAMC, Womens Hlth Clin, Ambulatory Care Serv Line, Salem, VA USA. RP Lynn, MM (reprint author), Denver VAMC, Denver, CO USA. NR 35 TC 5 Z9 5 U1 0 U2 1 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21704 USA SN 0361-6274 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD FAL PY 1999 VL 24 IS 4 BP 80 EP 93 PG 14 WC Health Policy & Services SC Health Care Sciences & Services GA 254FM UT WOS:000083601300010 PM 10572792 ER PT J AU Carey, K Burgess, JF AF Carey, K Burgess, JF TI On measuring the hospital cost/quality trade-off SO HEALTH ECONOMICS LA English DT Article DE hospitals; cost functions; quality of care ID COST-FUNCTIONS; EARLY READMISSION; PANEL-DATA; QUALITY; CARE; INDICATOR; INDUSTRY AB This paper explores the relationship between cost and quality of hospital care. A total operating cost function is estimated for 137 US Department of Veterans Affairs hospitals for 1988-1993 using three rate-based measures of quality as regressors. The high likelihood of the existence of measurement error in quality in the cross section leads to the application of novel instrumental variable techniques. Results suggest that mortality and readmission indices are adjusted inadequately for illness severity. The measure on the failure to follow up inpatient discharges with outpatient care, however, appears to increase cost. The results of this paper underscore a number of practical difficulties and challenges facing government or other systems in evaluating the relative performance of their hospitals. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 US Dept Vet Affairs, Management Sci Grp, Bedford, MA 01730 USA. RP Carey, K (reprint author), US Dept Vet Affairs, Management Sci Grp, Bldg 12,200 Springs Rd, Bedford, MA 01730 USA. NR 21 TC 40 Z9 40 U1 3 U2 7 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-9230 J9 HEALTH ECON JI Health Econ. PD SEP PY 1999 VL 8 IS 6 BP 509 EP 520 DI 10.1002/(SICI)1099-1050(199909)8:6<509::AID-HEC460>3.0.CO;2-0 PG 12 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 242RZ UT WOS:000082956600003 PM 10544316 ER PT J AU Wang, YP Ripperger, J Fey, GH Samols, D Kordula, T Wetzler, M Van Etten, RA Baumann, H AF Wang, YP Ripperger, J Fey, GH Samols, D Kordula, T Wetzler, M Van Etten, RA Baumann, H TI Modulation of hepatic acute phase gene expression by epidermal growth factor and Src protein tyrosine kinases in murine and human hepatic cells SO HEPATOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; DNA-BINDING ACTIVITY; ONCOSTATIN-M; FACTOR-RECEPTOR; INTERLEUKIN-6 FAMILY; LIVER-REGENERATION; PLASMA-PROTEINS; FACTOR-BETA; TRANSCRIPTION FACTOR; STIMULATING FACTOR AB As part of systemic inflammatory reactions, interleukin 6 (IL-6) induces acute phase protein (APP) genes through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway Epidermal growth factor (EGF), which contributes to the regenerative process after liver injury and also activates STATs, does not induce but attenuates IL-6-stimulated expression of several APP genes in primary mouse hepatocytes. The APP-modifying action of EGF receptor (EGFR) was characterized in HepG2 cells, Although EGF less effectively engages STAT proteins in these cells, it reduces expression of fibrinogen and haptoglobin, but stimulates production of alpha(1)-antichymotrypsin and induces transcription through the alpha(1)-antichymotrypsin and C-reactive protein promoter. The stimulatory EGFR signal is insensitive to inhibition of JAKs and appears to involve Src kinases and STAT proteins as shown by inhibition through overexpression of C-terminal Src kinase (Csk) and transdominant negative STAT3, respectively. A mediator role of Src is supported by the ability of c-Src and v-Src to activate STATs and induce transcription through APP promoters. Src kinases have been observed in association with the IL-6 receptor; however, inhibition of Src kinases by Csk enhances IL-6-induced transcription. The Csk effect is attributed to prevention of Src kinases from phosphorylating gp130 at the docking site for the signal-moderating protein tyrosine phosphatase SHP-2. The inhibitory EGFR signal on APP expression correlates with the activation of Erk1 and Erk2. The study shows a dual signaling function for EGFR and suggests that the ratio of receptor-activated STATs and Erks influence the level of stimulated or inhibited expression of individual APPs. C1 Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. Univ Erlangen Nurnberg, D-8520 Erlangen, Germany. Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. Jagiellonian Univ, Inst Mol Biol, Krakow, Poland. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. RP Baumann, H (reprint author), Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Elm & Carlton St, Buffalo, NY 14263 USA. FU NCI NIH HHS [CA26122]; NIA NIH HHS [AG-02467]; NIDDK NIH HHS [DK33886] NR 87 TC 44 Z9 45 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1999 VL 30 IS 3 BP 682 EP 697 DI 10.1002/hep.510300318 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 230PL UT WOS:000082259500014 PM 10462375 ER PT J AU Hocker, M John, M Anagnostopoulos, J Buhr, HJ Solimena, M Gasnier, B Henry, JP Wang, TC Wiedenmann, B AF Hocker, M John, M Anagnostopoulos, J Buhr, HJ Solimena, M Gasnier, B Henry, JP Wang, TC Wiedenmann, B TI Molecular dissection of regulated secretory pathways in human gastric enterochromaffin-like cells: an immunohistochemical analysis SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article ID VESICULAR MONOAMINE TRANSPORTER; PANCREATIC BETA-CELLS; SYNAPTIC VESICLES; ENDOCRINE-CELLS; TUMOR-DIAGNOSIS; ACID-SECRETION; RAT STOMACH; SYNAPTOPHYSIN; EXPRESSION; PROTEIN AB Enterochromaffin-like (ECL) cells regulate gastric acid secretion through vesicular release of histamine. Until now, the molecular machinery of human ECL cells involved in the formation and release of vesicles is largely unknown. We analyzed tissue samples obtained from normal human gastric mucosa (n=4) and ECLomas (n=5) immunohistochemically using the APAAP method or double immunofluorescence confocal laser microscopy. Human pheochromocytomas (n=5) were investigated in parallel and compared to ECL cells. Secretory pathways were characterized using antibodies specific for marker proteins of large dense-core vesicles (LDCVs; islet cell antigen 512, chromogranin A, pancreastatin, and vesicular monoamine transporter 2) and small synaptic vesicle (SSV) analogues (synaptophysin). Tissues were also analyzed for expression of the peptide hormone processing enzymes, carboxypeptidase E and prohormone convertase 1, as well as the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, 25-kDa synaptosome-associated protein (SNAP25), syntaxin, and syn aptobrevin. Immunoreactivity for markers of LDCVs and SSV analogues were detected in normal ECL cells and ECLomas. Both tissues also showed expression of carboxypeptidase E and prohormone convertase 1. Analysis of vesicular SNARE (v-SNARE) and target membrane SNARE (t-SNARE) proteins revealed the presence of SNAP25, syntaxin, and synaptobrevin in normal and neoplastic ECL cells. Our data suggest that ECL cells possess the two vesicle types of regulated neuroendocrine secretory pathways, LDCVs and SSV analogues. Since ECL cells also contain typical SNARE proteins, the molecular machinery underlying secretory processes in this cell type appears to be identical to the secretory apparatus of neuroendocrine cells and neurons. In addition, our findings suggest that the secretory apparatus of ECL cells is maintained during neoplastic transformation. C1 Humboldt Univ, Klinikum Charite, Med Klin Schwerpunkt Hepatol & Gastroenterol, D-13353 Berlin, Germany. Free Univ Berlin, Klinikum Benjamin Franklin, Med Klin 1, D-12002 Berlin, Germany. Free Univ Berlin, Klinikum Benjamin Franklin, Abt Pathol, D-12002 Berlin, Germany. Free Univ Berlin, Klinikum Benjamin Franklin, Allgemeinchirurg Abt, D-12002 Berlin, Germany. Yale Univ, Sch Med, Div Med, New Haven, CT USA. Yale Univ, Sch Med, Div Endocrinol, New Haven, CT USA. Inst Biol Phys Chim, F-75005 Paris, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA USA. RP Wiedenmann, B (reprint author), Humboldt Univ, Klinikum Charite, Med Klin Schwerpunkt Hepatol & Gastroenterol, Campus Virchow Klinikum,Augustenburger Pl 1, D-13353 Berlin, Germany. RI Solimena, Michele/E-1275-2011 NR 37 TC 14 Z9 14 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD SEP PY 1999 VL 112 IS 3 BP 205 EP 214 DI 10.1007/s004180050408 PG 10 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 336QF UT WOS:000088313900003 PM 10502067 ER PT J AU Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Levy, D AF Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Levy, D TI Differential impact of systolic and diastolic blood pressure level on JNC-VI staging SO HYPERTENSION LA English DT Article DE hypertension, detection and control; risk factors; epidemiology; guidelines ID CORONARY HEART-DISEASE; HYPERTENSION; FRAMINGHAM; PLACEBO AB The sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classifies blood pressure into stages on the basis of both systolic (SBP) and diastolic (DBP) blood pressure levels. When a disparity exists between SEP and DBP stages, patients are classified into the higher stage ("up-staged"). We evaluated the effect of disparate levels of SEP and DBP on blood pressure staging and eligibility for therapy. We examined 4962 Framingham Heart Study subjects between 1990 and 1995 and determined blood pressure stages on the basis of SEP alone, DBP alone, or both. After the exclusion of subjects on antihypertensive therapy (n=1306), 3656 subjects (mean age 58+/-13 years; 55% women) were eligible. In this sample, 64.6% of subjects had congruent stages of SEP and DBP, 31.6% were up-staged on the basis of SEP, and 3.8% on the basis of DBP; thus, SEP alone correctly classified JNC-VI stage in approximate to 96% (64.6% +31.6%) of the subjects. Among subjects >60 years of age, SEP alone correctly classified 99% of subjects; in those less than or equal to 60 years old, SEP alone correctly classified 95%. Of 1488 subjects with high-normal blood pressure or hypertension, who were potentially eligible for drug therapy, 13.0% had congruent elevations of SEP and DBP, 77.7% were up-staged on the basis of SEP, and 9.3% were up-staged on the basis of DBP; SEP alone correctly classified 91%, whereas DBP alone correctly classified only 22%. SEP elevation out of proportion to DBP is common in middle-aged and older persons. SEP appears to play a greater role in the determination of JNC-VI blood pressure stage and eligibility for therapy. Given these results, combined with evidence from hypertension treatment trials, future guidelines might consider a greater role for SEP than for DBP in determining the presence of hypertension, risk of cardiovascular events, eligibility for therapy, and benefits of treatment. C1 NHLBI, Framingham Heart Study, NIH, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02114 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, NIH, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-38038] NR 24 TC 84 Z9 88 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1999 VL 34 IS 3 BP 381 EP 385 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 239JU UT WOS:000082765600004 PM 10489380 ER PT J AU Andes, DR Craig, WA AF Andes, DR Craig, WA TI Pharmacokinetics and pharmacodynamics of antibiotics in meningitis SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID EXPERIMENTAL PNEUMOCOCCAL MENINGITIS; RESISTANT STREPTOCOCCUS-PNEUMONIAE; EXPERIMENTAL ESCHERICHIA-COLI; CEREBROSPINAL-FLUID CONCENTRATIONS; EXPERIMENTAL PENICILLIN-RESISTANT; TICARCILLIN-CLAVULANIC ACID; ACUTE BACTERIAL-MENINGITIS; LACTAMASE-PRODUCING STRAIN; ANTIMICROBIAL RESISTANCE; PURULENT-MENINGITIS AB It is the ability of a drug to reach and maintain effective concentrations at the infection site that determines its efficacy. This article reviews the pharmacokinetics and pharmacodynamics of antimicrobials used in the treatment of meningitis. A better understanding of the interrelationship between pharmacokinetics-the time course of antimicrobial concentrations in serum and at the infection site-and pharmacodynamics-the relationships between antimicrobial concentration and antimicrobial effect-should facilitate the establishment of optimal dosage regimens for this life-threatening bacterial infection. C1 Univ Wisconsin, Sch Med, Dept Med, Infect Dis Sect, Madison, WI 53792 USA. Univ Wisconsin, Sch Med, Dept Med, Clin Pharmacol Sect, Madison, WI 53792 USA. William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. RP Andes, DR (reprint author), Univ Wisconsin, Sch Med, Dept Med, Infect Dis Sect, 600 Highland Ave,Room H4-570, Madison, WI 53792 USA. NR 133 TC 58 Z9 60 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 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 1999 VL 13 IS 3 BP 595 EP + DI 10.1016/S0891-5520(05)70096-9 PG 25 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 229BA UT WOS:000082172400006 PM 10470557 ER PT J AU De Vriese, AS Vanholder, RC Pascual, M Lameire, NH Colardyn, FA AF De Vriese, AS Vanholder, RC Pascual, M Lameire, NH Colardyn, FA TI Can inflammatory cytokines be removed efficiently by continuous renal replacement therapies? SO INTENSIVE CARE MEDICINE LA English DT Review ID CONTINUOUS ARTERIOVENOUS HEMOFILTRATION; CONTINUOUS VENOVENOUS HEMOFILTRATION; TUMOR-NECROSIS-FACTOR; COMPLEMENT FACTOR-D; RESPONSE SYNDROME; HEMODIALYSIS MEMBRANES; DIALYSIS MEMBRANES; ENDOTOXIN REMOVAL; CARDIOPULMONARY BYPASS; CARDIAC-SURGERY C1 State Univ Ghent Hosp, Dept Med, Div Renal, B-9000 Ghent, Belgium. State Univ Ghent Hosp, Intens Care Unit, B-9000 Ghent, Belgium. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP De Vriese, AS (reprint author), State Univ Ghent Hosp, Dept Med, Div Renal, De Pintelaan 185, B-9000 Ghent, Belgium. NR 64 TC 77 Z9 81 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 1999 VL 25 IS 9 BP 903 EP 910 DI 10.1007/s001340050981 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 242BK UT WOS:000082918200009 PM 10501744 ER PT J AU Villar, J Perez-Mendez, L Kacmarek, RM AF Villar, J Perez-Mendez, L Kacmarek, RM TI Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome SO INTENSIVE CARE MEDICINE LA English DT Article DE ARDS; acute lung injury; sepsis; outcome; risk factor; positive end-expiratory pressure; oxygenation index; definition ID INTENSIVE-CARE PATIENTS; SYSTEM ORGAN FAILURE; VENTILATION STRATEGY; MORTALITY; INFECTION; SURVIVAL; INDEX; ARDS AB Background: Despite intensive research, there are no universally accepted clinical definitions for acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS), A recent joint American-European Consensus Conference on ARDS formally defined the difference between ALI and ARDS based on the degree of oxygenation impairment. However, this definition may not reflect the true prevalence, severity and prognosis of these syndromes. Methods: During a 22-month period, 56 consecutive mechanically ventilated patients who met the American-European Consensus definition for ARDS [arterial oxygen tension/fractional inspired oxygen (PaO2/FIO2 less than or equal to 200 mmHg regardless of the level of positive end-expiratory pressure (PEEP), bilateral pulmonary infiltrates, and no evidence of left heart failure] were admitted into the intensive care units (ICU) of the Hospital del Pine, Las Palmas, Spain, and prospectively studied, The diagnosis of ALI and ARDS was made by a PEEP-FIO2 trial, 24 h after patients met the Consensus inclusion criteria. Patients were classified as having ALI(-24h) if the PaO2/FIO2 was > 150 mmHg with PEEP = 5 cmH(2)O, and ARDS(-24h) if the PaO2/FIO2 was less than or equal to 150 mmHg with PEEP greater than or equal to 5 cmH(2)O. Results: Overall mortality was 43 % (24 of 56), However, 24 h after inclusion, PaO2 response to PEEP 5 cmH(2)O allowed the separation of our patients into two different groups: 31 patients met our ALI(-24h) criteria (PaO2/FIO2 > 150 mmHg) and their mortality was 22.6 %; 25 patients met our ARDS(-24h) criteria (PaO2/FIO2 less than or equal to 150 mmHg) and their mortality was 68 % (p = 0.0016). The differences in the respiratory severity index during the first 24 h of inclusion, PaO2/FIO2 ratio at baseline and at 24 h, maximum plateau airway pressure, maximum level of PEEP, and number of organ system failures during the ICU stay were statistically significant. Conclusions: Since the use of PEEP in the American-European Consensus criteria for ARDS is not mandatory, that definition does not reflect the true severity of lung damage and outcome. Our data support the need for guidelines based on a specific method of evaluating oxygenation status before the American-European Consensus definition is adopted. C1 Hosp Candelaria, Inst Res, Dept Epidemiol, Santa Cruz De Tenerife 38010, Spain. Samuel Lunenfeld Res Inst, Toronto, ON, Canada. Mercer Univ, Macon, GA 31207 USA. Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Harvard Univ, Dept Anesthesia, Boston, MA 02115 USA. RP Villar, J (reprint author), Hosp Candelaria, Inst Res, Dept Epidemiol, Carretera Rosario S-N, Santa Cruz De Tenerife 38010, Spain. NR 26 TC 120 Z9 129 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 1999 VL 25 IS 9 BP 930 EP 935 DI 10.1007/s001340050984 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 242BK UT WOS:000082918200012 PM 10501747 ER PT J AU Gilbertson, LI Hurford, WE AF Gilbertson, LI Hurford, WE TI Conscious sedation: An anesthesiologist's responsibility - Preface SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Editorial Material C1 Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Gilbertson, LI (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD FAL PY 1999 VL 37 IS 4 BP XI EP XII PG 2 WC Anesthesiology SC Anesthesiology GA 254GG UT WOS:000083603100001 ER PT J AU Hurford, WE AF Hurford, WE TI Sedation in the intensive care unit SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Article ID CRITICALLY-ILL PATIENTS; MECHANICAL VENTILATION; INTRAVENOUS HALOPERIDOL; CONTINUOUS INFUSION; PROPOFOL; MIDAZOLAM; KETAMINE; THERAPY C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Hurford, WE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 32 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD FAL PY 1999 VL 37 IS 4 BP 113 EP 122 DI 10.1097/00004311-199903740-00011 PG 10 WC Anesthesiology SC Anesthesiology GA 254GG UT WOS:000083603100010 PM 10614022 ER PT J AU Maron, R Hancock, WW Slavin, A Hattori, M Kuchroo, V Weiner, HL AF Maron, R Hancock, WW Slavin, A Hattori, M Kuchroo, V Weiner, HL TI Genetic susceptibility or resistance to autoimmune encephalomyelitis in MHC congenic mice is associated with differential production of pro- and anti-inflammatory cytokines SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE autoimmunity; experimental allergic encephalomyelitis; genetics; NOD; transforming growth factor-beta ID GROWTH-FACTOR-BETA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CD4(+) T-CELLS; ORAL TOLERANCE; PROSTAGLANDIN-E; EXPRESSION; INTERLEUKIN-4; DISEASE; RESPONSES; COLITIS AB Experimental allergic encephalomyelitis (EAE) is a T(h)1-type cell-mediated autoimmune disease induced by immunization with myelin proteins and mediated by CD4(+) T cells. Although susceptibility to EAE is dependent largely on MHC background, the B10.S strain is resistant to induction of EAE despite sharing the I-A(S) MHC locus with the susceptible SJL strain. Furthermore, NOD mice which spontaneously develop diabetes are susceptible to EAE induction with myelin oligodendrocyte glycoprotein (MOG) 35-55, whereas a MHC congenic strain, III, which also expresses I-A(g7) MHC haplotype does not develop diabetes and is also resistant to EAE induction, We induced EAE in these four strains of mice with MOG peptides 92-106 (for I-A(S) strains) and 35-55 (for I-A(g7) strains) in complete Freund's adjuvant, In the susceptible strains (SJL and NOD) in vitro, there are high levels of IFN-gamma production, whereas the resistant strains (B10.S or III) secreted primarily IL-4/IL-10 and transforming growth factor (TGF)-beta, and had decreased levels of IFN-gamma, When brains from susceptible and resistant mice were examined by immunohistochemical methods for cytokine expression, the brains from resistant mice showed fewer infiltrates which predominantly expressed IL-4 and IL-10 and/or TGF-beta. Brains from NOD and SJL with EAE showed mainly IL-2 and IFN-gamma positive cells. Thus, resistance to MOG induced EAE in B10.S and III mouse strains is related to non-MHC genes and is associated with an altered balance of pro- and anti-inflammatory cytokines both in lymphoid tissue and in the brain following immunization with myelin antigens. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Leukosite, Cambridge, MA 02142 USA. Joslin Diabet Ctr, Boston, MA 02115 USA. RP Weiner, HL (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, 77 Ave Louis Pasteur,HIM 730, Boston, MA 02115 USA. FU NIAID NIH HHS [AI43458] NR 34 TC 50 Z9 51 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 SEP PY 1999 VL 11 IS 9 BP 1573 EP 1580 DI 10.1093/intimm/11.9.1573 PG 8 WC Immunology SC Immunology GA 237YY UT WOS:000082685200022 PM 10464178 ER PT J AU Terahara, A Niemierko, A Goitein, M Finkelstein, D Hug, E Liebsch, N O'Farrell, D Lyons, S Munzenrider, J AF Terahara, A Niemierko, A Goitein, M Finkelstein, D Hug, E Liebsch, N O'Farrell, D Lyons, S Munzenrider, J TI Analysis of the relationship between tumor dose inhomogeneity and local control in patients with skull base chordoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 38th Annual Meeting of American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 26-30, 1996 CL LOS ANGELES, CALIFORNIA SP Amer Soc Therapeut Radiol & Oncol DE chordoma; dose-volume histogram; dose inhomogeneity; skull base; proton ID RELATIVE BIOLOGICAL EFFECTIVENESS; CHARGED-PARTICLE IRRADIATION; PROTON RADIATION-THERAPY; INTRACRANIAL TUMORS; CERVICAL-SPINE; CHONDROSARCOMA; RECEPTORS; SEX AB Purpose: When irradiating a tumor that abuts or displaces any normal structures, the dose constraints to those structures (if lower than the prescribed dose) may cause dose inhomogeneity in the tumor volume at the tumor-critical structure interface. The low-dose region in the tumor volume may be one of the reasons for local failure. The aim of this study is to quantitate the effect of tumor dose inhomogeneity on local control and recurrence-free survival in patients with skull base chordoma. Methods and Materials: 132 patients with skull base chordoma were treated with combined photon and proton irradiation between 1978 and 1993. This, study reviews 115 patients whose dose-volume data and follow-up data are available. The prescribed doses ranged from 66.6 Cobalt-Gray-Equivalent (CGE) to 79.2 CGE (median of 68.9 CGE). The dose to the optic structures (optic nerves and chiasm), the brain stem surface, and the brain stem center was limited to 60, 64, and 53 CGE, respectively. We used the dose-volume histogram data derived with the three-dimensional treatment planning system to evaluate several dose-volume parameters including the Equivalent Uniform Dose (EUD). We also analyzed several other patient and treatment factors in relation to local control and recurrence-free survival. Results: Local failure developed in 42 of 115 patients, with the actuarial local control rates at 5 and 10 years being 59% and 44%. Gender was a significant predictor for local control with the prognosis in males being significantly better than that in females (P = 0.004, hazard ratio = 2.3). In a Cox univariate analysis, with stratification by gender, the significant predictors for local control (at the probability level of 0.05) were EUD, the target volume, the minimum dose, and the D-5cc dose. The prescribed dose, histology, age, the maximum dose, the mean dose, the median dose, the D-90% dose, and the overall treatment time were not significant factors. In a Cox multivariate analysis, the models including gender and EUD, or gender and the target volume, or gender and the minimum target dose were significant. The more biologically meaningful of these models is that of gender and EUD. Conclusion: This study suggests that the probability of recurrence of skull base chordomas depends on gender, target volume, and the level of target dose inhomogeneity. EUD was shown to be a useful parameter to evaluate dose distribution for the target volume. (C) 1999 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Tokyo, Fac Med, Dept Radiol, Tokyo 113, Japan. Loma Linda Univ, Med Ctr, Dept Radiat Med, Loma Linda, CA 92350 USA. RP Niemierko, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [CA 50628, CA 21239] NR 32 TC 96 Z9 98 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 1999 VL 45 IS 2 BP 351 EP 358 DI 10.1016/S0360-3016(99)00146-7 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 232VT UT WOS:000082391200014 PM 10487555 ER PT J AU Chan, RY Bhol, K Tesavibul, N Letko, E Simmons, RK Foster, CS Ahmed, AR AF Chan, RY Bhol, K Tesavibul, N Letko, E Simmons, RK Foster, CS Ahmed, AR TI The role of antibody to human beta 4 integrin in conjunctival basement membrane separation: Possible in vitro model for ocular cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ALPHA-6-BETA-4 INTEGRIN; AUTOANTIBODIES; ZONE; IMMUNOFLUORESCENCE; EPILIGRIN; SAMPLES; SKIN AB PURPOSE. TO demonstrate the specific binding of autoantibodies present in the sera of patients with ocular cicatricial pemphigoid (OCP) to human beta 4 integrin present in the normal human conjunctiva (NHC) and to study the role of OCP autoantibodies and antibody to human beta 4 integrin in the pathogenesis of subepithelial lesion formation in OCP. METHODS. Indirect immunofluorescence assay and in vitro organ culture method using NHC were used. Sera and IgG fractions from 10 patients with OCP; immunoaffinity-purified OCP autoantibody; antibodies to human beta 4, beta 1, alpha 6, and alpha 5 integrins; and sera from patients with pemphigus vulgaris, bullons pemphigoid (BP), and chronic atopic and chronic ocular rosacea cicatrizing conjunctivitis; and normal human serum (NHS) were used. RESULTS. Nine of 10 OCP sera or IgG fractions, immunoaffinity-purified OCP autoantibody, antibodies to human beta 4 and alpha 6 integrins, and sera from patients with BP showed homogenous, smooth linear binding along the basement membrane zone (BMZ) of the NHC. NHS, antibodies to other integrins, and sera from patients with chronic cicatrizing conjunctivitis from other causes showed no such binding. When NHC was first absorbed with OCP sera and then reacted with anti-beta 4 antibodies or vice versa, the intensity of the BMZ binding was dramatically reduced or completely eliminated, indicating that there were autoantibodies in OCP sera specific for the beta 4 integrin. BMZ separation developed 48 to 72 hours after addition of total OCP sera, IgG fractions from OCP sera, immunoaffinity-purified autoantibodies from sera of patients with OCP, or anti-beta 4 antibodies to the NHC cultures, but not after addition of normal control sera, sera from patients with chronic cicatrizing conjunctivitis from causes other than OCP, or sera from patients with OCP in clinical remission. CONCLUSION. Circulating anti-beta 4 integrin antibody may have an important role in the pathogenesis of OCP. C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, 188 Longwood Ave, Boston, MA 02115 USA. FU NEI NIH HHS [EY08378] NR 24 TC 52 Z9 53 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 1999 VL 40 IS 10 BP 2283 EP 2290 PG 8 WC Ophthalmology SC Ophthalmology GA 230EX UT WOS:000082239800016 PM 10476794 ER PT J AU Husain, D Kramer, M Kenny, AG Michaud, N Flotte, TJ Gragoudas, ES Miller, JW AF Husain, D Kramer, M Kenny, AG Michaud, N Flotte, TJ Gragoudas, ES Miller, JW TI Effects of photodynamic therapy using verteporfin on experimental choroidal neovascularization and normal retina and choroid up to 7 weeks after treatment SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SUBRETINAL NEOVASCULARIZATION; BENZOPORPHYRIN; MONKEYS AB PURPOSE. To study the long-term effects of photodynamic therapy (PDT), using liposomal benzoporphyrin derivative (BPD) or Verteporfin, on experimental choroidal neovascularization (CNV) and on normal retina and choroid (with no CNV) in the cynomolgus monkey eye. METHODS. Photodynamic therapy was performed in 8 cynomolgus monkey eyes with experimental CNV induced by laser injury. The effect of PDT on normal retina and choroid (with no CNV) was studied in 9 monkey eyes. Liposomal BPD was administered intravenously (0.375 mg/kg) either as a bolus, as a slow infusion over 32 minutes, or as a fast infusion over 10 minutes. Photodynamic therapy was performed using light at a wavelength of 689 or 692 nm, With an irradiance of 600 mW/cm(2) and fluence of 150 J/cm(2). Follow-up studies, including fundus photography and FA were performed at 24 hours after PDT and then weekly. Indocyanine green and BPD angiography were performed in selected cases. Tissues were examined with light;Ind electron microscopy at the end of follow-up. RESULTS. Twenty-three of the 32 areas of CNV treated with PDT showed absence of angiographic leakage at 24 hours. Twenty-eight areas of CNV were followed for 4 weeks; 22 of 28 showed absence of angiographic leakage at 2 weeks; and 20 of 28 at 4 weeks of follow-up. Forty spots on the normal retina and choroid were treated with PDT and were followed for 4 to 7 weeks. These spots showed pigment-laden cells in the outer retina, variably pigmented retinal pigment epithelium (RPE) in the treated areal intact neurosensory retina, and reperfusion of the choriocapillaris. CONCLUSIONS. Photodynamic therapy leads to absence of angiographic leakage for at least 4 weeks in experimental CNV in the monkey model. In the normal monkey eye the RPE and choriocapillaris show generalized recovery with preservation of the neurosensory retina 7 weeks after PDT. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Laser Res Lab,Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Laser Res Lab,Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 25 TC 97 Z9 103 U1 0 U2 2 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 SEP PY 1999 VL 40 IS 10 BP 2322 EP 2331 PG 10 WC Ophthalmology SC Ophthalmology GA 230EX UT WOS:000082239800021 PM 10476799 ER PT J AU Sandberg, MA Pawlyk, BS Berson, EL AF Sandberg, MA Pawlyk, BS Berson, EL TI Acuity recovery and cone pigment regeneration after a bleach in patients with retinitis pigmentosa and rhodopsin mutations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID VITAMIN-A-DEFICIENCY; MACULAR DEGENERATION; FOVEAL DENSITOMETRY; DARK-ADAPTATION; GENE AB PURPOSE. TO assess visual acuity recovery times and cone photopigment regeneration kinetics after a bleach in the fovea of patients with dominant retinitis pigmentosa due to rhodopsin mutations. METHODS. The authors measured acuity recovery times by computerized photostress testing in 13 patients with dominant retinitis pigmentosa and one of eight rhodopsin mutations. The authors also measured their time constants of cone photopigment regeneration with a video imaging fundus reflectometer to determine whether acuity recovery time depended on pigment regeneration kinetics. These values were compared with those of normal subjects, by the Mann-Whitney U test. The relationship between acuity recovery time and the time constant of cone photopigment regeneration among the patients was quantified by the Spearman rank correlation. RESULTS. The visual acuity recovery times, which averaged 22.0 seconds for the patients with retinitis pigmentosa and 11.2 seconds for the normal subjects, were significantly slower for the patient group, (P < 0.001). The time constants of cone pigment regeneration, which averaged 172 seconds for the patients with retinitis pigmentosa and 118 seconds for the normal subjects, also were significantly slower for the patient group (P = 0.043). The authors also found a significant, positive correlation ben een the visual acuity recovery time and the time constant of pigment regeneration for the patients with retinitis pigmentosa (r = 0.65, P = 0.017). CONCLUSIONS. A slowing of foveal visual acuity recovery and cone pigment regeneration, which are related to each other, can occur in patients with retinitis pigmentosa, due to a rod-specific gene defect. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Sandberg, MA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY00169] NR 19 TC 12 Z9 12 U1 0 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 SEP PY 1999 VL 40 IS 10 BP 2457 EP 2461 PG 5 WC Ophthalmology SC Ophthalmology GA 230EX UT WOS:000082239800042 PM 10476820 ER PT J AU Campbell, EG Blumenthal, D AF Campbell, EG Blumenthal, D TI Perils of university-industry collaboration SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. RP Campbell, EG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD FAL PY 1999 VL 16 IS 1 BP 15 EP 15 PG 1 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA 316KW UT WOS:000087167000013 ER PT J AU Mannick, JB Stamler, JS Teng, E Simpson, N Lawrence, J Jordan, J Finberg, RW AF Mannick, JB Stamler, JS Teng, E Simpson, N Lawrence, J Jordan, J Finberg, RW TI Nitric oxide modulates HIV-1 replication SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; nitric oxide; virus replication; peripheral blood mononuclear cells; U1 cells ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; INHIBITS VIRAL REPLICATION; BLOOD MONONUCLEAR-CELLS; IN-VITRO; RIBONUCLEOTIDE REDUCTASE; GENERATING COMPOUNDS; SYNTHASE ACTIVITY; L-ARGININE; T-CELLS AB Although nitric oxide (NO) production is increased in HIV-1-infected patients, and NO is known to inhibit the replication of several viruses, very little is known about the effects of NO on HIV-1 replication. In the present studies, we find that S-nitrosothiols (RSNOs), a class of NO donor compounds present in the human circulatory system, inhibit HIV-1 replication in acutely infected human peripheral blood mononuclear cells (PBMCs) and have an additive inhibitory effect on HIV-1 replication in combination with 3'-azido-3'-deoxythymidylate (AZT). RSNOs inhibit HIV-1 replication in acutely infected PBMCs at a step in the viral replicative cycle after reverse transcription, but before or during viral protein expression through a cGMP-independent mechanism. In the latently infected U1 cell line, NO donor compounds and intracellular NO production stimulate HIV-1 reactivation. These studies suggest that NO both inhibits HIV-1 replication in acutely infected cells and stimulates HIV-1 reactivation in chronically infected cells. Thus, NO may have a physiologic role in HIV-1 replication, and NO donor compounds, which have been used for decades in the treatment of coronary artery disease with limited toxicity, might be useful in the treatment of HIV-1 disease by inhibiting acute infection, reactivating latent virus, or both. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Med, Div Resp Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. RP Mannick, JB (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 1440,44 Binney St, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 NR 62 TC 30 Z9 31 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD SEP 1 PY 1999 VL 22 IS 1 BP 1 EP 9 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 245TV UT WOS:000083125000001 PM 10534141 ER PT J AU Amsterdam, J Garcia-Espana, F Fawcett, J Quitkin, F Reimherr, F Rosenbaum, J Beasley, C AF Amsterdam, J Garcia-Espana, F Fawcett, J Quitkin, F Reimherr, F Rosenbaum, J Beasley, C TI Fluoxetine efficacy in menopausal women with and without estrogen replacement SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE fluoxetine; menopause; estrogen replacement major depression ID DEPRESSED-PATIENTS; HEALTHY-SUBJECTS; DOUBLE-BLIND; THERAPY; MULTICENTER; CROSSOVER; RESPONSES; HORMONE; SEX AB A gradual decline in estrogen levels after the age of 40 may contribute to a higher rate of depression in women over 45 years of age. Estrogen replacement therapy (ERT) has been shown to produce cognitive and mood-enhancing effects in women and may facilitate antidepressant activity. Methods: We examined the efficacy rates in women on ERT greater than or equal to 45 years (n = 40) compared to women greater than or equal to 45 years not on ERT (n = 132) and to women < 45 years (n = 396) and to men (n = 262) with major depression during fluoxetine 20 mg daily up to 8 weeks. Remitters with a HAM-D-17 score less than or equal to 7 from week 9 to 12 were then treated up to 1-year in a placebo-controlled, relapse-prevention trial. Results: Efficacy rates were similar in women greater than or equal to 45 years on ERT when compared to women greater than or equal to 45 years taking fluoxetine alone, and when compared to women < 45 years and men taking fluoxetine. A Kaplan-Meier survival analysis in fluoxetine responders treated up to 26 weeks showed a somewhat greater relapse rate in women greater than or equal to 45 years taking ERT compared to other treatment groups (P < 0.06). Limitations: This study was retrospective nature and ERT was given in an uncontrolled fashion: 63% of women received estrogen alone while 37% also took intermittent progesterone. Other variables include the absence of hormonal documentation of menopausal status, no direct assessment of ERT compliance and the use of fixed-dose fluoxetine 20 mg daily. Conclusion: In contrast to prior reports suggesting that ERT may facilitate antidepressant activity, we observed similar efficacy in depressed women greater than or equal to 45 years taking fluoxetine plus ERT compared to those taking fluoxetine alone. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Penn, Med Ctr, Depress Res Unit, Philadelphia, PA 19104 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. New York State Psychiat Inst, New York, NY 10032 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. RP Amsterdam, J (reprint author), Univ Penn, Med Ctr, Depress Res Unit, 3600 Market St,8th Fl, Philadelphia, PA 19104 USA. OI Beasley, Charles/0000-0001-8743-7691 NR 32 TC 79 Z9 85 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 1999 VL 55 IS 1 BP 11 EP 17 DI 10.1016/S0165-0327(98)00203-1 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 240DN UT WOS:000082810700002 PM 10512601 ER PT J AU Cannon, B Mulroy, R Otto, MW Rosenbaum, JF Fava, M Nierenberg, AA AF Cannon, B Mulroy, R Otto, MW Rosenbaum, JF Fava, M Nierenberg, AA TI Dysfunctional attitudes and poor problem solving skills predict hopelessness in major depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE hopelessness; depression; dysfunctional attitudes; problem solving; suicidal risk ID SUICIDAL IDEATION; STATE; MODEL; MOOD AB Background: Hopelessness is a significant predictor of suicidality, but not all depressed patients feel hopeless. If clinicians can predict hopelessness, they may be able to identify those patients at risk of suicide and focus interventions on factors associated with hopelessness. In this study, we examined potential predictors of hopelessness in a sample of depressed outpatients. Methods: In this study, we examined potential demographic, diagnostic, and symptom predictors of hopelessness in a sample of 138 medication-free outpatients (73 women and 65 men) with a primary diagnosis of major depression. The significance of predictors was evaluated in both simple and multiple regression analyses. Results: Consistent with previous studies, we found no significant associations between demographic and diagnostic variables and greater hopelessness. Hopelessness was significantly associated with greater depression severity, poor problem solving abilities as assessed by the Problem Solving Inventory, and each of two measures of dysfunctional cognitions (the Dysfunctional Attitudes Scale and the Cognitions Questionnaire). In a stepwise multiple regression equation, however, only dysfunctional cognitions and poor problem solving offered non-redundant prediction of hopelessness scores, and accounted for 20% of the variance in these scores. Limitations: This study is based on depressed patients entering into an outpatient treatment protocol. All analyses were correlational in nature, and no causal links can be concluded. Conclusions: Our findings, identifying clinical correlates of hopelessness, provide clinicians with potential additional targets for assessment and treatment of suicidal risk. In particular, clinical attention to dysfunctional attitudes and problem solving skills may be important for further reduction of hopelessness and perhaps suicidal risk. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, WACC-815,15 Parkman St, Boston, MA 02114 USA. NR 22 TC 28 Z9 30 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 1999 VL 55 IS 1 BP 45 EP 49 DI 10.1016/S0165-0327(98)00123-2 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 240DN UT WOS:000082810700006 PM 10512605 ER PT J AU Jain, U Blais, MA Otto, MW Hirshfeld, DR Sachs, GS AF Jain, U Blais, MA Otto, MW Hirshfeld, DR Sachs, GS TI Five-factor personality traits in patients with seasonal depression: treatment effects and comparisons with bipolar patients SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE personality; depression; seasonal affective disorder; five factor model; NEO ID MAJOR DEPRESSION; 5-FACTOR MODEL AB Background: Increasingly, the Five Factor Model (FFM) of personality is being used to assess personality characteristics of patients with Axis I disorders. Recent study indicates that patients with the seasonal subtype of major depression (SAD) may differ meaningfully from other depressed patients. In the present study, we further examined this finding, with attention to the stability of personality characteristics across treatment. Methods: We used the NEO-FFM to assess the personality characteristics of two samples of depressed outpatients: patients with SAD and patients with bipolar disorder. Assessment was repeated in the SAD patients after light therapy. Results: Consistent with previous research, we found elevated scores on the Openness domain in the SAD patients. SAD patients also scored significantly lower on Neuroticism and significantly higher on the Conscientiousness and Extroversion domains than patients with bipolar disorder. Scores on the Openness domain remained elevated after treatment of SAD; this occurred in the context of significant decreases in Neuroticism and increases in Extroversion scores. Limitations: These results were obtained in a relatively small-sample study. Although our sample of bipolar patients were taking mood stabilizers, it is unlikely that medication effects could explain our results. Conclusions: Our findings are consistent with those reported by Bagby et al. (Major depression and the five-factor model of personality. J. Pers. Disord. 1995;9:224-234) and suggests that Neuroticism and Extroversion are the FFM domains most responsive to treatment for depression. Our results also suggest that elevations on the Openness domain do not change with treatment and may be an enduring characteristic of patients with SAD. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 8 TC 42 Z9 43 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 1999 VL 55 IS 1 BP 51 EP 54 DI 10.1016/S0165-0327(98)00206-7 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 240DN UT WOS:000082810700007 PM 10512606 ER PT J AU Regan, MM Catalano, PJ AF Regan, MM Catalano, PJ TI Bivariate dose-response modeling and risk estimation in developmental toxicology SO JOURNAL OF AGRICULTURAL BIOLOGICAL AND ENVIRONMENTAL STATISTICS LA English DT Article DE binary outcome; clustered data; continuous outcome; generalized estimating equations; probit model; risk assessment ID CORRELATED BINARY REGRESSION; LONGITUDINAL DATA-ANALYSIS; FETAL WEIGHT; CONTINUOUS OUTCOMES; DISCRETE; TOXICITY; MALFORMATION; VARIABLES; MICE AB With the recent developments in quantitative risk assessment for noncancer outcomes, dose-response models for developmental toxicity outcomes are being pursued. Among Live fetuses, the presence of malformations and reduction in fetal weight are of primary interest. The dose-response relationships are often fit to each of the outcomes separately using appropriate methods to account for clustering due to litter effects. Jointly modeling the outcomes, allowing different relationships with dose while incorporating the correlation between the outcomes and the fetuses, may be more appropriate. We propose modeling the bivariate outcome, malformation (binary) and fetal weight (continuous), where the bivariate correlation and the clustering of fetuses within litters are taken into account. We avoid fully specifying the joint distribution of outcomes within a litter by specifying only the marginal distribution of the bivariate outcome and using generalized estimating equation methodology to account for correlations due to clustering. To characterize joint risk to the fetus for quantitative risk assessment, the bivariate correlation is required and is therefore a focus of inference. Dose-response models and their application to quantitative risk assessment are illustrated using data from a developmental toxicology experiment of ethylene glycol in rats. C1 Harvard Univ, Sch Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Biometr Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Regan, MM (reprint author), Harvard Univ, Sch Med, 330 Brookline Ave, Boston, MA 02215 USA. NR 34 TC 16 Z9 16 U1 1 U2 3 PU AMER STATISTICAL ASSOC & INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1444 I ST NW, STE 700, WASHINGTON, DC 20005 USA SN 1085-7117 J9 J AGRIC BIOL ENVIR S JI J. Agric. Biol. Environ. Stat. PD SEP PY 1999 VL 4 IS 3 BP 217 EP 237 DI 10.2307/1400383 PG 21 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 251JH UT WOS:000083441700002 ER PT J AU Bush, RK Sanchez, H Geisler, D AF Bush, RK Sanchez, H Geisler, D TI Molecular cloning of a major Alternaria alternata allergen, rAlt a 2 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Alternaria alternata; recombinant allergens; rAlt a 2 ID NUTRITION EXAMINATION SURVEY; 2ND NATIONAL-HEALTH; FUNGAL ALLERGENS; ALT; PURIFICATION; ASTHMA; REACTIVITY AB Background: Sensitivity to the fungus Alternaria alternata is a common cause of asthma, Epidemiologic studies from a variety of locations worldwide indicate that A alternata sensitivity is closely linked with the development of asthma. Furthermore, A alternata sensitivity has been associated with severe and potentially fatal attacks of asthma, Objective: The diagnosis of A alternata sensitivity is hampered by the lack of standardized and well-characterized allergenic extracts. Molecular cloning of allergens offers the possibility of providing large quantities of purified, well-characterized allergens not only for diagnostic purposes but also for studying the pathogenesis of A alternata sensitivity, We used molecular cloning to identify, purify, and produce a majors alternata allergen in quantity. Methods: We prepared messenger (m)RNA from A alternata to produce a complementary (c)DNA library The library was screened for A alternata allergens by using sera from A alternata-sensitive individuals. A recombinant allergen was isolated, the cDNA sequence was determined, and the protein was expressed in Pichia pastoris, Results: A unique A alternata allergen, rAlt a 2, was identified. A 2.2-kb cDNA sequence was obtained that has homology with a common transposable region and mouse RNA-dependent eukaryote initiation factor-2 a-kinase but no homology to any known allergen, No N-glycosylation sites were found in the cDNA sequence. The recombinant allergen was recognized by IgE antibodies in the sera of 16 of 26 (61%) individuals allergic to A alternata, which defines Alt a 2 as a major allergen. Conclusions: We have molecularly cloned a unique major A alternata allergen, rAlt a 2. Identification and expression of the recombinant allergen should enhance the development of standardized A alternata allergenic extracts and provide stable reagents for investigating the pathogenesis of A alternata sensitivity. C1 William S Middleton Mem Vet Adm Hosp, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. RP Bush, RK (reprint author), William S Middleton Mem Vet Adm Hosp, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 33 TC 24 Z9 25 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 1999 VL 104 IS 3 BP 665 EP 671 DI 10.1016/S0091-6749(99)70340-4 PN 1 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 241EP UT WOS:000082870000032 PM 10482844 ER PT J AU Roep, BO Atkinson, MA van Endert, PM Gottlieb, PA Wilson, SB Sachs, JA AF Roep, BO Atkinson, MA van Endert, PM Gottlieb, PA Wilson, SB Sachs, JA TI Autoreactive T cell responses in insulin-dependent (type 1) diabetes mellitus. Report of the First International Workshop for Standardization of T cell assays SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE autoimmune; insulin-dependent diabetes mellitus; proliferation; T cell; workshop ID GLUTAMIC-ACID DECARBOXYLASE; BLOOD MONONUCLEAR-CELLS; CELIAC-DISEASE PATIENTS; PERIPHERAL-BLOOD; IMMUNE-RESPONSE; INTERFERON-GAMMA; IDDM PATIENTS; BETA-CASEIN; HLA-DR; ONSET AB Type 1 diabetes is thought to result from a T cell-mediated destruction of the pancreatic beta-cells. Multiple and sometimes conflicting studies have identified a variety of aberrations in the cellular immune response to autoantigens in persons with the disease. Potential explanations for these discrepancies include incomparable techniques or culture conditions, diversity in the populations of patients or controls tested, and differences in autoantigen preparations. A T cell workshop was organized by the Immunology of Diabetes Society with the aim of appreciating and identifying problems associated with autoreactive T cell assays in type 1 diabetes. As a first phase, a series of candidate autoantigens were analysed by reference laboratories for quality. Subsequently, these preparations, as well as control stimuli, were distributed in a blind fashion to 26 laboratories worldwide, including all experienced centres, for analysis of T cell proliferation assays in 10 recent onset type 1 diabetes and 10 non-diabetic controls. For this analysis, participants used their own assays and references. The islet autoantigen quality control analyses performed prior to the distribution indicate that the quality of recombinant autoantigen preparations requires improvement. For example, several T cell clones specific for glutamic acid decarboxylase (GAD65) were unable to cross-react with GAD65 expressed in baculovirus, yeast or bacteria. Moreover, autoantigens expressed in E. coli interfered with autoantigen-specific proliferation of both T cell clones and peripheral blood mononuclear cells. Nonetheless,responses could be measured to all autoantigen preparations evaluated in the workshop. During the blind phase of the study, all centres were able to reproducibly measure T cell responses to two identical samples of tetanus toroid, but there was significant interlaboratory variation in sensitivity and extent of the proliferative response measured. Third, the results using candidate autoantigens indicated that although a few laboratories could distinguish type 1 diabetes patients from non-diabetic controls in proliferative responses to individual islet autoantigens, in general, no differences in T cell proliferation between the two groups could be identified. This first T cell workshop on T cell autoreactivity in type 1 diabetes confirms that this was a difficult area for interlaboratory investigations, but provided insight towards future efforts focused on standardizing autoreactive T cell measurements. Some previously reported conflicting results can in part be explained by the observed interlaboratory variability. The inability to discriminate normal controls from new onset type 1 diabetes patients suggests that measuring proliferative responses in PBMC represents an incomplete picture of the immune response, perhaps complicated by difficulties in identifying suitable antigens and assays for standardized use. (C) 1999 Academic Press. C1 Leiden Univ, Med Ctr, Dept Immunohaematol, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Blood Bank, NL-2300 RC Leiden, Netherlands. Univ Florida, Dept Pathol, Gainesville, FL 32611 USA. Necker Hosp, INSERM, U25, Paris, France. Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO 80262 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. St Bartholomews & Royal London Sch Med & Dent, London, England. RP Roep, BO (reprint author), Leiden Univ, Med Ctr, Dept Immunohaematol, POB 9600, NL-2300 RC Leiden, Netherlands. OI van Endert, Peter/0000-0003-3782-0750 NR 65 TC 104 Z9 105 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD SEP PY 1999 VL 13 IS 2 BP 267 EP 282 DI 10.1006/jaut.1999.0312 PG 16 WC Immunology SC Immunology GA 234FP UT WOS:000082474100010 PM 10479395 ER PT J AU Baek, KH Lee, KY AF Baek, KH Lee, KY TI Signal transduction pathway for anterior-posterior development in Drosophila SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Review DE signal transduction; receptor tyrosine kinase; oncogene; Raf ID RECEPTOR TYROSINE KINASE; NUCLEOTIDE EXCHANGE; ADAPTER PROTEIN; PLASMA-MEMBRANE; BICOID PROTEIN; RAF; EMBRYO; TORSO; ACTIVATION; SEVENLESS AB In Drosophila, the establishment of embryonic polarity along the anterior-posterior axis of the egg is determined by the activity of maternal gene products that accumulate during oogenesis, Amongst these are the Bicoid, the Nanos, and the terminal class gene products, some of which are oncoproteins involved in signal transduction for the formation of terminal structures in the embryo. Several signal transduction pathways have been described in Drosophila, and this review explores the potential of oncogene studies using one of those pathways - the terminal class signal transduction pathway - to better understand the cellular mechanisms of proto-oncogenes that mediate cellular responses in vertebrates including humans. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Baek, KH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. OI Baek, Kwang-Hyun/0000-0001-7662-7190 NR 55 TC 3 Z9 3 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD SEP-OCT PY 1999 VL 6 IS 5 BP 314 EP 319 PG 6 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 234GB UT WOS:000082475200003 PM 10494038 ER PT J AU Aarts, MM Rix, A Guo, J Bringhurst, R Henderson, JE AF Aarts, MM Rix, A Guo, J Bringhurst, R Henderson, JE TI The nucleolar targeting signal (NTS) of parathyroid hormone related protein mediates endocytosis and nucleolar translocation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID FIBROBLAST GROWTH-FACTOR; HIV-1 TAT PROTEIN; NUCLEAR TRANSLOCATION; PEPTIDE PTHRP; BINDING-PROTEIN; RECEPTOR GENE; LOCALIZATION; EXPRESSION; CHONDROCYTES; CELLS AB Previous work has identified the parathyroid hormone-related protein (PTHrP) nucleolar targeting signal (NTS) as both necessary and sufficient for localization of PTHrP to the nucleus and nucleolus of a variety of cells where it is believed to participate in the regulation of cell proliferation, differentiation, and apoptotic cell death. The mechanism whereby a secreted peptide, such as PTHrP, gains access to the nuclear compartment remains a question of debate. The current work examines the possibility that exogenous PTHrP is internalized and transported to the nuclear compartment by a mechanism that is dependent on preservation of the PTHrP NTS. Transiently expressed, PTHrP(1-141) was detected at the cell surface as well as in the cytoplasmic and nuclear compartments of COS-1 cells. Deletion of the NTS, or mutation of the conserved GxKKxxK motif within the NTS, effectively prevented both cell-surface binding and nuclear/nucleolar accumulation of PTHrP(1-141). A biotinylated peptide corresponding to the PTHrP NTS (PTHrP-NTS-biotin) was internalized and translocated to the nucleus and nucleolus in a time-, temperature-, and concentration-dependent manner, whereas a peptide representing a similar bipartite NTS from Nucleolin was not. Internalization and nucleolar targeting of PTHrP-NTS-biotin were indistinguishable in CFK2 cells, which express the common PTH/PTHrP receptor, and in 27m21 cells, which do not. In addition, pretreatment with a saturating dose of synthetic PTHrP(74-113) was capable of abrogating nucleolar accumulation of the PTHrP-NTS peptide, whereas pretreatment with PTHrP(1-34) or PTHrP(67-86) was not. These observations demonstrate that binding of exogenous, full-length PTHrP to the cell. surface is mediated through a conserved motif embedded in the NTS and suggest that internalization and nucleolar targeting of an NTS peptide are mediated through binding to a cell surface protein distinct from the PTH/PTHrP receptor. In total, the data support the hypothesis that secreted PTHrP(1-141) can be endocytosed and targeted to the nucleolus through a mechanism that is dependent on preservation of a core motif within the PTHrP NTS. C1 McGill Univ, Lady Davis Inst, Dept Med, Montreal, PQ H3T 1E2, Canada. Jewish Gen Hosp, SMBD, Montreal, PQ, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Henderson, JE (reprint author), McGill Univ, Lady Davis Inst, Dept Med, Room 602,3755 Cote St Catherine Rd, Montreal, PQ H3T 1E2, Canada. RI Aarts, Michelle/C-5766-2008 OI Aarts, Michelle/0000-0002-9171-0571 NR 46 TC 64 Z9 67 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 IS 9 BP 1493 EP 1503 DI 10.1359/jbmr.1999.14.9.1493 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 230XB UT WOS:000082276000004 PM 10469277 ER PT J AU Bastepe, M Shlossberg, AH Murdock, H Juppner, H Rittmaster, RS AF Bastepe, M Shlossberg, AH Murdock, H Juppner, H Rittmaster, RS TI A Lebanese family with osteosclerosis and hypophosphatemia. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. QEII Hlth Sci Ctr, Div Endocrinol & Metab, Halifax, NS, Canada. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA WG16 BP S558 EP S558 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101694 ER PT J AU Carter, PH Gardella, TJ AF Carter, PH Gardella, TJ TI Residues within the third extracellular loops of the parathyroid hormone type-1 and type-2 receptors determines the receptor-selective antagonist properties of [Bpa2,Ile5,Trp23]-PTHrP(1-36). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU447 BP S543 EP S543 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101637 ER PT J AU Carter, PH Gardella, TJ AF Carter, PH Gardella, TJ TI Zinc(II)-mediated enhancement of the cAMP signaling activity of histidine-substituted PTH(1-14) analogs. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU446 BP S543 EP S543 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101636 ER PT J AU Chung, U Guiducci, J McMahon, AP Kronenberg, H AF Chung, U Guiducci, J McMahon, AP Kronenberg, H TI Rigorous test for the direct involvement of Indian hedgehog (Ihh) and parathyroid hormone-related peptide (PTHrP) in a negative feedback loop controlling chondrocyte differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU456 BP S545 EP S545 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101646 ER PT J AU Colman, RJ Weindruch, R Kemnitz, JW Binkley, N AF Colman, RJ Weindruch, R Kemnitz, JW Binkley, N TI Long-term dietary restriction does not negatively affect rhesus monkey skeletal status. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. Univ Wisconsin, Inst Aging, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SA343 BP S394 EP S394 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101044 ER PT J AU Demay, MB Schipani, E Chapin, K AF Demay, MB Schipani, E Chapin, K TI Analysis of growth plate abnormalities in vitamin D receptor null mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA F457 BP S301 EP S301 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100674 ER PT J AU Gunness, ME Shea, M Pelz, G Gillard, J Olson, D Chambers, VK Orwoll, ES Klein, RF AF Gunness, ME Shea, M Pelz, G Gillard, J Olson, D Chambers, VK Orwoll, ES Klein, RF TI Breeding for peak bone mass: Selected histomorphometric, geometric, and biomechanical properties of divergent mouse lines. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Portland VA Med Ctr, Dept Pathol, Portland, OR USA. Oregon Hlth Sci Univ, Orthopaed Res Lab, Portland, OR 97201 USA. Portland VA Med Ctr, Bone & Mineral Res Unit, Portland, ME USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU474 BP S550 EP S550 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101664 ER PT J AU Guo, J Chung, U Bringhurst, FR Kronenberg, HM AF Guo, J Chung, U Bringhurst, FR Kronenberg, HM TI Introduction of phospholipase C-defective mutations into the murine PTH/PTHrP receptor gene by homologous recombination in embryonic stem cells using the Cre-LoxP recombinase system. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU452 BP S544 EP S544 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101642 ER PT J AU Holm, IA Nelson, AE Carpenter, TO Robinson, BG Cowell, C Mason, RS Crawford, J AF Holm, IA Nelson, AE Carpenter, TO Robinson, BG Cowell, C Mason, RS Crawford, J TI Mutational analysis and genotype-phenotype correlation of the PHEX gene in X-linked hypophosphatemie rickets. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Royal N Shore Hosp, Kolling Inst, Sydney, NSW, Australia. New Childrens Hosp, Sydney, NSW, Australia. Univ Sydney, Dept Physiol, Sydney, NSW 2006, Australia. Yale Univ, Sch Med, New Haven, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA WG17 BP S559 EP S559 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101695 ER PT J AU Hunzelman, JL Saxton, JM Schipani, E AF Hunzelman, JL Saxton, JM Schipani, E TI In vivo targeted expression of constitutively active PTH/PTHrP receptors in osteoblasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA 1092 BP S155 EP S155 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100094 ER PT J AU Imanishi, Y Palaniswamy, N Tahara, H Vickery, A Cryns, VL Gaz, RD Shoback, D Clark, O Monchik, J Wierman, M AF Imanishi, Y Palaniswamy, N Tahara, H Vickery, A Cryns, VL Gaz, RD Shoback, D Clark, O Monchik, J Wierman, M TI Molecular pathogenetic analysis of parathyroid carcinoma. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Connecticut, Ctr Hlth, Storrs, CT 06269 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Osaka City Univ, Sch Med, Osaka, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Rhode Isl Hosp, Providence, RI 02903 USA. Univ Colorado, Boulder, CO 80309 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Jikei Univ, Sch Med, Tokyo, Japan. NR 0 TC 5 Z9 5 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SA446 BP S421 EP S421 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101147 ER PT J AU Jemtland, R Divieti, P Lee, K Segre, GV AF Jemtland, R Divieti, P Lee, K Segre, GV TI Recombinant sonic hedgehog promotes differentiation of primary mouse calvarial osteoblasts and increases PTHrP mRNA expression. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA F419 BP S293 EP S293 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100643 ER PT J AU Kamolmatyakul, S Chen, W Li, YP AF Kamolmatyakul, S Chen, W Li, YP TI Interferon-g inhibit osteoclast formation and cathepsin K gene expression. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SA193 BP S357 EP S357 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100894 ER PT J AU Keutmann, HT Sidis, Y Schneyer, AL Johnson, LN Wang, QF Sluss, PM AF Keutmann, HT Sidis, Y Schneyer, AL Johnson, LN Wang, QF Sluss, PM TI Structure and activity of follistatin: Essential role for N-terminal hydrophobic residues in activin binding. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU003 BP S432 EP S432 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101193 ER PT J AU Klein, RF Vartanian, KA Chambers, VK Turner, RS Carlos, AS Belknap, JK Orwoll, ES AF Klein, RF Vartanian, KA Chambers, VK Turner, RS Carlos, AS Belknap, JK Orwoll, ES TI Chromosomal localization of genes regulating peak bone mineral density in mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Portland VA Med Ctr, Bone & Mineral Res Unit, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA 1168 BP S174 EP S174 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100170 ER PT J AU Kovacs, CS Chafe, L Manley, NR Moseley, J Martin, TJ Kronenberg, HM AF Kovacs, CS Chafe, L Manley, NR Moseley, J Martin, TJ Kronenberg, HM TI Parathyroid glands are not required to maintain circulating PTHrP levels in the fetus. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Mem Univ Newfoundland, St Johns, NF, Canada. Med Coll Georgia, IMMAG, Augusta, GA 30912 USA. Univ Melbourne, St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA 1014 BP S136 EP S136 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100016 ER PT J AU Kuizon, BD Salusky, IB Sanchez, CP Juppner, H Goodman, WG AF Kuizon, BD Salusky, IB Sanchez, CP Juppner, H Goodman, WG TI Assessment of renal osteodystrophy using in situ hybridization in human growth plate cartilage. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Wisconsin, Sch Med, Madison, WI USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SA453 BP S422 EP S422 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101154 ER PT J AU Li, YP Chen, W Liang, YQ Li, E Stashenko, P AF Li, YP Chen, W Liang, YQ Li, E Stashenko, P TI OC-116KDa-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA 1180 BP S177 EP S177 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100182 ER PT J AU Liu, YY Nguyen, C Peleg, S AF Liu, YY Nguyen, C Peleg, S TI Regulation of heterodimerization and coactivator binding by the activation function 2 domain of the vitamin D receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA 1142 BP S168 EP S168 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100144 ER PT J AU Lupu, F Shen, Z Lee, K Segre, GV AF Lupu, F Shen, Z Lee, K Segre, GV TI Growth hormone stimulates skeletal development independently of IGF-I. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA 1113 BP S161 EP S161 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100115 ER PT J AU MacLean, HE Guo, J Bringhurst, FR Kronenberg, HM AF MacLean, HE Guo, J Bringhurst, FR Kronenberg, HM TI Developing an in vitro model of mouse chondrocyte differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA F026 BP S219 EP S219 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100346 ER PT J AU McDougall, S Chen, S Hahn, TJ Peters, JH AF McDougall, S Chen, S Hahn, TJ Peters, JH TI Gene expression patterns in rat chondrocytes using DNA microarray. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Educ & Clin Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA F014 BP S217 EP S217 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100337 ER PT J AU Muller, R Barragan, J AF Muller, R Barragan, J TI Long term prediction of bone architecture and bone strength in simulations of pre-, peri- and post-menopausal microstructural bone loss and antiresorptive treatment. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Orthoped Biomech Lab, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU379 BP S526 EP S526 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101569 ER PT J AU Orwoll, ES Belknap, JK Klein, RF AF Orwoll, ES Belknap, JK Klein, RF TI Gender-specific genetic determinants of peak bone mass. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Portland VA Med Ctr, Bone & Mineral Unit, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA 1170 BP S175 EP S175 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100172 ER PT J AU Qian, F Tawfeek, H Abou-Samra, A AF Qian, F Tawfeek, H Abou-Samra, A TI The role of phosphorylation in PTH/PTHrP receptor internalization. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU445 BP S543 EP S543 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101635 ER PT J AU Rankin, W Grubbs, BG Chirgwin, JM Dallas, M Jueppner, H Schipani, E Mundy, GR Guise, TA AF Rankin, W Grubbs, BG Chirgwin, JM Dallas, M Jueppner, H Schipani, E Mundy, GR Guise, TA TI Constitutively active PTH/PTHrP (PTHR) receptor signaling by breast cancer cells decreases bone metastases and TGF beta-stimulated PTHrP production. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA F412 BP S292 EP S292 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100637 ER PT J AU Reppe, S Rian, E Jemtland, R Olstad, OK Gautvik, VT Gautvik, KM AF Reppe, S Rian, E Jemtland, R Olstad, OK Gautvik, VT Gautvik, KM TI Sox-4 mRNA is expressed in the embryonic growth plate and regulated via the PTH/PTHrP receptor in osteoblast-like cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Oslo, Dept Med Biochem, Oslo, Norway. Massachusetts Gen Hosp, Endocrine Unit 1, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA T418 BP S211 EP S211 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100315 ER PT J AU Rubin, DA Juppner, H AF Rubin, DA Juppner, H TI Functional characterization of the zebrafish PTH/PTHrP receptor (PTH1R) and a novel receptor (PTH3R) which is preferentially activated by mammalian and teleost PTHrP. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA T394 BP S210 EP S210 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100312 ER PT J AU Sakai, Y Demay, MB AF Sakai, Y Demay, MB TI Evaluation of keratinocyte differentiation in vitamin D receptor knockout mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA F459 BP S302 EP S302 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100675 ER PT J AU Shimizu, M Potts, JT Gardella, TJ AF Shimizu, M Potts, JT Gardella, TJ TI Type-substitution analysis of the amino-terminal fragment of parathyroid hormone, PTH(1-14): An approach toward new low molecular weight PTH agonists. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA F398 BP S289 EP S289 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100625 ER PT J AU Shin, HI Divieti, P Kobayashi, T Chung, U Taga, T Suda, T Bringhurst, RF Kronenberg, H AF Shin, HI Divieti, P Kobayashi, T Chung, U Taga, T Suda, T Bringhurst, RF Kronenberg, H TI gp130 deficiency results in fetal hypocalcemia with increased blood serum PTH level. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Med Univ, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. Tokyo Med & Dent Univ, Tokyo, Japan. Showa Univ, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA T165 BP S197 EP S197 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100260 ER PT J AU Silverman, SL Chesnut, C Maricic, MJ Andriano, K Gimona, A Baylink, D AF Silverman, SL Chesnut, C Maricic, MJ Andriano, K Gimona, A Baylink, D TI Age and lumbar spine BMD are the strongest predictors of vetebral fracture through five years - Evidence from the placebo group in the PROOF study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Washington, Seattle, WA 98195 USA. Univ Arizona, Arizona Hlth Sci Ctr, Tucson, AZ USA. Novartis Pharma Basle, E Hanover, NJ USA. Loma Linda Univ, Jerry L Pettis Mem Vet Hosp, Loma Linda, CA 92357 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU337 BP S516 EP S516 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101528 ER PT J AU Soegiarto, DW Kobayashi, T Chung, U Fassler, R St-Jacques, B McMahon, AP Kronenberg, HM Lanske, B AF Soegiarto, DW Kobayashi, T Chung, U Fassler, R St-Jacques, B McMahon, AP Kronenberg, HM Lanske, B TI The role of Indian hedgehog in osteoblast development and maturation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Max Planck Inst Biochem, D-82152 Martinsried, Germany. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Lund Univ, Dept Expt Pathol, Lund, Sweden. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA T146 BP S196 EP S196 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100254 ER PT J AU Tawfeek, HA Abou-Samra, AB AF Tawfeek, HA Abou-Samra, AB TI Over-expression of beta arrestin-2 in LLCPK-1 cells stably expressing a green fluorescent protein tagged PTH/PTHrP receptor increases PTH/PTHrP receptor internalization. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU444 BP S542 EP S542 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101634 ER PT J AU Wang, Y Zhao, W Krane, SM AF Wang, Y Zhao, W Krane, SM TI Normal closure of cranial sutures is dependent upon collagenase cleavage of type I collagen. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA 1097 BP S157 EP S157 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100099 ER PT J AU Williams, LJS Abou-Samra, AB AF Williams, LJS Abou-Samra, AB TI The transcription factor SP1 from ROS 17/2.8 cells binds to an element within the rat PTH/PTHrP receptor promoter. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SU152 BP S469 EP S469 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101342 ER PT J AU Yamaguchi, DT Lee, TM Wang, PKC Tachiki, K AF Yamaguchi, DT Lee, TM Wang, PKC Tachiki, K TI Magnetic fields inhibit sodium/proton antiport activity and alters proliferation of MC3T3-E1 pre-osteoblastic cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Dept Elect Engn, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA F130 BP S238 EP S238 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347100421 ER PT J AU Yates, KE Kaban, LB Glowacki, J AF Yates, KE Kaban, LB Glowacki, J TI Molecular evidence that TGF-b, IGF-1, and BMP4 are expressed during distraction osteogenesis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1999 VL 14 SU 1 MA SA469 BP S426 EP S426 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232CA UT WOS:000082347101170 ER PT J AU Sheridan, R Weber, J Prelack, K Petras, L Lydon, M Tompkins, R AF Sheridan, R Weber, J Prelack, K Petras, L Lydon, M Tompkins, R TI Early burn center transfer shortens the length of hospitalization and reduces complications in children with serious burn injuries SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID PROMPT ESCHAR EXCISION; MORTALITY AB Prompt transfer of the child with acute burns can be difficult from distant or inaccessible locations, and it is believed that the outcomes of children with serious burns whose transfer to a specialized burn care facility is delayed may be compromised. A 4-year experience with 16 consecutive children with serious burns (greater than or equal to 20% of the body surface area) whose transfer to a burn care facility was delayed for 5 or more days was reviewed to document the difficulties that can follow such delays. These 16 children had an average age of 8.6 +/- 1.6 years and an average wound size of 57.6% +/- 5.8% of the body surface area, and they arrived a mean of 16.3 +/- 3.4 days after the injury (range, 5 to 44 days). These children had undergone an average of 1 operation, excluding escharotomies, at referring facilities. Only 4 (25%) of the children had no infectious focus at transfer, and at admission resistant bacteria were recovered from 9 (56%) of the children and fungal organisms were found in 10 (63%). Compared with a concurrently managed matched control group of patients admitted to the burn center within 24 hours of injury, the delayed-transfer group had statistically significantly more bacteremia, renal dysfunction, wound sepsis, and central venous catheter days. It was also more expensive to manage these children; the delayed-transfer group required statistically significantly longer to achieve 95% wound closure, and they had greater total lengths of hospital stay and more rehabilitation days. The early transfer of children with serious burns to a specialized burn center may truncate hospitalization and thereby reduce costs. C1 Shriners Burn Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Sheridan, R (reprint author), Shriners Burn Inst, 51 Blossom St, Boston, MA 02114 USA. NR 9 TC 32 Z9 32 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD SEP-OCT PY 1999 VL 20 IS 5 BP 347 EP 350 DI 10.1097/00004630-199909000-00002 PG 4 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 237DM UT WOS:000082640100001 PM 10501318 ER PT J AU Singh, G Lakkis, CL Laucirica, R Epner, DE AF Singh, G Lakkis, CL Laucirica, R Epner, DE TI Regulation of prostate cancer cell division by glucose SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID CHICK-EMBRYO FIBROBLASTS; CYCLE PROGRESSION; ENERGY-METABOLISM; KINASE-C; GLYCOLYSIS; GROWTH; P53; PROLIFERATION; DIACYLGLYCEROL; GLUTAMINOLYSIS AB Previous studies have shown that rapid cell proliferation is associated with elevated glucose consumption. However, those studies did not establish whether glucose is required for prostate cancer cell proliferation or define the molecular mechanisms by which glucose regulates cell division. We addressed these issues by studying two metastatic human prostate cancer cell lines: DU145, which is androgen independent and highly proliferative; and LNCaP, which is androgen dependent and relatively slow growing. We found that proliferation of DU145 cells was significantly inhibited by reduction of glucose in the medium to 0.5 g/L, which is half the physiologic concentration, whereas LNCaP cells grew at control rates even in the presence of only 0.05 g/L glucose. Glucose deprivation of DU145 cells caused a 90% reduction in DNA synthesis; a 10-20-fold reduction in cyclins D and E and CDK4 levels; and cell cycle arrest in G(0)-G(1). However, glucose deprivation did not cause global inhibition of protein synthesis, since mutant p53 levels increased in glucose-deprived DU145 cells. This observed increase in mutant p53 levels was not associated with a rise in p21 levels. Glucose deprivation of DU145 cells also led to apparent dephosphorylation of mutant retinoblastoma (RB) protein. We conclude that: 1) high levels of glucose consumption are required for rapid proliferation of androgen-independent prostate canter cells, 2) glucose may not be required for slow growth of androgen-dependent prostate cancer cells, and 3) glucose promotes passage of cells through early G(1) by increasing the expression of several key cell cycle regulatory proteins that normally inhibit RE function. (C) 1999 Wiley-Liss, Inc. C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Epner, DE (reprint author), VAMC, Med Serv, 111H,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [1R29CA/78355-01] NR 46 TC 45 Z9 46 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 1999 VL 180 IS 3 BP 431 EP 438 DI 10.1002/(SICI)1097-4652(199909)180:3<431::AID-JCP14>3.0.CO;2-O PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 218LQ UT WOS:000081554400014 PM 10430183 ER PT J AU Greene, RW Biederman, J Faraone, SV Wilens, TE Mick, E Blier, HK AF Greene, RW Biederman, J Faraone, SV Wilens, TE Mick, E Blier, HK TI Further validation of social impairment as a predictor of substance use disorders: Findings from a sample of siblings of boys with and without ADHD SO JOURNAL OF CLINICAL CHILD PSYCHOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC-DISORDERS; ADJUSTMENT INVENTORY; ADOLESCENTS; CHILDREN; ABUSE; DISABILITY; BEHAVIOR; RISK AB Examined predictors of substance use disorders in nonreferred siblings of boys with and without attention deficit hyperactivity disorder to further investigate whether previous findings documenting the role of social impairment in predicting substance use disorders would be replicated. Participants were comprehensively assessed at Time I and at 4-year follow-up. We found that social impairment was the sole significant predictor of alcohol and substance abuse and smoking after controlling for other variables previously shown to be predictors of substance use disorders. These results confirmed prior findings documenting the critical role of social impairment in predicting later substance use disorders. C1 Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Greene, RW (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU PHS HHS [R01 MG-41314-01A2] NR 31 TC 45 Z9 45 U1 1 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0047-228X J9 J CLIN CHILD PSYCHOL JI J. Clin. Child Psychol. PD SEP PY 1999 VL 28 IS 3 BP 349 EP 354 DI 10.1207/S15374424jccp280307 PG 6 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 223KQ UT WOS:000081840600007 PM 10446684 ER PT J AU Schipani, E Langman, C Hunzelman, J Le Merrer, M Loke, KY Dillon, MJ Silve, C Juppner, H AF Schipani, E Langman, C Hunzelman, J Le Merrer, M Loke, KY Dillon, MJ Silve, C Juppner, H TI A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen's metaphyseal chondrodysplasia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ENDOCHONDRAL BONE-FORMATION; BLOMSTRAND-CHONDRODYSPLASIA; INACTIVATING MUTATION; CONSTITUTIVE ACTIVITY; PRECOCIOUS PUBERTY; GENE; PTH; EXPRESSION; DYSPLASIA; CALCIUM AB Two heterozygous PTH/PTH-related peptide (PTHrP) receptor missense mutations were previously identified in patients with Jansen's metaphyseal chondrodysplasia (JMC), a rare form of short limb dwarfism associated with hypercalcemia and normal or undetectable levels of PTH and PTHrP. Both mutations, H223R and T410P, resulted in constitutive activation of the cAMP signaling pathway and provided a plausible explanation for the abnormalities in skeletal development and mineral ion homeostasis. In the present study we analyzed genomic DNA from four additional sporadic cases with JMC to search for novel activating mutations in the PTH/PTHrP receptor, to determine the frequency of the two previously identified missense mutations, H223R and T410P, and to determine whether different mutations present with different severity of the disease. The H223R mutation was identified in three novel JMC patients and is, therefore, to date the mast frequent; cause of JMC. In the fourth patient, a novel heterozygous missense mutation was found that changes isoleucine 458 in the receptor's seventh membrane-spanning region to arginine (I458R). In COS-7 cells expressing the human PTH receptor with the I458R mutation, basal cAMP accumulation was approximately 8 times higher than that in cells expressing the wild-type receptor despite impaired surface expression of the mutant receptor. Furthermore, the I458R mutant showed higher responsiveness to PTH than the wild-type receptor in its ability to activate both down-stream effecters, adenylyl cyclase and phospholipase C. Like the H223R and the T410P mutants, the I458R mutant had no detectable effect on basal inositol phosphate accumulation. Overall, the patient. with the I458R mutation exhibited clinical and biochemical abnormalities similar to those in patients with the previously identified H223R and T410P mutations. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Childrens Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Paris 07, INSERM, U426, F-75870 Paris 18, France. Hop Necker Enfants Malad, INSERM, U393, F-75870 Paris 18, France. Natl Univ Singapore Hosp, Dept Pediat, Singapore 119074, Singapore. Great Ormond St Hosp Sick Children, London WC1N 3JH, England. Childrens Mem Hosp, Div Nephrol, Chicago, IL 60614 USA. RP Schipani, E (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu RI Loke, Kah Yin/E-6586-2015 FU NIDDK NIH HHS [DK-50708-01] NR 36 TC 54 Z9 55 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 SEP PY 1999 VL 84 IS 9 BP 3052 EP 3057 DI 10.1210/jc.84.9.3052 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232FQ UT WOS:000082360600010 PM 10487664 ER PT J AU Duerr, EM Gimm, O Neuberg, DS Kum, JB Clifford, SC Toledo, SPA Maher, ER Dahia, PLM Eng, C AF Duerr, EM Gimm, O Neuberg, DS Kum, JB Clifford, SC Toledo, SPA Maher, ER Dahia, PLM Eng, C TI Differences in allelic distribution of two polymorphisms in the VHL-associated gene CUL2 in pheochromocytoma patients without somatic CUL2 mutations SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; HIPPEL-LINDAU-DISEASE; MEDULLARY-THYROID CARCINOMA; NEOPLASIA TYPE 2B; RET PROTOONCOGENE; SPORADIC PHEOCHROMOCYTOMAS; CERVICAL-CANCER; CODON 72; P53; INFECTION AB Although the two major familial forms of pheochromocytomas, multiple endocrine neoplasia type 2 and von-Hippel-Lindau disease (VHL), have been associated with mutations of the RET and VHL genes, respectively, the molecular pathogenesis of sporadic pheochromocytomas is largely unknown. Recently, a putative tumor suppressor gene has been identified, CUL2, whose product has been shown to interact with the VHL tumor suppressor. To examine whether CUL2 plays a role in pheochromocytoma pathogenesis, we analyzed a series of 26 distinct tumor samples for mutations in the whole coding region of this gene. There were no somatic pathogenic mutations in CUL2, except for 1 sporadic tumor that had a hemizygous gene deletion. We also found 3 novel polymorphisms in the gene. One of these variants, IVS5-6C/T, as well as another previously described one, c.2057G/A, were overrepresented among the pheochromocytoma patients compared to that in a control population (P < 0.005 and P < 0.01, respectively). Although our findings suggest that CUL2 does not play a major role in the pathogenesis of pheochromocytomas, it is still unknown whether epigenetic mechanisms are involved in its inactivation in VHL-associated tumors. Furthermore, the potential role for the overrepresented alleles in the pheochromocytoma group requires further investigation. C1 Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Bonn, Sch Med, D-53105 Bonn, Germany. Univ Birmingham, Sch Med, Dept Pediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TG, W Midlands, England. Univ Sao Paulo, Sch Med, Endocrine Genet Unit, BR-54199 Sao Paulo, Brazil. Univ Cambridge, Canc Res Campaign Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, 690C Med Res Facil,420 W 12th Ave, Columbus, OH 43210 USA. EM patricia_dahia@dfci.harvard.edu; eng-1@medctr.osu.edu OI Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [P30CA16058] NR 33 TC 5 Z9 6 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 1999 VL 84 IS 9 BP 3207 EP 3211 DI 10.1210/jc.84.9.3207 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232FQ UT WOS:000082360600034 PM 10487688 ER PT J AU Rollins, BJ AF Rollins, BJ TI Physiological coreceptor use by dual-tropic HIV-1: one plus one equals one SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID GP120 ENVELOPE GLYCOPROTEIN; RECEPTOR; ENTRY; LESTR/FUSIN; INFECTION; LIGAND; SDF-1; CELLS C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, M430,44 Binney St, Boston, MA 02115 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1999 VL 104 IS 5 BP 531 EP 532 DI 10.1172/JCI8160 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WF UT WOS:000083468800002 PM 10487766 ER PT J AU Christie, PD Edelberg, JM Picard, MH Foulkes, AS Mamuya, W Weiler-Guettler, H Rubin, RH Gilbert, P Rosenberg, RD AF Christie, PD Edelberg, JM Picard, MH Foulkes, AS Mamuya, W Weiler-Guettler, H Rubin, RH Gilbert, P Rosenberg, RD TI A murine model of myocardial microvascular thrombosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PLASMINOGEN-ACTIVATOR; ENDOTHELIAL-CELLS; INHIBIT FIBRINOLYSIS; PROTEIN-C; THROMBOMODULIN; EXPRESSION; MICE; COAGULATION; RECEPTOR; GENE AB Disorders of hemostasis lead to vascular pathology. Endothelium-derived gene products play a critical role in the formation and degradation of fibrin. We sought to characterize the importance of these locally produced factors in the formation of fibrin in the cardiac macrovasculature and microvasculature. This study used mice with modifications of the thrombomodulin (TM) gene, the tissue-type plasminogen activator (tPA) gene, and the urokinase-type plasminogen activator (uPA) gene. The results revealed that tPA played the most important role in local regulation of fibrin deposition in the heart, with lesser contributions by TM and uPA (least significant). Moreover, a synergistic relationship in fibrin formation existed in mice with concomitant modifications of tPA and TM, resulting in myocardial necrosis and depressed cardiac function. The data were fit to a statistical model that may offer a foundation for examination of hemostasis-regulating gene interactions. C1 MIT, Dept Biol 68 480, Cambridge, MA 02139 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02124 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Blood Ctr SE Wisconsin Inc, Blood Res Inst, Milwaukee, WI 53226 USA. Harvard Univ, MIT, Ctr Expt Pharmacol & Therapeut, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Rosenberg, RD (reprint author), MIT, Dept Biol 68 480, 77 Massachusetts Ave, Cambridge, MA 02139 USA. OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [T32 HL007604, HL-41484, HL-07604]; NIAID NIH HHS [T32 AI007358]; PHS HHS [P01-41484] NR 41 TC 47 Z9 48 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1999 VL 104 IS 5 BP 533 EP 539 DI 10.1172/JCI7141 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WF UT WOS:000083468800003 PM 10487767 ER PT J AU Martinez-Picado, J Sutton, L De Pasquale, MP Savara, AV D'Aquila, RT AF Martinez-Picado, J Sutton, L De Pasquale, MP Savara, AV D'Aquila, RT TI Human immunodeficiency virus type 1 cloning vectors for antiretroviral resistance testing SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID URACIL DNA GLYCOSYLASE; REVERSE-TRANSCRIPTASE; PROTEASE INHIBITORS; IN-VIVO; DRUG-RESISTANCE; THERAPY; HIV-1; INFECTION; MUTATIONS; ASSAY AB Better detection of minority human immunodeficiency virus type 1 (HIV-1) populations containing gene mutations may improve the usefulness of antiretroviral resistance testing for clinical management. Molecular cloning of HIV-1 PCR products which might improve minority detection can be slow and difficult, and commercially available recombinant virus assays test drug susceptibility of virus pools. We describe novel plasmids and simple methods for rapid cloning of HIV-1 PCR products from patient specimens and their application to generate infectious recombinant virus clones for virus phenotyping and genotyping, Eight plasmids with differing deletions of sequences encoding HIV-1 protease, reverse transcriptase, or Gag p7/p1 and Gag p1/p6 cleavage sites were constructed for cloning HIV-1 PCR products. A simple HIV-1 sequence-specific uracil deglycosylase-mediated cloning method with the vectors and primers designed here was more rapid than standard ligase-mediated cloning. Pooled and molecularly cloned infectious recombinant viruses were generated with these vectors. Replicative viral fitness and drug susceptibility phenotypes of cloned infectious viruses containing patient specimen-derived sequences were measured. Clonal resistance genotyping analyses were also performed from virus isolates, plasma HIV-1 RNA, and infected cell DNA, Sequencing of a limited number of molecular clones detected minorities of resistant virus not identified in the pooled population PCR product sequence and linkage of minority mutations. C1 Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. Fdn Irsi Caixa, Barcelona, Spain. RP D'Aquila, RT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 149 13th St, Charlestown, MA 02129 USA. RI Martinez-Picado, Javier/G-5507-2012 OI Martinez-Picado, Javier/0000-0002-4916-2129 FU NIAID NIH HHS [AI 27659, AI-29193, R01 AI029193, U01 AI027659] NR 35 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 1999 VL 37 IS 9 BP 2943 EP 2951 PG 9 WC Microbiology SC Microbiology GA 226TV UT WOS:000082038900036 PM 10449480 ER PT J AU Janne, PA Datta, MW Johnson, BE AF Janne, PA Datta, MW Johnson, BE TI Case 2: Acrometastasis as an initial presentation of non-small-cell lung carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Dana Farber Canc Inst, Dept Adult Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. NR 7 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1999 VL 17 IS 9 BP 2998 EP 3001 PG 4 WC Oncology SC Oncology GA 232QG UT WOS:000082381000045 PM 10561378 ER PT J AU Colombo, AP Haffajee, AD Smith, CM Cugini, MA Socransky, SS AF Colombo, AP Haffajee, AD Smith, CM Cugini, MA Socransky, SS TI Discrimination of refractory periodontitis subjects using clinical and laboratory parameters alone and in combination SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontal diseases; periodontitis; refractory; bacteria; antibody; multivariate analyses ID ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; MICROBIOLOGICAL FEATURES; TOOTH LOSS; LONG-TERM; DISEASE AB The purpose of the present investigation was to use baseline clinical and laboratory parameters to distinguish subjects refractory to conventional periodontal therapy. Baseline clinical, microbial and host parameters were compared in 61 successfully-treated and 27 refractory subjects. Refractory subjects showed mean full-mouth attachment level (AL) loss and/or >3 sites with new AL loss >2.5 mm within 1 year after both scaling and root planing and surgery with systemic tetracycline. Successfully-treated subjects showed mean AL gain and no sites with new AL loss >2.5 mm after either regimen. Gingival redness, bleeding on probing, suppuration, supragingival plaque accumulation, pocket depth and AL were measured at 6 sites per tooth in each subject. The levels of 40 subgingival taxa were determined in subgingival plaque samples from up to 28 sites in each subject using checkerboard DNA-DNA hybridization. Serum antibody (Ab) to 85 subgingival species was determined using checkerboard immunoblotting. Levels of serum IgG2 and Gm23 allotype were measured using radial immunodiffusion; Fc gamma RIIa and Fc gamma RIIIb receptor haplotypes were determined using PCR and allele specific oligonucleotide probes. Odds ratios of a subject being refractory were determined by comparing measured parameters in the 2 subject groups using univariate and multivariate techniques. 17 of 151 clinical, microbial and immunological variables were significant using chi(2) analysis after adjusting for multiple comparisons. For example, the odds ratios of a subject being refractory were 12.2, 5.4 and 6.9 if the subject had Ab >50 mu g/ml to >9 species; S, constellatus counts >2.4% of the total DNA probe count or >2.1% of sites with AL >6 mm. The 17 significant predictor variables were used in logistic regression and discriminant analyses. Similar variables were selected using both analyses including the number of serum Ab to subgingival species >50 mu g/ml, % S. constellatus in plaque samples and % sites with attachment loss >6 mm. In the logistic regression analysis model, the odds ratios associated with >9 species exhibiting >Ab 50 mu g/ml, >2.1% of sites with AL >6 mm and >2.4% S. constellatus in plaque were 8.7, 6.8 and 2.4, respectively, after adjusting for other variables in the model. Discriminant analysis using these variables provided sensitivity, specificity, positive and negative predictive values of 0.66, 0.92, 0.80 and 0.85 respectively. Refractory periodontitis subjects could be distinguished using a subset of clinical, microbiological and immunological parameters. C1 Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Dent Ctr, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-10977, DE-04881] NR 27 TC 12 Z9 12 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD SEP PY 1999 VL 26 IS 9 BP 569 EP 576 DI 10.1034/j.1600-051X.1999.260902.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 228YD UT WOS:000082164400002 PM 10487306 ER PT J AU Sonawalla, SB Spillmann, MK Kolsky, AR Alpert, JE Nierenberg, AA Rosenbaum, JF Fava, M AF Sonawalla, SB Spillmann, MK Kolsky, AR Alpert, JE Nierenberg, AA Rosenbaum, JF Fava, M TI Efficacy of fluvoxamine in the treatment of major depression with comorbid anxiety disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; DOUBLE-BLIND; CLINICAL PHARMACOKINETICS; IMIPRAMINE; PLACEBO; CLOMIPRAMINE AB Background: Major depression with comorbid anxiety disorder is associated with poor antidepressant outcome compared with major depression without comorbid anxiety disorder. The purpose of our study was to assess changes in depressive symptoms and anxiety levels in outpatients with major depression with comorbid anxiety disorder following 12 weeks of open treatment with fluvoxamine. Method: We enrolled 30 outpatients (mean +/- SD age = 39.4 +/- 11.3 years; 16 women and 14 men) with DSM-IV major depressive disorder accompanied by one or more current comorbid DSM-IV anxiety disorders in our study. Patients were treated openly with fluvoxamine initiated at 50 mg/day, with an upward titration to a maximum of 200 mg/day (mean +/- SD dose = 143 +/- 45 mg/day). Efficacy assessments included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales for both depression and anxiety. Intent-to-treat analysis was used to assess outcome. Results: The mean +/- SD number of comorbid anxiety disorders per patient was 2.1 +/- 1.1. Following fluvoxamine treatment, the mean +/- SD HAM-D-17 score dropped from 20.2 +/- 3.3 to 11.0 +/- 7.0 (p <.0001). The mean +/- SD depression CGI-S score dropped from 4.0 +/- 0.6 to 2.4 +/- 1.1 (p <.0001), and the mean si: SD anxiety CGI-S score decreased from 4.1 +/- 0.8 to 2.5 +/- 1.2 (p <.0001). Eighteen (60%) of the 30 patients had CGI-I scores less than or equal to 2 for both anxiety and depression at endpoint, with 53% showing a greater than or equal to 50% reduction in HAM-D-17 scores at endpoint. Conclusion: Although preliminary, our findings suggest that fluvoxamine is effective in treating outpatients with major depression with comorbid anxiety disorder, having a significant effect on both depression and anxiety symptoms. Further double-blind, placebo-controlled trials are needed, in a larger sample, to confirm our findings. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sonawalla, SB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 29 TC 19 Z9 21 U1 0 U2 1 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 1999 VL 60 IS 9 BP 580 EP 583 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 240ZK UT WOS:000082856500003 PM 10520975 ER PT J AU Moroz, G Rosenbaum, JF AF Moroz, G Rosenbaum, JF TI Efficacy, safety, and gradual discontinuation of clonazepam in panic disorder: A placebo-controlled, multicenter study using optimized dosages SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; ALPRAZOLAM; AGORAPHOBIA; BENZODIAZEPINES; THERAPY; ANXIETY; TRIAL AB Background: The purpose of this multicenter, double-blind, placebo-controlled study was to evaluate the efficacy and safety of optimized dosages of clonazepam for the treatment of panic disorder and assess the tolerability of a schedule for gradual discontinuation. Method: Adult patients with panic disorder with or without agoraphobia (DSM-III-R criteria) were randomly assigned to receive either placebo or clonazepam in individually adjusted doses over 3 weeks to approximate an optimal dosage, which was then maintained for an additional 3 weeks, amounting to a 6-week therapeutic phase. The daily dose range was 0.25 to 4.0 mg administered in 2 divided doses. In the following 7-week discontinuance phase, the doses were tapered gradually to cessation. Results: At the therapeutic endpoint, clonazepam (N = 222) proved clinically and statistically superior to placebo (N = 216) in change in the number of panic attacks and in Clinical Global Impressions-Severity of Illness (CGI-S) and CGI-Change scores, Patient's Global Impression of Change scores, amount of fear and avoidance associated with phobic symptoms, and duration of anticipatory anxiety. The gradual tapering of clonazepam was not associated with symptoms suggestive of withdrawal syndrome. Although patients taking clonazepam experienced some clinical worsening compared with the status achieved at endpoint, particularly in terms of number of panic attacks, no deterioration was observed using their condition at baseline as point of reference. No overall evidence of rebound was found. All regimens were generally well tolerated. Somnolence wets the main adverse event associated with clonazepam therapy. The percentage of patients who reported adverse events was higher in the clonazepam group than in the placebo group, as was the mean number of adverse events per patient. Conclusion: In this placebo-controlled trial, clonazepam was an efficacious and safe shortterm treatment of the symptoms of panic disorder. Discontinuance during and after slow tapering was well tolerated. C1 Hoffmann La Roche Inc, Dept Clin Sci, Nutley, NJ 07110 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Moroz, G (reprint author), Hoffmann La Roche Inc, Dept Clin Sci, 340 Kingsland St, Nutley, NJ 07110 USA. NR 32 TC 34 Z9 36 U1 0 U2 5 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 1999 VL 60 IS 9 BP 604 EP 612 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 240ZK UT WOS:000082856500007 PM 10520979 ER PT J AU Benacerraf, BR Shipp, TD Bromley, B AF Benacerraf, BR Shipp, TD Bromley, B TI Does the 10-MHz transvaginal transducer improve the diagnostic certainty that an intrauterine fluid collection is a true gestational sac? SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Article DE ultrasonography; gestational sac; pregnancy ID INTRADECIDUAL SIGN; ECTOPIC PREGNANCY AB Purpose. We studied whether a 10-MHz transvaginal transducer improves the diagnostic certainty that a small intrauterine fluid collection is a true gestational sac. Methods. Over a 6-week period, women who presented with a positive pregnancy test and a fluid collection (devoid of any characteristics such as yolk sac or fetal pole) in the uterus seen with a standard 6-7-MHz transvaginal transducer were entered in the study; The patients were immediately rescanned with a 10-MHz transvaginal probe, and characteristics of the fluid collection using this probe were noted. Specifically, the visualization of a yolk sac or the intradecidual or double decidual sign was considered an objective improvement in the certainty that the fluid collection was a gestational sac. Results. Twelve patients presented with a positive pregnancy test and a fluid collection in the uterus seen with a 6-7-MHz probe. Eight of these fluid collections were smaller than 1 cm in mean diameter, and all 8 of these patients had an objective improvement in the diagnosis of an intrauterine pregnancy using the 10-MHz probe. The other 4 patients had fluid collection 1-2 cm in mean diameter seen at 6-7 MHz. The 10-MHz probe improved the diagnostic confidence in 2 of these 4 patients. Conclusions. In patients with early pregnancies who have questionable gestational sacs on sonography with standard 6-7-MHz transducers, the 10-MHz probe improves the diagnostic confidence of the presence of an intrauterine gestational sac. (C) 1999 John Wiley & Sons, Inc. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD SEP PY 1999 VL 27 IS 7 BP 374 EP 377 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 226TX UT WOS:000082039100003 PM 10440785 ER PT J AU Li, KK Teknos, TN Lai, A Lauretano, A Terrell, J Joseph, MP AF Li, KK Teknos, TN Lai, A Lauretano, A Terrell, J Joseph, MP TI Extracranial optic nerve decompression: A 10-year review of 92 patients SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Review DE optic nerve; optic neuropathy; optic nerve decompression; traumatic optic neuropathy; visual loss ID VISUAL IMPROVEMENT; INDIRECT INJURY; ORBITAL APEX; NEUROPATHY; CORTICOSTEROIDS; BLINDNESS; SECONDARY AB Over a 10-year period the authors have performed 92 transethmoidal optic nerve decompressions for the treatment of visual loss due to various pathological processes, including 45 cases of trauma 32 cases of neoplasm, 2 cases of bacterial pansinusitis, 5 cases of sphenoethmoidal mucocele, 4 cases of aspergillosis (all were immunocompetent patients), 2 cases of Wegener's granulomatosis, and 2 cases of sarcoidosis. Forty-eight patients (52%) had preoperative visual acuity of light perception or better, and in 44 patients (48%) the preoperative vision was no light perception. Sixty-five patients (71%) achieved improvement of vision postoperatively. Twenty-four patients (26%) had no change in vision and 3 patients (3%) had deterioration of vision after surgery. The mean percentage of improvement was 40.7% +/- 6.9% in the trauma group, 61.6% +/- 23.2% in the neoplasm group, 66.4% +/- 25.2% in the infectious/mucocele group, and only one patient in the inflammatory group had slight visual improvement from no light perception to counting fingers. Extracranial optic nerve decompression can result in the improvement of visual function in some patients with optic nerve injury from various causes. C1 Facial Reconstruct Surg, Palo Alto, CA 94304 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Weber Med Clin, Olney, IL USA. RP Li, KK (reprint author), Facial Reconstruct Surg, 750 Welch Rd,Suite 317, Palo Alto, CA 94304 USA. NR 34 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD SEP PY 1999 VL 10 IS 5 BP 454 EP 459 PG 6 WC Surgery SC Surgery GA 236RE UT WOS:000082611700013 PM 10726518 ER PT J AU Rosen, CL Adler, JN Rabban, JT Sethi, RK Arkoff, L Blair, JA Sheridan, R AF Rosen, CL Adler, JN Rabban, JT Sethi, RK Arkoff, L Blair, JA Sheridan, R TI Early predictors of myoglobiniuria and acute renal failure following electrical injury SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE electrical injury; renal failure; myoglobinuria ID TRAUMATIC RHABDOMYOLYSIS; MANAGEMENT; BICARBONATE; CLEARANCE; URINE; SERUM AB Myoglobinuria-induced acute renal failure (ARF) is a potentially lethal consequence of electrical injury. We describe clinical variables that can predict the risk of myoglobinuria and ARF following electrical injury. This was a retrospective multivariate analysis of risk factors among electrically injured patients over a 26-year period. Urine myoglobin status was documented in 162 patients; 14% had myoglobinuria. No patient developed ARF, Multivariate modeling revealed that high-voltage exposure, prehospital cardiac arrest, full-thickness burns, and compartment syndrome were associated with myoglobinuria, Using a prediction rule defined as positive when a patient had greater than or equal to 2 risk factors yielded a sensitivity of 96% and negative predictive value of 99%. Electrical injury patients with myoglobinuria have little risk of developing ARF, A prediction rule can be used to screen out patients at low risk for myoglobinuria and identify high-risk patients who warrant early aggressive treatment and a more definitive myoglobin test. (C) 1999 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Shriners Burns Inst, Boston, MA USA. RP Rosen, CL (reprint author), Beth Israel Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. NR 29 TC 11 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD SEP-OCT PY 1999 VL 17 IS 5 BP 783 EP 789 DI 10.1016/S0736-4679(99)00084-0 PG 7 WC Emergency Medicine SC Emergency Medicine GA 235YY UT WOS:000082572500003 PM 10499690 ER PT J AU Legome, EL Sims, C Rao, PM AF Legome, EL Sims, C Rao, PM TI Epiploic appendagitis: Adding to the differential of acute abdominal pain SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE epiploic; appendagitis; abdominal; torsion; acute ID INFARCTION AB We report a patient with epiploic appendagitis who presented with acute abdominal pain. Emergency Department and discharge courses are described. The pathophysiology, presentation, diagnosis, and treatment of this disorder are discussed. Knowledge of this uncommonly diagnosed entity and its usual benign course may allow the Emergency Physician to order the appropriate studies to help avoid unnecessary surgical treatment. (C) 1999 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02139 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02139 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02139 USA. RP Legome, EL (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin Bldg 115, Boston, MA 02139 USA. NR 15 TC 21 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD SEP-OCT PY 1999 VL 17 IS 5 BP 823 EP 826 DI 10.1016/S0736-4679(99)00089-X PG 4 WC Emergency Medicine SC Emergency Medicine GA 235YY UT WOS:000082572500009 PM 10499696 ER PT J AU Brown, DFM Nadel, ES Davis, M Rosen, C Wolfe, R Sagarin, M Adler, J Nagurney, JT Walls, RM AF Brown, DFM Nadel, ES Davis, M Rosen, C Wolfe, R Sagarin, M Adler, J Nagurney, JT Walls, RM TI Abrupt severe chest and abdominal pain SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID AORTIC DISSECTION C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD SEP-OCT PY 1999 VL 17 IS 5 BP 893 EP 898 PG 6 WC Emergency Medicine SC Emergency Medicine GA 235YY UT WOS:000082572500022 PM 10499709 ER PT J AU Tyler, LW Matossian, K Todd, R Gallagher, GT White, RR Wong, DTW AF Tyler, LW Matossian, K Todd, R Gallagher, GT White, RR Wong, DTW TI Eosinophil-derived transforming growth factors (TGF-alpha and TGF-beta(1)) in human periradicular lesions SO JOURNAL OF ENDODONTICS LA English DT Article ID BIOLOGICAL-ACTIVITIES; CYTOKINES; CELLS; TISSUE AB Inflammatory mediators of periradicular lesions ave poorly understood. Transforming growth factors-alpha and -beta(1), (TGF-alpha and TGF-beta(1)) have been linked with the cellular processes for both soft and hard tissue wound healing. The purpose of this study is to demonstrate the cellular sources of TGF-alpha and TGF-beta(1) mRNA and protein in periapical lesions by in situ hybridization and immunohistochemistry. Nine periapical granulomas and nine periapical cysts were examined. TGF-alpha mRNA and protein were not detectable in the granulomas examined. However, eosinophils surrounding the periapical cysts demonstrated both TGF-alpha mRNA and protein. The vast majority of eosinophils present in the periapical granulomas and cysts also demonstrated TGF-beta(1) mRNA and protein. Other cells producing TGF-beta(1) were lymphocytes, fibroblasts, and monocytes. The presence of wound repair cytokines, such as TGF-alpha and TGF-beta(1), suggests a mechanism by which the host inflammatory response may participate in the repair and remodeling of periapical tissues. C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Div Oral Pathol, Boston, MA 02115 USA. Tufts Sch Dent Med, Boston, MA USA. Boston Univ, Sch Dent Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Restorat Dent, Boston, MA 02115 USA. RP Wong, DTW (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Div Oral Pathol, 188 Longwood Ave, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-11983, DE-10335, DE-08680] NR 20 TC 20 Z9 20 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD SEP PY 1999 VL 25 IS 9 BP 619 EP 624 DI 10.1016/S0099-2399(99)80322-7 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 231WU UT WOS:000082335000010 PM 10687542 ER PT J AU Rudnick, DM Bennett, PM Dretler, SP AF Rudnick, DM Bennett, PM Dretler, SP TI Retrograde renoscopic fragmentation of moderate-size (1.5-3.0-cm) renal cystine stones SO JOURNAL OF ENDOUROLOGY LA English DT Article ID SHOCK-WAVE LITHOTRIPSY; URINARY CALCULI; MANAGEMENT; EXPERIENCE AB Purpose: We present a series of cystinuric patients with renal cystine calculi between 1.5 and 3.0 cm treated with retrograde renoscopy and intracorporeal lithotripsy and report our results, complications, and inpatient utilization with this approach. Patients and Methods: The hospital and office charts of five consecutive patients with six treated renal units who underwent retrograde renoscopy and electrohydraulic lithotripsy for renal cystine stones between 1.5 and 3.0 cm were reviewed. Data on stone size and location, procedures performed, results, complications, and inpatient hospital days were compiled. Results: Five of the six renal units were either rendered stone free or had fragments totalling 3 mm or less. Three renal units required only a single procedure, one required repeat ureteroscopy for Steinstrasse, and one required SWL and repeat ureteroscopy for Steinstrasse. One renal unit was left with a 6-mm fragment for which the patient refused further treatment. There were no major complications. The mean hospital stay was 1 day, and the mean number of procedures per patient was 1,3, Conclusion: Retrograde renoscopy and intracorporeal lithotripsy for renal cystine stones 1.5 to 3.0 cm is safe and effective and should be considered as an alternative to percutaneous nephrolithotomy in these patients. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Rudnick, DM (reprint author), Univ Calif San Francisco, Dept Urol, 533 Parnassus Ave, San Francisco, CA 94143 USA. NR 9 TC 16 Z9 16 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD SEP PY 1999 VL 13 IS 7 BP 483 EP 485 DI 10.1089/end.1999.13.483 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 254ZX UT WOS:000083645400006 PM 10569520 ER PT J AU Itani, KMF Karni, A Green, L AF Itani, KMF Karni, A Green, L TI Squamous cell carcinoma of the pancreas SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE pancreas; squamous; carcinoma ID ADENOSQUAMOUS-CARCINOMA AB Squamous cell carcinoma of the pancreas is a controversial entity. Although some reports show that it is metastatic from another source, others demonstrate that it is a primary tumor. Between 1988 and 1997, fourteen cases of pancreatic squamous cell carcinoma were identified in the records of our pathology department. In seven instances the features were consistent with squamous cell carcinoma with no adenomatous component. The records of six of these patients were available for review and constitute the basis for this report. Five patients were diagnosed by means of percutaneous CT-guided fine-needle aspiration, whereas the sixth patient was diagnosed using a transduodenal core needle biopsy. At the time of diagnosis four patients had lung lesions, three patients had liver lesions, and two patients had lytic bone lesions. One patient had a 6 cm esophageal lesion. Surgical intervention had no impact on treatment or palliation in one of the patients. Chemotherapy and radiation therapy, alone or in combination, were ineffective in all patients. Median survival from the time of diagnosis was 2 months. We conclude that in cases of squamous cell carcinoma of the pancreas, every effort should be made to exclude adenomatous components histologically within the tumor and to exclude another primary source of squamous cell carcinoma. This will allow a better understanding of this entity and a refinement of therapy. C1 Houston VAMC, Dept Surg 112A, Houston, TX 77030 USA. Houston VAMC, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Itani, KMF (reprint author), Houston VAMC, Dept Surg 112A, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 13 TC 15 Z9 16 U1 0 U2 1 PU QUALITY MEDICAL PUBLISHING INC PI ST LOUIS PA 11970 BORMAN DR, STE 222, ST LOUIS, MO 63146 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD SEP-OCT PY 1999 VL 3 IS 5 BP 512 EP 515 DI 10.1016/S1091-255X(99)80105-X PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 248KC UT WOS:000083272800010 PM 10482708 ER PT J AU Grant, RW Charlebois, ED Wachter, RM AF Grant, RW Charlebois, ED Wachter, RM TI Risk factors for early hospital readmission in patients with AIDS and pneumonia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hospital readmission; AIDS; pneumonia ID HUMAN-IMMUNODEFICIENCY-VIRUS; INPATIENT CARE; DRUG-USE; BACTERIAL PNEUMONIA; QUALITY; INFECTION; ASSOCIATION; PROGRESSION; DISEASE AB OBJECTIVE: To determine risk factors for early readmission to the hospital in patients with AIDS and pneumonia. DESIGN: Case-control analysis. SETTING: A municipal teaching hospital serving an indigent population. PATIENTS: Case patients were all AIDS patients hospitalized with Pneumocystis carinii pneumonia or bacterial pneumonia between January 1992 and March 1995 who were readmitted for any nonelective reason within 2 weeks of discharge (n = 90). Control patients were randomly selected AIDS patients admitted during the study period who were not early readmissions (n. = 87), matched by proportion of Pneumocystis carinii to bacterial pneumonia. MEASUREMENTS AND MAIN RESULTS: Demographics, social support, health-related behaviors, clinical aspects of the acute hospitalization, and general medical status were the main predictors measured. RESULTS: Patients were at significantly increased risk of early readmission if they left the hospital unaccompanied by family or friend (odds ratio [OR] 4.76; 95% confidence interval [CI] 2.06, 11.0; p = .0003), used crack cocaine (OR 3.40; 95% CI 1.02, 11.3; p = .046), had one or more coincident AIDS diagnoses (OR 3.65; 95% CI 1.44, 9.26; p = .0065), or had been admitted in the preceding 6 months (OR 2.82; 95% CI 1.21, 6.57; p = .016). Demographic characteristics, alcoholism, intravenous drug use, illness severity on admission, and length of hospitalization did not predict early readmission. CONCLUSIONS: Absence of companion at discharge and crack use were important risk factors for early readmission in patients with AIDS and pneumonia. Additional AIDS comorbidity and recent antecedent hospitalization were also risk factors; however. demographics and measures of acute illness during index hospitalization did not predict early readmission. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Grant, RW (reprint author), 14 Roberts St 1, Brookline, MA 02445 USA. OI Grant, Richard/0000-0002-6164-8025 NR 27 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 1999 VL 14 IS 9 BP 531 EP 536 DI 10.1046/j.1525-1497.1999.08157.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 236JC UT WOS:000082595600001 PM 10491241 ER PT J AU Lee, WPA Mathes, DW AF Lee, WPA Mathes, DW TI Hand transplantation: Pertinent data and future outlook SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE hand transplant; composite tissue allografts; immunosuppression; tolerance ID TISSUE LIMB ALLOGRAFTS; LOW-DOSE CYCLOSPORINE; LONG-TERM; INDEFINITE SURVIVAL; RATS; FK-506; REPLANTATION; RECIPIENTS; REJECTION; INFECTION AB Transplantation of composite tissue allografts, such as a hand, offers immense potential in reconstructive surgery. Review of current replantation literature suggests the prospect for significant functional return following hand transplant, provided appropriate patient is selected and allograft rejection is prevented. Experimental studies of limb transplantation in rodents have demonstrated the efficacy of combination therapy using multiple immunosuppressants. However, long-term survival of limb allografts could not be achieved in large animal models without significant drug toxicity. Given the potential for organ failure, opportunistic infection, and malignancy resulting from long-term immunosuppression, the risk-benefit ratio for hand transplant must be carefully weighed. Our laboratory has been able to achieve allograft survival with minimum immunosuppression by MHC matching or donor antigen exposure prior to immune maturity in the swine. Future transplantation of composite tissue allografts, therefore, may depend upon such modalities to induce host tolerance without long-term immunosuppression. (J Hand Surg 1999;24A:906-913. Copyright (C) 1999 by the American Society for Surgery of the Hand.) C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Plast Surg, Wang Ambulatory Care Ctr 453, Boston, MA 02114 USA. RP Lee, WPA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Plast Surg, Wang Ambulatory Care Ctr 453, 15 Parkman St, Boston, MA 02114 USA. NR 47 TC 60 Z9 64 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 1999 VL 24A IS 5 BP 906 EP 913 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 238ER UT WOS:000082698400004 PM 10509267 ER PT J AU Milner, JD Kent, SC Ashley, TA Wilson, SB Strominger, JL Hafler, DA AF Milner, JD Kent, SC Ashley, TA Wilson, SB Strominger, JL Hafler, DA TI Differential responses of invariant V alpha 24J alpha Q T cells and MHC class II-restricted CD4(+) T cells to dexamethasone SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GLUCOCORTICOID-INDUCED APOPTOSIS; PROMPTLY PRODUCE INTERLEUKIN-4; SELECTIVE REDUCTION; POSITIVE SELECTION; ANTIGEN RECEPTOR; TH1/TH2 BALANCE; TCR EXPRESSION; IMMUNE-SYSTEM; FAS LIGAND AB NK T cells are a T cell subset in the human that express an invariant alpha-chain (V alpha 24(invt) T cells), Because of the well-described immunomodulation by glucocorticoids on activation-induced cell death (AICD), the effects of dexamethasone and anti-CD3 stimulation on V alpha 24(invt) T cell clones and CD4(+) T cell clones were investigated. Dexamethasone significantly enhanced anti-CD3- mediated proliferation of V alpha 24(invt) T cells, whereas CD4+ T cells were inhibited. Addition of neutralizing IL-2 Ab partially abrogated dexamethasone-induced potentiation of V alpha 24(invf) T cell proliferation, indicating a role for autocrine IL-2 production in corticosteroid-mediated proliferative augmentation. Dexametbasone treatment of anti-CD3-stimulated V alpha/24(invt) T T cells did not synergize with anti-Pas blockade in enhancing proliferation or preventing AICD, The V alpha 24(invt) T cell response to dexamethasone was dependent on the TCR signal strength, In the presence of dexamethasone, lower doses of anti-CD3 inhibited proliferation of V alpha 24(invt) T cells and CD4(+) T cells; at higher doses of anti-CD3, which caused inhibition of CD4(+) T cells, the V alpha 24(invt) T cell clones proliferated and were rescued from AICD, These results demonstrate significant differences in TCR signal strength required between V alpha 24(invt) T cells and CD4+ cells, and suggest important immunomodulatory consequences for endogenous and exogenous corticosteroids in immune responses. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hafler, DA (reprint author), Ctr Neurol Dis, 77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NIAID NIH HHS [P01 AI39671, R01 AI39229-01, R01 AI44447-01] NR 47 TC 19 Z9 21 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 1999 VL 163 IS 5 BP 2522 EP 2529 PG 8 WC Immunology SC Immunology GA 228FA UT WOS:000082125400025 PM 10452989 ER PT J AU Pratt, JC van den Brink, MRM Igras, VE Walk, SF Ravichandran, KS Burakoff, SJ AF Pratt, JC van den Brink, MRM Igras, VE Walk, SF Ravichandran, KS Burakoff, SJ TI Requirement for Shc in TCR-mediated activation of a T cell hybridoma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FAS LIGAND EXPRESSION; PHOSPHOTYROSINE-BINDING DOMAIN; ADAPTER PROTEIN SHC; ANTIGEN RECEPTOR; TYROSINE KINASE; ZETA-CHAIN; APOPTOSIS; LYMPHOCYTES; ASSOCIATION; SITES AB Engagement of tbe TCR determines the fate of T cells to activate their functional programs, proliferate, or undergo apoptosis. The intracellular signal transduction pathways that dictate the specific outcome of receptor engagement have only been partially elucidated. The adapter protein, She, is involved in cytokine production mitogenesis, transformation, and apoptosis in different cell systems. We found that She becomes phosphorylated on tyrosine residues upon stimulation of the TCR in D011.10 hybridoma T cells; therefore, we investigated the role of She in activation-induced cell death in these cells by creating a series of stably transfected cell lines. Expression of Shc-SH2 (the SH2 domain of She) or Shc-Y239/240F (full-length She in which tyrosines 239 and 240 have been mutated to phenylalanine) resulted in the inhibition of activation-induced cell death and Fas ligand upregulation after TCR cross-linking. Expression of wild-type She or Shc-Y317F had no significant effect. In addition, we found that Shc-SH2 and Shc-Y239/240F, but not Shc-Y317F, inhibited phosphorylation of extracellular signal-regulated protein kinase and production of IL-2 after TCR cross-linking. These results indicate an important role for She in the early signaling events that had to activation-induced cell death and IL-2 production after TCR activation. C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA 02115 USA. Univ Virginia, Beirne Carter Ctr Immunol Res, Charlottesville, VA 22908 USA. RP Burakoff, SJ (reprint author), Dana Farber Canc Inst, Div Pediat Oncol, Dana 1840,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA70758] NR 41 TC 27 Z9 27 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 SEP 1 PY 1999 VL 163 IS 5 BP 2586 EP 2591 PG 6 WC Immunology SC Immunology GA 228FA UT WOS:000082125400033 PM 10452997 ER PT J AU Manilay, JO Waneck, GL Sykes, M AF Manilay, JO Waneck, GL Sykes, M TI Levels of Ly-49 receptor expression are determined by the frequency of interactions with MHC ligands: Evidence against receptor calibration to a "useful" level SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; CLASS-I MHC; NK CELLS; MICE; GENE; LY49A; CLONING; FAMILY; REPERTOIRE; TOLERANCE AB Ly-49 receptor expression was studied in NK cells that developed in fully MHC-mismatched mixed bone marrow chimeras, in which host and donor MHC ligands were expressed solely on various proportions of hemopoietic cells or on both hemopoietic and nonhemopoietic cells. When hemopoietic cells were the only source of MHC ligand, a strong correlation between the level of down-regulation of Ly-49A, Ly-49C, and Ly-49G2 and the number of hemopoietic cells expressing their MHC ligands was observed on both donor and host NK cells. In some animals with low levels of donor hemopoietic chimerism, NK cells of donor origin expressed Ly-49 receptors at higher levels than was observed in normal mice of the same strain. This unexpected observation is inconsistent with the receptor calibration theory, which states that expression of Ly-49 inhibitory receptors is calibrated to an optimal level to maintain an Mt cell repertoire that is sensitive to perturbations in normal class I ligand expression, Our data suggest a model in which Ly-49 receptors down-modulate in accordance with the frequency of their interactions with ligand-bearing cells, rather than a model in which these receptors calibrate to a specific "useful" level in response to ligands present in their environment. C1 Harvard Univ, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Massachusetts Gen Hosp,Sch Med,Surg Serv, Boston, MA 02129 USA. Harvard Univ, Lab Mol & Cellular Immunol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Harvard Univ, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Massachusetts Gen Hosp,Sch Med,Surg Serv, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM sykes@helix.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL49915, 5 F31 HL09733-02] NR 28 TC 17 Z9 18 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1999 VL 163 IS 5 BP 2628 EP 2633 PG 6 WC Immunology SC Immunology GA 228FA UT WOS:000082125400038 PM 10453002 ER PT J AU Kasyapa, CS Stentz, CL Davey, MP Carr, DW AF Kasyapa, CS Stentz, CL Davey, MP Carr, DW TI Regulation of IL-15-stimulated TNF-alpha production by rolipram SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; IV PHOSPHODIESTERASE INHIBITOR; COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; T-CELLS; ENDOTHELIAL-CELLS; PROINFLAMMATORY CYTOKINE; INTERFERON-GAMMA; INTERLEUKIN-15; SUPPRESSION AB Agents that increase intracellular cAMP have been shown to reduce joint inflammation in experimental arthritis, presumably by lowering the release of proinflammatory cytokines, such as TNF-alpha. Recent studies suggest that, in joints of patients with rheumatoid arthritis, TNF-alpha release from macrophages is triggered by their interaction with IL-15-stimulated T lymphocytes, In this report, we analyze the effect of rolipram, a cAMP-specific phosphodiesterase inhibitor, on TNF-alpha production in this experimental system. Cocultures of U937 cells with IL-15-stimulated T cells, but not control T cells, resulted in increased release of TNF-alpha. Pretreatment of T cells with rolipram or cAMP analogues inhibited the IL-15-stimulated increases in proliferation, expression of cell surface molecules CD69, ICAM-1, and LFA-1, and release of TNF-alpha from macrophages, Addition of PMA. to T cells dramatically increased the expression of cell surface molecules, but had little or no effect on TNF-alpha release from either T cells or from cocultures, suggesting that other surface molecules must also be involved in T cell/macrophage contact-mediated production of TNF-alpha, Addition of PMA synergistically increased the proliferation of IL-15-stimulated T cells and the secretion of TNF-alpha from IL-15-stimulated T cell/macrophage cocultures, Rolipram and 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) blocked these increases. Measurement of protein kinase A (PKA) activity and the use of inhibitory cAMP analogues (RpCPT-cAMP) confirmed that rolipram worked by stimulating PKA, These data suggest that PKA-activating agents, such as rolipram, can block secretion of TNF-alpha from macrophages by inhibiting T cell activation and expression of surface molecules. C1 Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. RP Carr, DW (reprint author), Portland Vet Affairs Med Ctr, R&D8,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 42 TC 25 Z9 26 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 SEP 1 PY 1999 VL 163 IS 5 BP 2836 EP 2843 PG 8 WC Immunology SC Immunology GA 228FA UT WOS:000082125400065 PM 10453029 ER PT J AU Lin, Y Soares, MP Sato, K Takigami, K Csizmadia, E Smith, N Bach, FH AF Lin, Y Soares, MP Sato, K Takigami, K Csizmadia, E Smith, N Bach, FH TI Accommodated xenografts survive in the presence of anti-donor antibodies and complement that precipitate rejection of naive xenografts SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BABOON CARDIAC TRANSPLANTS; VENOM FACTOR THERAPY; LONG-TERM SURVIVAL; ENDOTHELIAL-CELLS; GUINEA-PIG; CYTOKINE PRODUCTION; PROTECTIVE GENES; HAMSTER HEARTS; RAT MODEL; XENOTRANSPLANTATION AB Hamster hearts transplanted into transiently complement-depleted and continuously cyclosporin A (CyA)-immunosuppressed rats survive long-term despite deposition of anti-donor IgM Abs and complement on the graft vascular endothelium. This phenomenon is referred to as "accommodation." The hypothesis tested here is that accommodated xenografts are resistant to IgM Abs and complement that could result in rejection of naive xenografts, After first hamster hearts had been surviving in cobra venom factor (CVF) + CyA-treated rats for 10 days, a time when the anti-donor IgM Ab level was maximal and complement activity had returned to approximately 50% of pretreatment levels, naive hamster hearts or hamster hearts that had been accommodating in another rat for 14 days were transplanted into those rats carrying the surviving first graft. The naive hearts were all hyperacutely rejected, In contrast, a majority of regrafted accommodating hearts survived long-term, There was widespread Ab and activated complement deposition on the vascular endothelium of accommodating first hearts, second accommodating hearts, and rejected second naive hearts. However, only the rejected naive hearts showed extensive endothelial cell damage, myocardial necrosis, fibrin deposition, and other signs of inflammation, Accommodating first and second hearts but not rejected second naive hearts expressed high levels of the protective genes A20, heme oxygenase-l (HO-1), bcl-2, and bcl-x(L). These data demonstrate that accommodated xenografts become resistant to effects of anti-donor IgM Abs and complement that normally mediate rejection of xenografts, We hypothesize that this resistance involves expression by accommodated xenografts of protective genes. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr,Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02215 USA. RP Lin, Y (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr,Dept Surg, 99 Brookline Ave, Boston, MA 02215 USA. OI Soares, Miguel/0000-0002-9314-4833 FU NHLBI NIH HHS [1R01 HL58688] NR 44 TC 60 Z9 64 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 SEP 1 PY 1999 VL 163 IS 5 BP 2850 EP 2857 PG 8 WC Immunology SC Immunology GA 228FA UT WOS:000082125400067 PM 10453031 ER PT J AU Hirsch, M Steigbigel, R Staszewski, S Mellors, J Scerpella, E Hirschel, B Lange, J Squires, K Rawlins, S Meibohm, A Leavitt, R AF Hirsch, M Steigbigel, R Staszewski, S Mellors, J Scerpella, E Hirschel, B Lange, J Squires, K Rawlins, S Meibohm, A Leavitt, R CA Protocol 039 Study Grp TI A randomized, controlled trial of indinavir, zidovudine, and lamivudine in adults with advanced human immunodeficiency virus type 1 infection and prior antiretroviral therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 5th Conference on Retroviruses and Opportunistic Infections CY FEB 01-05, 1998 CL CHICAGO, ILLINOIS AB A randomized, double-blind, multicenter study of indinavir, zidovudine, and lamivudine was conducted in 320 adults with human immunodeficiency virus type 1 (HIV-1) infection, less than or equal to 50 CD4 cells/mm(3), and extensive prior zidovudine therapy. Patients received indinavir, 800 mg every 8 h; zidovudine, 200 mg every 8 h, and lamivudine, 150 mg twice daily; or all 3 drugs for 24 weeks, In an intention-to-treat analysis, proportions of patients with HIV-1 RNA <500 and <50 copies/mL, respectively, at week 24 were 56% and 45% in the indinavir-zidovudine-lamivudine group, 3% and 2% in the indinavir group, and 0% in the zidovudine-lamivudine group, Observed mean CD4 cell increases were 95, 78, and 6 cells/mm(3) in the three-, one-, and two-drug arms, respectively. Regimens were generally well tolerated. Patients with advanced HIV-1 infection benefit from triple therapy with indinavir, zidovudine, and lamivudine, although the proportion with optimal response appeared to be lower in patients with low CD4 cell counts. C1 Merck & Co Inc, Res Labs, W Point, PA 19486 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Hosp, Div Infect Dis, Stony Brook, NY USA. Univ Frankfurt Klinikum, D-6000 Frankfurt, Germany. Univ Pittsburgh, Med Ctr, Div Infect Dis, Pittsburgh, PA 15260 USA. Univ Miami, Dept Med, Coral Gables, FL 33124 USA. Hop Cantonal Univ Geneva, Geneva, Switzerland. Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands. Univ Alabama, Div Infect Dis, Birmingham, AL USA. RP Leavitt, R (reprint author), Merck & Co Inc, Res Labs, POB 4, W Point, PA 19486 USA. NR 12 TC 73 Z9 74 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1999 VL 180 IS 3 BP 659 EP 665 DI 10.1086/314948 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 230HT UT WOS:000082246300012 PM 10438352 ER PT J AU Tashima, KT Caliendo, AM Ahmad, M Gormley, JM Fiske, WD Brennan, JM Flanigan, TP AF Tashima, KT Caliendo, AM Ahmad, M Gormley, JM Fiske, WD Brennan, JM Flanigan, TP TI Cerebrospinal fluid human immunodeficiency virus type 1 (HIV-1) suppression and efavirenz drug concentrations in HIV-1-infected patients receiving combination therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Neuroscience of HIV Infection-Basic Research and Clinical Frontiers Congress CY JUN 03-06, 1998 CL CHICAGO, ILLINOIS ID AIDS DEMENTIA; ZIDOVUDINE; RNA AB Efavirenz, a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcript ase, is a promising addition to the antiretroviral armamentarium. Efavirenz levels and HIV-1 RNA levels were measured in ccrebrospinal fluid (CSF) and plasma of 10 HIV-1-infected patients taking efavirenz, 600 mg daily, in combination with other antiretroviral medications. Efavirenz was detected in the CSF at a mean concentration of 35.1 nM (range, 6.6-58.9 nM), which was above the IC95 for wild-type HIV-1, The mean CSF-to-plasma ratio was 0.61% (range, 0.26%-0.99%). CSF HIV-1 RNA levels were ascertained in 9 of the patients; all were <400 copies/mL after a mean of 26 weeks on therapy. Eight of the 9 patients had no detectable virus in plasma. These results indicate that efavirenz is present in the CSF at low levels and is effective in suppressing CSF viral levels when used in combination therapy. C1 Brown Univ, Miriam Hosp, Dept Med, Providence, RI 02906 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. DuPont Pharmaceut Co, Drug Metab & Pharmacokinet, Newark, DE USA. RP Tashima, KT (reprint author), Brown Univ, Miriam Hosp, Dept Med, 164 Summit Ave, Providence, RI 02906 USA. NR 15 TC 73 Z9 78 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1999 VL 180 IS 3 BP 862 EP 864 DI 10.1086/314945 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 230HT UT WOS:000082246300041 PM 10438381 ER PT J AU Rajadhyaksha, M Gonzalez, S Zavislan, JM Anderson, RR Webb, RH AF Rajadhyaksha, M Gonzalez, S Zavislan, JM Anderson, RR Webb, RH TI In vivo confocal scanning laser microscopy of human skin II: Advances in instrumentation and comparison with histology SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE dermatology; morphology; non-invasive imaging; optical imaging ID IN-VIVO; REFRACTIVE-INDEX; IMAGING PROPERTIES; ABERRATION; DETECTOR; CONTRAST; SYSTEMS; DEPTH; FIELD AB In 1995, we reported the construction of a video-rate scanning laser confocal microscope for imaging human skin in vivo. Since then, we have improved the resolution, contrast, depth of imaging, and field of view. Confocal images of human skin are shown with experimentally measured lateral resolution 0.5-1.0 mu m and axial resolution (section thickness) 3-5 mu m at near-infrared wavelengths of 830 nm and 1064 nm; this resolution compares well, to that of histology which is based on typically 5 mu m thin sections, Imaging is possible to maximum depth of 350 mu m over held of view of 160-800 mu m, A mechanical skin-contact device was developed to laterally stabilize the imaging site to within +/- 25 mu m in the presence of subject motion. Based on these results, we built a small, portable, and robust confocal microscope that is capable of imaging normal and abnormal skin morphology and dynamic processes in vivo, in both laboratory and clinical settings. We report advances in confocal microscope instrumentation and methods, an optimum range of parameters, improved images of normal human skin, and comparison of confocal images with histology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. Lucid Inc, Henrietta, NY USA. RP Rajadhyaksha, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Bartlett Hall Ext 630, Boston, MA 02114 USA. FU NCI NIH HHS [1R43CA580540] NR 40 TC 504 Z9 518 U1 6 U2 39 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1999 VL 113 IS 3 BP 293 EP 303 DI 10.1046/j.1523-1747.1999.00690.x PG 11 WC Dermatology SC Dermatology GA 233BQ UT WOS:000082406000001 PM 10469324 ER PT J AU Streit, M Velasco, P Richard, L Brown, L Detmar, M AF Streit, M Velasco, P Richard, L Brown, L Detmar, M TI Delayed mound healing in transgenic mice overexpressing the endogenous angiogenesis inhibitor thrombospondin-1 in the skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Dermatol, CBRC, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1999 VL 113 IS 3 MA 007 BP 432 EP 432 PG 1 WC Dermatology SC Dermatology GA 233BQ UT WOS:000082406000033 ER PT J AU Kaya, G Augsburger, E Stamenkovic, I Saurat, JH AF Kaya, G Augsburger, E Stamenkovic, I Saurat, JH TI Decrease in epidermal CD44 expression as a potential mechanism for abnormal hyaluronate accumulation in superficial dermis in lichen sclerous and atrophicus SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Hosp Geneva, Dept Dermatol, DHURDV, Geneva, Switzerland. Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1999 VL 113 IS 3 MA 052 BP 439 EP 439 PG 1 WC Dermatology SC Dermatology GA 233BQ UT WOS:000082406000079 ER PT J AU Podda, M Beschmann, HA Duijvestijn, A von Andrian, UH Kaufmann, R Zollner, TM AF Podda, M Beschmann, HA Duijvestijn, A von Andrian, UH Kaufmann, R Zollner, TM TI alpha 1,3-fucosylkransferase VII mRNA expression is induced by superantigen stimulation and inhibited by N-acetylcysteine SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Frankfurt, Dept Dermatol, D-6000 Frankfurt, Germany. Univ Maastricht, Dept Internal Med, Maastricht, Netherlands. Harvard Univ, Sch Med, CBR, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1999 VL 113 IS 3 MA 275 BP 476 EP 476 PG 1 WC Dermatology SC Dermatology GA 233BQ UT WOS:000082406000296 ER PT J AU Boedeker, JC Doolittle, M Santamarina-Fojo, S White, AL AF Boedeker, JC Doolittle, M Santamarina-Fojo, S White, AL TI Role of N-linked carbohydrate processing and calnexin in human hepatic lipase secretion SO JOURNAL OF LIPID RESEARCH LA English DT Article DE chaperone; endoplasmic reticulum; ER glucosidase; Lec23 cells; Lec1 cells ID LIPOPROTEIN-LIPASE; TRIGLYCERIDE LIPASE; ENDOPLASMIC-RETICULUM; DENSITY-LIPOPROTEIN; POSTHEPARIN PLASMA; CATALYTIC ACTIVITY; HDL CHOLESTEROL; BINDING-PROTEIN; RAT HEPATOCYTES; CDNA SEQUENCE AB The addition and endoplasmic reticulum (ER) glucosidase processing of N-linked glycans is essential for the secretion of rat hepatic lipase (HL), Human HL is distinct from rat HL by the presence of four as opposed to two N-linked carbohydrate side chains. We examined the role of N-linked glycosylation and calnexin interaction in human HL secretion from Chinese hamster ovary (CHO) cells stably expressing a human HL cDNA, Steady-state and pulse-chase labeling experiments established that human HL was synthesized as an ER-associated precursor containing high mannose N-linked glycans, Secreted HL had a molecular mass of similar to 65 kDa and contained mature N-linked sugars, Inhibition of N-linked glycosylation with tunicamycin (TM) prevented secretion of HL enzyme activity and protein mass. in contrast, incubation of cells with the ER glucosidase inhibitor, castanospermine (CST), decreased human HL protein secretion by 60%, but allowed 40% of fully active HL to be secreted, HL protein mass and enzyme activity were also recovered from the media of a CHO-derivative cell line genetically deficient in ER glucosidase I activity (Lec23) that was transiently transfected with a human HL cDNA, Co-immunoprecipitation experiments demonstrated that newly synthesized human HL bound to the lectin-like ER chaperone, calnexin, and that this interaction was inhibited by TM and CST. These results suggest that under normal conditions calnexin may increase the efficiency of HL expert from the ER. Whereas a significant proportion of human HL can attain activity and become secreted in the absence of glucose trimming and calnexin association, these interrelated processes are nevertheless essential for the expression of full HL activity. C1 Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP White, AL (reprint author), Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. FU NCRR NIH HHS [MO-IRR00663]; NHLBI NIH HHS [HL28481] NR 45 TC 11 Z9 11 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 1999 VL 40 IS 9 BP 1627 EP 1635 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 233MF UT WOS:000082430100008 PM 10484609 ER PT J AU Waeber, C Chiu, ML AF Waeber, C Chiu, ML TI In vitro autoradiographic visualization of guanosine-5 '-O-(3-[S-35]thio)triphosphate binding stimulated by sphingosine 1-phosphate and lysophosphatidic acid SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE G protein; oligodendrocytes; endothelium-differentiation gene receptors; ventricular zone gene-1; spatial distribution; mapping ID BOVINE BRAIN MEMBRANES; G-PROTEINS; CHROMAFFIN CELLS; RECEPTOR; GUANOSINE; GTP; VZG-1/LP(A1)/EDG-2; PURIFICATION; EXOCYTOSIS; ANALOGS AB Sphingosine 1-phosphate or lysophosphatidic acid activation of guanosine-5'-O-(3-[S-35]thio)triphosphate ([S-35]GTP gamma S) binding to G proteins was studied by in vitro autoradiography in rat and guinea pig brain. The highest stimulation of [S-35]GTP gamma S binding by sphingosine 1-phosphate was observed in the molecular layer of the cerebellum. Marked stimulation was observed in most forebrain areas, including neocortex and striatum. With the exception of the substantia gelatinosa and nucleus of the solitary tract, sphingosine 1-phosphate-enhanced binding was weaker in the brainstem and spinal cord. Lysophosphatidic acid-enhanced labeling was only observed in white matter areas. The G protein inhibitor 5'-p-fluorosulfonylbenzoyl guanosine completely inhibited lysophosphatidic acid-enhanced [S-35]GTP gamma S binding but only partially sphingosine 1-phosphate-enhanced binding. N-Ethylmaleimide abolished binding stimulated by both agonists. Sphingosine 1-phosphate enhanced labeling by another GTP analogue (beta, gamma-imido[8-H-3]guanosine-5'-triphosphate) similarly to that of [S-35]GTP gamma S. Lysophosphatidic acid stimulated [S-35]GTP gamma S binding in the olfactory bulb, glia limitans, and cortical subventricular zone of 1-day-old rats, whereas enhanced labeling was not observed in the latter area of 5-day-old rats. Sphingosine 1-phosphate stimulated binding in the cortical and striatal subventricular zones and olfactory bulb in 1- and 5-day-old rats. In the absence of radioligand for sphingosine 1-phosphate and lysophosphatidic acid receptors, [S-35]GTP gamma S autoradiography provides a unique opportunity to study the spatial distribution, ontogeny, and coupling properties of these receptors. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Waeber, C (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [1P01NS35611-01] NR 40 TC 27 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1999 VL 73 IS 3 BP 1212 EP 1221 DI 10.1046/j.1471-4159.1999.0731212.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 226TD UT WOS:000082037000037 PM 10461914 ER PT J AU Litvan, I Grimes, DA Lang, AE Jankovic, J McKee, A Verny, M Jellinger, K Chaudhuri, KR Pearce, RKB AF Litvan, I Grimes, DA Lang, AE Jankovic, J McKee, A Verny, M Jellinger, K Chaudhuri, KR Pearce, RKB TI Clinical features differentiating patients with postmortem confirmed progressive supranuclear palsy and corticobasal degeneration SO JOURNAL OF NEUROLOGY LA English DT Article; Proceedings Paper CT 7th Symposium on the Treatment of Parkinsons Disease CY OCT 03, 1998 CL OSAKA, JAPAN DE progressive supranuclear palsy; corticobasal degeneration; diagnosis; clinical ID RICHARDSON-OLSZEWSKI-SYNDROME; NATURAL-HISTORY; CRITERIA; DIAGNOSIS; ACCURACY AB Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are often clinically confused with each other because they share a rapid disease progression parkinsonism that responds poorly or transiently to levodopa therapy, and associated signs (e.g., ocular abnormalities, pyramidal signs and cognitive involvement). To improve the accuracy in diagnosing these disorders, this study examined the clinical features of 51 patients pathologically diagnosed with PSP and CBD. Logistic regression analysis identified two sets of predictors (models) for CBD patients, one consisting of asymmetric parkinsonism, cognitive disturbances at onset and instability and falls at first clinic visit, and the other one of asymmetric parkinsonism, cognitive disturbances at symptom onset and speech disturbances. While PSP patients often had severe postural instability at onset, symmetric parkinsonism, vertical supranuclear gaze palsy, speech and frontal lobe-type features, CBD patients presented with lateralized motor (e.g., parkinsonism, dystonia or myoclonus) and cognitive signs (e.g., ideomotor apraxia, aphasia or alien limb). On the other hand, CBD patients presenting with an alternate phenotype characterized by early severe frontal dementia and bilateral parkinsonism were generally misdiagnosed. PSP patients without vertical supranuclear gaze palsy were misdiagnosed. Recognizing the features which differentiate these disorders and the less obvious disease presentations as well as developing an increased index of suspicion will improve the diagnostic accuracy of these disorders. C1 Henry M Jackson Fdn, Def & Vet Head Injury Program, Bethesda, MD 20892 USA. Toronto Hosp, Movement Disorders Ctr, Toronto, ON M5T 2S8, Canada. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Bedford VA Med Ctr, GRECC, Boston, MA USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Hop La Pitie Salpetriere, Lab Neuropathol R Escourolle, INSERM, U360, F-75651 Paris, France. Ludwig Boltzmann Inst Clin Neurobiol, Vienna, Austria. Inst Psychiat, Dept Neurol, London SE5 8AF, England. Inst Neurol, Parkinsons Dis Soc, Brain Tissue Bank, London WC1N 3BG, England. RP Litvan, I (reprint author), Henry M Jackson Fdn, Def & Vet Head Injury Program, Fed Bldg,Room 714, Bethesda, MD 20892 USA. NR 22 TC 64 Z9 64 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD SEP PY 1999 VL 246 SU 2 BP 1 EP 5 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 246NA UT WOS:000083168800001 ER PT J AU Teneback, CC Nahas, Z Speer, AM Molloy, M Stallings, LE Spicer, KM Risch, SC George, MS AF Teneback, CC Nahas, Z Speer, AM Molloy, M Stallings, LE Spicer, KM Risch, SC George, MS TI Changes in prefrontal cortex and paralimbic activity in depression following two weeks of daily left prefrontal TMS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; ANTERIOR CINGULATE CORTEX; HUMAN MOTOR CORTEX; MAJOR DEPRESSION; GLUCOSE-METABOLISM; SLEEP-DEPRIVATION; BLOOD-FLOW; BRAIN; MOOD; CONNECTIVITY AB Twenty-two depressed adults were scanned with perfusion single-photon computed emission tomography before and after 2 weeks of left prefrontal transcranial magnetic stimulation (TMS) in a parallel design, double-blind treatment study. At medication-free baseline, across all subjects, blood flow in the bilateral medial temporal lobes, left prefrontal cortex, and caudate significantly declined with increased depression severity. Also at baseline, depressed adults who responded to TMS, compared with nonresponders, showed increased inferior frontal lobe activity. Following treatment, there was an even greater difference in inferior frontal blood flow in responders compared with nonresponders, and the negative baseline correlations between depression severity and limbic and prefrontal blood flow disappeared. These results suggest that in depressed adults, 10 days of prefrontal TMS affects prefrontal and paralimbic activity, which may explain its antidepressant effects. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Funct Neuroimaging Res Div, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Radiol, Room D297,171 Ashley Ave, Charleston, SC 29425 USA. NR 62 TC 145 Z9 148 U1 6 U2 12 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1999 VL 11 IS 4 BP 426 EP 435 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 254QC UT WOS:000083622800003 PM 10570754 ER PT J AU Altshuler, L Rausch, R Delrahim, S Kay, J Crandall, P AF Altshuler, L Rausch, R Delrahim, S Kay, J Crandall, P TI Temporal lobe epilepsy, temporal lobectomy, and major depression SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID COMPLEX PARTIAL SEIZURES; QUALITY-OF-LIFE; UNIPOLAR DEPRESSION; FOLLOW-UP; PERSONALITY; LATERALITY; SURGERY; ELECTROENCEPHALOGRAPHY; PSYCHOSIS; BEHAVIOR AB Sixty-two patients with medically intractable complex partial seizures who had either surgical or no surgical intervention were followed up at a mean of 10.9 years after surgery or initial evaluation. Of the 49 surgical patients, 45% had a lifetime history of depression, versus 15% of the 13 patients in the nonsurgical comparison group. In the surgical group, 77% had prior history of depression; of these, 47% experienced no further episodes after surgery. Depression occurred de novo after lobectomy in 5 surgical patients (similar to 10%), 4 developing depression within 1 year. Presurgical presence of depressive episodes predicted continued postoperative depressive episodes. The significantly higher depression rate in patients with temporal lobe seizure foci suggests limbic system dysfunction in the increased risk for depression. Postsurgical resolution of episodes in almost 50% of these patients supports the tenet that depression per se is not a contraindication for surgery in patients with intractable seizures. C1 Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Mood Disorders Res Program, Los Angeles, CA 90095 USA. W Los Angeles VA Med Ctr, Psychiat Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90024 USA. RP Altshuler, L (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Mood Disorders Res Program, 300 UCLA Med Plaza,Suite 1544, Los Angeles, CA 90095 USA. FU NINDS NIH HHS [NS31277] NR 54 TC 71 Z9 73 U1 1 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1999 VL 11 IS 4 BP 436 EP 443 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 254QC UT WOS:000083622800004 PM 10570755 ER PT J AU Bronstein, YL Mendez, MF Vinters, HV AF Bronstein, YL Mendez, MF Vinters, HV TI Clinicopathologic case report: Rapidly progressive dementia with demyelinating polyneuropathy SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; FATAL FAMILIAL INSOMNIA; CEREBROSPINAL-FLUID; PERIPHERAL NEUROPATHY; PRION PROTEIN; SPONGIFORM ENCEPHALOPATHIES; DIAGNOSTIC-CRITERIA; AMYLOID ANGIOPATHY; ALZHEIMERS-DISEASE; COEXISTENCE C1 Univ Calif Los Angeles, Med Ctr, W Los Angeles Vet Affairs Med Ctr, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, W Los Angeles Vet Affairs Med Ctr, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIA NIH HHS [P50 AG16570] NR 41 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1999 VL 11 IS 4 BP 507 EP 513 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 254QC UT WOS:000083622800015 PM 10570766 ER PT J AU Lu, CW Vihtelic, TS Hyde, DR Li, TS AF Lu, CW Vihtelic, TS Hyde, DR Li, TS TI A neuronal-specific mammalian homolog of the Drosophila retinal degeneration B gene with expression restricted to the retina and dentate gyrus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE rdgB; retinal degeneration; PITP; dentate gyrus; hippocampus; autism ID PHOSPHATIDYLINOSITOL TRANSFER PROTEIN; PHOSPHOLIPID TRANSFER PROTEINS; MELANOGASTER; CLONING; TRANSDUCTION; CAVEOLAE; PATHWAY; YEAST; LONG AB Mutations in the Drosophila retinal degeneration B (rdgB) gene cause a rapid loss of the electrophysiological light response and subsequent light-enhanced photoreceptor degeneration. The rdgB gene encodes a protein with an N-terminal phosphatidylinositol transfer protein domain, a large C-terminal segment, and several hydrophobic regions thought to multiply span the subrhabdomeric cisternal membrane. A mammalian rdgB homolog (m-rdgB1) was previously identified and shown to exhibit widespread tissue distribution and functionally rescue the Drosophila rdgB mutant phenotypes. We describe a second mammalian rdgB homolog (m-rdgB2) that possesses 46% amino acid identity to Drosophila RdgB and 56% identity to M-RdgB1. M-RdgB2 possesses a neuronal-specific expression pattern, with high levels in the retina and the dentate gyrus mossy fibers and dendritic field. Using M-RdgB2-specific antibodies and subcellular fractionation, we demonstrate that M-RdgB2 is not an integral membrane protein but is stably associated with a particulate fraction through protein-protein interactions. Although transgenic expression of M-RdgB2 in rdgB2 null mutant flies suppressed the retinal degeneration, it failed to fully restore the electrophysiological light response. Because transgenic expression of M-RdgB2 does not restore the wild-type phenotype to rdgB2 mutant flies to the same extent as M-RdgB1, functional differences likely exist between the two M-RdgB homologs. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. RP Li, TS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY08058, EY10309] NR 37 TC 32 Z9 33 U1 0 U2 0 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 SEP 1 PY 1999 VL 19 IS 17 BP 7317 EP 7325 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 233TL UT WOS:000082442600011 PM 10460238 ER PT J AU Hsueh, YP Sheng, M AF Hsueh, YP Sheng, M TI Regulated expression and subcellular localization of syndecan heparan sulfate proteoglycans and the syndecan-binding protein CASK/LIN-2 during rat brain development SO JOURNAL OF NEUROSCIENCE LA English DT Article DE syndecan; CASK/LIN-2; heparan sulfate proteoglycan; MAGUK; subcellular targeting; axon ID MOLECULE HB-GAM; N-SYNDECAN; BASOLATERAL MEMBRANE; EPITHELIAL-CELLS; RECEPTOR; NEUREXINS; FAMILY; ACTIVATION; ADHESION; COMPLEX AB The syndecan family of cell surface heparan sulfate proteoglycans interacts via their cytoplasmic C-terminal tail with the PDZ domain of CASK/LIN-2, a membrane-associated guanylate kinase homolog. The syndecan-CASK interaction may be involved in intercellular signaling and/or cell adhesion. Here we show that syndecan-1 to syndecan-4 have distinctive mRNA distributions in adult rat brain by in situ hybridization, with syndecan-2 and -3 being the major syndecans expressed in neurons of the forebrain. At the protein level, syndecan-2 and -3 are differentially localized within neurons; syndecan-3 is concentrated in axons, whereas syndecan-2 is localized in synapses. The synaptic accumulation of syndecan-2 occurs late in synapse development. CASK is a cytoplasmic-binding partner for syndecans, and its subcellular distribution changes strikingly during development, shifting from a primarily axonal distribution in the first 2 postnatal weeks to a somatodendritic distribution in adult brain. This change in CASK distribution correlates temporally and spatially with the expression patterns of syndecan-3 and -2, consistent with the association of both of these syndecans with CASK in vivo. In support of this, we were able to coimmunoprecipitate a complex of CASK and syndecan-3 from brain extracts. Our results indicate that specific syndecans are differentially expressed in various cell types of the brain and are targeted to distinct subcellular compartments in neurons, where they may serve specialized functions. Moreover, CASK is appropriately expressed and localized to interact with both syndecan-2 and -3 in different compartments of the neuron throughout postnatal development. 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. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 423,50 Blossom St, Boston, MA 02114 USA. OI Hsueh, Yi-Ping/0000-0002-0866-6275 FU NINDS NIH HHS [NS35050] NR 35 TC 137 Z9 139 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 1999 VL 19 IS 17 BP 7415 EP 7425 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 233TL UT WOS:000082442600021 PM 10460248 ER PT J AU Hug, EB Loredo, LN Slater, JD DeVries, A Grove, RI Schaefer, RA Rosenberg, AE Slater, JM AF Hug, EB Loredo, LN Slater, JD DeVries, A Grove, RI Schaefer, RA Rosenberg, AE Slater, JM TI Proton radiation therapy for chordomas and chondrosarcomas of the skull base SO JOURNAL OF NEUROSURGERY LA English DT Article DE chordoma; chondrosarcoma; skull base tumor; charged-particle therapy; radiation therapy; proton ID CERVICAL-SPINE; FOLLOW-UP; IRRADIATION; PHOTON; TUMORS AB Object. Local tumor control, patient survival, and treatment failure outcomes were analyzed to assess treatment efficacy in 58 patients in whom fractionated proton radiation therapy (RT) was administered for skull base chordomas and chondrosarcomas. Methods. Between March 1992 and January 1998, a total of 58 patients who could be evaluated were treated for skull base tumors, 33 for chordoma and 25 for chondrosarcoma. Following various surgical procedures, residual tumor was detected in 91% of patients; 59% demonstrated brainstem involvement. Target dosages ranged from 64.8 and 79.2 (mean 70.7) Co Gy equivalent. The range of follow up was 7 to 75 months (mean 33 months). In 10 patients (17%) the treatment failed locally, resulting in local control rates of 92% (23 of 25 patients) for chondrosarcomas and 76% (25 of 33 patients) for chordomas. Tumor volume and brainstem involvement influenced control rates. All tumors with volumes of 25 mi or less remained locally controlled, compared with 56% of tumors larger than 25 mi (p = 0.02); 94% of patients without brainstem involvement did not experience recurrence; in patients with brainstem involvement land dose reduction because of brainstem tolerance constraints) the authors achieved a tumor control rate of 53% (p = 0.04). Three patients died of their disease, and one died of intercurrent disease. Actuarial 5-year survival rates were 100% for patients with chondrosarcoma and 79% for patients with chordoma. Grade 3 and 4 late toxicities were observed in four patients (7%) and were symptomatic in three (5%). Conclusions. High-dose proton RT offers excellent chances of lasting tumor control and survival, with acceptable risks. In this series all small- and medium-sized tumors with no demonstrable brainstem involvement have been controlled; all such patients are alive. Surgical debulking enhanced delivery of full tumoricidal doses, but even patients with large tumors and disease abutting crucial normal structures benefited. C1 Loma Linda Univ, Med Ctr, Dept Radiat Med, Loma Linda, CA 92354 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Innsbruck, Dept Radiat Therapy, A-6020 Innsbruck, Austria. RP Hug, EB (reprint author), Loma Linda Univ, Med Ctr, Dept Radiat Med, 11234 Anderson St, Loma Linda, CA 92354 USA. EM ehug@dominion.llumc.edu NR 32 TC 237 Z9 243 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 1999 VL 91 IS 3 BP 432 EP 439 DI 10.3171/jns.1999.91.3.0432 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 232WN UT WOS:000082393100012 PM 10470818 ER PT J AU McCowen, KC Glickman, JN Black, PM Zervas, NT Lidov, HGW Garber, JR AF McCowen, KC Glickman, JN Black, PM Zervas, NT Lidov, HGW Garber, JR TI Gangliocytoma masquerading as a prolactinoma - Case report SO JOURNAL OF NEUROSURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Clinical-Endocrinology CY 1998 CL ORLANDO, FLORIDA SP Amer Assoc Clin Endocrinol DE gangliocytoma; prolactinoma; bromocriptine; synaptophysin; neurofilament ID HYPOTHALAMIC NEURONAL HAMARTOMA; PITUITARY-ADENOMA; CUSHINGS-DISEASE; CHORISTOMA; FOSSA; GLAND AB The authors describe the case of a 36-year-old man who presented with bitemporal hemianopsia and a serum prolactin concentration of 1440 ng/ml. Magnetic resonance imaging of the pituitary revealed a presumed macroadenoma with suprasellar and temporal lobe extension. Although the patient's prolactin level was lowered to 55 ng/ml by bromocriptine therapy, no tumor shrinkage occurred. Fourteen months later, progression of visual field defects necessitated transsphenoidal resection, which was incomplete. Immunocytochemical analysis of the biopsy tissue was positive for prolactin and, in view of the clinical picture, more detailed analysis was not performed. External-beam radiotherapy was given 2 years later because of enlargement of residual tumor. Subsequently, despite a fall in the serum prolactin concentration to less than 20 ng/ml in response to the course of bromocriptine, the mass displayed further extension into the temporal lobe. Nine years after the patient's initial presentation, he underwent transfrontal craniotomy for sudden deterioration in visual acuity caused by hemorrhage into the mass. No adenohypophyseal tissue was identified in the resected tissue. The mass was composed of dysplastic neurons that were strongly immunoreactive for synaptophysin and neurofilament (indicating neural differentiation) and prolactin. Review of the original biopsy specimen indicated that the prolactin-positive cells had striking neuronal morphological characteristics. The final diagnosis in this case is prolactin-secreting gangliocytoma. Although exceedingly rare, this disease must be added to the differential diagnosis in cases of "prolactinoma" when bromocriptine therapy is followed by a marked decline in serum prolactin that is not accompanied by significant tumor shrinkage. Furthermore, in such instances, consideration should be given to obtaining a biopsy sample prior to electing for radiotherapy. C1 Harcard Vanguard Med Associates, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McCowen, KC (reprint author), Joslin Diabet Ctr, Metab Sect, 1 Joslin Pl, Boston, MA 02215 USA. NR 23 TC 23 Z9 25 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 1999 VL 91 IS 3 BP 490 EP 495 DI 10.3171/jns.1999.91.3.0490 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 232WN UT WOS:000082393100020 PM 10470826 ER PT J AU Bode, BP Souba, WW AF Bode, BP Souba, WW TI Glutamine transport and human hepatocellular transformation SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article; Proceedings Paper CT International Symposium on Growth Factors and Nutrients in Intestinal Health and Disease CY OCT 31-NOV 03, 1998 CL OSAKA, JAPAN ID AMINO-ACID-TRANSPORT; PERFUSED-RAT-LIVER; HUMAN HEPATOMA-CELLS; NITROGEN-METABOLISM; CIRRHOTIC LIVER; HETEROGENEITY; AMMONIA; SYSTEM; ORGANIZATION; HEPATOCYTES AB Among other functions, the liver serves to regulate both glucose and nitrogen economy in the body, and in humans, the amino acid glutamine is a major gluconeogenic substrate and the primary extrahepatic ammonia shuttle. Accordingly, the liver acinus possesses a unique heterogeneous metabolic architecture suited to carry out these functions with glutamine-consuming urea cycle and gluconeogenic enzymes in the periportal hepatocytes and a high capacity for glutamine synthesis in the perivenous hepatocytes, resulting in net glutamine balance across the hepatic bed under most conditions. Cytoplasmic levels of glutamine are significantly governed by the activity of the System N transporter in the plasma membrane of parenchymal cells; in this capacity, this glutamine carrier has been shown to represent a rate-limiting step in metabolism via glutaminase. The unique properties of System N allow it to rapidly adapt in support of the dynamic demands of whole body ammonia and glucose homeostasis. In contrast to System N in normal hepatocytes, human hepatoma cells take up glutamine at rates severalfold faster through a broad-specificity higher affinity transporter with characteristics of System ASC or B-0. It is currently hypothesized that the expression of this high activity carrier by hepatoma cells combined with accelerated metabolism and tumor-induced derangements in hepatocellular architecture result in net glutamine consumption, and may underlie the diminished plasma glutamine levels observed in patients with hepatocellular carcinoma (HCC). The transport of glutamine through System ASC has been shown to regulate growth in some human hepatoma cells, which suggests this transporter may warrant consideration as a therapeutic target for HCC. C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bode, BP (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Gray Jackson 918,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [1R29 CA69505] NR 45 TC 16 Z9 18 U1 0 U2 0 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD SEP-OCT PY 1999 VL 23 IS 5 SU S BP S33 EP S37 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 231UJ UT WOS:000082328900009 PM 10483891 ER PT J AU Hoppin, AG Kaplan, LM AF Hoppin, AG Kaplan, LM TI The leptin era: New insight into the mechanisms of body weight homeostasis SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Review ID IDIOPATHIC INTRACRANIAL HYPERTENSION; PROOPIOMELANOCORTIN MESSENGER-RNA; BETA-3 ADRENERGIC-RECEPTOR; INFLAMMATORY BOWEL-DISEASE; EARLY-ONSET OBESITY; MASS INDEX; NEUROPEPTIDE-Y; FOLLOW-UP; OB GENE; FOOD-INTAKE C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Boston, MA USA. RP Hoppin, AG (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ-802,32 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [AI33455]; NIDDK NIH HHS [DK02671, DK43351] NR 163 TC 7 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD SEP PY 1999 VL 29 IS 3 BP 250 EP 264 DI 10.1097/00005176-199909000-00005 PG 15 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 226VM UT WOS:000082043300005 PM 10467989 ER PT J AU Baldessarini, RJ Viguera, AC Tondo, L AF Baldessarini, RJ Viguera, AC Tondo, L TI Discontinuing psychotropic agents SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Editorial Material ID RISK C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Psychiat Res Labs, Mailman Res Ctr, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Perinatal Psychopharmacol Unit, Belmont, MA 02478 USA. Univ Cagliari, Sardinia, Italy. RP Baldessarini, RJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. FU NIMH NIH HHS [MH-47370] NR 9 TC 8 Z9 8 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 1999 VL 13 IS 3 BP 292 EP 293 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 236QL UT WOS:000082610000015 PM 10512088 ER PT J AU Bardgette, J Abboud, HE Choudhury, GG AF Bardgette, J Abboud, HE Choudhury, GG TI Activation of STAT1 alpha by phosphatase inhibitor vanadate in glomerular mesangial cells: Involvement of tyrosine and serine phosphorylation SO JOURNAL OF RECEPTOR AND SIGNAL TRANSDUCTION RESEARCH LA English DT Article ID GROWTH-FACTOR; INSULINOMIMETIC AGENTS; SIGNALING PROTEINS; RAT ADIPOCYTES; KINASE; TRANSCRIPTION; STAT3; RECEPTOR; PATHWAYS; REQUIRES AB Vanadate is an insulinomimetic agent that has potent inhibitory effect on tyrosine phosphatases. We have recently demonstrated that low concentration of vanadate stimulates phosphotyrosine-dependent signal transduction pathways leading to gene expression and DNA synthesis in mesangial cells. To further examine the mechanisms by which vanadate activates mesangial cell, we studied its effect on signal transducer and activators of transcription (STAT). Incubation of lysates from vanadate-stimulated mesangial cells with a specific high affinity sis-inducible DNA element (SIE) resulted in the formation of protein-DNA complex. Supershift analysis using monoclonal antibody against STAT1 alpha showed its exclusive presence in the DNA-protein complex. Incubation of cell lysate with antiphosphotyrosine antibody or with excess phosphotyrosine caused decrease in binding of STAT1 alpha to SIE probe indicating that tyrosine phosphorylation and dimerization of this transcription factor are necessary for its activation. Immunoprecipitation followed by immunecomplex kinase assay showed increased tyrosine kinase activity of Janus kinase 2 (JAK2) in vanadate-treated mesangial cells. The addition of a monoclonal antiphosphoserine antibody to lysates from vanadate-treated mesangial cells results in supershift of protein-DNA complex indicating the presence of serine phosphorylated STAT1 alpha in this complex. Treatment of lystates from vanadated-stimulated mesangial cells with serine phosphatase PP2A causes inhibition of DNA-protein interaction. Collectively, our data indicate that at least one mechanism of activation of mesangial cells during vanadate treatment is increased activation of STAT la by both tyrosine and serine phosphorylation. C1 S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78284 USA. RP Choudhury, GG (reprint author), S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. FU NIDDK NIH HHS [DK-50190, DK-43988] NR 32 TC 7 Z9 7 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1079-9893 J9 J RECEPT SIGNAL TR R JI J. Recept. Signal Transduct. Res. PD SEP PY 1999 VL 19 IS 5 BP 865 EP 884 DI 10.3109/10799899909042878 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 198TN UT WOS:000080440500006 PM 10349599 ER PT J AU Bostic, JQ AF Bostic, JQ TI Depressive and disruptive disorders and mental health service utilization in children and adolescents - Commentary SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bostic, JQ (reprint author), Massachusetts Gen Hosp, Dept Child Psychiat, WAC 725,15 Parkman St, Boston, MA 02114 USA. NR 4 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 1999 VL 38 IS 9 BP 1090 EP 1092 DI 10.1097/00004583-199909000-00011 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 230DY UT WOS:000082237600011 ER PT J AU Tanew, A Ortel, B Honigsmann, H AF Tanew, A Ortel, B Honigsmann, H TI Half-side comparison of erythemogenic versus suberythemogenic UVA doses in oral photochemotherapy of psoriasis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID METHOXSALEN-PHOTOCHEMOTHERAPY; PUVA THERAPY; SKIN-CANCER; FOLLOW-UP; 8-METHOXYPSORALEN; COMBINATION; ACITRETIN; EFFICACY; TRIAL; NM AB Background: Early American and European multicenter trials on the efficacy of photochemotherapy (PUVA) for psoriasis have clearly shown that the treatment protocol has a crucial impact on the cumulative LNA dose required for clearing patients, Most, if not ail, treatment protocols rely on the PUVA-induced erythema as a guideline for UVh dosimetry! Objective,: Our aim was to investigate whether phototoxic erythema is integral to an optimized PUVA protocol or reflects an unnecessary overexposure of patients. Methods: A standard high-dose WA regimen using minimal phototoxic, doses (hLPD) was compared against two different low-dose regimens. To this purpose a bilateral comparison study was performed on 31 patients and divided in two parts. In the first trial on 14 patients, half of each patient's body was irradiated at each visit with 1 MPD, whereas the other half received only two thirds of the MPD. In the second trial on 17 patients treatment with 1 MPD was compared against treatment with one half of the MPD. Results: A total of 27 patients (12 patients in the first trial, 15 patients in the second trial) completed the study In both trials the suberythemogenic doses were therapeutically as effective as the minimal phototoxic doses. Conclusions: We conclude that PUVA-induced erythema is not a prerequisite for effective psoriasis treatment and that a low-dose WA regimen is a promising approach to increase the short- and long-term safety of photochemotherapy. C1 Univ Vienna, Sch Med, Dept Dermatol, Div Special & Environm Dermatol, A-1090 Vienna, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP Tanew, A (reprint author), Univ Vienna, Sch Med, Dept Dermatol, Div Special & Environm Dermatol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. NR 43 TC 7 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 1999 VL 41 IS 3 BP 408 EP 413 DI 10.1016/S0190-9622(99)70113-1 PN 1 PG 6 WC Dermatology SC Dermatology GA 231WJ UT WOS:000082334200004 PM 10459114 ER PT J AU Moonka, R Stiens, SA Resnick, WJ McDonald, JM Eubank, WB Dominitz, JA Stelzner, MG AF Moonka, R Stiens, SA Resnick, WJ McDonald, JM Eubank, WB Dominitz, JA Stelzner, MG TI The prevalence and natural history of gallstones in spinal cord injured patients SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID GENERAL-POPULATION; RISK FACTOR; DISEASE; GALLBLADDER; CHOLELITHIASIS; CONTRACTILITY; PHYSIOLOGY; COMMUNITY; ABDOMEN AB Background: Individuals with a spinal cord injury are at increased risk for the development of gallstones. Because these patients cannot reliably manifest classic symptoms of biliary colic, they may be more likely to present with advanced biliary complications than patients with intact abdominal innervation. The natural history of gallstones in spinal cord injured patients has not been described. Study Design: All spinal cord injured patients seen at the Seattle Veterans Affairs Medical Center from January 1, 1993, to December 31, 1997 were included in the study. For each patient, the presence or absence of gallstones had been determined previously through screening abdominal ultrasonographic evaluations. Pertinent-demographic information was obtained from medical records and patient interviews. Patients with gallstones were followed until death, cholecystectomy, or the conclusion of the study, and the annual incidence of biliary complications and patients requiring a cholecystectomy were determined. The prevalence of gallstones was established by studying the subset of patients seen at the Seattle Spinal Cord Injury Unit from January 1, 1995 to December 31, 1997 Results: Among the spinal cord injured patients, 31% either had gallstones or had undergone a cholecystectomy at some point after their injury. Increasing age, female gender, and greater severity of injury were risk factors for the formation of gallstones. Over the first 5 years after the diagnosis of gallstones, the annual incidence of cholecystectomy or biliary complications was 6.3% and 2.2%, respectively. Conclusions: Spinal cord injured patients are at-increased risk for the development of gallstones. Patients with gallstones are at an increased risk for the development of biliary complications compared with neurologically intact patients, but the magnitude of this risk does not warrant prophylactic cholecystectomy. (J Am Cell Surg 1999;189:274-281. (C) 1999 by the American College of Surgeons). C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Dept Surg,Div Gen Surg, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Dept Med,Div Gastroenterol, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Dept Radiol, Seattle, WA 98195 USA. RP Moonka, R (reprint author), Virginia Mason Med Ctr, 1100 9th Ave,POB 900, Seattle, WA 98111 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 38 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 1999 VL 189 IS 3 BP 274 EP 281 DI 10.1016/S1072-7515(99)00143-X PG 8 WC Surgery SC Surgery GA 230EK UT WOS:000082238700007 PM 10472928 ER PT J AU Hester, EJ Cook, DR Robbins, LJ AF Hester, EJ Cook, DR Robbins, LJ TI The VA and medicare HMOs: Complimentary or redundant? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1999 VL 47 IS 9 MA P151 BP S49 EP S49 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233LU UT WOS:000082429000219 ER PT J AU Piper, PK Royall, DR Chiodo, LK AF Piper, PK Royall, DR Chiodo, LK TI Longitudinal impact of depressive symptoms among elderly retirees SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1999 VL 47 IS 9 MA P300 BP S86 EP S86 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 233LU UT WOS:000082429000367 ER PT J AU Ha, TS Barnes, JL Stewart, JL Ko, CW Miner, JH Abrahamson, DR Sanes, JR Kasinath, BS AF Ha, TS Barnes, JL Stewart, JL Ko, CW Miner, JH Abrahamson, DR Sanes, JR Kasinath, BS TI Regulation of renal laminin in mice with type II diabetes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCAN; GLOMERULAR EPITHELIAL-CELLS; BASEMENT-MEMBRANE; GENE-EXPRESSION; MESANGIAL CELLS; MESSENGER-RNA; HIGH GLUCOSE; PROLIFERATIVE GLOMERULONEPHRITIS; S-LAMININ; RATS AB This study examines the regulation of renal laminin in the db/db mouse, a model of type II diabetes characterized by extensive remodeling of extracellular matrix. Immunohistochemistry demonstrated an increase in the contents of laminin chains including beta 1 chain in the mesangium and tubular basement membranes at 1, 2, 3, and 4 mo of diabetes. Immunofluorescence with an antibody against the recently discovered laminin alpha 5 chain showed that in the normal mouse, the protein had a restricted distribution to the glomerular and tubular basement membranes with scant expression in the mesangium of older mice. In the diabetic mouse, the laminin alpha 5 chain content of the glomerular and tubular basement membranes was increased, with marked expression in the mesangium. Northern analysis revealed a significant decrease in the renal cortical contents of alpha 5, beta 1, and gamma 1 chain mRNA in the diabetic mice compared to control, at each of the time points. In situ hybridization showed decreased abundance of alpha 5 transcripts in the glomeruli of diabetic mice compared to nondiabetic controls. Analysis of mRNA changes by Northern and in situ hybridization studies demonstrated that the reduction in laminin transcripts involved both glomerular and tubular elements. These observations demonstrate that laminin accumulation in the db/db mice with type II diabetes is due to nontranscriptional mechanisms. Because previous investigations in rodents with type I diabetes have shown that the increase in renal laminin content was associated with a corresponding increment in laminin chain transcript levels, it appears that the mechanisms underlying augmentation in renal matrix laminin content may be distinct in the two types of diabetes. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. AL Murphy Vet Adm Hosp, San Antonio, TX USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. RP Kasinath, BS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 37 TC 34 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1999 VL 10 IS 9 BP 1931 EP 1939 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 229UB UT WOS:000082213200010 PM 10477145 ER PT J AU Geys, H Molenberghs, G Ryan, LM AF Geys, H Molenberghs, G Ryan, LM TI Pseudolikelihood modeling of multivariate outcomes in developmental toxicology SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE clustered multivariate binary data; fractional polynomial; likelihood; normalizing constant ID CLUSTERED BINARY DATA; SAMPLE SURVEY DATA; LOGISTIC-REGRESSION; LIKELIHOOD; TOXICITY; TERATOLOGY; GLYCOL; TESTS; MICE AB The primary goal of this article is to determine benchmark doses based on the ethylene glycol study, which comprises data from a developmental toxicity study in mice. Because the data involve a vector of malformation indicators, a flexible model for multivariate clustered data is required. An exponential family model is considered and pseudolikelihood-based inferential tools are proposed, hence avoiding excessive computational requirements. C1 Limburgs Univ Ctr, Ctr Stat, B-3590 Diepenbeek, Belgium. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Geys, H (reprint author), Limburgs Univ Ctr, Ctr Stat, Univ Campus, B-3590 Diepenbeek, Belgium. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 39 TC 57 Z9 58 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 1999 VL 94 IS 447 BP 734 EP 745 DI 10.2307/2669986 PG 12 WC Statistics & Probability SC Mathematics GA 239ET UT WOS:000082756400014 ER PT J AU Chen, MH Ibrahim, JG Sinha, D AF Chen, MH Ibrahim, JG Sinha, D TI A new Bayesian model for survival data with a surviving fraction SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE cure rate model; Gibbs sampling; historical data; latent variables; posterior distribution; Weibull distribution ID NATURAL EXPONENTIAL-FAMILIES; QUADRATIC VARIANCE FUNCTIONS; MIXTURE-MODELS; CURE; TESTS; REGRESSION; RISK AB We consider Bayesian methods for right-censored survival data for populations with a surviving (cure) fraction. We propose a model that is quite different from the standard mixture model for cure rates. We provide a natural motivation and interpretation of the model and derive several novel properties of it. First, we show that the model has a proportional hazards structure, with the covariates depending naturally on the cure rate. Second, we derive several properties of the hazard function for the proposed model and establish mathematical relationships with the mixture model for cure rates. Prior elicitation is discussed in detail, and classes of noninformative and informative prior distributions are proposed. Several theoretical properties of the proposed priors and resulting posteriors are derived, and comparisons are made to the standard mixture model. A real dataset from a melanoma clinical trial is discussed in detail. C1 Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ New Hampshire, Dept Math, Durham, NH 03824 USA. RP Chen, MH (reprint author), Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. NR 24 TC 168 Z9 170 U1 1 U2 13 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 1999 VL 94 IS 447 BP 909 EP 919 DI 10.2307/2670006 PG 11 WC Statistics & Probability SC Mathematics GA 239ET UT WOS:000082756400034 ER PT J AU Rebbeck, TR Levin, AM Eisen, A Snyder, C Watson, P Cannon-Albright, L Isaacs, C Olopade, O Garber, JE Godwin, AK Daly, MB Narod, SA Neuhausen, SL Lynch, HT Weber, BL AF Rebbeck, TR Levin, AM Eisen, A Snyder, C Watson, P Cannon-Albright, L Isaacs, C Olopade, O Garber, JE Godwin, AK Daly, MB Narod, SA Neuhausen, SL Lynch, HT Weber, BL TI Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OVARIAN-CANCER; GERMLINE MUTATIONS; HYSTERECTOMY; WOMEN; GENE AB Background: The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. Methods: We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and gear of birth. Results: We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33-0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0.28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12-0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. Conclusions: Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations. C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Karmanos Canc Inst, Detroit, MI USA. Creighton Univ, Dept Prevent Med, Omaha, NE 68178 USA. Univ Utah, Dept Genet Epidemiol, Salt Lake City, UT USA. Georgetown Univ, Dept Med, Washington, DC USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Dana Farber Canc Inst, Dept Canc Epidemiol & Control, Boston, MA 02115 USA. Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, 904 Blockley Hall,23 Guardian Dr, Philadelphia, PA 19104 USA. OI albright, lisa/0000-0003-2602-3668 FU NCI NIH HHS [CA74415, CA57601, P30CA16520] NR 16 TC 403 Z9 409 U1 3 U2 19 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 SEP 1 PY 1999 VL 91 IS 17 BP 1475 EP 1479 DI 10.1093/jnci/91.17.1475 PG 5 WC Oncology SC Oncology GA 232NU UT WOS:000082377500010 PM 10469748 ER PT J AU Rehring, TF Winter, CB Chambers, JA Bourg, PW Wachtel, TL AF Rehring, TF Winter, CB Chambers, JA Bourg, PW Wachtel, TL TI Osteomyelitis and mediastinitis complicating blunt sternal fracture SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID CARDIOPULMONARY-RESUSCITATION; MANAGEMENT; EXPERIENCE; FLAPS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Vasc Surg, Boston, MA 02114 USA. Univ Colorado, Hlth Sci Ctr, St Anthonys Hosp, Dept Surg, Denver, CO USA. RP Rehring, TF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Vasc Surg, Boston, MA 02114 USA. NR 17 TC 4 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD SEP PY 1999 VL 47 IS 3 BP 594 EP 596 DI 10.1097/00005373-199909000-00034 PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 236PL UT WOS:000082607700037 PM 10498324 ER PT J AU Kaufman, JA Brewster, DC Geller, SC Fan, CM Cambria, RP Abbott, WA Waltman, AC AF Kaufman, JA Brewster, DC Geller, SC Fan, CM Cambria, RP Abbott, WA Waltman, AC TI Custom bifurcated stent-graft for abdominal aortic aneurysms: Initial experience SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE aorta, grafts and prostheses; stents and prostheses; aneurysms, aortic; angiography ID LIFE TABLE METHOD; AORTOILIAC ANEURYSMS; ENDOVASCULAR REPAIR; PLACEMENT AB PURPOSE: To describe a custom bifurcated stent-graft for possible treatment of abdominal aortic aneurysm (AAA), MATERIALS AND METHODS: Five male patients (mean age, 76 +/- 6 years), who had AAA (mean diameter, 4.7 +/- 0.4 cm) and who were considered to be at high risk for conventional surgery, were treated with a custom medullar bifurcated stent-graft constructed with bifurcated 24-mm x 12-mm (upper body diameter x iliac limb diameter) Cooley Veri-Soft Woven polyester grafts and Gianturco-Rosch Z stents, The stent-graft body was delivered through 20-22-F sheaths, and the contralateral iliac limb was delivered through a 16-F sheath by means of surgical exposure of the common femoral arteries. A flared distal limb extender (12 mm to 14 mm) was created for one patient to accommodate a large common iliac artery. RESULTS: Stent-grafts were successfully deployed without complications in all five patients. There were no proximal or distal leaks. A lumbar-to-inferior mesenteric artery leak was seen in one patient at 24 hours. At B-month follow-up, all devices were intact, with complete exclusion and shrinkage of the aneurysm in four of five patients. Aneurysm size remained stable in the one patient with a lumbar-to-inferior mesenteric artery leak. CONCLUSION: A custom, bifurcated stent-graft was utilized for endovascular treatment of AAA, Long-term follow-up is necessary for the device. C1 Massachusetts Gen Hosp, Dept Radiol, Div Vasc Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Vasc Surg, Dept Surg, Boston, MA 02114 USA. RP Kaufman, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Vasc Radiol, GRB 290, Boston, MA 02114 USA. NR 17 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 1999 VL 10 IS 8 BP 1099 EP 1106 DI 10.1016/S1051-0443(99)70198-3 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 234ZN UT WOS:000082514400016 PM 10496714 ER PT J AU Tseng, JF Cambria, RP Aretz, HT Brewster, DC AF Tseng, JF Cambria, RP Aretz, HT Brewster, DC TI Thoracoabdominal aortic aneurysm in Cogan's syndrome SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID PERSPECTIVES; PATHOGENESIS; REPAIR AB Cogan's syndrome is an autoimmune disease of unknown etiology, clinically manifested as non-syphilitic interstitial keratitis and audiovestibular symptoms. Increasing evidence suggests that Cogan's may be a systemic vasculitis. In this report, we review the vascular manifestations of Cogan's syndrome and report two cases of thoracoabdominal aortic aneurysm in patients with this disorder. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Vasc Surg, Boston, MA 02114 USA. RP Cambria, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Vasc Surg, Boston, MA 02114 USA. NR 12 TC 13 Z9 14 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 SEP PY 1999 VL 30 IS 3 BP 565 EP 568 DI 10.1016/S0741-5214(99)70086-8 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 234YP UT WOS:000082512200035 PM 10477652 ER PT J AU Blake, NW Moghaddam, A Rao, P Kaur, A Glickman, R Cho, YG Marchini, A Haigh, T Johnson, RP Rickinson, AB Wang, F AF Blake, NW Moghaddam, A Rao, P Kaur, A Glickman, R Cho, YG Marchini, A Haigh, T Johnson, RP Rickinson, AB Wang, F TI Inhibition of antigen presentation by the glycine/alanine repeat domain is not conserved in simian homologues of Epstein-Barr virus nuclear antigen 1 SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPHOCYTE GROWTH TRANSFORMATION; NF-KAPPA-B; IMMUNODEFICIENCY VIRUS; HERPESVIRUS PAPIO; T-LYMPHOCYTES; CELLS; PROTEIN; RESPONSES; INFECTION; EPITOPE AB Most humans and Old World nonhuman primates are infected for life with Epstein-Barr virus (EBV) or closely related gammaherpesviruses in the same lymphocryptoviros (LCV) subgroup. Several potential strategies for immune evasion and persistence have been proposed based on studies of EBV infection in humans, but it has been difficult to test their actual contribution experimentally. Interest has focused an the EBV nuclear antigen 1 (EBNA1) because of its essential role in the maintenance and replication of the episomal viral genome in latently infected cells and because EBNA1 endogenously expressed in these cells is protected from presentation to the major histocompatibility complex class-I restricted cytotoxic T-lymphocyte (CTL) response through the action of an internal glycine-alanine repeat (GAR). Given the high degree of biologic conservation among LCVs which infect humans and Old World primates, we hypothesized that strategies essential for viral persistence would be well conserved among viruses of this subgroup. We show that the rhesus LCV EBNA1 shares sequence homology with the EBV and baboon LCV EBNA1 and that the rhesus LCV EBNA1 is a functional homologue for EBV EBNA1-dependent plasmid maintenance and replication. Interestingly, all three LCVs possess a GAR domain, but the baboon and rhesus LCV EBNA1 GARs fail to inhibit antigen processing and presentation as determined by using three different in vitro CTL assays. These studies suggest that inhibition of antigen processing and presentation by the EBNA1 GAR may not be an essential mechanism for persistent infection by all LCV and that other mechanisms may be important for immune evasion during LCV infection. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Labs, Boston, MA 02115 USA. Univ Birmingham, Sch Med, CRC, Inst Canc Studies, Birmingham B15 2TA, W Midlands, England. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Dept Immunol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08544 USA. RP Wang, F (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA65319, CA68051, R01 CA068051]; NCRR NIH HHS [P51 RR000168, P51RR00168] NR 39 TC 38 Z9 40 U1 1 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 SEP PY 1999 VL 73 IS 9 BP 7381 EP 7389 PG 9 WC Virology SC Virology GA 225ME UT WOS:000081964700034 PM 10438828 ER PT J AU Ogris, E Mudrak, I Mak, E Gibson, D Pallas, DC AF Ogris, E Mudrak, I Mak, E Gibson, D Pallas, DC TI Catalytically inactive protein phosphatase 2A can bind to polyomavirus middle tumor antigen and support complex formation with pp60(c-src) SO JOURNAL OF VIROLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; SMALL-T-ANTIGENS; TYROSINE PHOSPHORYLATION; SACCHAROMYCES-CEREVISIAE; PHOSPHATIDYLINOSITOL KINASE; MUTATIONAL ANALYSIS; CELLULAR PROTEINS; HUMAN CALCINEURIN; OKADAIC ACID; SUBUNIT AB Interaction between the heterodimeric form of protein phosphatase 2A (PP2A) and polyomavirus middle T antigen (MT) is required for the subsequent assembly of a transformation-competent MT complex. To investigate the role of PP2A catalytic activity in MT complex formation, we undertook a mutational analysis of the PP2A 36-kDa catalytic C subunit. Several residues likely to be involved in the dephosphorylation mechanism were identified and mutated, The resultant catalytically inactive C subunit mutants were then analyzed for their ability to associate with a cellular (B subunit) or a viral (MT) B-type subunit, Strikingly, while all of the inactive mutants were severely impaired in their interaction with B subunit, most of these mutants formed complexes with polyomavirus MT. These findings indicate a potential role for these catalytically important residues in complex formation with cellular B subunit, but not in complex formation with MT. Transformation-competent MT is known to associate with, and modulate the activity of, several cellular proteins, including pp60(c-src) family kinases. To determine whether association of MT with an active PP2A A-C heterodimer is necessary for subsequent association with pp60(c-src), catalytically inactive C subunits were examined for their ability to form complexes containing pp60(c-src) in MT-expressing cells. Two catalytically inactive C subunit mutants that efficiently formed complexes with MT also formed complexes that included an active pp60(c-src) kinase, demonstrating that PP2A activity is not essential in cis in MT complexes for subsequent pp60(c-src) association. C1 Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Vienna, Inst Mol Biol, A-1030 Vienna, Austria. Emory Univ, Sch Med, Winship Canc Ctr, Atlanta, GA 30322 USA. RP Pallas, DC (reprint author), Emory Univ, Sch Med, Dept Biochem, 1510 Clifton Rd, Atlanta, GA 30322 USA. FU NCI NIH HHS [CA57327, R01 CA057327] NR 74 TC 33 Z9 33 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 SEP PY 1999 VL 73 IS 9 BP 7390 EP 7398 PG 9 WC Virology SC Virology GA 225ME UT WOS:000081964700035 PM 10438829 ER PT J AU Chung, RY Saeki, Y Chiocca, EA AF Chung, RY Saeki, Y Chiocca, EA TI B-myb promoter retargeting of herpes simplex virus gamma 34.5 gene-mediated virulence toward tumor and cycling cells SO JOURNAL OF VIROLOGY LA English DT Article ID CONFERS ENHANCED TUMORIGENICITY; HUMAN-MALIGNANT GLIOMA; PROTEIN-KINASE PKR; BRAIN-TUMORS; RIBONUCLEOTIDE REDUCTASE; THYMIDINE KINASE; IN-VIVO; NERVOUS-SYSTEM; DNA-SYNTHESIS; VIRAL MUTANT AB Deletion of the gamma 34.5 gene coding for virulence markedly reduces cytotoxicity mediated by herpes simplex virus type 1 (HSV-1) (J. M. Markert et al., Neurosurgery 32:597-603, 1993; N. S. Markovitz et at, J. Virol. 71:5560-5569, 1997), To target lytic virulence to tumors, we have created a novel HSV-1 mutant, designated Myb34.5. This viral mutant is characterized by a deletion of the gene for infected cell polypeptide 6 (ICP6; also known as UL39 or ribonucleotide reductase) and of the two endogenous copies of the gamma 34.5 gene (RL1) and by reintroduction of one copy of gamma 34,5 under control of the E2F-responsive, cellular B-myb promoter. On direct intracerebral inoculation in BALB/c mice, the 50% lethal dose (LD50) for Myb34,5 was 2.7 x 10(7) PFU while that for HSVs with mutations in the gamma 34,5 gene could not be technically achieved with available viral stocks and it was estimated as >1 x 10(7) PFU. The LD50 for an HSV with a single defect in ICP6 function was 1.3 x 10(6) PFU. Conversely, Myb34.5's oncolytic efficacy against a variety of human glioma cells in culture and in vivo was enhanced compared to that of HSVs with gamma 34.5 mutations, and in fact, it was comparable to that of the wild-type F strain and of viral mutants that possess a wild-type gamma 34.5 gene. The characteristic shutoff of host protein synthesis, occurring after infection of human SK-N-SH neuroblastoma cells by gamma 34,5 mutant viruses (J. Chou and B. Roizman, Proc. Natl. Acad. Sci. USA 89:3266-3270, 1992), was not present after infection with Myb34.5. There was an increase of almost 3 logarithmic units in the production of progeny virus in arrested fibroblasts compared to that in cycling fibroblasts infected with Myb34.5. These results suggest that transcriptional regulation of gamma 34.5 by cell cycle-regulated promoters can be used to target HSV-1 virulence toward tumors while maintaining the desirable neuroattenuated phenotype of a gamma 34.5 mutant. C1 Massachusetts Gen Hosp, Neurosurg Serv, Mol Neurooncol Labs, Charlestown, MA 02129 USA. RP Chiocca, EA (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Mol Neurooncol Labs, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA6924602] NR 53 TC 85 Z9 89 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 SEP PY 1999 VL 73 IS 9 BP 7556 EP 7564 PG 9 WC Virology SC Virology GA 225ME UT WOS:000081964700051 PM 10438845 ER PT J AU Ubel, PA AF Ubel, PA TI The challenge of measuring community values in ways appropriate for setting health care priorities SO KENNEDY INSTITUTE OF ETHICS JOURNAL LA English DT Article ID COST-EFFECTIVENESS; PUBLIC-ATTITUDES; DECISION-MAKING; TRANSPLANTATION; EQUITY; OREGON; ELICITATION; PREFERENCES; ALLOCATION; PHYSICIANS AB The move from a notion that community values ought to play a role in health care decision making to the creation of health care policies that in some way reflect such values is a challenging one. No single method will adequately measure community values in a way appropriate for setting health care priorities. Consequently, multiple methods to measure community values should be employed, thereby allowing the strengths and weaknesses of the various methods to complement each other. A preliminary research agenda to bring together empirical research on community values with more traditional research on health care ethics is outlined, with the goal of identifying and measuring acceptable community values that are relatively consistent across measurement methods and, ultimately developing ways to incorporate these values into health care priority decision making. C1 Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Ubel, PA (reprint author), Vet Affairs Med Ctr, Philadelphia, PA USA. NR 44 TC 19 Z9 19 U1 1 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1054-6863 J9 KENNEDY INST ETHIC J JI Kennedy Inst. Ethics J. PD SEP PY 1999 VL 9 IS 3 BP 263 EP 284 DI 10.1353/ken.1999.0021 PG 22 WC Ethics; Philosophy; Social Issues SC Social Sciences - Other Topics; Philosophy; Social Issues GA 254UG UT WOS:000083630100004 PM 11657717 ER PT J AU Kelly, KJ Meehan, SM Colvin, RB Williams, WW Bonventre, JV AF Kelly, KJ Meehan, SM Colvin, RB Williams, WW Bonventre, JV TI Protection from toxicant-mediated renal injury in the rat with anti-CD54 antibody SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Society-of-Nephrology CY NOV 03-06, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Soc Nephrol DE nephrotoxicity; acute renal failure; intercellular adhesion molecule-1; adhesion receptors; cisplatin toxicity; leukocyte ID INTERCELLULAR-ADHESION MOLECULE-1; CISPLATIN NEPHROTOXICITY; REPERFUSION INJURY; CLINICAL-TRIALS; TUBULAR CELLS; CIS-PLATINUM; FAILURE; TOXICITY; ICAM-1; KIDNEY AB Background. The benefit of the potent chemotherapeutic agent cisplatin in treating neoplasms is limited by nephrotoxicity. We tested the hypothesis that CD54 [intercellular adhesion molecule-1 (ICAM-1)] is an important mediator in cisplatin-mediated renal failure. Methods. The effect of a monoclonal anti-CD54 antibody was evaluated in a rat model of cisplatin toxicity. Renal function, histopathology, renal myeloperoxidase activity, and mortality were determined in the anti-CD54 and placebo groups. Results. Renal CD54 mRNA expression was markedly increased by 24 hours after exposure to cisplatin in mice. An improvement in renal function, mortality, and histological abnormalities was evident in animals exposed to cisplatin and treated with anti-CD54 antibody (mAb). Seven days after the administration of cisplatin, the mean creatinine was 0.65 +/- 0.05 mg/dl in the rats that received anti-CD54 mAb and 4.76 +/- 1.42 in control animals (P < 0.02). Mortality was lower in experimental animals (0 vs. 29% in control rats seven days following cisplatin, P < 0.04). Histological evidence of cell injury was markedly attenuated (P < 0.04) in the treated compared with the control rats. Conclusion. CD54 may be critical in the pathophysiology of renal injury following cisplatin, perhaps by its effects on leukocyte-endothelial interactions. C1 Univ Cincinnati, Coll Med, Div Nephrol & Hypertens, Dept Internal Med, Cincinnati, OH 45267 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Med Serv, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Pathol Serv, Boston, MA USA. RP Kelly, KJ (reprint author), Univ Cincinnati, Coll Med, Div Nephrol & Hypertens, Dept Internal Med, 231 Bethesda Ave,POB 670585, Cincinnati, OH 45267 USA. FU NIDDK NIH HHS [DK39773, DK02364, T32DK07540] NR 47 TC 64 Z9 64 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1999 VL 56 IS 3 BP 922 EP 931 DI 10.1046/j.1523-1755.1999.00629.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 228CN UT WOS:000082119300012 PM 10469360 ER PT J AU Nielsen, GP Stemmer-Rachamimov, AO Shaw, J Roy, JE Koh, J Louis, DN AF Nielsen, GP Stemmer-Rachamimov, AO Shaw, J Roy, JE Koh, J Louis, DN TI Immunohistochemical survey of p16(INK4A) expression in normal human adult and infant tissues SO LABORATORY INVESTIGATION LA English DT Article ID TUMOR-SUPPRESSOR GENE; KINASE-4 INHIBITOR GENE; HOMOZYGOUS DELETIONS; MTS1 P16(INK4A); RB ALTERATIONS; HUMAN CANCERS; CELL; MUTATIONS; P16; SENESCENCE AB p16(INK4A) is a cell cycle inhibitor that is commonly inactivated in human tumors and tumor cell lines. Despite its importance in human neoplasia, the normal pattern of p16 expression remains largely unknown. Therefore, we analyzed the immunohistochemical localization of p16 in all human organs and demonstrated that cellular p16 expression is highly selective. In adults, proliferative endometrium, breast ductal epithelium, squamous and tubal metaplastic epithelium of the uterine cervix, esophageal squamous epithelium, salivary glands, and antral gastric glands all strongly express the protein. p16 is also widely expressed in endocrine glands, including Langerhans cells in the pancreas and anterior pituicytes and Leydig and Sertoli cells in testis. Within each tissue, however, p16 expression does not correlate with cellular proliferation or maturation. In infants, p16 staining was limited to thymic Hassall's corpuscles, occasional thymic lymphocytes, and only rare pancreatic epithelial cells. Therefore, increased expression of p16 in adult tissues, as in mouse tissues, may reflect a role of p16 in cellular senescence. Restriction of p16 expression in infants to the thymus, the only organ committed to early senescence, is also consistent with such a role. Documentation of the pattern of p16 expression in normal tissues will contribute to our understanding of the normal function of this protein and to interpretation of potentially altered p16 expression in human tumors. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Vermont, Ctr Canc, Burlington, VT USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp E, Mol Neurooncol Lab, CNY6,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA57683]; NINDS NIH HHS [NS24279] NR 37 TC 130 Z9 133 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD SEP PY 1999 VL 79 IS 9 BP 1137 EP 1143 PG 7 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 236CU UT WOS:000082581300013 PM 10496532 ER PT J AU Hadlock, T Sundback, C Koka, R Hunter, D Cheney, M Vacanti, J AF Hadlock, T Sundback, C Koka, R Hunter, D Cheney, M Vacanti, J TI A novel, biodegradable polymer conduit delivers neurotrophins and promotes nerve regeneration SO LARYNGOSCOPE LA English DT Article DE inosine; polymers; nerve regeneration; biodegradable; slow release ID RAT AB Objective/Hypothesis: A wide variety of substances have been shown to promote neuritic extension after nerve injury, An obstacle to achieving the maximal benefit from these substances has been the difficulty in effectively delivering the substances over a protracted time course that promotes maximal, directed growth. In this study the delivery of a growth-promoting substance through a biodegradable conduit, using materials originally designed for drug delivery applications, was hypothesized to promote more robust neural regeneration than through conduits lacking the substance. The objectives of this study were to create a growth factor-loaded biodegradable nerve guidance conduit, and to assess in vivo nerve regeneration through the conduit compared with that through conduits lacking the substance. Materials/Methods: Inosine, a purine analogue thought to promote axonal extension following neural injury, was loaded into cylindrical polymer foams composed of a polylactide-co-glycolide copolymer. First, in vitro extravasation of inosine was measured over a several week period using spectrophotometry. Second, the foams were fashioned into single-channel cylindrical nerve guidance conduits via a novel, low-pressure injection molding technique. The conduits were then used to bridge 7-mm defects in the rat sciatic nerve (n=8), Control conduits lacking inosine were implanted into another set of animals as controls (n=12). Results: In vitro spectrophotometric measurements indicated appreciable leaching of inosine from the loaded foams over a period of at least 9 weeks. In the in vivo model, after 10 weeks, a higher percentage cross sectional area composed of neural tissue existed through the inosine-loaded conduits compared with controls (mean 44%, SD 7.5% vs. 36%, SD 8.6%, respectively). A difference was also found in mean fiber diameter between the two groups, with the inosine-loaded tubes showing a statistically significantly larger diameter than controls (P < .05), Conclusions: A nerve regeneration conduit was successfully created that delivers growth promoting substances over a protracted time course, In an in vivo model, the presence of inosine, a purine analogue, yielded neural regeneration whose histological features suggest possible superior long-term motor function. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Washington Univ, Dept Plast Surg, St Louis, MO USA. RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 45 Z9 48 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 1999 VL 109 IS 9 BP 1412 EP 1416 DI 10.1097/00005537-199909000-00010 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 233AT UT WOS:000082403900010 PM 10499046 ER PT J AU Busaba, NY Salman, SD AF Busaba, NY Salman, SD TI Maxillary sinus mucoceles: Clinical presentation and long-term results of endoscopic surgical treatment SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 29-31, 1999 CL PROVIDENCE, RHODE ISLAND SP Amer Laryngol Rhinol & Otol Soc, Eastern Sect DE maxillary sinus; mucocele; endoscopic sinus surgery ID PARA-NASAL SINUSES; ANTRAL MUCOCELE AB Objective: To describe the clinical presentation of maxillary sinus mucoceles, understand their pathogenesis, and determine the long-term efficacy of the endoscopic surgical treatment, Study Design: Retrospective review, Methods: Thirteen consecutive patients who presented with maxillary sinus muco(pyo) celes were studied. Subjects with history of preceding sinus/nasal surgery or facial trauma were excluded, The presenting signs and symptoms, radiological findings, and surgical management were reviewed, Results: There were six women and seven men with an age range of 31 to 71 years. Two patients had environmental allergies, Nine patients complained of cheek pressure, or pain, six of nasal obstruction, and eight of nasal drainage. On endoscopic nasal examination, the medial wall of maxillary sinus was bulging with prolapsed middle meatal mucosa in 10; drainage was seen in 7,but none had polyps. The sinus involvement was limited to the maxillary sinus and the ipsilateral ethmoid on computed tomographic studies ill 10 cases, Patients were treated with endoscopic ethmoidectomy, middle meatal antrostomy, and marsupialization of the mucocele, Intraoperative cultures grew organisms in five patients. Postoperative follow-up ranged between 10 and 66 months. Two patients required lysis of adhesions in the middle meatus, and one, revision antrostomy, All patients had a patent middle meatal antrostomy and healthy maxillary sinus mucosa at latest follow-up. The presenting symptoms resolved or improved in 12 cases. Conclusions: The etiology of maxillary sinus mucoceles is not well understood. Mechanical obstruction or allergy or both do not seem to play an important role,An infectious origin is also not supported by the above data. Endoscopic sinus surgery is a reliable therapeutic measure with a favorable long-term outcome. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Div Otolaryngol, W Roxbury, MA USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 26 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 1999 VL 109 IS 9 BP 1446 EP 1449 DI 10.1097/00005537-199909000-00017 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 233AT UT WOS:000082403900017 PM 10499053 ER PT J AU Garrido, L Young, VL AF Garrido, L Young, VL TI Analysis of periprosthetic capsular tissue from women with silicone breast implants by magic-angle spinning NMR SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE nuclear magnetic resonance; magic-angle spinning; periprosthetic tissue; silicone; breast implants ID AUGMENTATION MAMMAPLASTY; FILLED IMPLANTS; GEL; CONTRACTURE; PROSTHESES; MIGRATION; RECONSTRUCTION; DISEASES AB The amount of silicone (polydimethylsiloxane [PDMS]) in capsular tissue surgically removed from women with breast implants was measured by using Si-29 and H-1 magic-angle spinning solid-state NMR spectroscopy. Twelve women having smooth surface silicone gel-filled implants, including a subject with "low-bleed" double-lumen implants, had detectable levels of PDMS ranging from 0.05 to 9.8% silicon in wet tissue (w/w). No silicon-containing compounds other than PDMS were detected. No correlation was found between the amount of PDMS measured in the capsular tissue and the length of implantation time (Pearson correlation coefficient, r = 0.22). The results showed no relationship between higher amounts of PDMS and capsular contracture (p = 0.74) or other symptoms (p = 0.53). (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Biomat Lab, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA USA. Washington Univ, Sch Med, Cosmet Surg Ctr, St Louis, MO USA. RP Garrido, L (reprint author), Massachusetts Gen Hosp, NMR Ctr, Biomat Lab, 149 13th St, Charlestown, MA 02129 USA. RI Garrido, Leoncio/K-3092-2014 OI Garrido, Leoncio/0000-0002-7587-1260 FU NCI NIH HHS [CA 59651] NR 32 TC 10 Z9 10 U1 3 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 1999 VL 42 IS 3 BP 436 EP 441 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 232BR UT WOS:000082346300005 PM 10467287 ER PT J AU Mandeville, JB Marota, JJA AF Mandeville, JB Marota, JJA TI Vascular filters of functional MRI: Spatial localization using BOLD and CBV contrast SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; BOLD; CBV; iron oxide; forepaw ID CEREBRAL BLOOD-VOLUME; OXIDATIVE-METABOLISM; PHYSIOLOGICAL-BASIS; SIGNAL CHANGES; RAT-BRAIN; STIMULATION; FLOW; TOMOGRAPHY; SEPARATION AB The spatial distributions of functional activation of rat somatosensory cortex by forepaw stimulation were quantitatively compared using blood oxygen level dependent (BOLD) signal and signal weighted by cerebral blood volume (CBV). The BOLD contrast to noise (CNR) distribution showed a significant dorsal shift with respect to the CBV method at fields strengths of 2 T (0.69 +/- 0.09 mm) and 4.7 T (0.44 +/- 0.15 mm), These shifts were attributed to the gradient of resting state blood volume across somatosensory cortex and the different CNR characteristics of the two image methods. The underlying principles suggest that the CBV method has a more uniform sensitivity to percent changes in functional indicators (blood volume or deoxygenated hemoglobin) across regions of variable resting state CBV. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Mandeville, JB (reprint author), Massachusetts Gen Hosp, NMR Ctr, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIDA NIH HHS [DA09467, DA00384] NR 21 TC 85 Z9 86 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 1999 VL 42 IS 3 BP 591 EP 598 DI 10.1002/(SICI)1522-2594(199909)42:3<591::AID-MRM23>3.0.CO;2-8 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 232BR UT WOS:000082346300023 PM 10467305 ER PT J AU Campbell, SM Hann, M Roland, MO Quayle, JA Shekelle, PG AF Campbell, SM Hann, M Roland, MO Quayle, JA Shekelle, PG TI The effect of panel membership and feedback on ratings in a two-round Delphi survey - Results of a randomized controlled trial SO MEDICAL CARE LA English DT Article DE consensus; panels; feedback; RAND; Delphi ID MEDICAL PROCEDURES; PHYSICIAN RATINGS; CONSENSUS METHODS; APPROPRIATENESS; CARE; GUIDELINES; NECESSITY; SERVICES AB BACKGROUND. Past observational studies of the RAND/UCLA Appropriateness Method have shown that the composition of panels affects the ratings that are obtained, Panels of mixed physicians make different judgments from panels of single specialty physicians, and physicians who use a procedure are more likely to rate it more highly than those who do not. OBJECTIVES. To determine the effect of using physicians and health care managers within a panel designed to assess quality indicators for primary care and to test the effect of different types of feedback within the panel process. METHOD. A two-round postal Delphi survey of health care managers and family physicians rated 240 potential indicators of quality of primary care in the United Kingdom to determine their face validity. Following round one, equal numbers of managers and physicians were randomly allocated to receive either collective (whole sample) or group-only (own professional group only) feedback, thus, creating four subgroups of two single-specialty panels and two mixed panels. RESULTS. Overall, managers rated the indicators significantly higher than physicians, Second-round stores were moderated by the type of feedback received with those receiving collective feedback influenced by the other professional group. CONCLUSIONS. This paper provides further experimental evidence that consensus panel judgments are influenced both by panel composition and by the type of feedback which is given to participants during the panel process. Careful attention must be given to the methods used to conduct consensus panel studies, and methods need to be described in detail when such studies are reported. C1 Univ Manchester, Natl Primary Care Res & Dev Ctr, Manchester M13 9PL, Lancs, England. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Rand Corp, Hlth Program, Santa Monica, CA USA. NR 22 TC 77 Z9 78 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 1999 VL 37 IS 9 BP 964 EP 968 DI 10.1097/00005650-199909000-00012 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 235AA UT WOS:000082515500012 PM 10493474 ER PT J AU Almond, PR Biggs, PJ Coursey, BM Hanson, WF Huq, MS Nath, R Rogers, DWO AF Almond, PR Biggs, PJ Coursey, BM Hanson, WF Huq, MS Nath, R Rogers, DWO TI AAPM's TG-51 protocol for clinical reference dosimetry of high-energy photon and electron beams SO MEDICAL PHYSICS LA English DT Article ID STOPPING-POWER RATIOS; IONIZATION CHAMBERS; RECOMBINATION CORRECTION; QUALITY SPECIFICATION; PLANE-PARALLEL; ION-CHAMBER; RADIATION; CALIBRATION; COLLECTION; THIMBLE AB A protocol is prescribed for clinical reference dosimetry of external beam radiation therapy using photon beams with nominal energies between Co-60 and 50 MV and electron beams with nominal energies between 4 and 50 MeV. The protocol was written by Task Group 51 (TG-51) of the Radiation Therapy Committee of the American Association of Physicists in Medicine (AAPM) and has been formally approved by the AAPM for clinical use. The protocol uses ion chambers with absorbed-dose-to-water calibration factors, N-D,w(60Co), which are traceable to national primary standards, and the equation D-w(Q) = Mk(Q)N(D,w)(60Co), where Q is the beam quality of the clinical beam, DP is the absorbed dose to water at the point of measurement of the ion chamber placed under reference conditions, M is the fully corrected ion chamber reading, and kg is the quality conversion factor which converts the calibration factor for a Co-60 beam to that for a beam of quality Q. Values of ka are presented as a function of Q for many ion chambers. The value of M is given by M = PionPTPPelecPpolMraw, where M-raw is the raw, uncorrected ion chamber reading and P-ion corrects for ion recombination, P-TP for temperature and pressure variations, P-elec for inaccuracy of the electrometer if calibrated separately, and P-pol for chamber polarity effects. Beam quality, Q, is specified (i) for photon beams, by %dd(10)(x), the photon component of the percentage depth dose at 10 cm depth for a field size of 10 x 10 cm(2) on the surface of a phantom at an SSD of 100 cm and (ii) for electron beams, by R-50, the depth at which the absorbed-dose falls to 50% of the maximum dose in a beam with field size greater than or equal to 10 x 10 cm(2) on the surface of the phantom (greater than or equal to 20 x 20 cm(2) for R-50> 8.5 cm) at an SSD of 100 cm. R-50 is determined directly from the measured value of I-50, the depth at which the ionization falls to 50% of its maximum value. All clinical reference dosimetry is performed in a water phantom. The reference depth for calibration purposes is 10 cm for photon beams and 0.6R(50)-0.1 cm for electron beams. For photon beams clinical reference dosimetry is performed in either an SSD or SAD setup with a 10 x 10 cm(2) field size defined on the phantom surface for an SSD setup or at the depth of the detector for an SAD setup. For electron beams clinical reference dosimetry is performed with a field size of greater than or equal to 10 x 10 cm(2) (greater than or equal to 20 x 20 cm(2) for R-50> 8.5 cm) at an SSD between 90 and 110 cm. This protocol represents a major simplification compared to the AAPM's TG-21 protocol in the sense that large tables of stopping-power ratios and mass-energy absorption coefficients are not needed and the user does not need to calculate any theoretical dosimetry factors. Worksheets for various situations are presented along with a list of equipment required. (C) 1999 American Association of Physicists in Medicine. [S0094-2405(99)00209-6]. C1 Brown Canc Ctr, Louisville, KY 40202 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Natl Inst Stand & Technol, Ionizing Radiat Div, Gaithersburg, MD 20899 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Yale Univ, Sch Med, New Haven, CT 06510 USA. Natl Res Council Canada, Ottawa, ON K1A 0R6, Canada. RP Almond, PR (reprint author), Brown Canc Ctr, Louisville, KY 40202 USA. RI Rogers, David/A-1973-2008; Grams, Michael/G-5197-2011 NR 52 TC 616 Z9 629 U1 2 U2 26 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD SEP PY 1999 VL 26 IS 9 BP 1847 EP 1870 DI 10.1118/1.598691 PG 24 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 237AV UT WOS:000082632200016 PM 10505874 ER PT J AU Endo, M Jain, RK Witwer, B Brown, D AF Endo, M Jain, RK Witwer, B Brown, D TI Water channel (aquaporin 1) expression and distribution in mammary carcinomas and glioblastomas SO MICROVASCULAR RESEARCH LA English DT Article ID CELL CHIP28 PROTEIN; MICROVASCULAR PERMEABILITY; GROWTH-FACTOR; RAT-KIDNEY; TUMOR; LOCALIZATION; ANTIGEN; THROMBOMODULIN; RECONSTITUTION; LIPOSOMES AB The aquaporins represent a family of transmembrane water channel proteins that are widely distributed in various tissues throughout the body and play a major role in transcellular and transepithelial water movement. Most tumors have been shown to exhibit high vascular permeability and high interstitial fluid pressure, but the transport pathways for water within tumors remain unknown. In this study, we examined the distribution of the aquaporin 1 (AQP1) water channel protein in several types of transplanted tumor. Two mammary carcinomas, MCaIV and R3230AC, and three glioblastomas, HGL21, U87, and F98, were implanted in rats and mice. Two sites of implantation in rodents were chosen: a cranial window (CW) region and a subcutaneous (SC) region. Tissues were studied using immunoblot analysis and immunofluorescence staining. In the mammary carcinomas, AQP1 was localized in vascular structures; no differences between CW and SC regions were observed. Among the three glioblastomas, HGL21 and U87 exhibited similar AQP1 localization in vascular structures, whereas the center of F98 did not show vascular staining. Cell membranes of normal epithelial cells did not show AQP1 expression, while membranes of most tumor cells exhibited significant AQP1 expression. Interestingly, however, HGL21 and F98 in the CW locations showed no AQP1 expression on tumor cell membranes. These results show that the AQP1 water channel is heterogeneously expressed in tumor cells and their vasculature, and that the level of expression is determined not only by the specific cellular origin of the tumor, but also by the location of the tumor in the host animal, (C) 1999 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Renal Unit, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Program Membrane Biol, Boston, MA 02129 USA. RP Endo, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02129 USA. FU NCI NIH HHS [R35-CA-56591]; NIDDK NIH HHS [DK-38452] NR 31 TC 109 Z9 130 U1 1 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD SEP PY 1999 VL 58 IS 2 BP 89 EP 98 DI 10.1006/mvre.1999.2158 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 232TE UT WOS:000082385400002 PM 10458924 ER PT J AU Grosskreutz, CL Anand-Apte, B Duplaa, C Quinn, TP Terman, BI Zetter, B D'Amore, PA AF Grosskreutz, CL Anand-Apte, B Duplaa, C Quinn, TP Terman, BI Zetter, B D'Amore, PA TI Vascular endothelial growth factor-induced migration of vascular smooth muscle cells in vitro SO MICROVASCULAR RESEARCH LA English DT Article DE vascular smooth muscle cells; vascular endothelial growth factor; migration; angiogenesis; vascular endothelial growth factor receptors ID ANGIOGENIC CYTOKINES; RETINAL CELLS; EXPRESSION; RECEPTOR; HYPOXIA; GENE; IDENTIFICATION; PROLIFERATION; KINASE-1; PROTEINS AB Angiogenesis is a complex process that includes recruitment and proliferation of mural cells-smooth muscle cells (SMC) and pericytes. Vascular endothelial growth factor (VEGF) has been shown to play an important role in angiogenesis and is an endothelial cell chemoattractant. In addition, certain VEGF isoforms have been implicated in the normal formation of smooth muscle cell-surrounded arteries. Because VEGF's role as a mural cell chemoattractant had not been explored, we examined the ability of VEGF to influence vascular SMC migration in vitro. A Boyden chamber migration assay demonstrated that VEGF (0-100 ng/ml) caused a dose-dependent migration of SMC. VEGF did not cause proliferation of SMC. Reverse transcriptase-polymerase chain reaction analysis demonstrated the presence of both KDR and fit mRNA, two known VEGF receptors, in SMC cultures. Western blot analysis of SMC lysates confirmed these data, revealing bands migrating at approximately 200 kDa and slightly below 200 kDa consistent with KDR and fit. These observations demonstrate that VEGF receptors are present on SMC, and that VEGF can act as an SMC chemoattractant, (C) 1999 Academic Press. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Surg,Lab Surg Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Cleveland Clin, Res Inst, Dept Cell Biol, Cleveland, OH 44106 USA. INSERM, Pessac, France. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Wyeth Ayerst Res, Pearl River, NY USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Schepens Eye Res Inst, Boston, MA USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [K11-EY00342, R01EY05318] NR 28 TC 156 Z9 163 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD SEP PY 1999 VL 58 IS 2 BP 128 EP 136 DI 10.1006/mvre.1999.2171 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 232TE UT WOS:000082385400006 PM 10458928 ER PT J AU Koochekpour, S Jeffers, M Wang, PH Gong, CN Taylor, GA Roessler, LM Stearman, R Vasselli, JR Stetler-Stevenson, WG Kaelin, WG Linehan, WM Klausner, RD Gnarra, JR Vande Woude, GF AF Koochekpour, S Jeffers, M Wang, PH Gong, CN Taylor, GA Roessler, LM Stearman, R Vasselli, JR Stetler-Stevenson, WG Kaelin, WG Linehan, WM Klausner, RD Gnarra, JR Vande Woude, GF TI The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FACTOR SCATTER FACTOR; MET PROTOONCOGENE; MESSENGER-RNA; MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; METASTASIS; EXPRESSION; RECEPTOR; IDENTIFICATION AB Loss of function in the von Hippel-Lindau (VHL) tumor suppressor gene occurs in familial and most sporadic renal cell carcinomas (RCCs). VHL has been linked to the regulation of cell cycle cessation (G(0)) and to control of expression of various mRNAs such as for vascular endothelial growth factor. RCC cells express the Met receptor tyrosine kinase, and Met mediates invasion and branching morphogenesis in many cell types in response to hepatocyte growth factor/scatter factor (HGF/SF). We examined the HGF/SF responsiveness of RCC cells containing endogenous mutated (mut) forms of the VHL protein (VHL-negative RCC) with that of isogenic cells expressing exogenous wild-type (wt) VEL (VHL-positive RCC). We found that VHL-negative 786-0 and UOK-101 RCC cells were highly invasive through growth factor-reduced (GFR) Matrigel-coated filters and exhibited an extensive branching morphogenesis phenotype in response to HGF/SP in the three-dimensional (3D) GFR Matrigel cultures. In contrast, the phenotypes of A498 VHL-negative RCC cells were weaker, and isogenic RCC cells ectopically expressing wt VHL did not respond at all. We found that all VHL-negative RCC cells expressed reduced levels of tissue inhibitor of metalloproteinase 2 (TIMP-2) relative to the wt VHL-positive cells, implicating VHL in the regulation of this molecule. However, consistent with the more invasive phenotype of the 786-0 and UOK-101 VHL-negative RCC cells, the levels of TIMP-1 and TIMP-2 were reduced and levels of the matrix metalloproteinases 2 and 9 were elevated compared to the noninvasive VHL-positive RCC cells. Moreover, recombinant TIMPs completely blocked HGF/SF-mediated branching morphogenesis, while neutralizing antibodies to the TIMPs stimulated HGF/SF-mediated invasion in vitro. Thus, the loss of the VHL tumor suppressor gene is central to changes that control tissue invasiveness, and a more invasive phenotype requires additional genetic changes seen in some but not all RCC lines. These studies also demonstrate a synergy between the loss of VHL function and Met signaling. C1 NCI, ABL Basic Res Program, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Off Director, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Vande Woude, GF (reprint author), NCI, ABL Basic Res Program, Div Basic Sci, Frederick Canc Res & Dev Ctr, POB B,Bldg 469, Frederick, MD 21702 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [CA783356] NR 59 TC 153 Z9 156 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 1999 VL 19 IS 9 BP 5902 EP 5912 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 228LK UT WOS:000082137800008 PM 10454537 ER PT J AU McCaffrey, J Yamasaki, L Dyson, NJ Harlow, E Griep, AE AF McCaffrey, J Yamasaki, L Dyson, NJ Harlow, E Griep, AE TI Disruption of retinoblastoma protein family function by human papillomavirus type 16 E7 oncoprotein inhibits lens development in part through E2F-1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID S-PHASE ENTRY; FIBER CELL-DIFFERENTIATION; TUMOR-SUPPRESSOR PROTEIN; MOUSE LENS; P53-DEPENDENT APOPTOSIS; TRANSCRIPTION FACTOR; DNA-SYNTHESIS; GENE-PRODUCT; HUMAN KERATINOCYTES; GAMMA-CRYSTALLIN AB Complexes between the retinoblastoma protein (pRb) and the transcription factor E2F-1 are thought to be important for regulating cell proliferation. We have shown previously that the E7 oncoprotein from human papillomavirus type 16, dependent upon its binding to pRb proteins, induces proliferation, disrupts differentiation, and induces apoptosis when expressed in the differentiating, or fiber, cells of the ocular lenses in transgenic mice, Mice that carry a null mutation in E2F-1 do not exhibit any defects in proliferation and differentiation in the lens. By examining the lens phenotype in mice that express E7 on an E2F-1 null background, we now show genetic evidence that E7's ability to alter the fate of fiber cells is partially dependent on E2F-1. On the other hand, E2F-1 status does not affect E7-induced proliferation in the undifferentiated lens epithelium. These data provide genetic evidence that E2F-1, while dispensible for normal fiber cell differentiation, is one mediator of E7's activity in vivo and that the requirement for E2F-1 is context dependent. These data suggest that an important role for pRb-E2F-1 complex during fiber cell differentiation is to negatively regulate cell cycle progression, thereby allowing completion of the differentiation program to occur. C1 Univ Wisconsin, Sch Med, Dept Anat, Madison, WI 53706 USA. Massachusetts Gen Hosp, Ctr Canc, Oncol Mol Lab, Charlestown, MA 02129 USA. RP Griep, AE (reprint author), Univ Wisconsin, Sch Med, Dept Anat, 1300 Univ Ave, Madison, WI 53706 USA. FU NEI NIH HHS [R01 EY009091, R01-EY09091, F32-EY06709, F32 EY006709] NR 59 TC 33 Z9 35 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 SEP PY 1999 VL 19 IS 9 BP 6458 EP 6468 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 228LK UT WOS:000082137800062 PM 10454591 ER PT J AU Inukai, T Inoue, A Kurosawa, H Goi, K Shinjyo, T Ozawa, K Mao, M Inaba, T Look, AT AF Inukai, T Inoue, A Kurosawa, H Goi, K Shinjyo, T Ozawa, K Mao, M Inaba, T Look, AT TI SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein SO MOLECULAR CELL LA English DT Article ID PROGRAMMED CELL-DEATH; SURVIVAL-PROMOTING PROTEINS; BCL-X-L; C-ELEGANS; DNA-BINDING; TRANSACTIVATION DOMAINS; CAENORHABDITIS-ELEGANS; MAMMALIAN-CELLS; E2A GENE; APOPTOSIS AB The E2A-HLF fusion gene transforms human pro-B lymphocytes by interfering with an early step in apoptotic signaling. In a search for E2A-HLF-responsive genes, we identified a zinc finger transcription factor, SLUG, whose product belongs to the Snail family of developmental regulatory proteins. Importantly, SLUG bears close homology to the CES-1 protein of C. elegans, which acts downstream of CES-2 in a neuron-specific cell death pathway. Consistent with the postulated role of CES-1 as an antiapoptotic transcription factor, SLUG was nearly as active as Bcl-2 or Bcl-x(L) in promoting the survival of IL-3-dependent murine pro-B cells deprived of the cytokine. We conclude that SLUG is an evolutionarily conserved transcriptional repressor whose activation by E2A-HLF promotes the aberrant survival and eventual malignant transformation of mammalian pro-B cells otherwise slated for apoptotic death. C1 St Jude Childrens Res Hosp, Dept Expt Oncol, Memphis, TN 38105 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Jichi Med Sch, Dept Mol Biol, Minami Kawachi, Tochigi 32904, Japan. Jichi Med Sch, Dept Hematol, Minami Kawachi, Tochigi 32904, Japan. Shanghai Second Med Univ, Rui Jin Hosp, Shanghai Inst Hematol, Shanghai 200025, Peoples R China. RP Look, AT (reprint author), St Jude Childrens Res Hosp, Dept Expt Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. FU NCI NIH HHS [CA 21765, CA 59571] NR 63 TC 149 Z9 150 U1 0 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 1999 VL 4 IS 3 BP 343 EP 352 DI 10.1016/S1097-2765(00)80336-6 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 241KT UT WOS:000082882800006 PM 10518215 ER PT J AU Ni, TT Marsischky, GT Kolodner, RD AF Ni, TT Marsischky, GT Kolodner, RD TI MSH2 and MSH6 are required for removal of adenine misincorporated opposite 8-oxo-guanine in S-cerevisiae SO MOLECULAR CELL LA English DT Article ID OXIDATIVE DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; MISMATCH REPAIR; HUMAN HOMOLOG; HUMAN CANCER; OGG1 GENE; CLONING; 8-OXOGUANINE; GLYCOSYLASE AB Oxidation of G in DNA yields 8-oxo-G (GO), a mutagenic lesion that leads to misincorporation of A opposite GO. In E. coli, GO in GO:C base pairs is removed by MutM, and A in GO:A mispairs is removed by MutY. In S. cerevisiae, mutations in MSH2 or MSH6 caused a synergistic increase in mutation rate in combination with mutations in OGG1, which encodes a MutM homolog, resulting in a 140- to 218-fold increase in the G:C-to-T:A transversion rate. Consistent with this, MSH2-MSH6 complex bound to GO:A mispairs and GO:C base pairs with high affinity and specificity. These data indicate that in S. cerevisiae, MSH2-MSH6-dependent mismatch repair is the major mechanism by which misincorporation of A opposite GO is corrected. C1 Univ Calif San Diego, Sch Med, Dept Med, Canc Ctr,Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Kolodner, RD (reprint author), Univ Calif San Diego, Sch Med, Dept Med, Canc Ctr,Ludwig Inst Canc Res, La Jolla, CA 92093 USA. FU NIGMS NIH HHS [GM50006] NR 38 TC 172 Z9 174 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 1999 VL 4 IS 3 BP 439 EP 444 DI 10.1016/S1097-2765(00)80346-9 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 241KT UT WOS:000082882800016 PM 10518225 ER PT J AU Song, CS Jung, MH Supakar, PC Chatterjee, B Roy, AK AF Song, CS Jung, MH Supakar, PC Chatterjee, B Roy, AK TI Negative regulation of the androgen receptor gene promoter by NFI and an adjacently located multiprotein-binding site SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID NUCLEAR FACTOR-I; DNA-BINDING; POSTTRANSCRIPTIONAL REGULATION; TRANSCRIPTIONAL ACTIVATION; EUKARYOTIC TRANSCRIPTION; MESSENGER-RNA; RAT-LIVER; PROTEIN; EXPRESSION; ELEMENT AB The upstream promoter of the rat androgen receptor (AR) gene contains a strong negative regulatory region located at the -388 to -340 nucleotide position. The distal part (-388/-373) of this regulatory region binds NFI, a ubiquitous transcription factor, while the proximal portion (-372/-340) contains an overlapping binding site for two nuclear proteins. This composite regulatory region (-388/-340) was initially defined by deoxyribonuclease I footprinting as the continuous stretch of a nuclease-protected site. NFI specificity of the distal portion (-388/-373) of the footprint was established through cross-competition in electrophoretic mobility shift assay (EMSA) using the well characterized NFI element of the adenovirus major late promoter and by immunoreactivity to the NFI antibody. EMSA with oligonucleotide duplexes corresponding to the proximal domain (-372/-340) indicated multiple retarded bands with at least two major DNA-protein complexes. Further analysis with truncated oligonucleotide duplexes showed that these two major proteins bind to this domain in an overlapping manner. Within this overlapping area, the position spanning -359 to -347 is essential for the formation of either of these two complexes. Substitution of four G with T residues in the overlapping area totally abolished all protein binding at the downstream -372/-340 site. Point mutations that abolish specific binding at either the NFI or immediately downstream multiprotein-binding site caused about a 10-fold increase in AR promoter activity in transfected HepG2 cells. Double mutation involving both the NFI and proximal overlapping protein-binding sites failed to cause any additional increase in promoter function. From these results we conclude that the AR promoter contains a composite negative regulatory region at -388/-340, and the repressor function may involve a coordinate interaction between NFI and at least two other nuclear factors. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Roy, AK (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG-10486]; NIDDK NIH HHS [DK-14744] NR 48 TC 21 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1999 VL 13 IS 9 BP 1487 EP 1496 DI 10.1210/me.13.9.1487 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 230MZ UT WOS:000082256100005 PM 10478840 ER PT J AU Fusunyan, RD Quinn, JJ Fujimoto, M MacDermott, RP Sanderson, IR AF Fusunyan, RD Quinn, JJ Fujimoto, M MacDermott, RP Sanderson, IR TI Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation SO MOLECULAR MEDICINE LA English DT Article ID CHAIN FATTY-ACIDS; INFLAMMATORY BOWEL-DISEASE; SCAFFOLD-ATTACHED REGIONS; NUCLEOSOME CORE PARTICLE; HUMAN-COLON; ULCERATIVE-COLITIS; GENE-EXPRESSION; SODIUM-BUTYRATE; CHROMATIN; DIFFERENTIATION AB Background: Butyrate, a fermentation product of intestinal bacteria, modifies chromatin structure through histone acetylation, thereby altering gene transcription. IL-8 and MCP-1 are chemokines, expressed by intestinal epithelial cells, which attract neutrophils and monocytes, respectively. We hypothesized that butyrate may alter IL-8 and MCP-1 expression by intestinal epithelial cells through histone acetylation. Materials and Methods: IL-8 and MCP-1 expression was measured by ELISA and RNA transfer blots. Acetylated histones were separated on acetic acid-urea-triton gels. Butyrate was compared to Trichostatin-A, a specific inhibitor of histone deacetylase and to other short chain fatty acids. Results: Caco-2 cells constitutively secreted MCP-1 but not IL-8. Butyrate reversibly decreased MCP-1 secretion. In contrast, butyrate increased IL-8 production. The effects of butyrate and Trichostatin-A were greater when cells were stimulated with IL-1 beta. Butyrate and Trichostatin-A both increased histone acetylation. Trichostatin-A and other shea chain fatty acids altered chemokine secretion according to their effect on histone acetylation. Conclusions: Butyrate reversibly switches chemokine secretion by epithelial cells through histone acetylation. We speculate that butyrate carries information from resident bacteria to epithelial cells. Epithelial cells transduce this signal through histone acetylation modulating the secretion of chemokines. C1 Massachusetts Gen Hosp, Harvard Clin Nutr Res Ctr, Dev Gastroenterol Lab, Boston, MA 02114 USA. Lahey Hitchcock Clin, Gastrointestinal Sect, Burlington, MA USA. RP Sanderson, IR (reprint author), St Bartholomews & Royal London Sch Med & Dent, Dept Paediat Gastroenterol, Suite 42,Domin House,59 Bartholomew Close, London EC1A 7BE, England. FU NIAID NIH HHS [AI 43472]; NIDDK NIH HHS [DK21474, DK47753] NR 38 TC 74 Z9 75 U1 0 U2 2 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 1999 VL 5 IS 9 BP 631 EP 640 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 255AE UT WOS:000083646600006 PM 10551904 ER PT J AU Karkera, JD Zeng, J Jacobowitz, D Leonard, S Moses, T Detera-Wadleigh, SD AF Karkera, JD Zeng, J Jacobowitz, D Leonard, S Moses, T Detera-Wadleigh, SD TI Detection of candidate genes for bipolar disorder through differential display-PCR. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 NIMH, Intramural Program, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver VA Med Ctr, Denver, CO 80262 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 105 BP S60 EP S60 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800205 ER PT J AU Tsuang, D Almqvist, EW Strgar, F DiGiacomo, L Hoff, D Eugenio, C Hayden, MR Bird, TD AF Tsuang, D Almqvist, EW Strgar, F DiGiacomo, L Hoff, D Eugenio, C Hayden, MR Bird, TD TI Familial aggregation of psychotic symptoms in Huntington's disease. SO MOLECULAR PSYCHIATRY LA English DT Meeting Abstract C1 Univ Washington, Mental Illness Res Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, Seattle Div,Dept Psychiat & Behav Sci, Seattle, WA USA. Univ Washington, Dept Neurol, Seattle, WA USA. Univ Washington, Dept Med Genet, Seattle, WA USA. Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Vancouver, BC, Canada. RI Hayden, Michael/D-8581-2011 OI Hayden, Michael/0000-0001-5159-1419 NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1999 VL 4 SU 1 MA 93 BP S57 EP S57 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 254FG UT WOS:000083600800193 ER PT J AU Weinberg, DH Rizzo, JF Hayes, MT Kneeland, MD Kelly, JJ AF Weinberg, DH Rizzo, JF Hayes, MT Kneeland, MD Kelly, JJ TI Ocular myasthenia gravis: Predictive value of single fiber electromyography SO MUSCLE & NERVE LA English DT Article DE myasthenia gravis; ocular; generalized; single-fiber electromyography; prognosis ID EMG REFERENCE VALUES; MUSCLE; DIAGNOSIS AB Extraocular muscle weakness is the most common presenting sign of myasthenia gravis (MG). More than half of patients presenting with symptoms isolated to these muscles (OMG) develop generalized myasthenia gravis (GMG) over the course of their illness, No clinical, laboratory, or electrophysiological features are recognized that identify these highrisk patients. We have therefore assessed the ability of single-fiber electromyography (SFEMG) to predict the development of GMG in patients presenting with OMG. Thirty-nine consecutive patients presenting with OMG underwent SFEMG of the extensor digitorum communis muscle as well as a battery of other laboratory and imaging studies at the time of diagnosis. Ail patients were followed prospectively for a minimum of 24 months or until they developed GMG. Two patients were excluded, leaving 37 for assessment. Twenty remained with pure OMG for the entire follow-up period (mean, 55 months). Twenty-six of the 37 had abnormal SFEMG studies at presentation. Eleven of these remained with OMG and 15 developed GMG. Fifty-eight percent of patients with an abnormal SFEMG developed GMG, whereas 82% of those with a normal study remained with OMG. Thus, a normal SFEMG was associated with MG remaining restricted to the extraocular muscles. (P = 0.036, Fisher's exact test), but an abnormal SFEMG was not predictive of subsequent development of GMG. (C) 1999 John Wiley & Sons, Inc. C1 St Elizabeths Med Ctr, Dept Neurol, Boston, MA 02135 USA. Tufts Univ, Sch Med, Boston, MA 02135 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. St Elizabeths Med Ctr, Dept Med, Boston, MA 02135 USA. George Washington Univ, Med Ctr, Dept Neurol, Washington, DC 20037 USA. RP Weinberg, DH (reprint author), St Elizabeths Med Ctr, Dept Neurol, Boston, MA 02135 USA. NR 30 TC 19 Z9 22 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD SEP PY 1999 VL 22 IS 9 BP 1222 EP 1227 DI 10.1002/(SICI)1097-4598(199909)22:9<1222::AID-MUS8>3.0.CO;2-R PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 231PM UT WOS:000082319000008 PM 10454717 ER PT J AU White, K AF White, K TI The Third Horseman takes wing SO NATURE CELL BIOLOGY LA English DT Article ID CYTOCHROME-C; APOPTOSIS; ACTIVATION; PROCASPASE-9; CASPASE-9; PATHWAYS; ENCODES; APAF-1; DEATH; CED-4 AB The identification of a Drosophila homologue of the nematode cell-death protein CED-4 indicates a role for the apoptosome - a complex consisting of CED-4, CED-3 and CED-9 - in developmental cell deaths in Drosophila. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP White, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI White, Kristin/D-7936-2013 NR 14 TC 0 Z9 0 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 1999 VL 1 IS 5 BP E123 EP E124 DI 10.1038/12953 PG 2 WC Cell Biology SC Cell Biology GA 246NJ UT WOS:000083169600007 PM 10559952 ER PT J AU Withers, DJ Burks, DJ Towery, HH Altamuro, SL Flint, CL White, ME AF Withers, DJ Burks, DJ Towery, HH Altamuro, SL Flint, CL White, ME TI Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling SO NATURE GENETICS LA English DT Article ID FACTOR-I RECEPTOR; ENDOCRINE PANCREAS; GROWTH-FACTORS; MICE; GENE; SUBSTRATE-2; EXPRESSION; APOPTOSIS; PHOSPHORYLATION; RAT AB Insulin receptor substrates (Irs proteins) mediate the pleiotropic effects of insulin and Igf-l (insulin-like growth factor-1), including regulation of glucose homeostasis and cell growth and survival. We intercrossed mice heterozygous for two null alleles (Irs1(+/-) and Irs2(+/-)) and investigated growth and glucose metabolism in mice with viable genotypes. Our experiments revealed that Irs-1 and Irs-2 are critical for embryonic and post-natal growth, with Irs-l having the predominant role. By contrast, both Irs-l and Irs-2 function in peripheral carbohydrate metabolism, but Irs-2 has the major role in beta-cell development and compensation for peripheral insulin resistance. To establish a role for the Igf-l receptor in beta-cells, we intercrossed mice heterozygous for null alleles of Igf1r and Irs2. Our results reveal that Igf-l receptors promote beta-cell development and survival through the Irs-2 signalling pathway. Thus, Irs-2 integrates the effects of insulin in peripheral target tissues with Igf-l in pancreatic beta-cells to maintain glucose homeostasis. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. RP White, ME (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. RI Withers, Dominic/D-7671-2014 OI Withers, Dominic/0000-0002-8009-7521 FU NIDDK NIH HHS [DK43808] NR 36 TC 386 Z9 404 U1 1 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1999 VL 23 IS 1 BP 32 EP 40 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 231XU UT WOS:000082337300012 PM 10471495 ER PT J AU Xu, PX Adams, J Peters, H Brown, MC Heaney, S Maas, R AF Xu, PX Adams, J Peters, H Brown, MC Heaney, S Maas, R TI Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia SO NATURE GENETICS LA English DT Article ID BRANCHIOOTORENAL BOR SYNDROME; RECEPTOR TYROSINE KINASE; C-RET PROTOONCOGENE; EYES ABSENT; DEVELOPMENTAL DEFECTS; VARIABLE EXPRESSIVITY; MULTIPLE STEPS; GENE; PAX2; MUTATION AB Haploinsufficiency for human EYA1, a homologue of the Drosophila melanogaster gene eyes absent (eya), results in the dominantly inherited disorders branchio-oto-renal (BOR) syndrome(1-3) and branchio-oto (BO) syndrome(4), which are characterized by craniofacial abnormalities and hearing loss with (BOR) or without (BO) kidney defects. To understand the developmental pathogenesis of organs affected in these syndromes, we inactivated the gene Eya1 in mice. Eya1 heterozygotes show renal abnormalities and a conductive hearing loss similar to BOR syndrome, whereas Eya1 homozygotes lack ears and kidneys due to defective inductive tissue interactions and apoptotic regression of the organ primordia. Inner ear development in Eya1 homozygotes arrests at the otic vesicle stage and all components of the inner ear and specific cranial sensory ganglia fail to form. In the kidney, Eya1 homozygosity results in an absence of ureteric bud outgrowth and a subsequent failure of metanephric induction. Gdnf expression, which is required to direct ureteric bud outgrowth via activation of the c-ret Rtk (refs 5-8), is not detected in Eya1(-/-) metanephric mesenchyme. In Eya1(-/-) ear and kidney development, Six but not Pax expression is Eya1 dependent, similar to a genetic pathway elucidated in the Drosophila eye imaginal disc. Our results indicate that Eya1 controls critical early inductive signalling events involved in ear and kidney formation and integrate Eya1 into the genetic regulatory cascade controlling kidney formation upstream of Gdnf. In addition, our results suggest that an evolutionarily conserved Pax-Eya-Six regulatory hierarchy is used in mammalian ear and kidney development. C1 Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Maas, R (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. FU NEI NIH HHS [R01 EY10123, F32 EY006869]; NIDCR NIH HHS [R01 DE11697] NR 29 TC 402 Z9 412 U1 3 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1999 VL 23 IS 1 BP 113 EP 117 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 231XU UT WOS:000082337300028 PM 10471511 ER PT J AU Enjyoji, K Sevigny, J Lin, Y Frenette, PS Christie, PD Esch, JSA Imai, M Edelberg, JM Rayburn, H Lech, M Beeler, DL Csizmadia, E Wagner, DD Robson, SC Rosenberg, RD AF Enjyoji, K Sevigny, J Lin, Y Frenette, PS Christie, PD Esch, JSA Imai, M Edelberg, JM Rayburn, H Lech, M Beeler, DL Csizmadia, E Wagner, DD Robson, SC Rosenberg, RD TI Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation SO NATURE MEDICINE LA English DT Article ID ATP-DIPHOSPHOHYDROLASE; PLATELET ACTIVATION; ENDOTHELIAL-CELLS; MOLECULAR-CLONING; EXTRACELLULAR ATP; ADP; RECEPTORS; NUCLEOTIDES; EXPRESSION; THROMBOSIS AB CD39, or vascular adenosine triphosphate diphosphohydrolase, has been considered an important inhibitor of platelet activation. Unexpectedly, cd39-deficient mice had prolonged bleeding times with minimally perturbed coagulation parameters. Platelet interactions with injured mesenteric vasculature were considerably reduced in vivo and purified mutant platelets failed to aggregate to standard agonists in vitro. This platelet hypofunction was reversible and associated with purinergic type P2Y1 receptor desensitization. In keeping with deficient vascular protective mechanisms, fibrin deposition was found at multiple organ sites in cd39-deficient mice and in transplanted cardiac grafts. Our data indicate a dual role for adenosine triphosphate diphosphohydrolase in modulating hemostasis and thrombotic reactions. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. RP Rosenberg, RD (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Sevigny, Jean/E-8039-2012; Frenette, Paul/J-8272-2012 OI Sevigny, Jean/0000-0003-2922-1600; FU NHLBI NIH HHS [HL57307, HL41002]; PHS HHS [P01-41484] NR 45 TC 374 Z9 377 U1 0 U2 5 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 1999 VL 5 IS 9 BP 1010 EP 1017 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 231XT UT WOS:000082337200034 PM 10470077 ER PT J AU Tomazin, R Boname, J Hegde, NR Lewinsohn, DM Altschuler, Y Jones, TR Cresswell, P Nelson, JA Riddell, SR Johnson, DC AF Tomazin, R Boname, J Hegde, NR Lewinsohn, DM Altschuler, Y Jones, TR Cresswell, P Nelson, JA Riddell, SR Johnson, DC TI Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4(+) T cells SO NATURE MEDICINE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; HEAVY-CHAINS; HLA-DM; EXPRESSION; GENE; DEGRADATION; PROTEASOME; LYMPHOCYTES AB Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that causes life-threatening disease in patients who are immunosuppressed for bone marrow or tissue transplantation or who have AIDS (ref. 1). HCMV establishes lifelong latent infections and, after periodic: reactivation from latency, uses a panel of immune evasion proteins to survive and replicate in the face of robust, fully primed host immunity(2,3). Monocyte/macrophages are important host cells for HCMV, serving as a latent reservoir and as a means of dissemination throughout the body(4). Macrophages and other HCMV-permissive cells, such as endothelial and glial cells, can express MHC class II proteins and present antigens to CD4+ T lymphocytes. Here, we show that the HCMV protein US2 causes degradation of two essential proteins in the MHC class II antigen presentation pathway: HLA-DR-c( and DM-a. This was unexpected, as US2 has been shown to cause degradation of MHC class I (refs. 5,6), which has only limited homology with class II proteins. Expression of US2 in cells reduced or abolished their ability to present antigen to CD4+ T lymphocytes. Thus, US2 may allow HCMV-infected macrophages to remain relatively 'invisible' to CD4+ T cells, a property that would be important after virus reactivation. C1 Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Portland VA Med Ctr, Div Pulm & Crit Care Med, Portland, OR 97207 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Wyeth Ayerst Res, Dept Biol Mol, Pearl River, NY 10965 USA. Yale Univ, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06510 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Johnson, DC (reprint author), Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RI Lewinsohn, David/I-4936-2013 OI Boname, Jessica/0000-0002-5149-5934; Lewinsohn, David/0000-0001-9906-9494 FU NEI NIH HHS [EY11245]; NIAID NIH HHS [AI24178, AI41754] NR 28 TC 180 Z9 185 U1 0 U2 5 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 1999 VL 5 IS 9 BP 1039 EP 1043 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 231XT UT WOS:000082337200038 PM 10470081 ER PT J AU Peters, N Smith, JS Tachibana, I Lee, HK Pohl, U Portier, BP Louis, DN Jenkins, RB AF Peters, N Smith, JS Tachibana, I Lee, HK Pohl, U Portier, BP Louis, DN Jenkins, RB TI The human glia maturation factor-gamma gene: genomic structure and mutation analysis in gliomas with chromosome 19q loss SO NEUROGENETICS LA English DT Article DE human glia maturation factor-gamma; genomic structure; chromosome 19q; glioma ID FACTOR-BETA; PROTEIN; EXPRESSION; HETEROZYGOSITY; CLONING; 19Q13.3; REGION; CELLS; RNA AB Human glia maturation factor-gamma (hGMF-gamma) is a recently identified gene that may be involved in glial differentiation, neural regeneration, and inhibition of tumor cell proliferation. The gene maps to the long arm of chromosome 19 at band q13.2, a region that is frequently deleted in human malignant gliomas and is thus suspected to harbor a glioma tumor suppressor gene. Given the putative role of hGMF-gamma in cell differentiation and proliferation and its localization to chromosome 19q13, this gene is an interesting candidate for the chromosome 19q glioma tumor suppressor gene, To evaluate this possibility, we determined the genomic structure of human hGMF-gamma and performed mutation screening in a series of 41 gliomas with and,without allelic loss of chromosome 19q, Mutations were not detected, which suggests that hGMF-gamma is not the chromosome 19q glioma suppressor gene. However, the elucidation of the genomic structure of hGMF-gamma may prove useful in future investigations of hGMF-gamma in the normal adult and developing human nervous system. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol Neuropathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Jenkins, RB (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol Neuropathol, Charlestown, MA 02129 USA. RI imoto, Issei/D-8065-2012; Kigawa, Takanori/A-7679-2010 OI Kigawa, Takanori/0000-0003-0146-9719 FU NCI NIH HHS [CA69285, CA50905] NR 19 TC 9 Z9 10 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD SEP PY 1999 VL 2 IS 3 BP 163 EP 166 DI 10.1007/s100480050077 PG 4 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 245WU UT WOS:000083131700005 PM 10541589 ER PT J AU Schmahmann, JD Doyon, J McDonald, D Holmes, C Lavoie, K Hurwitz, AS Kabani, N Toga, A Evans, A Petrides, M AF Schmahmann, JD Doyon, J McDonald, D Holmes, C Lavoie, K Hurwitz, AS Kabani, N Toga, A Evans, A Petrides, M TI Three-dimensional MRI atlas of the human cerebellum in proportional stereotaxic space SO NEUROIMAGE LA English DT Article; Proceedings Paper CT 2nd International Conference on Functional Mapping of the Human Brain CY JUN 17-21, 1996 CL BOSTON, MASSACHUSETTS DE cerebellum; atlas; anatomy; human; proportional stereotaxic (Talairach) space; brain mapping ID SAGITTAL PLANE; REGISTRATION; SELECTION AB We have prepared an atlas of the human cerebellu using high-resolution magnetic resonance-derived images warped into the proportional stereotaxic space of Talairach and Tournoux, Software that permits simultaneous visualization of the three cardinal planes facilitated the identification of the cerebellar fissures and lobules, A revised version of the Larsell nomenclature facilitated a simple description of the cerebellum. This atlas derived from a single individual was instrumental in addressing longstanding debates about the gross morphologic organization of the cerebellum. It may serve as the template for more precise identification of cerebellar topography in functional imaging studies in normals, for investigating clinical-pathologic correlations in patients, and for the development of future probabilistic maps of the human cerebellum. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Laval, Francois Charon Ctr, Dept Psychol, Quebec City, PQ, Canada. Univ Laval, Francois Charon Ctr, Rehabil Res Grp, Quebec City, PQ, Canada. Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. Montreal Neurol Inst, Cognit Neurosci Unit, Montreal, PQ, Canada. Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab Neuroimaging, Los Angeles, CA 90024 USA. McGill Univ, Montreal, PQ, Canada. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 60 TC 379 Z9 384 U1 0 U2 16 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 1999 VL 10 IS 3 BP 233 EP 260 DI 10.1006/nimg.1999.0459 PN 1 PG 28 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 235RF UT WOS:000082555800001 PM 10458940 ER PT J AU Silberstein, S Merriam, G AF Silberstein, S Merriam, G TI Sex hormones and headache 1999 (menstrual migraine) SO NEUROLOGY LA English DT Article; Proceedings Paper CT Symposium on Womens Health Initiatives - Management of Migraine and Epilepsy Throughout the Reproductive Cycle CY NOV 21, 1998 CL TORONTO, CANADA SP Canadian League Against Epilepsy, Canadian Headache Soc ID GONADOTROPIN-RELEASING-HORMONE; PREMENSTRUAL TENSION SYNDROME; ESTROGEN-WITHDRAWAL MIGRAINE; ATTEMPTED PROPHYLAXIS; MELATONIN EXCRETION; FEMALE MIGRAINEURS; OVARIAN-STEROIDS; BETA-ENDORPHIN; NERVOUS-SYSTEM; DURA MATER AB The normal female life cycle is associated with a number of hormonal milestones: menarche, pregnancy, contraceptive use, menopause, and the use of replacement sex hormones. All these events and interventions alter the levels and cycling of sex hormones and may cause a change in the prevalence or intensity of headache. The menstrual cycle is the result of a carefully orchestrated sequence of interactions among the hypothalamus, pituitary, ovary, and endometrium, with the sex hormones acting as modulators and effecters at each level. Estrogen and progestins have potent effects on central serotonergic and opioid neurons, modulating both neuronal activity and receptor density. The primary trigger of menstrual migraine appears to be the withdrawal of estrogen rather than the maintenance of sustained high or low estrogen levels. However, changes in the sustained estrogen levels with pregnancy (increased) and menopause (decreased) appear to affect headaches. Headaches that occur with premenstrual syndrome appear to be centrally generated, involving the inherent rhythm of CNS neurons, including perhaps the serotonergic pain-modulating systems. C1 Thomas Jefferson Univ Hosp, Sch Med, Philadelphia, PA 19107 USA. Univ Washington, Sch Med, Seattle, WA USA. VA Puget Sound HCS, Tacoma, WA USA. RP Silberstein, S (reprint author), Jefferson Headache Ctr, 111 S 11th St,Suite 8130, Philadelphia, PA 19107 USA. NR 113 TC 36 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1999 VL 53 IS 4 SU 1 BP S3 EP S13 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 235MN UT WOS:000082545600002 PM 10487507 ER PT J AU Oaklander, AL AF Oaklander, AL TI The pathology of pain SO NEUROSCIENTIST LA English DT Article DE pain/physiopathology; nociceptors; human; ganglia; spinal; nerve degeneration/physiology; spinal cord/pathology; disease models; animal; sciatic nerve/injuries; nerve compression syndromes/physiopathology ID PERIPHERAL-NERVE INJURY; DORSAL-ROOT-GANGLIA; PRIMARY SENSORY NEURONS; PHANTOM-LIMB PAIN; SPINAL-CORD; SCIATIC-NERVE; POSTHERPETIC NEURALGIA; CONSTRICTION INJURY; NEUROPATHIC PAIN; RAT MODEL AB It has recently become recognized that neuropathic forms of chronic pain represent true neurologic disease. Current investigations are largely molecular, yet knowledge of the anatomy and cell biology of pain is also important for the development of more effective medications. Although acute pain is beneficial, neuropathic pain is pathological and creates devastating disability. It occurs when an abnormal somatosensory system chronically transmits pain signals despite the absence of acute injury. Any type of lesion anywhere in the peripheral or central spinothalamic pathway can cause it. The most common scenario involves interruption of peripheral sensory axons with distal Wallerian degeneration. Regenerating peripheral sensory axons can develop ongoing spontaneous action potentials or ectopic mechano- and chemosensitivity that contribute to pain. Axotomy also induces morphological and functional alterations proximally that can contribute to pain. Central axon terminals can degenerate or sprout aberrantly within the dorsal horn. Higher order sensory neurons within the CNS can experience trans-synaptic damage. Lesions wholly within the CNS, such as stroke and multiple sclerosis, can also produce neuropathic pain. This review of a nascent field is presented in hopes of stimulating further investigation into this common, under-recognized medical problem. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM alo@etherdome.mgh.harvard.edu NR 69 TC 3 Z9 4 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD SEP PY 1999 VL 5 IS 5 BP 302 EP 310 DI 10.1177/107385849900500516 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 234RQ UT WOS:000082498500016 ER PT J AU Buckley, DA Guanci, MM AF Buckley, DA Guanci, MM TI Spinal cord trauma SO NURSING CLINICS OF NORTH AMERICA LA English DT Article ID CONTROLLED TRIAL; BROWN-SEQUARD; INJURY; METHYLPREDNISOLONE; MANAGEMENT; NALOXONE; OUTCOMES; RECOVERY AB The earliest reference to spinal cord injury was recorded in 3000 B.C. Egyptian and Latin physicians detected that patients with vertebral trauma had paralysis of the arms and legs as well as urinary incontinence, suggesting a relationship between vertebral injuries and spinal cord damage and functional loss. Treatment at that time consisted of grease, fresh meat, and honey applied to the neck of the patient. Treatment of spinal cord injury (SCI) has become more sophisticated but we are still unable to reverse the effects of the initial injury. The major focus in the acute treatment of spinal cord trauma has remained prevention of secondary injury and complications thereafter.(6) There has been renewed interest in research and treatment in patients with SCI over the past two decades due to advances in research and technology. Great strides have been made toward improving emergency care and initial medical and surgical treatment as well as rehabilitation of the person who sustains a spinal cord injury. C1 Massachusetts Gen Hosp, VBK, Boston, MA 02114 USA. RP Buckley, DA (reprint author), Massachusetts Gen Hosp, VBK, 710,55 Fruit St, Boston, MA 02114 USA. NR 43 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD SEP PY 1999 VL 34 IS 3 BP 661 EP + PG 28 WC Nursing SC Nursing GA 235BM UT WOS:000082519100009 PM 10433653 ER PT J AU King, DS AF King, DS TI Central nervous system infections - Basic concepts SO NURSING CLINICS OF NORTH AMERICA LA English DT Article AB The central nervous system (CNS) is the foremost initiator, regulator, and terminator of human activity. The CNS is magnificently complex and has been the object of much inquiry and research. Research findings have increased our understanding of the impact on the CNS when infection prevails. Although the CNS is well protected by the bones of the cranium, the meninges, cerebrospinal fluid (CSF), and the blood-brain barrier, the CNS is not impervious to infection. At best, infections of the CNS, if quickly diagnosed and appropriately treated, may not permanently harm or significantly debilitate an individual. Often they are devastating to an individual's ability to function in his or her fullest capacity. At times infections are life threatening and result in death. The role of the nurse is paramount in all of these situations. The major CNS infections include meningitis, encephalitis, and brain abscesses. These infections are caused by bacterial, viral, and fungal organisms. Streptococcus pneumonia, Neisseria meningitidis, and Haemophilus influenzae are the bacteria that are most commonly responsible for causing bacterial meningitis. Viruses from the coxsackie family as well as viruses of the echovirus family cause viral meningitis. Cryptococcus neoformans, a fungus, is responsible for causing fungal meningitis. When these pathogens gain access to the CNS and the meninges, the membranes that cover the brain and spinal column, an inflammatory process results. Although bacterial and fungal meningitis are dangerous diseases, viral meningitis is not considered to be as serious or potentially life threatening. Beneath the meningeal layers lies the brain. The brain is composed of millions of cells. When a pathogen invades brain tissue and begins an inflammatory process, the term encephalitis is used. Encephalitis is characterized by marked and severe inflammation of brain tissue. There is usually concurrent inflammation of the meningeal tissue due to the close proximity to brain parenchyma. The herpesvirus, including types I and type 2, and arbovirus are the viruses that most frequently cause encephalitis. The third type of infection within the CNS results from abscess formation. A brain abscess is the result of bacterial infection that begins in another site in the body. Abscesses may lie within brain matter itself, in a particular area of brain (i.e., in the frontal lobe), or above or beneath the dura. An extradural abscess lies between skull bone and dura, whereas; an abscess beneath the dura and above the arachnoid membrane is known as a subdural empyema; it is an accumulation of purulent exudate. The danger of CNS infection is manifest not only by endotoxin release from the invading pathogens and subsequent inflammatory processes but also by the increase in intracranial pressure (TCP) that may result. Brain damage may result from pathogen damage to the CNS; life-threatening complications may arise with unchecked increased ICP. C1 Massachusetts Gen Hosp, Brain Aneurysm AYM Ctr, Boston, MA 02114 USA. RP King, DS (reprint author), 72 D St, Hull, MA 02045 USA. NR 8 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 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD SEP PY 1999 VL 34 IS 3 BP 761 EP + PG 12 WC Nursing SC Nursing GA 235BM UT WOS:000082519100013 PM 10433657 ER PT J AU Lin, CM Abcouwer, SF Souba, WW AF Lin, CM Abcouwer, SF Souba, WW TI Effect of dietary glutamate on chemotherapy-induced immunosuppression SO NUTRITION LA English DT Article DE glutamate; glutamine; glutathione; amino acid diet; immunity; chemotherapy; rats ID PARENTERAL-NUTRITION; IMMUNE; GLUTATHIONE; LYMPHOCYTES; RATS; IMMUNODEFICIENCY; SYSTEM; CELLS AB Chemotherapy causes severe host immune depression and consequently increases susceptibility to infection. Dietary glutamate (GLU) serves as a stable substrate for the formation of glutamine (GLN), which is an important fuel and metabolic precursor for the immune cells. The effect of addition of GLU to a GLN/GLU-free amino acid diet upon immune response was studied in rats recovering from chemotherapy. Animals were fed a 0, 4, or 8% GLU diet and received a single intraperitoneal injection of methotrexate (MTX, 20 mg/kg BW). Two in vivo immune tests, delayed-type hypersensitivity (DTH) and popliteal lymphoproliferation (PLP), were performed 3 and 7 d after MTX treatment. Food intake and body weight decreased significantly immediately after MTX treatment and gradually recovered after 8 d with no significant difference among treatment groups. In a 23-d feeding study, no significant difference was found in the DTH response, but the PLP response increased in a GLU dose related fashion (83 and 133% increases for the 4 and 8% GLU diets, respectively). In a 44-d feeding study, the DTH response increased 61 and 83%, while the PLP response increased 191 and 382% for the 4 and 8% GLU diets, respectively. Plasma GLN, GLU, or glutathione (GSH) levels were increased by dietary GLU, but only in the immediate postprandial state. In summary, dietary GLU improves immune status of rats recovering from MTX treatment. The immune-enhancing effect of dietary GLU was dose-dependent and more pronounced after a longer duration of dietary GLU intake. (C) Elsevier Science Inc. 1999. C1 Massachusetts Gen Hosp, Surg Oncol Res Labs, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Abcouwer, SF (reprint author), Massachusetts Gen Hosp, Surg Oncol Res Labs, Dept Surg, 55 Fruit St,Jackson 918, Boston, MA 02114 USA. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NCI NIH HHS [R01-CA57690] NR 24 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD SEP PY 1999 VL 15 IS 9 BP 687 EP 696 DI 10.1016/S0899-9007(99)00153-7 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 228UU UT WOS:000082154700008 PM 10467614 ER PT J AU Schorge, JO Lee, KR Lee, SJ Flynn, CE Goodman, A Sheets, EE AF Schorge, JO Lee, KR Lee, SJ Flynn, CE Goodman, A Sheets, EE TI Early cervical adenocarcinoma: Selection criteria for radical surgery SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; STAGE-IB; UTERINE CERVIX; GYNECOLOGIC-ONCOLOGY; NODE METASTASIS; CANCER; HYSTERECTOMY; RADIOTHERAPY; SURVIVAL AB Objective: To identify selection criteria for radical surgery in early cervical adenocarcinoma based on pretreatment clinical stage and correlation with high-risk surgical-pathologic factors. Methods: One hundred seventy-five women with International Federation of Gynecology and Obstetrics (FIGO) clinical stage IB1 (n = 132) and IB2-IIA (n = 43) cervical adenocarcinoma were treated primarily at our institutions from 1982 to 1996. Histopathologic sections were reviewed by a gynecologic pathologist. Medical records were reviewed retrospectively and clinical follow-up was done. Results: The overall 5-year survival rate was 87% (95% confidence interval [CI] 81%, 93%) for stage IB1 and 61% (95% CI 46%, 77%) for stage IB2-IIA (P < .001). Adenosquamous cell type, deep cervical invasion, and lymph-vascular space invasion were significant independent high-risk surgical-pathologic factors that affected disease-free survival (each P < .002). One hundred fourteen (86%) of 132 stage IB1 patients and 19 (44%) of 43 stage IB2-IIA subjects were treated primarily with radical surgery. Lymph node metastases, lymph-vascular space invasion, adenosquamous cell type, deep cervical invasion, and positive surgical margins were more than twice as frequent in stage IB2-IIA patients who had radical surgery than in stage IB1 patients (each P < .05). Based on high-risk surgical-pathologic factors in 133 subjects who had radical surgery, postoperative radiotherapy was recommended for 18 (16%) of 114 stage IB1 patients and 18 (95%) of 19 stage IB2-IIA subjects (P < .001). Conclusion: Radical surgery for FIGO clinical stage IB1 cervical adenocarcinoma and primary radiotherapy for stage IB2-IIA disease would largely avoid combined-modality therapy, thereby reducing treatment-related toxicity and cost. (C) 1999 by The American College of Obstetricians and Gynecologists. C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Schorge, JO (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. NR 19 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 1999 VL 94 IS 3 BP 386 EP 390 DI 10.1016/S0029-7844(99)00312-9 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 230JY UT WOS:000082249100012 PM 10472864 ER PT J AU Merayo-Lloves, J Power, WJ Rodriguez, A Pedroza-Seres, M Foster, CS AF Merayo-Lloves, J Power, WJ Rodriguez, A Pedroza-Seres, M Foster, CS TI Secondary glaucoma in patients with uveitis SO OPHTHALMOLOGICA LA English DT Article DE uveitis; glaucoma; ocular hypertension; iritis; iridocyclitis ID JUVENILE RHEUMATOID-ARTHRITIS; SARCOIDOSIS; IRIDOCYCLITIS AB Purpose: To evaluate the prevalence of secondary glaucoma (SG), clinical forms of uveitis more frequently associated with glaucoma, and describe the treatment and complications encountered in a cohort of patients with glaucoma and uveitis during a 10-year period. Methods: The hospital records of patients with uveitis referred to the Immunology Service of the Massachusetts Eye and Ear Infirmary for a decade were reviewed for cases of SG. Results: One hundred and twenty of the 1,254 patients (9.6%) with uveitis developed SG. SG was more frequent in anterior uveitis (67%) but was also associated with posterior uveitis (13%) and pars planitis (4%). Herpetic keratouveitis (22%), Fuchs' iridocyclitis (19%), juvenile rheumatoid arthritis-associated iridocyclitis (16%), syphilis (14%), and sarcoidosis (12%) were the leading types of uveitis associated with SG. Despite aggressive medical and surgical therapy, SG was associated with progressive visual field loss and optic nerve damage in 39 patients (33%). Conclusion: SG is an underappreciated, vision-threatening complication in patients with uveitis. Increased vigilance for emergence of this complicating problem during the care of patients with uveitis is warranted, and medical and surgical treatment for reducing IOP should be especially aggressive in these patients. We hypothesize that earlier, more aggressive treatment of uveitis will reduce the presence of glaucoma as an additional vision-robbing complication of uveitis. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. OI Rodriguez-Garcia, Alejandro/0000-0002-1419-2109 NR 22 TC 58 Z9 62 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3755 J9 OPHTHALMOLOGICA JI Ophthalmologica PD SEP-OCT PY 1999 VL 213 IS 5 BP 300 EP 304 DI 10.1159/000027443 PG 5 WC Ophthalmology SC Ophthalmology GA 243GT UT WOS:000082989200006 PM 10516518 ER PT J AU Akpek, EK Ahmed, I Hochberg, FH Soheilian, M Dryja, TP Jakobiec, FA Foster, CS AF Akpek, EK Ahmed, I Hochberg, FH Soheilian, M Dryja, TP Jakobiec, FA Foster, CS TI Intraocular-central nervous system lymphoma - Clinical features, diagnosis, and outcomes SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT American-Uveitis-Society Meeting CY OCT 26-27, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Uveitis Soc ID RETICULUM-CELL SARCOMA; INTERLEUKIN-10; MANAGEMENT AB Objective: To analyze the clinical features, laboratory investigations, and diagnosis of intraocular-central nervous system (CNS) lymphoma in a cohort of patients who underwent diagnostic vitrectomy. Design: Retrospective case series. Method and Study Materials: Thirty-four vitreous biopsy specimens obtained from 26 patients with treatment-resistant or unusual uveitis were re-evaluated in a masked fashion. The specimens were classified into three groups: "negative," "suspicious of malignancy," and "positive" based on the cytologic features, immunomarkers, and flow cytometry. The medical records of the patients were reviewed retrospectively. Main Outcome Measures: The reliability of vitreous cytology in diagnosing intraocular-CNS lymphoma and the differences in clinical features of patients with intraocular-CNS lymphoma and uveitis. Results: The two ocular pathologists concurred in their criteria for interpretation of all specimens. There was 100% concordance between the cytologic reports read independently by the two ocular pathologists over the 5-year period and the read-out done in a masked fashion at the time of the study. Ten patients were diagnosed with intraocular-CNS lymphoma based on the vitreous cytology and clinical features. The time interval between the initial presentation and vitreous biopsy was 1 week to 2 years, with 80% of the patients diagnosed within the first year. Retinal involvement in the form of lymphomatous subretinal pigment epithelial infiltrates, vasculitis, and apparent retinochoroiditis was present in six cases. Initial neuroimaging studies revealed concomitant CNS involvement in three patients, and an additional three developed CNS lymphoma following diagnosis by vitreous biopsy. Patients were treated with radiotherapy, chemotherapy, or both. Two of the four patients with a follow-up of greater than 12 months died due to CNS involvement. Conclusions: Vitreous cytology is a sensitive, reliable, and reproducible method of diagnosing intraocular-CNS lymphoma. A high index of suspicion based on the clinical findings and course of the uveitis is critically important in decision-making for diagnostic vitrectomy. Central nervous system involvement is frequent and associated with a high mortality rate. C1 Massachusetts Eye & Ear Infirm, Ocular Immunol Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Ocular Pathol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurooncol & Brain Tumor Ctr, Neurooncol Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Serv Immunol, 243 Charles St, Boston, MA 02114 USA. NR 28 TC 94 Z9 100 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1999 VL 106 IS 9 BP 1805 EP 1810 DI 10.1016/S0161-6420(99)90341-X PG 6 WC Ophthalmology SC Ophthalmology GA 230QG UT WOS:000082261400047 PM 10485554 ER PT J AU Rappaport, JM Nadol, JB McKenna, MJ Ojemann, RG Thornton, AR Cortese, RA AF Rappaport, JM Nadol, JB McKenna, MJ Ojemann, RG Thornton, AR Cortese, RA TI Standardized format for depicting hearing preservation results in the management of acoustic neuroma SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 2nd International Skull Base Congress / 7th Annual Meeting of the North-American-Skull-Base-Society CY JUN 29-JUL 04, 1996 CL SAN DIEGO, CALIFORNIA SP N Amer Skull Base Soc ID VESTIBULAR SCHWANNOMA; TUMOR SURGERY; CONSERVATION; REMOVAL AB The Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery recently published guidelines for reporting hearing preservation in the treatment of acoustic neuromas. These suggestions included pretreatment and posttreatment pure-tone hearing thresholds, word recognition scores, and hearing classification. We present a standardized reporting format that addresses the Committee's recommendations and displays individual patient audiologic data as a simple, concise plot of posttreatment hearing results. To illustrate the use of the recommended format, preoperative and postoperative hearing data from our institution are reported. Such reporting criteria will facilitate comparative reviews of studies of hearing preservation after surgical or radiotherapeutic management of acoustic neuromas, while providing specific data for individual patient outcome analysis. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rappaport, JM (reprint author), Sir Mortimer B Davis Jewish Hosp, Dept Otolaryngol, Room E-209,3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. NR 23 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 1999 VL 121 IS 3 BP 176 EP 179 DI 10.1016/S0194-5998(99)70167-1 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 233PY UT WOS:000082436300002 PM 10471853 ER PT J AU Nadol, JB AF Nadol, JB CA Resident Educ Comm Soc Univ Otolaryngologists TI Training the physician-scholar in otolaryngology-head and neck surgery SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID DISEASE; FACULTY AB The Resident Education Committee of the Society of University Otolaryngologists constructed a questionnaire for young academic otolaryngologist head and neck surgeons to better understand their training background and to garner their opinions concerning adequacy or deficiencies in various aspects of that training. The questionnaire was mailed to 145 individuals who were in academic posts for 5 years or fewer in 1997. There was an overall response rate of 88.3%. Of the 128 respondents, 89% identified additional training, most commonly a clinical fellowship, in preparation for an academic career. The median number of hours per week devoted to professionally related activity was 61, of which two thirds was spent in direct patient care. The most common source of funds to pursue research activities was intradepartmental resources. Most individuals were satisfied with their jobs, although one quarter were considering leaving academic practice within the year. The single most important reason motivating selection of an academic career was a desire to teach. Details of the specific training and competencies and recommendations for improvement in resident training were obtained. Specific recommendations were generated for improving the training of future academic otolaryngologists; these recommendations include clarify of job description, a single track for clinical training for academicians and nonacademicians, more training in pertinent skills including research training, protected time for research, and amelioration of some of the downsides of academic life. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 31 Z9 31 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 1999 VL 121 IS 3 BP 214 EP 219 DI 10.1016/S0194-5998(99)70174-9 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 233PY UT WOS:000082436300009 PM 10471860 ER PT J AU Orlov, MV Messenger, JC Tobias, S Smith, CW Waider, W Winters, R Schandling, A Castellanet, M AF Orlov, MV Messenger, JC Tobias, S Smith, CW Waider, W Winters, R Schandling, A Castellanet, M TI Transesophageal echocardiographic visualization of left ventricular malpositioned pacemaker electrodes: Implications for lead extraction procedures SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE transesophageal echocardiography; lead extraction; pacemaker lead; complications AB Two cases of malpositioned LV electrodes are presented. Transesophageal echocardiography (TEE) allowed for a careful inspection of left-sided leads and for tracking their course. One LV and two right-sided leads were safely retrieved with TEE monitoring. One chronic LV lead was left in place as it was heavily fibrosed. TEE was helpful in the inspection and monitoring of the extraction and also in guided traction efforts. This is the first published report of echocardiographic visualization of the lead retrieval procedure. C1 Univ Calif Irvine, Irvine, CA 92717 USA. Mem Heart Inst, Long Beach, CA USA. RP Orlov, MV (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. NR 8 TC 8 Z9 8 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD SEP PY 1999 VL 22 IS 9 BP 1407 EP 1409 DI 10.1111/j.1540-8159.1999.tb00638.x PG 3 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 243NG UT WOS:000083003700019 PM 10527026 ER PT J AU Poussaint, TY Yousuf, N Barnes, PD Anthony, DC Zurakowski, D Scott, RM Tarbell, NJ AF Poussaint, TY Yousuf, N Barnes, PD Anthony, DC Zurakowski, D Scott, RM Tarbell, NJ TI Cervicomedullary astrocytomas of childhood: clinical and imaging follow-up SO PEDIATRIC RADIOLOGY LA English DT Article ID BRAIN-STEM GLIOMAS; TUMORS; DIAGNOSIS; JUNCTION; CHILDREN AB Background. Cervicomedullary astrocytomas are a unique subset of brainstem tumors in children because they have a good prognosis when compared to the pontine subset of brainstem gliomas. Objective. To review the clinical and imaging findings in a series of children with cervicomedullary astrocytomas as to diagnosis and management. Materials and methods. A retrospective review of eleven children (six females, five males, age range: 10 days-18 years; mean = 7 years) with cervicomedullary tumors was done including the clinical presentation, imaging studies (MR: eleven, CT and MR: four), surgical findings, pathological results, and follow-up clinical and imaging findings (range: 0.2-11 years; mean = 5.2 years). Results. Symptoms and signs were delayed and protracted, often occurring over months to years (mean = 2.3 years, range 0.5-7 years). The tumors expanded the dorsal medulla and involved the upper cervical spinal cord (mean maximum tumor diameter = 4.4 cm). Only three patients had hydrocephalus. In three of four cases the tumor was not seen on CT. On MR, the majority of the tumors were T1 hypointense and T2 hyperintense. Treatment consisted of surgery only in six patients, surgery and radiation therapy in four, and surgery, chemotherapy, and radiation in one. There was recurrent local disease in four patients and on follow-up metastatic disease in the brain in one. On follow-up the majority of the patients are alive and stable (mean = 5.2 years, range 0.2-11 years). There has been one death. The majority of tumors were pilocytic astrocytomas. Conclusion. Cervicomedullary tumors are a unique subset of brainstem gliomas in childhood that present with a long duration of symptoms and a greater long-term survival than pontine gliomas. C1 Childrens Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Res Comp & Biostat, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Radiat Oncol Unit, Boston, MA 02114 USA. RP Poussaint, TY (reprint author), Childrens Hosp, Dept Radiol, Div Neuroradiol, 300 Longwood Ave, Boston, MA 02115 USA. OI Anthony, Douglas/0000-0002-3815-2240 NR 21 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD SEP PY 1999 VL 29 IS 9 BP 662 EP 668 PG 7 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 231GZ UT WOS:000082300900003 ER PT J AU Joffe, S Ray, GT Escobar, GJ Black, SB Lieu, TA AF Joffe, S Ray, GT Escobar, GJ Black, SB Lieu, TA TI Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants SO PEDIATRICS LA English DT Article DE respiratory syncytial virus infections; bronchiolitis; cost-effectiveness analysis; neonatal infections; prematurity; infections; respiratory; intensive care; neonatal; bronchopulmonary dysplasia; chronic lung disease; seasonal variation; prophylaxis; passive immunization ID BRONCHOPULMONARY DYSPLASIA; CANADIAN CHILDREN; IMMUNE GLOBULIN; RISK-FACTORS; INFECTION AB Objectives. To evaluate the costs and benefits of two new agents, respiratory syncytial virus immune globulin (RSVIG) and palivizumab, to prevent respiratory syncytial virus (RSV) infection among premature infants discharged from the neonatal intensive care unit (NICU) before the start of the RSV season. Method. Decision analysis was used to compare the projected societal cost-effectiveness of three strategies-RSVIG, palivizumab, and no prophylaxis-among a hypothetical cohort of premature infants. Probabilities and costs of hospitalization were derived from a cohort of 1721 premature infants discharged from six Kaiser Permanente-Northern California NICUs. Efficacies of prophylaxis were based on published trials. Costs of prophylaxis were derived from published sources. Mortality among infants hospitalized for RSV was assumed to be 1.2%. Future benefits were discounted at 3%. Results. Palivizumab was both more effective and less costly than RSVIG. Cost-effectiveness varied widely by subgroup. Palivizumab appeared most cost-effective for infants whose gestational age was less than or equal to 32 weeks, who required greater than or equal to 28 days of oxygen in the NICU, and who were discharged from the NICU from September through November. In this subgroup, palivizumab was predicted to cost $12 000 per hospitalization averted (after taking into account savings from prevention of RSV admissions) or $33 000 per life-year saved, and the number needed to treat to avoid one hospitalization was estimated at 7.4. However, for all other subgroups, ratios ranged from $39 000 to $420 000 per hospitalization averted or $110 000 to $1 200 000 per life-year saved, and the number needed to treat extended from 15 to 152. The results were sensitive to varying assumptions about the cost and efficacy of prophylaxis, as well as the probability of hospitalization, but were less sensitive to the cost of hospitalization. Conclusion. In our model, the cost of prophylaxis against RSV for most subgroups of preterm infants was high relative to the benefits realized. Lower costs might permit the benefits of prophylaxis to be extended to additional groups of preterm infants. C1 Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Kaiser Permanente Med Care Program, Dept Qual & Utilizat, Oakland, CA USA. Kaiser Permanente Med Care Program, Dept Pediat, Walnut Creek, CA USA. Kaiser Permanente Med Care Program, Div Res, Walnut Creek, CA USA. RP Lieu, TA (reprint author), Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, 126 Brookline Ave,Suite 200, Boston, MA 02215 USA. OI Joffe, Steven/0000-0002-0667-7384 NR 25 TC 136 Z9 137 U1 0 U2 1 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 1999 VL 104 IS 3 BP 419 EP 427 DI 10.1542/peds.104.3.419 PG 9 WC Pediatrics SC Pediatrics GA 240FV UT WOS:000082816000002 PM 10469764 ER PT J AU Maguire, CT Fisher, DE Berul, CI AF Maguire, CT Fisher, DE Berul, CI TI Cardiac conduction in mutant microphthalmia mice. SO PEDIATRICS LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER 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 1999 VL 104 IS 3 BP 655 EP 655 PN 3 PG 1 WC Pediatrics SC Pediatrics GA 243LR UT WOS:000082999600011 ER PT J AU Insoft, RM Carew, A AF Insoft, RM Carew, A TI A novel pediatric residency transport rotation curriculum: Meeting the RRC requirements and beyond. SO PEDIATRICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Pediat Transport Program, Partners Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 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 1999 VL 104 IS 3 BP 792 EP 792 PN 3 PG 1 WC Pediatrics SC Pediatrics GA 243LR UT WOS:000082999600330 ER PT J AU Duggan, C Lasche, J McCarty, M Mitchell, K Dershewitz, R Lerman, SJ Higham, M Radzevich, A Kleinman, RE AF Duggan, C Lasche, J McCarty, M Mitchell, K Dershewitz, R Lerman, SJ Higham, M Radzevich, A Kleinman, RE TI Oral rehydration solution for acute diarrhea prevents subsequent unscheduled follow-up visits SO PEDIATRICS LA English DT Article DE diarrhea; oral rehydration solutions; practice-based research; dehydration; vomiting ID UNITED-STATES; THERAPY; CHILDREN; BARRIERS AB Background. Oral rehydration solutions (ORS) for the treatment of acute diarrhea remain an underutilized therapy in the United States, despite multiple clinical trials confirming their efficacy and safety. Economic barriers to their use have been identified. Objective. To determine whether providing ORS to patients at the time of their office visit for acute diarrhea can increase ORS utilization and reduce unscheduled follow-up visits. Design. Randomized, controlled clinical trial. Setting. Seven health centers of a large health maintenance organization. Participants. Children (N = 479) 0 to 60 months of age with acute diarrhea (at least three watery or loose stools in the previous 24 hours for less than or equal to 7 days). Intervention. Prescription for 2 quarts of ORS filled for free at on-site pharmacy plus written instructions versus written instructions alone. Primary Outcome Measures. Self-reported use of ORS; unscheduled follow-up visits in office, urgent care, and/or emergency department setting. Results. Subjects in the intervention group were significantly more likely to use ORS after the initial office visit (85% vs 71%; RR: 1.19; 95% CI: 1.08-1.32). Of the standard treatment group subjects, 40 (17.3%) sought unscheduled follow-up care for diarrhea versus 27 (10.9%) of the intervention group subjects (RR: 0.63; 95% CI: 0.40-0.99). Subjects seeking unscheduled follow-up care tended to younger (15.7 vs 19.4 months old), have more stools (7.1 vs 6.2 stools), and more vomiting episodes (4.1 vs 3.0) in the 24 hours before initial evaluation than those not seeking unscheduled follow-up care. Multivariate analysis showed that randomization to the intervention group was associated with a 25% reduction in unscheduled follow-up visits for acute diarrhea. Conclusions. Providing ORS to families at the time of their office visit for acute diarrhea is associated with a significant increase in ORS use and substantially reduces the need for unscheduled follow-up visits. Health maintenance organizations should consider routine provision of ORS to children presenting with acute diarrhea. C1 Childrens Hosp, Clin Nutr Serv, Div GI Nutr, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Pilgrim Hlth Care, Harvard Vanguard Med Associates, Boston, MA USA. RP Duggan, C (reprint author), Childrens Hosp, Clin Nutr Serv, Div GI Nutr, Combined Program Pediat Gastroenterol & Nutr, 300 Longwood Ave, Boston, MA 02115 USA. FU NIDDK NIH HHS [5-T32-DK07477-12] NR 18 TC 8 Z9 9 U1 0 U2 1 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 1999 VL 104 IS 3 AR e29 DI 10.1542/peds.104.3.e29 PG 5 WC Pediatrics SC Pediatrics GA 240FV UT WOS:000082816000025 PM 10469812 ER PT J AU Belkin, GS AF Belkin, GS TI Writing about their science: American interest in Soviet psychiatry during the post-Stalin Cold War SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Article C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Erich Lindeman Mental Hlth Ctr, Boston, MA 02114 USA. RP Belkin, GS (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 25 Staniford St, Boston, MA 02114 USA. NR 37 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0031-5982 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD FAL PY 1999 VL 43 IS 1 BP 31 EP 46 PG 16 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA 275MN UT WOS:000084824100002 PM 10701220 ER PT J AU Elisseeff, J Anseth, K Sims, D McIntosh, W Randolph, M Yaremchuk, M Langer, R AF Elisseeff, J Anseth, K Sims, D McIntosh, W Randolph, M Yaremchuk, M Langer, R TI Transdermal photopolymerization of poly(ethylene oxide)-based injectable hydrogels for tissue-engineered cartilage SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 44th Annual Conference of the American-Society-for-Artificial-Internal-Organs CY APR 23-25, 1998 CL NEW YORK, NEW YORK SP Amer Soc Artificial Internal Organs ID IN-SITU PHOTOPOLYMERIZATION; BARRIERS; POLYMERS AB Transdermal photopolymerization, a minimally invasive method for implantation, was used to subcutaneously place a mixture of polymer and isolated chondrocytes to regenerate cartilage tissue in vivo. Semi-interpenetrating networks of varying proportions of poly(ethylene oxide)dimethacrylate and poly(ethylene oxide) and primary, bovine articular chondrocytes were implanted in athymic mice. Four mice (12 implants) were harvested at 2, 4, and 7 weeks. Chondrocytes survived implantation and photopolymerization and formed neocartilage containing 1.5 to 2.9% wet weight collagen and 4 to 7% glycosaminoglycan Thirty-five percent of the total collagen was type II collagen. Histologic analysis exhibited tissue structure resembling neocartilage, and safranin O staining demonstrated glycosaminoglycan distribution throughout the hydrogels. This study demonstrates the potential use of transdermal photopolymerization for minimally invasive subcutaneous implantation of hydrogels and chondrocytes for in vivo cartilage regeneration. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Univ Colorado, Dept Chem Engn, Boulder, CO 80309 USA. RP Langer, R (reprint author), MIT, Dept Chem Engn, E25-342, Cambridge, MA 02139 USA. FU NIDCR NIH HHS [DE13023] NR 19 TC 141 Z9 148 U1 1 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP PY 1999 VL 104 IS 4 BP 1014 EP 1022 DI 10.1097/00006534-199909040-00017 PG 9 WC Surgery SC Surgery GA 231HN UT WOS:000082302500017 PM 10654741 ER PT J AU Clark, RA AF Clark, RA TI Thematic review series VIII: Phagocyte antimicrobial systems - Introduction SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Editorial Material C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Clark, RA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. FU NIAID NIH HHS [R01 AI020866, AI20866, R37 AI020866] NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD SEP-OCT PY 1999 VL 111 IS 5 BP 371 EP 372 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 236KN UT WOS:000082598900001 PM 10519155 ER PT J AU Vallera, DA Seo, SY Panoskaltsis-Mortari, A Griffin, JD Blazar, BR AF Vallera, DA Seo, SY Panoskaltsis-Mortari, A Griffin, JD Blazar, BR TI Targeting myeloid leukemia with a DT390-mIL-3 fusion immunotoxin: ex vivo and in vivo studies in mice SO PROTEIN ENGINEERING LA English DT Article DE bone marrow transplantation; cancer; diphtheria toxin; IL-3; immunotoxin ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; CHRONIC MYELOGENOUS LEUKEMIA; BINDING DOMAIN SUBSTITUTION; DIPHTHERIA-TOXIN FRAGMENT; ACUTE MYELOCYTIC-LEUKEMIA; MARROW PROGENITOR CELLS; GENETIC CONSTRUCTION; GM-CSF; RECEPTOR EXPRESSION AB The IL-3 receptor was expressed on a high frequency of myeloid leukemia cells and also on hematopoietic and vascular cells. We previously showed that a recombinant IL-3 fusion immunotoxin (DT390IL-3) expressed by splicing the murine IL-3 gene to a truncated diphtheria toxin (DT390) gene selectively killed IL-3R(+) expressing cells and was not uniformly toxic to uncommited BM progenitor cells (Chan,C.-H,, Blazar,B,R., Greenfield,L., Kreitman,R.J. and Vallera,D.A., 1996, Blood, 88, 1445-1456), Thus, we explored the feasability of using DT390IL-3 as an antileukemia agent. DT390IL-3 was toxic when administered to mice at doses as low as 0.1 mu g/day, The dose limiting toxicity appeared to be related to platelet and bleeding effects of the fusion toxin, Because of these effects, DT390IL-3 was Studied ex vivo as a means of purging contaminating leukemia cells from BM grafts in a murine autologous BM transplantation. In this setting, as few as 1000 IL-3R-expressing, bcr/abl transformed myeloid 32Dp210 leukemia cells were lethal, An optimal purging interval of 10 nM/l for 8 h eliminated leukemia cells from 32Dp210/BM: mixtures given to lethally irradiated (8 Gy) C3H/HeJ syngeneic mice. Mice given treated grafts containing BM and a lethal dose of 32Dp210 cells survived over 100 days while mice given untreated grafts did not survive (P < 0.00001). DT390IL-3 may prove highly useful for ex vivo purging of lethal malignant leukemia cells from autologous BM grafts. C1 Univ Minnesota, Ctr Canc, Dept Therapeut Radiol, Sect Expt Canc Immunol, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Canc, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA. Dong A Univ, Coll Med, Dept Microbiol, Pusan, South Korea. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Vallera, DA (reprint author), Univ Minnesota, Ctr Canc, Dept Therapeut Radiol, Sect Expt Canc Immunol, Minneapolis, MN 55455 USA. FU NCI NIH HHS [R01-CA36725, R01-CA72669] NR 50 TC 12 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD SEP PY 1999 VL 12 IS 9 BP 779 EP 785 DI 10.1093/protein/12.9.779 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 246MN UT WOS:000083167700010 PM 10506288 ER PT J AU Goff, DC AF Goff, DC TI The comorbidity of obsessive-compulsive disorder and schizophrenia SO PSYCHIATRIC ANNALS LA English DT Editorial Material ID NEGATIVE SYMPTOMS; CONTROLLED TRIAL; FLUOXETINE C1 Massachusetts Gen Hosp, Psychot Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. RP Goff, DC (reprint author), Massachusetts Gen Hosp, Psychot Disorders Program, Boston, MA 02114 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD SEP PY 1999 VL 29 IS 9 BP 533 EP 536 PG 4 WC Psychiatry SC Psychiatry GA 236QQ UT WOS:000082610400010 ER PT J AU Kilzieh, N Akiskal, HS AF Kilzieh, N Akiskal, HS TI Rapid-cycling bipolar disorder - An overview of research and clinical experience SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID MANIC-DEPRESSIVE ILLNESS; THYROID-FUNCTION; PSYCHIATRIC-DISORDERS; LITHIUM TREATMENT; ANTI-DEPRESSANTS; FAMILY HISTORY; LONG-TERM; VALPROATE; THERAPY; ANTIDEPRESSANTS AB Rapid-cycling bipolar disorder (RCBD) has been recognized as a refractory course pattern of the illness in up to 20% of bipolar, especially type II, patients. Data are generally consistent in indicating that RCBD is more common in women. Familial bipolarity does not distinguish RCBD from other bipolar patients. This article reviews evidence of putative risk factors, such as antecedent cyclothymic temperament, borderline hypothyroidism, and exposure to antidepressant medications; however, de novo rapid-cycling in the absence of such factors also occurs. Clinicians are admonished to refrain from using antidepressants-with the possible exception of bupropion-and to maintain patients on mood stabilizer combinations of which valproate appears to be the most useful ingredient. C1 VA Puget Sound Hlth Care Serv, Amer Lake Div, Tacoma, WA 98493 USA. Univ Calif San Diego, Dept Psychiat, Int Mood Ctr, La Jolla, CA 92093 USA. San Diego VA Med Ctr, San Diego, CA USA. RP Kilzieh, N (reprint author), VA Puget Sound Hlth Care Serv, Amer Lake Div, 116-MHC, Tacoma, WA 98493 USA. NR 111 TC 83 Z9 85 U1 8 U2 16 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD SEP PY 1999 VL 22 IS 3 BP 585 EP + DI 10.1016/S0193-953X(05)70097-6 PG 24 WC Psychiatry SC Psychiatry GA 240LQ UT WOS:000082827800006 PM 10550857 ER PT J AU Lee, BX Wexler, BE AF Lee, BX Wexler, BE TI Physics and the quandaries of contemporary psychiatry: Review and research SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID QUANTUM-MECHANICS; BRAIN-FUNCTION; CONSCIOUSNESS; MICROTUBULES; COHERENCE; MODEL AB Although in physics, quantum mechanical principles have long replaced Newtonian ones, we continue to apply the latter in models of the mind and its diseases. This article discusses the possible theoretical application of quantum principles to mind-brain function. Empirically, this study tested which of these principles practicing psychiatrists found more applicable in clinical practice. Psychiatrists (N = 382) at universities around the United States were asked to answer a questionnaire that contained clinical scenarios reflecting mental, interpersonal, or therapeutic processes corresponding to quantum or classical physical principles. Respondents (N = 191) were significantly more likely to rate scenarios reflecting quantum principles as being consistent with their experience than they were those reflecting classical principles (p <.0005). This effect was significantly greater in more experienced psychiatrists. Quantum physics, a powerful tool in understanding properties of both micro- and macrolevel phenomena, may have implications at the human level, invoking the roles of observer, interpersonal relationships, and resources such as resiliency and creativity. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Lee, BX (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,WAC 812, Boston, MA 02114 USA. NR 38 TC 2 Z9 2 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD FAL PY 1999 VL 62 IS 3 BP 222 EP 234 PG 13 WC Psychiatry SC Psychiatry GA 263JN UT WOS:000084121700003 PM 10612114 ER PT J AU Goldstein, LE Sporn, J Brown, S Kim, H Finkelstein, J Gaffey, GK Sachs, G Stern, TA AF Goldstein, LE Sporn, J Brown, S Kim, H Finkelstein, J Gaffey, GK Sachs, G Stern, TA TI New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment SO PSYCHOSOMATICS LA English DT Article ID WEIGHT-GAIN; CLOZAPINE; PANCREATITIS C1 Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Psychiat, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Dept Psychiat, Worcester, MA 01655 USA. Boston Vet Affairs Outpatient Clin, Dept Psychiat, Boston, MA USA. RP Goldstein, LE (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Psychiat, Room 812, Boston, MA 02114 USA. NR 22 TC 156 Z9 160 U1 0 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 1999 VL 40 IS 5 BP 438 EP 443 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 231HL UT WOS:000082302200011 PM 10479950 ER PT J AU Powell, A AF Powell, A TI Body and soul: The role of object relations in faith, shame and healing SO PSYCHOSOMATICS LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Powell, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 1999 VL 40 IS 5 BP 446 EP 446 PG 1 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 231HL UT WOS:000082302200013 ER PT J AU Holmes, WC Shea, JA AF Holmes, WC Shea, JA TI Two approaches to measuring quality of life in the HIV/AIDS population: HAT-QoL and MOS-HIV SO QUALITY OF LIFE RESEARCH LA English DT Article DE acquired immunodeficiency syndrome; human immunodeficiency virus; quality of life ID FORM HEALTH SURVEY; IMMUNODEFICIENCY-VIRUS INFECTION; OF-LIFE; MEDICAL OUTCOMES; SURVEY SF-36; VALIDITY; RELIABILITY; INSTRUMENT; TESTS; DISEASE AB Objectives: Reduce the number of HIV/AIDS-Targeted Quality of Life (HAT-QoL) items, assess psychometric performance of the shortened HAT-QoL, and compare psychometric performance of HAT-QoL to that of Medical Outcomes study HIV Health Survey (MOS-HIV). Design/Subjects: Convenience sample of 215 cross-sectionally studied seropositive individuals. Methods: Subjects completed the HAT-QoL, MOS-HIV, and sociodemographic and disease-specific questions. HAT-QoL and MOS-HIV responses were entered, separately, into principal components analysis (PCA). Results from PCA, internal consistency and correlation assessments were used to aid the item removal process. Dimension characteristics (e.g., score distributions, internal consistency, scaling success rates, intercorrelations, construct validity) were evaluated. Results: PCA of subjects' (80% male; 45% white; 62% gay/bisexual) responses revealed nine previously identified HAT-QoL dimensions. The measure was shortened by removing 12 items. Two HAT-QoL dimensions (HIV mastery and provider trust) had ceiling effects. All internal consistency coefficients were > 0.80, except those for sexual function (0.57) and medication concerns (0.57). HAT-QoL scaling success rates were > 90% for 7 of 9 dimensions, and a majority of dimensions showed minimal to low intercorrelations. Validity assessments indicated consistent, expected relationships (p less than or equal to 0.05) for all dimensions except the medication concerns and provider trust dimensions. PCA indicated five MOS-HIV factors. Six of the 11 previously defined MOS-HIV dimensions - physical, role, social, and cognitive function, pain, and health transition - had substantial ceiling effects. MOS-HIV scaling success rates were > 90% for only 2 out of 8 evaluable dimensions; three dimensions had very low (40-73%) scaling success rates. Most MOS-HIV dimensions were moderately-to-highly intercorrelated. Validity assessments indicated consistent, expected relationships for all MOS-HIV dimensions. Conclusions: Six dimensions of the shortened HAT-QoL instrument (overall function, disclosure worries, health worries, financial worries, HIV mastery, and life satisfaction) exhibited good psychometric properties, including limited ceiling effects, low dimension intercorrelations, high internal consistency, and evidence for construct validity. All multi-item MOS-HIV dimensions had high internal consistency and all dimensions revealed consistent evidence for construct validity. C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Holmes, WC (reprint author), Philadelphia Vet Affairs Med Ctr, 733 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 35 TC 55 Z9 58 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD SEP PY 1999 VL 8 IS 6 BP 515 EP 527 DI 10.1023/A:1008931006866 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 235XA UT WOS:000082567700006 PM 10548867 ER PT J AU Novelline, RA AF Novelline, RA TI Advances in Emergency Radiology II - Preface SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Novelline, RA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 1999 VL 37 IS 5 BP IX EP IX PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 234LB UT WOS:000082485200001 ER PT J AU Rao, PM Rhea, JT Novelline, RA AF Rao, PM Rhea, JT Novelline, RA TI Helical CT of appendicitis and diverticulitis SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PRIMARY EPIPLOIC APPENDAGITIS; BARIUM ENEMA; COLONIC DIVERTICULITIS; PERCUTANEOUS DRAINAGE; QUADRANT PERITONITIS; COMPUTED-TOMOGRAPHY; CONTRAST MATERIAL; ABDOMINAL-PAIN; ARROWHEAD SIGN; DIAGNOSIS AB Helical CT, combined with advances in CT protocols, has significantly advanced diagnostic imaging of appendicitis and diverticulitis. Confirmation or exclusion of appendicitis or diverticulitis, and identification of most alternative conditions, can be accomplished accurately and quickly with CT. This article reviews the current state of clinical diagnosis, helical CT techniques, performance and interpretation, and indications for CT in patients with clinically suspected appendicitis and diverticulitis. C1 Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 61 TC 26 Z9 32 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 1999 VL 37 IS 5 BP 895 EP + DI 10.1016/S0033-8389(05)70137-8 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 234LB UT WOS:000082485200003 PM 10494277 ER PT J AU Weissleder, R AF Weissleder, R TI Molecular imaging: Exploring the next frontier SO RADIOLOGY LA English DT Editorial Material DE editorials; genes and genetics; magnetic resonance (MR), utilization; radionuclide imaging ID MAGNETIC-RESONANCE MICROSCOPY; POSITRON-EMISSION-TOMOGRAPHY; HERPES-SIMPLEX VIRUS; KINASE GENE-TRANSFER; IN-VIVO; P-GLYCOPROTEIN; DRUG DISCOVERY; TURBID MEDIA; EXPRESSION; THERAPY 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, Charlestown, MA 02129 USA. FU NCI NIH HHS [R0CA174424, R01CA54886]; NINDS NIH HHS [R01NS35258] NR 62 TC 223 Z9 303 U1 8 U2 42 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1999 VL 212 IS 3 BP 609 EP 614 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 229LT UT WOS:000082196600004 PM 10478223 ER PT J AU Sorensen, AG Wu, O Copen, WA Davis, TL Gonzalez, RG Koroshetz, WJ Reese, TG Rosen, BR Wedeen, VJ Weisskoff, RM AF Sorensen, AG Wu, O Copen, WA Davis, TL Gonzalez, RG Koroshetz, WJ Reese, TG Rosen, BR Wedeen, VJ Weisskoff, RM TI Human acute cerebral ischemia: Detection of changes in water diffusion anisotropy by using MR imaging SO RADIOLOGY LA English DT Article DE anisotropy; brain, diffusion; brain, infarction; brain, ischemia; brain, MR; diffusion tensor; magnetic resonance (MR), diffusion study; magnetic resonance (MR), echo planar ID MYELIN FIBER ORIENTATION; NORMAL BRAIN-DEVELOPMENT; HUMAN WHITE-MATTER; ACUTE HUMAN STROKE; WEIGHTED MR; LESION VOLUMES; SELF-DIFFUSION; B-MATRIX; TENSOR; ECHO AB PURPOSE: To determine the optimal choice of a scalar metric of anisotropy and (b) determine by means of magnetic resonance imaging if changes in diffusion anisptropy occurred in acute human ischemic stroke. MATERIALS AND METHODS: The full diffusion tensor over the entire brain was measured. To optimize the choice of a scalar anisotropy metric, the performances of scalar indices in simulated models and in a healthy volunteer were analyzed. The anisotropy, trace apparent diffusion coefficient (ADC), and eigenvalues of the diffusion tensor in lesions and contralateral normal brain were compared in 50 patients with stroke. RESULTS: Changes in anisotropy in patients-were quantified by using fractional anistropy because it provided the best performance in terms of contrast-to-noise ratio as a function of signal-to-noise ratio in simulations. The anisotropy of ischemic white matter decreased (P = .01). Changes in anisotropy in ischemic gray matter were not significant (P = .63). The trace ADC decreased for ischemic gray matter and white matter (P < .001). The first and second eigenvalues decreased in both ischemic gray and ischemic white matter (P < .001). The third eigenvalue decreased in ischemic gray (P = .001) and white matter (P = .03). CONCLUSION: Gray matter is mildly anisotropic in normal and early ischemic states. However, early white matter ischemia is associated with not only changes in trace ADC values but also significant changes in the anisotropy, or shape, of the water self-diffusion tensor. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02119 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02119 USA. Harvard Univ, Sch Med, Neuroradiol Sect, Boston, MA 02119 USA. Harvard Univ, Sch Med, MGH NMR Ctr, Boston, MA 02119 USA. RP Sorensen, AG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Mailcode CNY 149-2301, Boston, MA 02119 USA. NR 42 TC 210 Z9 244 U1 0 U2 7 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1999 VL 212 IS 3 BP 785 EP 792 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 229LT UT WOS:000082196600029 PM 10478247 ER PT J AU Carpo, BG Grevelink, JM Grevelink, SV AF Carpo, BG Grevelink, JM Grevelink, SV TI Laser treatment of pigmented lesions in children SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article ID SWITCHED RUBY-LASER; PULSED DYE-LASER; ND-YAG LASER; ALUMINUM-GARNET LASER; AU-LAIT MACULES; NEVUS-SPILUS; TRAUMATIC TATTOOS; CONGENITAL NEVI; SELECTIVE PHOTOTHERMOLYSIS; DOSE-RESPONSE AB A variety of losers can be used to effectively treat cutaneous pigmentation in children, Furthermore, using the principle of selective photothermolysis, several pigment-specific losers can be used to achieve significant clinical improvement if not complete removal of pigmented lesions with greatly reduced risks of scarring. textural or pigmentary changes, A summary of laser treatments for pigmented lesions that commonly present in children including cafe-au-lait macules, nevus of Ota and other dermal melanocytosis, congenital melanocytic nevus, nevus spilus, lentigines, epidermal nevus, Becker's nevus, and tattoos is presented. Overall, laser treatment is a very safe, effective treatment option that could offer distinct advantages compared with other conventional modalities. Copyright (C) 1999 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dermatol Laser Ctr, Boston, MA 02114 USA. RP Grevelink, SV (reprint author), Childrens Hosp, Dermatol Program, 300 Longwood Ave, Boston, MA 02115 USA. NR 60 TC 21 Z9 24 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 1085-5629 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD SEP PY 1999 VL 18 IS 3 BP 233 EP 243 DI 10.1016/S1085-5629(99)80021-2 PG 11 WC Dermatology; Surgery SC Dermatology; Surgery GA 227KD UT WOS:000082078800007 PM 10468043 ER PT J AU Sherman, GF Holmes, LB AF Sherman, GF Holmes, LB TI Cerebrocortical microdysgenesis is enhanced in C57BL/6J mice exposed in utero to acetazolamide SO TERATOLOGY LA English DT Article ID NEOCORTICAL ECTOPIAS; AUTOIMMUNE MICE; ENVIRONMENTAL ENRICHMENT; DEVELOPMENTAL DYSLEXIA; CARBONIC-ANHYDRASE; MOUSE; ANOMALIES; BEHAVIOR; MEMORY; CORTEX AB A small percentage of C57BL/6 mice spontaneously develop focal collections of neurons in the molecular layer of the cerebral neocortex. Usually only one "ectopia" is present in each affected brain. Studies in other mouse strains have shown that these ectopias occur before birth, probably because of a breach in the superficial glial membrane during neuronal migration. The ectopias are heritable and are caused by multiple genes. C57BL/6J mice exposed prenatally to acetazolamide, a carbonic anhydrase-specific inhibitor and teratogen, develop an increased frequency of limb malformations, especially in the right forelimb. In the present study, we hypothesized that the prevalence and severity of ectopias would be increased in acetazolamide-exposed mice because carbonic anhydrase plays a key role in brain development. Further, we wanted to determine whether there was a correlation between the side of limb deformity and the hemisphere containing an ectopia. Thus, we injected C57BL/6J time-mated mice intraperitoneally on embryonic day 9 with either sodium acetazolamide (750 mg/kg) or water. Histological analysis of the brains from 105 acetazolamide-exposed offspring and 89 control offspring revealed no difference in the overall prevalence of cerebrocortical ectopias between the acetazolamide and control groups: 34% of the acetazolamide-exposed and 28% of the control mice had ectopias. There was, however, a striking difference in the shape and size of ectopias: 67% of the ectopias were large in the acetazolamide-exposed group in comparison to 32% in controls. The acetazolamide-exposed offspring also were more likely to have multiple ectopias. Thus, there may be a genetic predisposition for developing ectopias in some mouse strains, but epigenetic factors such as prenatal exposure to acetazolamide can influence their severity. Teratology 60:137-142, 1999. (C) 1999 Wiley-Liss, Inc. C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Dyslexia Res Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. RP Sherman, GF (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Dyslexia Res Lab, Dana 752,330 Brookline Ave, Boston, MA 02215 USA. FU NICHD NIH HHS [HD 20806, HD 15241] NR 28 TC 5 Z9 5 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD SEP PY 1999 VL 60 IS 3 BP 137 EP 142 DI 10.1002/(SICI)1096-9926(199909)60:3<137::AID-TERA8>3.0.CO;2-1 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 233HJ UT WOS:000082421200008 PM 10471897 ER PT J AU Clavijo, OP Delgado, JC Yu, N Fraser, PA Yunis, EJ AF Clavijo, OP Delgado, JC Yu, N Fraser, PA Yunis, EJ TI HLA-Cw*1701 is associated with two sub-Saharan African-derived HLA haplotypes: HLA-B*4201, DRB1*03 and HLA-B*4202 without DRB1*03 SO TISSUE ANTIGENS LA English DT Article DE extended haplotypes; HLA-Cw alleles; HLA-B alleles; MHC; populations genetics ID CLASS-I; ALLELES; POLYMORPHISM; FREQUENCIES; POPULATION; GENE; DNA; MHC AB Different extended haplotypes have been described for many ethnic groups, such as African-Americans. The complotype FC(1,90)0 is in linkage disequilibrium with HLA-B42, DRB1*0302 in African-Americans and Southern African Xhosa individuals, suggesting a common ancestry. In order to analyze the distribution of Cw*17 alleles (Cw*1701, 1702) in relation to this African-derived extended haplotype, we studied a large panel of samples from African-American individuals and additionally a group of selected samples carrying HLA-B42, DR3 and HLA-B42, non-DR3 antigens. HLA alleles were assigned using sequence-specific amplification (SSP) and sequence-specific oligonucleotide probe hybridization (SSOP). We have found that all haplotypes (10 in total) carrying the extended haplotypes [HLA-B42, FC(1,90)0, DRB1*0302] were positive for HLA-Cw*1701. Interestingly, HLA B*4201 was found in all samples (17 in total) carrying HLA-B42, DR3, Cw*1701, whereas HLA-B*4202 was found in 10 out of 13 samples from individuals carrying HLA B42, Cw*1701 non-DR3. These findings suggest that HLA-Cw*17 polymorphism is conserved in different ethnic populations and that HLA-B42 alleles seem to separate at least different African-derived haplotypes. The historical context of these findings are important for the study of human evolution and they may be useful for the development of strategies in the search for possible donors in organ transplantation for African-derived populations. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Amer Red Cross, Dedham, MA USA. Ctr Blood Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. 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 [AI42374]; NIMH NIH HHS [MH-47029] NR 17 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 1999 VL 54 IS 3 BP 303 EP 306 DI 10.1034/j.1399-0039.1999.540316.x PG 4 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 240DV UT WOS:000082811300016 PM 10519372 ER PT J AU Imrich, A Ning, YY Koziel, H Coull, B Kobzik, L AF Imrich, A Ning, YY Koziel, H Coull, B Kobzik, L TI Lipopolysaccharide priming amplifies lung macrophage tumor necrosis factor production in response to air particles SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID ALVEOLAR MACROPHAGES; HOST-DEFENSE; POLLUTION; PULMONARY; PARTICULATE; ACTIVATION; INHALATION; CLEARANCE; MORTALITY; RECEPTORS AB Elevated concentrations of ambient air particles can result in increased mortality and morbidity, especially in people with preexisting pulmonary disease. We postulate that in the inflammatory milieu of diseased lungs, alveolar macrophages (AMs) may be primed for enhanced responses to stimuli such as inhaled air particles. To test this hypothesis in vitro, we first cultured normal AMs with or without lipopolysaccharide (LPS), We then incubated the cells with particle suspensions turban air particles (UAP, Washington, D.C,), residual oil fly ash (ROFA), concentrated respirable-size (PM2.5) air particles (CAPs), and inert TiO2) and compared rat and human AM production of the critical proinflammatory mediator, tumor necrosis factor (TNF). LPS priming amplified TNF production by both rat and human AMs in response to UAP and CAPs but not inert TiO2. There were also differences observed between rat and human AM responses to particle suspensions. Striking changes seen only in rat were cytotoxic effects of ROFA and diminished particle uptake in response to LPS priming. The potency of CAPs samples (which are collected on separate days) varied when comparing one day's sample with another. When centrifuged, the majority of bioactivity seen in particle suspensions (TNF release) remained within the pelleted fraction while the supernatant showed minimal bioactivity. The data suggest that AMs activated by extant pulmonary inflammation may promote further inflammation by an enhanced cytokine response to inhaled ambient air particles. (C) 1999 Academic Press. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Beth Israel Deaconnes Med Ctr, Div Pulm & Crit Care Med, Boston, MA 02115 USA. RP Imrich, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. FU NCEH CDC HHS [NIEHS 00002]; NIEHS NIH HHS [P01-ES-08129] NR 26 TC 55 Z9 58 U1 1 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP 1 PY 1999 VL 159 IS 2 BP 117 EP 124 DI 10.1006/taap.1999.8731 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 249RA UT WOS:000083345000006 PM 10495775 ER PT J AU Alwayn, IPJ van Bockel, HJ Daha, MR Scheringa, M AF Alwayn, IPJ van Bockel, HJ Daha, MR Scheringa, M TI Hyperacute rejection in the guinea pig-to-rat model without formation of the membrane attack complex SO TRANSPLANT IMMUNOLOGY LA English DT Article ID COBRA VENOM FACTOR; CARDIAC XENOGRAFT SURVIVAL; TOTAL-LYMPHOID IRRADIATION; CYCLOSPORINE; MECHANISM; COMBINATIONS; PROLONGATION; SPLENECTOMY; DEPLETION; THERAPY AB The guinea pig (GP)-to-rat transplantation model has been widely used to study hyperacute rejection (HAR) of xenografts. In this model heart graft survival beyond 8 days has never been reported. In contrast, survival times of kidney and heart grafts up to 62 days have been reported in the discordant pig-to-primate model. It is not clear why it is so much more difficult to obtain long-term graft survival in the GP-to-rat model as compared to the pig-to-primate model. We hypothesized that mechanisms other than activation of complement may be involved in the rejection of guinea pig grafts by rat recipients. Therefore, we have studied in detail the rejection of GP aortic grafts by rat recipients, either PVG/c(+) (complement competent, group 1), or PVG/c(-) (complement C6 deficient, group 2). PVG/c(-) rats are not able to form the membrane attack complex (MAC) of complement. Forty-four GP-to-rat aortic transplantations were performed successfully. Recipient rats were sacrificed at various intervals after transplantation (4, 24 and 48 h, and 7 and 28 days, three to six animals per time point per group). Twenty-four hours after transplantation the number of cells in the media was significantly decreased from 11.1 +/- 0.9 cells/mm(2) to 3.1 +/- 2.8 cells/mm(2) in group 1, whereas the number of medial cells in group 2 remained the same. The number of medial cells was significantly decreased in both groups at 48 h post-transplantation (group 1: 1.8 +/- 2.2 cells/mm(2); group 2: 5.5 +/- 3.0 cells/mm(2)). At that time no infiltrating cells were apparent in the grafts of either two groups. Seven days after transplantation, the number of medial cells remained low in group 1 (1.8 +/- 2.9 cells/mm2) but was increased in group 2 (10.7 +/- 2.6 cells/mm(2)) as a consequence of infiltrating immune cells. These infiltrating cells consisted mainly of macrophages, but also T cells and NK cells. At 28 days after transplantation the grafts in both groups were completely reorganized and no distinction could be made between media and adventitia. These results show that rejection of GP grafts by rat recipients can occur in the absence of both MAC of complement and immune competent cells. This MAC and immune cells independent type of rejection has not been described before and may explain the difficulty in obtaining long-term graft survival in the GP-to-rat xenotransplantation model. C1 Leiden Univ, Med Ctr, Dept Surg, Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands. RP Alwayn, IPJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. NR 19 TC 4 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD SEP PY 1999 VL 7 IS 3 BP 177 EP 182 DI 10.1016/S0966-3274(99)80037-9 PG 6 WC Immunology; Transplantation SC Immunology; Transplantation GA 262DF UT WOS:000084049800006 PM 10608301 ER PT J AU Fishman, JA AF Fishman, JA TI Infection in xenotransplantation: A clinical approach SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Vth Congress of the Catalan-Transplantation-Society CY JAN 24-27, 1999 CL BARCELONA, SPAIN SP Catalan Transplantat Soc ID ENDOGENOUS RETROVIRUS; NO EVIDENCE; HUMAN-CELLS; VIRUS; IDENTIFICATION; LYMPHOCYTES; INVITRO; INVIVO C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. NR 23 TC 5 Z9 5 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 1999 VL 31 IS 6 BP 2225 EP 2227 DI 10.1016/S0041-1345(99)00315-2 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 236PT UT WOS:000082608300012 PM 10500554 ER PT J AU Vidal, M Endoh, H AF Vidal, M Endoh, H TI Prospects for drug screening using the reverse two-hybrid system SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID RAS FARNESYLTRANSFERASE INHIBITORS; PROTEIN-PROTEIN INTERACTIONS; SACCHAROMYCES-CEREVISIAE; 2-HYBRID SYSTEM; GENETIC SELECTION; YEAST; DISSOCIATION; MUTATIONS; BINDING; IDENTIFICATION AB Rational drug-screening strategies have been limited by the number of available protein targets, The fields of genomics and functional genomics are now merging into 'chemical genomics' approaches, in which large numbers of potential target proteins can be used in standardized high-throughput drug-screening assays, Because protein-protein interactions are critical to most biological processes and can be tested in standardized assays, they may represent optimal targets in the chemical-genomics era. The reverse two-hybrid system appears to have several properties that would be critical for the success of this approach. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM Vidal@helix.mgh.harvard.edu FU NHGRI NIH HHS [1 RO1 HG01715-01] NR 57 TC 68 Z9 77 U1 1 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD SEP PY 1999 VL 17 IS 9 BP 374 EP 381 DI 10.1016/S0167-7799(99)01338-4 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 230RD UT WOS:000082263400008 PM 10461184 ER PT J AU Dirnagl, U Iadecola, C Moskowitz, MA AF Dirnagl, U Iadecola, C Moskowitz, MA TI Pathobiology of ischaemic stroke: an integrated view SO TRENDS IN NEUROSCIENCES LA English DT Review ID FOCAL CEREBRAL-ISCHEMIA; INTERLEUKIN-1-BETA CONVERTING-ENZYME; NECROSIS-FACTOR-ALPHA; BRAIN INJURY; ARTERY OCCLUSION; NEURONAL DAMAGE; TRANSGENIC MICE; CELL-DEATH; TRANSCRIPTION FACTOR; GLUCOSE DEPRIVATION AB Brain injury following transient or permanent focal cerebral ischaemia (stroke) develops from a complex series of pathophysiological events that evolve in time and space. In this article, the relevance of excitotoxicity, peri-infarct depolarizations, inflammation and apoptosis to delayed mechanisms of damage within the peri-infarct zone or ischaemic penumbra are discussed. While focusing on potentially new avenues of treatment, the issue of why many clinical stroke trials have so far proved disappointing is addressed. This article provides a framework that can be used to generate testable hypotheses and treatment strategies that are linked to the appearance of specific pathophysiological events within the ischaemic brain. C1 Charite Hosp, Dept Neurol, D-10098 Berlin, Germany. Univ Minnesota, Sch Med, Lab Cerebrovasc Biol & Stroke, Dept Neurol, Minneapolis, MN 55455 USA. Harvard Univ, Sch Med, Stroke Res Lab, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Neurosurg Serv, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Dirnagl, U (reprint author), Charite Hosp, Dept Neurol, D-10098 Berlin, Germany. RI Moskowitz, Michael/D-9916-2011; OI Dirnagl, Ulrich/0000-0003-0755-6119 FU NINDS NIH HHS [NS34179, NS35806, NS37853] NR 86 TC 1910 Z9 1979 U1 33 U2 208 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD SEP PY 1999 VL 22 IS 9 BP 391 EP 397 DI 10.1016/S0166-2236(99)01401-0 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 226LQ UT WOS:000082021800009 PM 10441299 ER PT J AU Duque, JLF Loughlin, KR Adam, RM Kantoff, PW Zurakowski, D Freeman, MR AF Duque, JLF Loughlin, KR Adam, RM Kantoff, PW Zurakowski, D Freeman, MR TI Plasma levels of vascular endothelial growth factor are increased in patients with metastatic prostate cancer SO UROLOGY LA English DT Article ID FACTOR VEGF; EXPRESSION; CELLS; PLATELETS; CARCINOMA; BIOLOGY AB Objectives. Vascular endothelial growth factor (VEGF) is a cytokine that plays an important role in tumor angiogenesis, VEGF is overexpressed in many human cancers, including prostate cancer, but circulating levels of VEGF in patients with prostate cancer have not been reported. In this study, we analyzed plasma concentrations of VEGF in a cohort of patients with prostate cancer and compared them with a normal population. Methods. Twenty-six healthy, cancer-free individuals and 80 patients with prostate cancer (54 patients with localized prostate cancer and 26 patients with metastatic prostate cancer [bone or lymph node positive]) were analyzed in this study. Blood was drawn in the same fashion from all individuals and deposited in tubes containing ethylenediaminetetraacetic acid as anticoagulant. Plasma was extracted and VEGF concentrations were determined using a quantitative sandwich enzyme immunoassay technique. Results. Median plasma VEGF was 28.5 pg/mL (interquartile range 19.3 to 57.0) in patients with metastases; 7.0 pg/mL (interquartile range 0 to 26.5) in patients with localized disease, and 0 pg/mL (interquartile range 0 to 24) in controls. These differences were statistically significant (P <0.001). When compared group by group, the metastatic group had significantly higher plasma VECF than the localized disease group and the control group (P = 0.003 and P <0.001, respectively), There was a tendency for plasma VEGF to be higher in the localized disease group than in the control group, a trend that almost reached statistical significance (P = 0.038). Using a cutoff of 18 pg/mL, the sensitivity and specificity of the test in differentiating between patients with and without metastatic disease was 81% and 71%, respectively. The odds of metastatic disease were almost 10 times greater for patients with VEGF values greater than 18 pg/mL than for those with values less than 18 pg/mL. There was no correlation between age and plasma VEGF values or between plasma VEGF and serum prostate-specific antigen (PSA). However, patients with serum PSA greater than 20 ng/mL had significantly higher plasma VEGF values than patients with serum PSA less than 20 ng/mL (P <0.001). No direct relation was found between Gleason sum and plasma VEGF, although VEGF levels were higher in patients with Gleason sums of 8 to 10 than in patients with lower Gleason sums. Conclusions. Our study indicates that patients with metastatic prostate cancer have higher plasma VEGF levels than patients with localized disease or healthy controls. A larger prospective study is needed to confirm the predictive utility of VEGF. (C) 1999, Elsevier Science Inc. C1 Childrens Hosp, Dept Urol, Urol Lab, Boston, MA 02115 USA. Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Freeman, MR (reprint author), Enders Res Labs, Room 1151,300 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA77386]; NIDDK NIH HHS [R01 DK47556] NR 17 TC 163 Z9 172 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 1999 VL 54 IS 3 BP 523 EP 527 DI 10.1016/S0090-4295(99)00167-3 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 230LC UT WOS:000082251800028 PM 10475365 ER PT J AU Gunthard, HF Leigh-Brown, AJ D'Aquila, RT Johnson, VA Kurizkes, DR Richman, DD Wong, JK AF Gunthard, HF Leigh-Brown, AJ D'Aquila, RT Johnson, VA Kurizkes, DR Richman, DD Wong, JK TI Higher selection pressure from antiretroviral drugs in vivo results in increased evolutionary distance in HIV-1 pol (vol 259, pg 154, 1999) SO VIROLOGY LA English DT Correction C1 Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. Vet Affairs San Diego Healthcare Syst, La Jolla, CA 92093 USA. Univ Edinburgh, Ctr HIV Res, Edinburgh EH9 3JN, Midlothian, Scotland. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Alabama, Sch Med, Dept Med, Birmingham, AL 35294 USA. Vet Affairs Med Ctr, Birmingham, AL 35294 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. RP Gunthard, HF (reprint author), Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. RI Leigh Brown, Andrew/F-3802-2010 NR 1 TC 1 Z9 1 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 1999 VL 261 IS 2 BP 367 EP 367 DI 10.1006/viro.1999.9935 PG 1 WC Virology SC Virology GA 234KW UT WOS:000082484700023 ER PT J AU Mar, C Bent, S AF Mar, C Bent, S TI Clinical evidence - An evidence-based review of the to most commonly used herbs SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; ALOE-VERA EXTRACT; DOUBLE-BLIND; GINKGO-BILOBA; CONTROLLED TRIAL; HYPERCHOLESTEROLEMIC MEN; HYDROPHILIC CREAM; SIBERIAN GINSENG; GARLIC POWDER; PLASMA-LIPIDS C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Osher Ctr Integrat Med, Div Internal Med, San Francisco, CA 94121 USA. RP Bent, S (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Osher Ctr Integrat Med, Div Internal Med, 4150 Clement St, San Francisco, CA 94121 USA. NR 41 TC 36 Z9 38 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 0093-0415 J9 WESTERN J MED JI West. J. Med. PD SEP PY 1999 VL 171 IS 3 BP 168 EP 171 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 248RP UT WOS:000083289400015 PM 10560291 ER PT J AU Jang, YC Arumugam, S Gibran, NS Isik, FF AF Jang, YC Arumugam, S Gibran, NS Isik, FF TI Role of alpha(v) integrins and angiogenesis during wound repair SO WOUND REPAIR AND REGENERATION LA English DT Article ID FIBROBLAST GROWTH-FACTOR; BLOOD-VESSELS; EXPRESSION; CELLS AB Angiogenesis, the formation of new blood vessels from pre-existing blood vessels, is thought to be critical for wound repair. Yet few studies have critically examined dermal wound repair in a system in which angiogenesis was impaired. Since alpha(v)-containing integrins are critical for angiogenesis, we administered either an alpha(v) integrin blocking antibody or cyclic arg-gly-asp peptide into a murine excisional wound model to restrict wound angiogenesis. Although both methods markedly decreased wound angiogenesis, decreased angiogenesis had no significant effect on wound epithelization, contraction, or ultimate wound closure. These results suggest that if other cellular components of wound healing are intact, moderate impairment of angiogenesis alone does not necessarily retard normal wound healing. C1 VA Puget Sound Hlth Care Syst, Dept Surg, Seattle, WA 98108 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. RP Isik, FF (reprint author), VA Puget Sound Hlth Care Syst, Dept Surg, 112,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIGMS NIH HHS [R01-GM57426] NR 24 TC 22 Z9 23 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD SEP-OCT PY 1999 VL 7 IS 5 BP 375 EP 380 DI 10.1046/j.1524-475X.1999.00375.x PG 6 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 250QE UT WOS:000083398400007 PM 10564566 ER PT J AU Giesler, M Pfob, A Levine, RA Hombach, V AF Giesler, M Pfob, A Levine, RA Hombach, V TI Aortic regurgitant flow by color Doppler measurement of the local velocity 7 mm above the leak orifice - Part 1: in vitro measurements SO ZEITSCHRIFT FUR KARDIOLOGIE LA English DT Article DE color Doppler; aortic regurgitation; flow convergence ID SURFACE-AREA METHOD; MITRAL REGURGITATION; CONVERGENCE REGION; IN-VITRO; QUANTIFICATION; VALIDATION; ECHOCARDIOGRAPHY; CONSTRAINT; PROFILE; INVITRO AB Aims: The flow convergence method enables the determination of flow across restrictive orifices. It was validated for planar orifice plates and atrioventricular valves. However, its quantitative application to aortic regurgitation is complicated due to the complex valve anatomy which distorts the converging flow field. An open angle formed by the leaflets causes relatively lower velocities in the region near the orifice, resulting in underestimation of flow. Confinement of the flow convergence region by the ascending aorta relatively increases the velocities at greater distance to the orifice and can cause overestimation of flow. We hypothesized that there is a region at intermediate distance to the orifice, where both these effects on the flow field are minimal, so that the local velocity there is only a function of flow. Methods and results: In a flow model, aortic regurgitation was simulated. The flow convergence was imaged by color Doppler. Different scanning directions were used (analogue to apical and parasternal approach). Velocity profiles across the flow convergence were read along the line from the scanhead to the orifice. At a distance of 7 mm to the orifice, a uniform value was found for the ratio of local v((7 mm))/flow (= 0.28 cm(-2)). Variations in size (3.5 to 7 mm), site (central versus lateral) and leaflet angle (planar versus inverted funnel) of the orifice and in the scanning approach had only a minimal effect on this value. Conclusion: The aortic regurgitant flow convergence is characterized by a relatively uniform V-(7 mm)/Q. Independent of variations in the anatomy and the scanning approach, this value directly reflects flow. C1 Univ Ulm, Med Klin & Poliklin, Innere Med Abt 2, D-89081 Ulm, Germany. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Giesler, M (reprint author), Univ Ulm, Med Klin & Poliklin, Innere Med Abt 2, Robert Koch Str 8, D-89081 Ulm, Germany. NR 30 TC 1 Z9 1 U1 0 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0300-5860 J9 Z KARDIOL JI Z. Kardiol. PD SEP PY 1999 VL 88 IS 9 BP 631 EP 639 DI 10.1007/s003920050338 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 245UM UT WOS:000083126600003 PM 10525924 ER PT J AU Hallen, S Branden, M Dawson, PA Sachs, G AF Hallen, S Branden, M Dawson, PA Sachs, G TI Membrane insertion scanning of the human ileal sodium/bile acid co-transporter SO BIOCHEMISTRY LA English DT Article ID IN-VITRO TRANSLATION; ENDOPLASMIC-RETICULUM; TOPOLOGY PREDICTION; EXPRESSION CLONING; PROTEINS; IDENTIFICATION; SEQUENCES; SEGMENTS; ATPASE; GENE AB Mammalian sodium-dependent bile acid transporters (SBATs) responsible for bile salt uptake across the liver sinusoidal or ileal/renal brush border membrane have been identified and share approximately 35% amino acid sequence identity. Programs for prediction of topology and localization of transmembrane helices identify eight or nine hydrophobic regions for the SEAT sequences as membrane spanning. Analysis of N-linked glycosylation has provided evidence for an exoplasmic N-terminus and a cytoplasmic C-terminus, indicative of an odd number of transmembrane segments. To determine the membrane topography of the human ileal SEAT (HISBAT), an in vitro translation/translocation protocol was employed using three different fusion protein constructs. Individual HISBAT segments were analyzed for signal anchor or stop translocation (stop transfer) activity by insertion between a cytoplasmic anchor (HK M0) or a signal anchor segment (HK M1) and a glycosylation flag (HK beta). To examine consecutive HISBAT sequences, sequential hydrophobic sequences were inserted into the HK MO vector or fusion vectors were made that included the glycosylated N-terminus of HISBAT, sequential hydrophobic sequences, and the glycosylation flag. Individual signal anchor (SA) and stop transfer (ST) properties were found for seven out of the nine predicted hydrophobic segments (H1, H2, H4, H5, H6, H7, and H9), supporting a seven transmembrane segment model. However, the H3 region was membrane inserted when translated in the context of the native HISBAT flanking sequences. Furthermore, results from translations of sequential constructs ending after H7 provided support for integration of H8, These data provide support for a SEAT transmembrane domain model with nine integrated segments with an exoplasmic N-terminus and a cytoplasmic C-terminus consistent with a recent predictive analysis of this transporter topology. C1 Univ Calif Los Angeles, Los Angeles, CA 90073 USA. Wadsworth Vet Adm Hosp, Los Angeles, CA 90073 USA. Wake Forest Univ, Sch Med, Dept Internal Med, Div Gastroenterol, Winston Salem, NC 27157 USA. RP Sachs, G (reprint author), W Los Angeles VA Med Ctr, Membrane Biol Lab, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [R01 DK047987, DK53462, DK41301, DK46917] NR 32 TC 40 Z9 45 U1 0 U2 1 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 31 PY 1999 VL 38 IS 35 BP 11379 EP 11388 DI 10.1021/bi990554i PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 235AG UT WOS:000082516100018 PM 10471288 ER PT J AU Albert, CM Manson, JE Cook, NR Ajani, UA Gaziano, JM Hennekens, CH AF Albert, CM Manson, JE Cook, NR Ajani, UA Gaziano, JM Hennekens, CH TI Moderate alcohol consumption and the risk of sudden cardiac death among US male physicians SO CIRCULATION LA English DT Article DE alcohol; death, sudden; arrhythmia; coronary disease; epidemiology ID CORONARY HEART-DISEASE; HIGH-DENSITY-LIPOPROTEIN; MYOCARDIAL-INFARCTION; MORTALITY; MEN; CLASSIFICATION AB Background-Individuals who consume high amounts of alcohol (>5 drinks/d) have increased risks of ventricular arrhythmia and sudden cardiac death (SCD). However, the relationship is less clear for drinkers of light-to-moderate amounts. Methods and Results-We prospectively assessed whether light-to-moderate alcohol drinkers have a decreased risk of SCD among 21 537 male participants in the Physicians Health Study who were free of self-reported cardiovascular disease and provided complete information on alcohol intake at study entry. Over 12 years of follow-up, 141 SCDs were confirmed. After control for multiple confounders, men who consumed 2 to 4 drinks/wk (RR=0.40; 95% CI, 0.22 to 0.75; P=0.004) or 5 to 6 drinks/wk (RR=0.21; 95% CI, 0.08 to 0.56; P=0.002) at baseline had significantly reduced risks of SCD compared with these who rarely or never consumed alcohol. The relationship for SCD was U-shaped (P=0.002), with the risk approaching unity at greater than or equal to 2 drinks/d, In contrast, the relationship of alcohol intake and nonsudden CHD death was L-shaped or linear (P for trend=0.02), Conclusions-In these prospective data, men who consumed light-to-moderate amounts of alcohol (2 to 6 drinks/wk) had a significantly reduced risk of SCD compared with those who rarely or never consumed alcohol. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA. RP Albert, CM (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NCI NIH HHS [CA-34944, CA-40360]; NHLBI NIH HHS [HL-26490] NR 32 TC 102 Z9 107 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 31 PY 1999 VL 100 IS 9 BP 944 EP 950 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 232DZ UT WOS:000082353000010 PM 10468525 ER PT J AU Davia, K Hajjar, RJ Terracciano, CMN Kent, NS Ranu, HK O'Gara, P Rosenzweig, A Harding, SE AF Davia, K Hajjar, RJ Terracciano, CMN Kent, NS Ranu, HK O'Gara, P Rosenzweig, A Harding, SE TI Functional alterations in adult rat myocytes after overexpression of phospholamban with use of adenovirus SO PHYSIOLOGICAL GENOMICS LA English DT Article DE gene transfer; cardiomyocyte; sarco( endo) plasmic reticulum; calcium-adenosinetriphosphatase; relaxation; calcium transient ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; FORCE-FREQUENCY-RELATIONSHIP; FAILING HUMAN MYOCARDIUM; STAGE HEART-FAILURE; VENTRICULAR MYOCYTES; DILATED CARDIOMYOPATHY; GENE-TRANSFER; INOTROPIC STIMULATION; PROTEIN-LEVELS; MESSENGER-RNA AB An increased phospholamban (PLB)-to-sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) ratio has been suggested to contribute to the slowing of relaxation in failing human ventricle. We have used an adenoviral vector carrying the sequence for PLB to increase this ratio in isolated adult rat ventricular myocytes, and we have examined the functional consequences. With use of adenoviral vectors, the PLB content of adult rat myocytes was increased 2.73-fold, with SERCA2a levels unchanged. Maximum contraction amplitude of PLB-overexpressing myocytes was decreased to 6.9 +/- 0.3% shortening compared with 11.2 +/- 0.8% for 24-h controls (Con; P < 0.001, 5 preparations, 103 myocytes). Maximum rates of shortening and relengthening were also significantly decreased. Ca2+ transient amplitudes were slightly depressed, and time to 50% decay of the transients was significantly increased: 237 +/- 18 (n = 14 myocytes) and 432 +/- 32 ms in Con and PLB (n = 15) myocytes, respectively (P < 0.001). The amount of Ca2+ in the sarcoplasmic reticulum stores was reduced by 21% (P < 0.05). Relaxation was significantly slower in PLB than in Con myocytes when the Na+/Ca2+ exchanger was blocked but not when sarcoplasmic reticulum Ca2+ uptake was inhibited. Adenovirus infection with Ad.RSV.PLB was therefore able to produce functional changes in adult cardiac myocytes within 24 h, consistent with overexpression of PLB and similar to those seen in failing human heart. C1 Natl Heart & Lung Inst, Imperial Coll Sch Med, London SW3 6LY, England. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Harding, SE (reprint author), Natl Heart & Lung Inst, Imperial Coll Sch Med, Dovehouse St, London SW3 6LY, England. FU NHLBI NIH HHS [HL-54202, HL-50361, HL-57623] NR 37 TC 39 Z9 43 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD AUG 31 PY 1999 VL 1 IS 2 BP 41 EP 50 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 317NZ UT WOS:000087232900001 PM 11015560 ER PT J AU Elgadi, KM Meguid, RA Qian, M Souba, WW Abcouwer, SF AF Elgadi, KM Meguid, RA Qian, M Souba, WW Abcouwer, SF TI Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicing SO PHYSIOLOGICAL GENOMICS LA English DT Article DE glutamine metabolism; mitochondrial proteins; gene expression; mRNA processing; CAG repeat polymorphisms; brain; kidney; muscle; mammary adenocarcinoma ID MEMBRANE-BOUND FORMS; MITOCHONDRIAL GLUTAMINASE; RAT-KIDNEY; METABOLIC-ACIDOSIS; RENAL GLUTAMINASE; MESSENGER-RNA; AMINO-ACIDS; EXPRESSION; IDENTITY; DECREASE AB Three human glutaminase (hGA) isoforms were identified, two of which represent isoforms previously unidentified in any species. One isoform contains an open reading frame with high homology with the rat kidney-type glutaminase, suggesting that this isoform represents the human kidney-type glutaminase, hKGA. A second isoform, termed hGAC, contains an open reading frame that matches hKGA except for a unique COOH-terminal amino acid sequence. In addition, a third human glutaminase isoform was identified from a computer search and on further analysis was found to represent an additional unique isoform, hGAM. hKGA is expressed predominantly in brain and kidney but not in liver, hGAC is expressed principally in cardiac muscle and pancreas but not in liver or brain, and hGAM is expressed solely in cardiac and skeletal muscle. hGAC is the predominant isoform expressed by a human breast cancer cell line that exhibits a high rate of glutamine utilization and glutaminase activity. Genomic Southern analysis as well as isolation and analysis of five glutaminase genomic clones suggested that all three hGA isoforms originate from the same locus and therefore represent mRNA species that are produced by tissue-specific alternative splicing of a single pre-mRNA. Furthermore, an RT-PCR assay was developed that can be used to easily differentiate between hKGA and hGAC mRNA species. C1 Massachusetts Gen Hosp, Surg Oncol Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Abcouwer, SF (reprint author), Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Biochem & Mol Biol, Basic Med Sci Bldg 249, Albuquerque, NM 87131 USA. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NCI NIH HHS [R29-CA-72772]; NIDDK NIH HHS [P30-DK-40561] NR 34 TC 92 Z9 94 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD AUG 31 PY 1999 VL 1 IS 2 BP 51 EP 62 PG 12 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 317NZ UT WOS:000087232900002 PM 11015561 ER PT J AU Kumar, A Bilker, W Jin, ZS Udupa, J Gottlieb, G AF Kumar, A Bilker, W Jin, ZS Udupa, J Gottlieb, G TI Age of onset of depression and quantitative neuroanatomic measures: absence of specific correlates SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE late onset depression; age of onset; atrophy; geriatric depression; neuroanatomical abnormalities; magnetic resonance imaging; high intensity lesions ID WHITE-MATTER LESIONS; LATE-LIFE; MAJOR DEPRESSION; GERIATRIC DEPRESSION; ELDERLY DEPRESSIVES; AFFECTIVE-DISORDER; DISTINCT SUBTYPE; BRAIN; MRI; DEFICITS AB The purpose of our study was to examine the relationship between volumetric neuroanatomic measures and age of onset of illness in subjects with late-life major depression. Our sample was composed of 51 elderly subjects with Major Depressive Disorder who were scanned using a 1.5-tesla GE magnetic resonance imaging scanner with head coil. Absolute total and focal brain volumes were obtained together with quantified estimates of high intensity lesions. The relationship of these measures to onset age was examined using a regression while adjusting for subjects' current age and total intracranial volume. There was no significant linear relationship between age of onset of the first episode and any of the neuroanatomic measures examined. These data do not support the notion that neuroanatomical contributions to depression increase with a later age of onset of illness. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kumar, A (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Room 37-384 B,760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIMH NIH HHS [MH 52129, MH 55115] NR 48 TC 27 Z9 27 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD AUG 31 PY 1999 VL 91 IS 2 BP 101 EP 110 DI 10.1016/S0925-4927(99)00021-9 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 241NB UT WOS:000082888500004 PM 10515465 ER PT J AU Brumback, BA Holmes, LB Ryan, LM AF Brumback, BA Holmes, LB Ryan, LM TI Adverse effects of chorionic villus sampling: a meta-analysis SO STATISTICS IN MEDICINE LA English DT Article ID INCORPORATING HISTORICAL CONTROLS; LIMB REDUCTION DEFECTS; PRENATAL-DIAGNOSIS; MATERNAL AGE; AMNIOCENTESIS; EXPERIENCE; ABNORMALITIES; METAANALYSIS; RISK; CVS AB Meta-analysis is a popular tool for combining evidence from several related studies. The technique is usually used to combine randomized clinical trials, case-control studies or prospective studies where each study has its own exposed and unexposed groups. By including separate 'study effects' (either fixed or random), one can combine information about differences between control and exposed groups, while still allowing for study heterogeneity. In this paper, we extend existing methods to combine studies of disparate designs, where some studies do not include concurrent controls. We apply the methods to a meta-analysis of the association of prenatal testing via chorionic villus sampling with the occurrence of terminal transverse limb defects. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. RP Ryan, LM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA-48061]; NICHD NIH HHS [HD-33222] NR 45 TC 15 Z9 17 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG 30 PY 1999 VL 18 IS 16 BP 2163 EP 2175 DI 10.1002/(SICI)1097-0258(19990830)18:16<2163::AID-SIM180>3.3.CO;2-8 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 231JQ UT WOS:000082305300009 PM 10441771 ER PT J AU Mulley, AG AF Mulley, AG TI Learning from differences within the NHS - Clinical indicators should be used to learn, not to judge SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID NEW-YORK-STATE; CARDIAC-SURGERY; MORTALITY DATA; OUTCOMES C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. RP Mulley, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. NR 12 TC 4 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 AUG 28 PY 1999 VL 319 IS 7209 BP 528 EP 530 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 232CB UT WOS:000082347200002 PM 10463877 ER PT J AU Aksoy, IA Ramsey, MJ Fruman, DA Aksoy, S Cantley, LC Tucker, JD Roberts, TM AF Aksoy, IA Ramsey, MJ Fruman, DA Aksoy, S Cantley, LC Tucker, JD Roberts, TM TI Mouse phosphoinositide 3-Kinase p110 alpha gene: Cloning, structural organization, and localization to chromosome 3 band B SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN PHOSPHATIDYLINOSITOL 3-KINASE; REGULATORY SUBUNIT; KINASE-ACTIVITY; P85-ALPHA GENE; GROWTH-FACTOR; INSULIN; SIGNAL; IDENTIFICATION; ACTIVATION; ENZYME AB Phosphoinositide 3-Kinases (PI3-Kinases) are a family of dual specificity enzymes with a unique lipid kinase activity toward the D-3 position of the inositol ring of phosphoinositides and a less well characterized serine/threonine protein kinase activity. Class IA PI3-Kinases comprise a 110-120 kDa catalytic subunit (usually termed p110) and an 85 kDa or 50 to 55 kDa regulatory subunit (often called p85). cDNAs for three mammalian Class IA PI3-Kinase catalytic subunits designated p110 alpha; p110 beta, and p110 delta have been cloned from several species. A YAC clone for the human p110 alpha gene has also been cloned and mapped to chromosome 3q26.3. However, structural organization for any of the PI3-Kinase p110 alpha genes has not been reported. Here, we report the cloning, structural organization, and chromosomal localization of the mouse PI3-Kinase p110 alpha gene. The translated portion of the mouse p110 alpha gene is encoded by 19 exons that span at least 24 kb. Dual color fluorescence in situ hybridization (FISH) was performed to determine the chromosomal localization of the mouse PI3-Kinase p110 alpha gene. FISH results and DAPI banding demonstrated localization of the p110 alpha gene to band B on mouse chromosome 3, a region syntenic with human chromosome 3q26.3. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 1 Jimmy Fund Way, Boston, MA 02115 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA 73155, CA30002]; NIGMS NIH HHS [R01 GM041890, GM41890] NR 37 TC 5 Z9 6 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 AUG 27 PY 1999 VL 262 IS 2 BP 438 EP 442 DI 10.1006/bbrc.1999.1150 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 232AF UT WOS:000082343000024 PM 10462494 ER PT J AU Markuns, JF Wojtaszewski, JFP Goodyear, LJ AF Markuns, JF Wojtaszewski, JFP Goodyear, LJ TI Insulin and exercise decrease glycogen synthase kinase-3 activity by different mechanisms in rat skeletal muscle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED GLUCOSE-TRANSPORT; EPIDIDYMAL FAT-CELLS; B C-AKT; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; SIGNALING PATHWAYS; ALPHA-ISOFORM; PHOSPHORYLATION; ACTIVATION; INHIBITION AB Glycogen synthase activity is increased in response to insulin and exercise in skeletal muscle. Part of the mechanism by which insulin stimulates glycogen synthesis may involve phosphorylation and activation of Akt, serine phosphorylation and deactivation of glycogen synthase kinase-3 (GSK-3), leading to dephosphorylation and activation of glycogen synthase, To study Akt and GSK-3 regulation in muscle, time course experiments on the effects of insulin injection and treadmill running exercise were performed in hindlimb skeletal muscle from male rats, Both insulin and exercise increased glycogen synthase activity (%I-form) by 2-3-fold over basal. Insulin stimulation significantly increased Akt phosphorylation and activity, whereas exercise had no effect. The time course of the insulin-stimulated increase in Akt was closely matched by GSK-3 alpha Ser(21) phosphorylation and a 40-60% decrease in GSK-3 alpha and GSK-3 beta activity. Exercise also deactivated GSK-3 alpha and beta activity by 40-60%. However, in contrast to the effects of insulin, there was no change in Ser21 phosphorylation in response to exercise. Tyrosine dephosphorylation of GSK-3, another putative mechanism for GSK-3 deactivation, did not occur with insulin or exercise, These data suggest the following: 1) GSK-3 is constitutively active and tyrosine phosphorylated under basal conditions in skeletal muscle, 2) both exercise and insulin are effective regulators of GSK-3 activity in vivo, 3) the insulin-induced deactivation of GSK-3 occurs in response to increased Akt activity and GSK-3 serine phosphorylation, and 4) there is an Akt-independent mechanism for deactivation of GSK-3 in skeletal muscle. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Wojtaszewski, Jorgen /P-6583-2014; OI Wojtaszewski, Jorgen /0000-0001-9785-6830; Markuns, Jeffrey/0000-0002-8044-2575 FU NIAMS NIH HHS [AR42238, AR45670]; PHS HHS [T32-DR07260-21] NR 52 TC 98 Z9 103 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 27 PY 1999 VL 274 IS 35 BP 24896 EP 24900 DI 10.1074/jbc.274.35.24896 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 229KH UT WOS:000082193400062 PM 10455163 ER PT J AU Wekerle, T Sykes, M AF Wekerle, T Sykes, M TI Mixed chimerism as an approach for the induction of transplantation tolerance SO TRANSPLANTATION LA English DT Review ID BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC STEM-CELLS; NONLETHAL PREPARATIVE REGIMEN; INTRATHYMIC CLONAL DELETION; DONOR-TYPE MICROCHIMERISM; SKIN ALLOGRAFT TOLERANCE; ANTIBODY MAB INJECTIONS; WHOLE-BODY IRRADIATION; NATURAL-KILLER-CELLS; LONG-TERM SURVIVAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,BMT Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,BMT Sect, MGH E,13th St,Bldg 149-5102, Boston, MA 02129 USA. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [R01 HL49915-04]; NIAID NIH HHS [P01 AI 39755] NR 117 TC 113 Z9 120 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 1999 VL 68 IS 4 BP 459 EP 467 DI 10.1097/00007890-199908270-00001 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 232VG UT WOS:000082390200001 PM 10480398 ER PT J AU Spitzer, TR Delmonico, F Tolkoff-Rubin, N McAfee, S AF Spitzer, TR Delmonico, F Tolkoff-Rubin, N McAfee, S TI Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: The induction of allograft tolerance through mixed lymphohematopoietic chimerism SO TRANSPLANTATION LA English DT Article ID CELL TRANSPLANTATION; CYNOMOLGUS MONKEYS; KIDNEY ALLOGRAFT; MINIATURE SWINE; RECIPIENTS; REGIMEN; BLOOD; PCR; IMMUNOSUPPRESSION; CHEMOTHERAPY AB Background Experimental and clinical evidence has demonstrated that the establishment of allogeneic chimerism after bone marrow transplantation may provide donor-specific tolerance for solid organ allografts. Methods. Based on the preliminary results of a clinical trial using nonmyeloablative preparative therapy for the induction of mixed lymphohematopoietic chimerism, we treated a 55-year-old woman with end stage renal disease secondary to multiple myeloma with a combined histocompatibility leukocyte antigen-matched bone marrow and renal transplant after conditioning with cyclophosphamide, antithymocyte globulin, and thymic irradiation. Results. The posttransplant course was notable for early normalization of renal function, the absence of acute graft-versus-host disease, and the establishment of mixed lymphohematopoietic chimerism. Cyclosporine, which was the only posttransplant immunosuppressive therapy, was tapered and discontinued on day +73 posttransplant. No rejection episodes occurred, and renal function remains normal on day +170 posttransplant (14 weeks after discontinuing cyclosporine). Although there is presently no evidence of donor hematopoiesis, there is evidence of an ongoing antitumor response with a recent staging evaluation showing no measurable urine kappa light chains. The patient remains clinically well and is off all immunosuppressive therapy. Conclusion. This is the first report of the deliberate induction of mixed lymphohematopoietic chimerism after a nonmyeloablative preparative regimen to treat a hematological malignancy and to provide allotolerance for a solid organ transplant. C1 Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplantat Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Program, Cox 640,55 Fruit St, Boston, MA 02114 USA. NR 41 TC 282 Z9 290 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 1999 VL 68 IS 4 BP 480 EP 484 DI 10.1097/00007890-199908270-00006 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 232VG UT WOS:000082390200006 PM 10480403 ER PT J AU Yamada, K Choo, JK Allan, JS Erhorn, AE Menard, MT Mawulawde, K Slisz, JK Aretz, HT Shimizu, A Sachs, DH Madsen, JC AF Yamada, K Choo, JK Allan, JS Erhorn, AE Menard, MT Mawulawde, K Slisz, JK Aretz, HT Shimizu, A Sachs, DH Madsen, JC TI The effect of thymectomy on tolerance induction and cardiac allograft vasculopathy in a miniature swine heart/kidney transplantation model SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the American-Society-of-Transplant-Surgeons CY MAY 10-16, 1997 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Surgeons ID MAJOR HISTOCOMPATIBILITY COMPLEX; DISPARATE RENAL-ALLOGRAFTS; CLASS-I; IMMUNE-MECHANISMS; TIME-COURSE; THYMUS; REJECTION; ALLOREACTIVITY; CYCLOSPORINE; PATHWAYS AB Background We have previously demonstrated that MHC class I disparate hearts transplanted into miniature swine treated with a short course of cyclosporine developed florid cardiac allograft vasculopathy (CAV) and were rejected within 55 days. However, when a donor-specific kidney is cotransplanted with the heart allograft, recipients become tolerant to donor antigen and accept both allografts long-term without the development of CAV, In the present study, we have investigated the role of the host thymus in the induction of tolerance and prevention of CAV in heart/kidney recipients. Methods. Total thymectomies were performed in six animals (postoperative day [POD]-21), which on day 0 received either an isolated MHC class I disparate heart allograft (n=3) or combined class I disparate heart and kidney allografts (n=3), followed in both cases by a 12-day course of cyclosporine (POD 0-11). Graft survival and the development of CAV in these thymectomized recipients were compared to the same parameters in non-thymectomized, cyclosporine-treated recipients bearing either class I disparate heart allografts (n=5) or heart and kidney allografts (n=4), Results. In the group of animals bearing isolated class I disparate heart allografts, the thymectomized recipients rejected their allografts earlier (POD 8, 22, 27) than the non-thymectomized recipients (POD 33,35,45,47,55). The donor hearts in both the thymectomized and non-thymectomized animals developed florid CAV, In the group of animals bearing combined class I disparate heart and kidney allografts, the non-thymectomized recipients accepted both donor organs long term with no evidence of CAV, In contrast, none of the thymectomized heart/kidney recipients survived >100 days, and they all developed the intimal proliferation of CAV, Conclusion. Thymic-dependent mechanisms are necessary for the induction of acquired tolerance and prevention of CAV in porcine heart/kidney recipients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Cardiac Surg, EDR 105, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01-HL54211, P01 HL08646-21A1]; NIAID NIH HHS [R01 AI31046-08] NR 27 TC 26 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 1999 VL 68 IS 4 BP 485 EP 491 DI 10.1097/00007890-199908270-00007 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 232VG UT WOS:000082390200007 PM 10480404 ER PT J AU Timms, JF Swanson, KD Marie-Cardine, A Raab, M Rudd, CE Schraven, B Neel, BG AF Timms, JF Swanson, KD Marie-Cardine, A Raab, M Rudd, CE Schraven, B Neel, BG TI SHPS-1 is a scaffold for assembling distinct adhesion-regulated multi-protein complexes in macrophages SO CURRENT BIOLOGY LA English DT Article ID TYROSINE-PHOSPHATASE SHP-1; MOLECULAR-CLONING; KINASE; SKAP55; FYN; SUBSTRATE; PHOSPHORYLATION; IDENTIFICATION; MEGAKARYOCYTES; ACTIVATION AB Inhibitory immunoreceptors downregulate signaling by recruiting Src homology 2 (SH2) domain containing tyrosine and/or lipid phosphatases to activating receptor complexes [1]. There are indications that some inhibitory receptors might also perform other functions [2,3], In adherent macrophages, two inhibitory receptors, SHPS-1 and PIR-B, are the major proteins binding to the tyrosine phosphatase SHP-1. SHPS-1 also associates with two tyrosine-phosphorylated proteins (pp55 and pp130) and a protein tyrosine kinase [4]. Here, we have identified pp55 and pp130 as the adaptor molecules SKAP55hom/R (Src-kinase-associated protein of 55 kDa homologue) and FYB/SLAP-130 (Fyn-binding protein/SLP-76-associated protein of 130 kDa), respectively, and the tyrosine kinase activity as PYK2, Two distinct SHPS-1 complexes were formed, one containing SKAP55hom/R and FYB/SLAP-130, and the other containing PYK2. Recruitment of FYB/SLAP-130 to SHPS-1 required SKAP55hom/R, whereas PYK2 associated with SHPS-1 independently. Formation of both complexes was independent of SHP-1 and tyrosine phosphorylation of SHPS-1, Finally, tyrosine phosphorylation of members of the SHPS-1 complexes was regulated by integrin-mediated adhesion. Thus, SHPS-1 provides a scaffold for the assembly of multi-protein complexes that might both transmit adhesion-regulated signals and help terminate such signals through SHP-1-directed dephosphorylation. Other inhibitory immunoreceptors might have similar scaffold-like functions. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Heidelberg, Inst Immunol, D-69120 Heidelberg, Germany. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Neel, BG (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA. RI Timms, John/A-1556-2010 OI Timms, John/0000-0002-4507-835X FU NHLBI NIH HHS [T32 HL07623]; NIDDK NIH HHS [P01 DK50654] NR 23 TC 68 Z9 74 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 26 PY 1999 VL 9 IS 16 BP 927 EP 930 DI 10.1016/S0960-9822(99)80401-1 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 230UJ UT WOS:000082268500028 PM 10469599 ER PT J AU Husain, SS Forman, SA Kloczewiak, MA Addona, GH Olsen, RW Pratt, MB Cohen, JB Miller, KW AF Husain, SS Forman, SA Kloczewiak, MA Addona, GH Olsen, RW Pratt, MB Cohen, JB Miller, KW TI Synthesis and properties of 3-(2-hydroxyethyl)-3-n-pentyldiazirine, a photoactivable general anesthetic SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; GABA(A) RECEPTOR; CHANNEL COMPLEX; BINDING-SITE; ION-CHANNEL; A RECEPTOR; TORPEDO; DESENSITIZATION; SYSTEM; IDENTIFICATION AB To overcome the difficulties of locating the molecular sites of general anesthetic action, we synthesized a novel photoactivable general anesthetic, 3-(2-hydroxyethyl)-3-n-pentyldiazirine (3-diazirinyloctanol), which anesthetized tadpoles with an ED50 of 160 mu M. Subanesthetic concentrations of 3-diazirinyloctanol enhanced GABA-induced currents in GABA(A) receptors, an effect that has been implicated in general anesthetic action. It also enhanced [H-3]muscimol binding to this receptor. In muscle nicotinic acetylcholine receptors (nAcChoR), it inhibited the response to acetylcholine with an IC50 of 33 mu M. 3-Diazirinyloctanol's pharmacological actions were comparable to those of octanol. 3-(2-Hydroxyethyl)-3-[4,5-H-3(2)]-n-pentyldiazirine photoincorporated into Torpedo nAcChoR-rich membranes mainly in the alpha subunit with 70% being in a proteolytic fragment containing the M4 transmembrane segment. Agonist enhanced the photolabeling 10-fold in a fragment containing the M1, M2, and M3 transmembrane segments. Thus, 3-diazirinyloctanol is a novel general anesthetic that acts on, and can be photoincorporated into, postsynaptic receptors. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. FU NIAAA NIH HHS [AA00206]; NIGMS NIH HHS [GM15904, GM58448] NR 40 TC 34 Z9 35 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 26 PY 1999 VL 42 IS 17 BP 3300 EP 3307 DI 10.1021/jm9806300 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 230FN UT WOS:000082241300012 PM 10464016 ER PT J AU Yin, XM Wang, K Gross, A Zhao, YG Zinkel, S Klocke, B Roth, KA Korsmeyer, SJ AF Yin, XM Wang, K Gross, A Zhao, YG Zinkel, S Klocke, B Roth, KA Korsmeyer, SJ TI Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis SO NATURE LA English DT Article ID CYTOCHROME-C; CELL-DEATH; PROTEASE; PATHWAYS; ANTIBODY; FAMILY; REQUIREMENT; ACTIVATION; CASPASE-9; INDUCTION AB The protein Bid is a participant in the pathway that leads to cell death (apoptosis), mediating the release of cytochrome c from mitochondria in response to signals from 'death' receptors known as TNFR1/Fas on the cell surface(1-7). It is a member of the pro-apoptotic Bcl-2 familys and is activated as a result of its cleavage by caspase 8, one of a family of proteolytic cell-death proteins. To investigate the role of Bid in vivo, we have generated mice deficient for Bid. We find that when these mice are injected with an antibody directed against Fas, they nearly all survive, whereas wild-type mice die from hepatocellular apoptosis and haemorrhagic necrosis. About half of the Bid-deficient animals had no apparent liver injury and showed no evidence of activation of the effector caspases 3 and 7, although the initiator caspase 8 had been activated. Other Bid-deficient mice survived with only moderate damage: all three caspases (8 and 37) were activated but their cell nuclei were intact and no mitochondrial cytochrome c was released. We also investigated the effects of Bid deficiency in cultured cells treated with anti-pas antibody (hepatocytes and thymocytes) or with TNF-alpha. (fibroblasts). In these Bid(-/-) cells, mitochondrial dysfunction was delayed, cytochrome c was not released, effector caspase activity was reduced and the cleavage of apoptosis substrates was altered. This loss-of-function model indicates that Bid is a critical substrate in vivo for signalling by death-receptor agonists, which mediates a mitochondrial amplification loop that is essential for the apoptosis of selected cells. C1 Washington Univ, Sch Med, Dept Pathol, Howard Hughes Med Inst, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Washington Univ, Sch Med, Dept Pathol, Howard Hughes Med Inst, St Louis, MO 63110 USA. OI Roth, Kevin/0000-0002-0643-995X NR 30 TC 760 Z9 782 U1 1 U2 9 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 26 PY 1999 VL 400 IS 6747 BP 886 EP 891 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 230CA UT WOS:000082233200049 PM 10476969 ER PT J AU Norton, JA Fraker, DL Alexander, HR Venzon, DJ Doppman, JL Serrano, J Goebel, SU Peghini, PL Roy, PK Gibril, F Jensen, RT AF Norton, JA Fraker, DL Alexander, HR Venzon, DJ Doppman, JL Serrano, J Goebel, SU Peghini, PL Roy, PK Gibril, F Jensen, RT TI Surgery to cure the Zollinger-Ellison syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ENDOCRINE NEOPLASIA TYPE-1; DUODENAL GASTRINOMAS; SURGICAL-MANAGEMENT; PROVOCATIVE TESTS; LONG-TERM; RESECTION; LOCALIZATION; SECRETIN; EXCISION AB Background and Methods The role of surgery in patients with the Zollinger-Ellison syndrome is controversial. To determine the efficacy of surgery in patients with this syndrome, we followed 151 consecutive patients who underwent laparotomy between 1981 and 1998. Of these patients, 123 had sporadic gastrinomas and 28 had multiple endocrine neoplasia type 1 with an imaged tumor of at least 3 cm in diameter. Tumor-localization studies and functional localization studies were performed routinely. All patients underwent surgery according to a similar operative protocol, and all patients who had surgery after 1986 underwent duodenotomy. Results The 151 patients underwent 180 exploratory operations. The mean (+/-SD) follow-up after the first operation was 8+/-4 years. Gastrinomas were found in 140 of the patients (93 percent), including all of the last 81 patients to undergo surgery. The tumors were located in the duodenum in 74 patients (49 percent) and in the pancreas in 36 patients (24 percent); however, primary tumors were found in lymph nodes in 17 patients (11 percent) and in another location in 13 patients (9 percent). The primary location was unknown in 24 patients (16 percent). Among the patients with sporadic gastrinomas, 34 percent were free of disease at 10 years, as compared with none of the patients with multiple endocrine neoplasia type 1. The overall 10-year survival rate was 94 percent. Conclusions All patients with the Zollinger-Ellison syndrome who do not have multiple endocrine neoplasia type 1 or metastatic disease should be offered surgical exploration for possible cure. (N Engl J Med 1999;341:635-44.) (C) 1999, Massachusetts Medical Society. C1 NIDDK, NIH, Digest Dis Branch, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. NCI, Surg Metab Sect, Surg Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, Digest Dis Branch, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 40 TC 273 Z9 281 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 26 PY 1999 VL 341 IS 9 BP 635 EP 644 DI 10.1056/NEJM199908263410902 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 229JY UT WOS:000082192500002 PM 10460814 ER PT J AU Ferris, FL Davis, MD Aiello, LM AF Ferris, FL Davis, MD Aiello, LM TI Treatment of diabetic retinopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID RETINAL MICROANEURYSM COUNTS; ALDOSE REDUCTASE INHIBITORS; GALACTOSE-FED DOGS; EYE-CARE; MICROVASCULAR COMPLICATIONS; VITREOUS SURGERY; COST-EFFECTIVENESS; INSULIN INFUSION; HARD EXUDATE; RISK-FACTORS C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Ferris, FL (reprint author), Div Biometry & Epidemiol, 31 Ctr Dr,MSC 2510,Bldg 31,Rm 6A52, Bethesda, MD 20892 USA. EM rickferris@nei.nih.gov NR 132 TC 101 Z9 107 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 26 PY 1999 VL 341 IS 9 BP 667 EP 678 DI 10.1056/NEJM199908263410907 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 229JY UT WOS:000082192500007 PM 10460819 ER PT J AU McKee, GT Tildsley, G Hammond, S AF McKee, GT Tildsley, G Hammond, S TI Cytologic diagnosis and grading of ductal carcinoma in situ SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 5th International Cambridge Conference on Breast Screening CY APR, 1997 CL CAMBRIDGE, ENGLAND DE ductal carcinoma in situ; high grade; cribriform; low grade; cytology; fine-needle aspiration cytology ID FINE-NEEDLE ASPIRATION; IN-SITU; INTRADUCTAL CARCINOMA; BREAST; INSITU; FEATURES; PROPORTIONS; PATHOLOGY; LESIONS; BIOPSY AB BACKGROUND. Fine-needle aspiration cytology plays an important role in the preoperative diagnosis of palpable masses as well as impalpable lesions that can only be sampled by stereotactic or ultrasound techniques. A further refinement of cytologic diagnosis would be the ability to distinguish among the different types of ductal carcinoma in situ (DCIS) also between in situ and invasive malignant disease. METHODS. Sixty-six cases of histologically proven, pure DCIS (39 high grade, 12 cribriform, and 15 low/intermediate grade) with a preoperative cytology report of carcinoma were retrieved from our files. All the cytology (wet-fixed and air-dried smears) was reviewed by G.M., and the histology sections were reviewed by G.T. Seven cytologic features, including cellularity, cell dissociation, nuclear size, cell uniformity, nucleoli, nuclear margins, and chromatin pattern, were assigned scores from 1 to 3. The presence of calcium, necrosis, and foamy macrophages was recorded. Cell clusters were examined for evidence of a cribriform pattern. Fat and stromal fragments were closely checked for infiltration by tumor cells. RESULTS. The cell type was predominantly large and pleomorphic in high grade DCIS, whereas it was mainly small and well differentiated in the cribriform and low grade types. Calcium and necrosis were seen in most high grade lesions and less frequently in the cribriform and low grade ones. Macrophages were more common in high grade and cribriform DCIS than in low/intermediate grade DCIS. Cribriform spaces were noted only in cribriform DCIS. Stromal and fat infiltration by tumor cells was not present in any of the aspirates. Myoepithelial cells were rarely seen. CONCLUSIONS. The presence of pleomorphic carcinoma cells, calcium, necrosis, and macrophages in the aspirate accompanied by "casting" calcification on the mammogram is virtually diagnostic of high grade (comedo) DCIS. Cribriform DCIS shows features of low grade carcinoma with a typical cribriform pattern of punched-out holes in the cell clusters. Low/intermediate grade DCIS has no particular distinguishing features. (C) 1999 American Cancer Society. C1 Royal Surrey Cty Hosp, Guildford, Surrey, England. Broadmoor Hosp, Clin Decis Making Support Unit, Crowthorne, Berks, England. RP McKee, GT (reprint author), Massachusetts Gen Hosp, Dept Cytopathol, WRN 2,55 Fruit St, Boston, MA 02114 USA. NR 27 TC 21 Z9 21 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD AUG 25 PY 1999 VL 87 IS 4 BP 203 EP 209 DI 10.1002/(SICI)1097-0142(19990825)87:4<203::AID-CNCR7>3.3.CO;2-5 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 226UP UT WOS:000082041000007 PM 10455208 ER PT J AU Ellis, SG Effron, MB Gold, HK Leon, MB Popma, JJ Serruys, PWJC Colombo, A Cohen, N Juran, N Werner, W Heuser, RR Spooner, S Rihal, CS Fox, R Leon, MB Brennan, J Ricci, D Fox, R Teirstein, PS Norman, S Morris, N Zidar, J Rund, M AF Ellis, SG Effron, MB Gold, HK Leon, MB Popma, JJ Serruys, PWJC Colombo, A Cohen, N Juran, N Werner, W Heuser, RR Spooner, S Rihal, CS Fox, R Leon, MB Brennan, J Ricci, D Fox, R Teirstein, PS Norman, S Morris, N Zidar, J Rund, M CA ERASER Investigators TI Acute platelet inhibition with abciximab does not reduce in-stent restenosis (ERASER study) SO CIRCULATION LA English DT Article ID CORONARY-ARTERY DISEASE; SERIAL INTRAVASCULAR ULTRASOUND; BALLOON ANGIOPLASTY; INTEGRIN; IIB/IIIA; LUMEN; ALPHA(V)BETA(3); QUANTIFICATION; PLACEMENT; BLOCKADE AB Background-Although stents reduce restenosis compared with balloon angioplasty, their long-term efficacy is limited by neointimal hyperplasia. Platelet and alpha(v)beta(3) integrin receptor inhibition limits neointimal proliferation in animal models of arterial injury. Methods and Results-We tested whether the dual beta(3) integrin blocking agent abciximab, administered for 12 or 24 hours at the same intravenous dose as that shown to reduce adverse clinical events (death, infarction, and revascularization) after angioplasty, would reduce restenotic tissue volume, as measured by intravascular ultrasound at 6 months. Two hundred twenty-five patients were randomly allocated to placebo or abciximab before coronary intervention. Of the 215 patients who received stents and study drug, 191 (88.8%) returned for late (greater than or equal to 4 months) coronary evaluation. Tissue volume, expressed as a percentage of stent volume, did not differ: 25+/-15%, 27+/-15%, and 29+/-14% for the patients in the placebo and the 12- and 24-hour abciximab groups, respectively. Lack of abciximab benefit was confirmed by quantitative coronary angiography (dichotomous restenosis: 11.6%, 18.9%, and 19.4%; loss index: 0.33, 0.52, and 0.47, respectively, P=NS). Conclusions-Potent platelet inhibition with abciximab, as administered in this study, does not reduce in-stent restenosis. The interrelationship between stents, platelets, and neointimal proliferation requires further study. C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Lenox Hill Hosp, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Arizona Heart Inst, Phoenix, AZ USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. Scripps Clin & Res Fdn, La Jolla, CA 92037 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Shaare Zedek Med Ctr, Jerusalem, Israel. Clin Columbus, Milan, Italy. Univ Essen Gesamthsch, Essen, Germany. Clin Bois de Verrieres Angio, Antony, France. Univ Munich, D-80539 Munich, Germany. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. London Chest Hosp, London E2 9JX, England. Acad Ziekenhuis, Rotterdam, Netherlands. RP Ellis, SG (reprint author), Cleveland Clin Fdn, 9500 Euclid Ave,F-25, Cleveland, OH 44195 USA. RI Effron, Mark/P-9300-2015 NR 35 TC 125 Z9 130 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 24 PY 1999 VL 100 IS 8 BP 799 EP 806 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 229AG UT WOS:000082170200007 ER PT J AU Purcell, K Artavanis-Tsakonas, S AF Purcell, K Artavanis-Tsakonas, S TI The developmental role of warthog, the Notch modifier encoding Drab6 SO JOURNAL OF CELL BIOLOGY LA English DT Article DE Drosophila; Drab6; warthog; bristle; Golgi network ID BINDING YPT1 PROTEIN; DROSOPHILA DEVELOPMENT; ENDOPLASMIC-RETICULUM; GOLGI-CISTERNAE; FUNCTIONAL LOSS; MEDIAL GOLGI; RAB PROTEINS; GTP; TRANSPORT; YEAST AB The warthog (wrt) gene, recovered as a modifier for Notch signaling, was found to encode the Drosophila homologue of rab6, Drab6. Vertebrate and yeast homologues of this protein have been shown to regulate Golgi network to TGN trafficking. To study the function of this protein in the development of a multicellular organism, we analyzed three different warthog mutants. The first was an R62C point mutation, the second a genomic null, and the third was an engineered GTP-bound form. Our studies show, contrary to yeast, that the Drosophila homologue of rab6 is an essential gene. However, it has limited effects on development beyond the larval stage. Only the mechanosensory bristles on the head, notum, and scutellum are affected by warthog mutations. We present models for the modifying effect of Drab6 on Notch signaling. C1 Yale Univ, Dept Cell Biol, New Haven, CT 06510 USA. RP Artavanis-Tsakonas, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, 13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R37 NS026084, NS26084, R01 NS026084] NR 40 TC 16 Z9 17 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 AUG 23 PY 1999 VL 146 IS 4 BP 731 EP 740 DI 10.1083/jcb.146.4.731 PG 10 WC Cell Biology SC Cell Biology GA 230HV UT WOS:000082246500005 PM 10459009 ER PT J AU Tachibana, I Hemler, ME AF Tachibana, I Hemler, ME TI Role of transmembrane 4 superfamily (TM4SF) proteins CD9 and CD81 in muscle cell fusion and myotube maintenance SO JOURNAL OF CELL BIOLOGY LA English DT Article DE TM4SF proteins; CD9; CD81; myoblast; myotube ID IMMUNODEFICIENCY VIRUS-INFECTION; MHC CLASS-II; SKELETAL-MUSCLE; ADHESION MOLECULE; MYOBLAST FUSION; N-CADHERIN; MYOGENIC DIFFERENTIATION; ALPHA-7-BETA-1 INTEGRIN; ALPHA-5-BETA-1 INTEGRIN; ALPHA-3-BETA-1 INTEGRIN AB The role of transmembrane 4 superfamily (TM4SF) proteins during muscle cell fusion has not been investigated previously, Here we show that the appearance of TM4SF protein, CD9, and the formation of CD9-beta 1 integrin complexes were both regulated in coordination with murine C2C12 myoblast cell differentiation. Also, anti-CD9 and anti-CD81 monoclonal antibodies substantially inhibited and delayed conversion of C2C12 cells to elongated myotubes, without affecting muscle-specific protein expression. Studies of the human myoblast-derived RD sarcoma cell line further demonstrated that TM4SF proteins have a role during muscle cell fusion. Ectopic expression of CD9 caused a four- to eightfold increase in RD cell syncytia formation, whereas anti-CD9 and anti-CD81 antibodies markedly delayed RD syncytia formation. Finally, anti-CD9 and anti-CD81 monoclonal antibodies triggered apoptotic degeneration of C2C12 cell myotubes after they were formed. In summary,TM4SF proteins such as CD9 and CD81 appear to promote muscle cell fusion and support myotube maintenance. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D-1430,44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM38903, R01 GM038903] NR 78 TC 157 Z9 161 U1 0 U2 2 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 AUG 23 PY 1999 VL 146 IS 4 BP 893 EP 904 DI 10.1083/jcb.146.4.893 PG 12 WC Cell Biology SC Cell Biology GA 230HV UT WOS:000082246500018 PM 10459022 ER PT J AU Sokolov, Y Mirzabekov, T Martin, DW Lehrer, RI Kagan, BL AF Sokolov, Y Mirzabekov, T Martin, DW Lehrer, RI Kagan, BL TI Membrane channel formation by antimicrobial protegrins SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE antimicrobial peptide; lipopolysaccharide; membrane channel; protegrin ID PHOSPHOLIPID-BILAYER MEMBRANES; DEFENSINS; PEPTIDES; PERMEABILIZATION; TACHYPLESINS; MECHANISMS; PORES AB Protegrins are small, arginine- and cysteine-rich, beta-sheet peptides with potent activity against bacteria, fungi, and certain enveloped viruses. We report that protegrins form weakly anion-selective channels in planar phospholipid bilayers, induce potassium leakage from liposomes and form moderately cation-selective channels in planar lipid membranes that contain bacterial lipopolysaccharide. The disruption of microbial membranes may be a central attribute related to the host defense properties of protegrins. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Mental Retardat Res Ctr, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Kagan, BL (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Suite 67-468 NPI,750 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIAID NIH HHS [AI 22839, AI 37945]; NIMH NIH HHS [MH 01174] NR 22 TC 95 Z9 97 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD AUG 20 PY 1999 VL 1420 IS 1-2 BP 23 EP 29 DI 10.1016/S0005-2736(99)00086-3 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 231EV UT WOS:000082295900003 PM 10446287 ER PT J AU Ubeda, M Schmitt-Ney, M Ferrer, J Habener, JF AF Ubeda, M Schmitt-Ney, M Ferrer, J Habener, JF TI CHOP/GADD153 and methionyl-tRNA synthetase (MetRS) genes overlap in a conserved region that controls mRNA stability SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TRANSCRIPTION FACTOR CHOP; TRANSFER-RNA-SYNTHETASE; AMINO-ACID LIMITATION; BINDING-PROTEIN; MESSENGER-RNAS; GROWTH ARREST; GADD153; EXPRESSION; CELLS; APOPTOSIS AB The transcription factor CHOP is involved in the regulation of the cell division cycle and the control of programmed cell death in response to cellular stress. CHOP expression has been linked with several forms of cancer. A reciprocal translocation between the CHOP and TLS RNA-binding protein gene results in myxoid liposarcoma and amplifications of the CHOP gene are associated with solid tumors including several types of sarcomas. Here we report the mapping of the methionyl tRNA synthetase (MetRS) gene to the identical 12q13 locus where the CHOP gene had previously been mapped. PCR analysis demonstrates a tail-to-tail overlap of both genes over a 55-bp region. As a result the two mRNAs share a 3' UTR complementary sequence allowing an in vivo interaction between the two mRNAs. An AU-rich regulatory element (ARE) known to control mRNA stability resides in the overlapping sequence. To test for functional significance of the ARE a luciferase reporter plasmid containing the 3'UTR of CHOP was constructed. Transfection experiments in NIH-3T3 cells show that CHOP 3'UTR confers a significantly lower activity than a control reporter or a reporter in which the region overlapping the MetRS mRNA is deleted. The conservation of this overlapping of the CHOP and MetRS genes and the role of their complementary sequence in the control of mRNA stability suggest the existence of a functional link between the expression of these two genes. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, 55 Fruit St,WEL320, Boston, MA 02114 USA. RI Ferrer, Jorge/A-3176-2012; OI Ferrer, Jorge/0000-0002-5959-5729 NR 31 TC 24 Z9 25 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 AUG 19 PY 1999 VL 262 IS 1 BP 31 EP 38 DI 10.1006/bbrc.1999.1140 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 230QC UT WOS:000082261000006 PM 10448063 ER PT J AU Alani, RM Hasskarl, J Grace, M Hernandez, HC Israel, MA Munger, K AF Alani, RM Hasskarl, J Grace, M Hernandez, HC Israel, MA Munger, K TI Immortalization of primary human keratinocytes by the helix-loop-helix protein, Id-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; HUMAN EPITHELIAL-CELLS; SENESCENT HUMAN FIBROBLASTS; REPLICATIVE SENESCENCE; TELOMERASE ACTIVITY; DNA-BINDING; GENE; DIFFERENTIATION; EXPRESSION; SUFFICIENT AB Basic helix-loop-helix (bHLH) DNA-binding proteins have been demonstrated to regulate tissue-specific transcription within multiple cell lineages. The Id family of helix-loop-helix proteins does not possess a basic DNA-binding domain and functions as a negative regulator of bHLH proteins. Overexpression of Id proteins within a variety of cell types has been shown to inhibit their ability to differentiate under appropriate conditions. We demonstrate that ectopic expression of Id-1 leads to activation of telomerase activity and immortalization of primary human keratinocytes. These immortalized cells have a decreased capacity to differentiate as well as activate phosphorylation of the retinoblastoma protein. Additionally, these cells acquire an impaired p53-mediated DNA-damage response as a late event in immortalization, We conclude that bHLH proteins play a pivotal role in regulating normal keratinocyte growth and differentiation, which can be disrupted by the immortalizing functions of Id-1 through activation of telomerase activity and inactivation of the retinoblastoma protein. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Neurosurg, Preuss Lab Mol Neurooncol, San Francisco, CA 94143 USA. RP Alani, RM (reprint author), Mem Sloan Kettering Canc Ctr, Cell Biol Program, 1275 York Ave,Box 241, New York, NY 10021 USA. OI Munger, Karl/0000-0003-3288-9935 FU NCI NIH HHS [CA66980, R01 CA066980]; NIAMS NIH HHS [K08 AR01975-01A1, P30 AR042689, T32 AR007098, T32 AR07098-21] NR 32 TC 142 Z9 146 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 17 PY 1999 VL 96 IS 17 BP 9637 EP 9641 DI 10.1073/pnas.96.17.9637 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227UN UT WOS:000082098500037 PM 10449746 ER PT J AU Tang, J Sawasdikosol, S Chang, JH Burakoff, SJ AF Tang, J Sawasdikosol, S Chang, JH Burakoff, SJ TI SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PHOSPHOTYROSINE-BINDING DOMAIN; TYROSINE KINASE; ZAP-70; TRANSDUCTION; ASSOCIATION; COMPLEX; CHAIN; SHC AB Engagement of the T cell antigen receptor (TCR) leads to rapid activation of protein tyrosine kinases, which in turn phosphorylate downstream enzymes and adapter proteins. Some adapter proteins, such as SLP-76, Vav, and LAT, positively regulate TCR-mediated signal transduction, whereas others, such as Cbl, play an inhibitory role. SLAP (Src-Like adapter protein), an adapter protein containing a Src homology 3 and a Src homology 2 domain,,vas isolated from a yeast interacting screen by using N-terminal Cbl as bait. N-terminal Cbl interacts with SLAP in vivo and in vitro in a tyrosine phosphorylation-independent manner. We observed that SLAP is expressed in T cells, and upon TCR activation, SLAP interacts with ZAP-70, Syk, LAT, and TCR zeta chain in Jurkat T cells. In transiently transfected COS-7 cells, SLAP forms separate complexes with ZAP-70, Syk, and LAT through its Src homology 2 domain. Overexpression of a C-terminal-truncated SLAP mutant down-regulates nuclear factor of activated T cells-AP1 activity. We have evidence that SLAP forms homodimers through its C-terminal region. Serial truncations and mutations in the C terminus of SLAP demonstrate that there is a correlation between the loss of dimerization and the inhibition of nuclear factor of activated T cells-AP1 activity. The in vivo association of SLAP with key signaling molecules and its inhibition of T cell activation suggests that SLAP plays an important role in TCR-mediated signal transduction. C1 Harvard Univ, Dept Pediat Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Burakoff, SJ (reprint author), Harvard Univ, Dept Pediat Oncol, Dana Farber Canc Inst, Sch Med, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA70758, R01 CA070758] NR 23 TC 53 Z9 59 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 17 PY 1999 VL 96 IS 17 BP 9775 EP 9780 DI 10.1073/pnas.96.17.9775 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227UN UT WOS:000082098500061 PM 10449770 ER PT J AU Bhide, PG Frost, DO AF Bhide, PG Frost, DO TI Intrinsic determinants of retinal axon collateralization and arborization patterns SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE retinal ganglion cell; axon branching; axon arbors; axon-target interactions ID LATERAL GENICULATE-NUCLEUS; MEDIAL GENICULATE; SYRIAN-HAMSTERS; SOMATOSENSORY THALAMUS; SYNAPTIC ORGANIZATION; PRENATAL DEVELOPMENT; NEURAL CONNECTIONS; TARGET RECOGNITION; CEREBRAL-CORTEX; CORPUS-CALLOSUM AB Permanent, novel retinal projections to the principal thalamic somatosensory (ventrobasal) or auditory (medial geniculate) nuclei can be produced in adult hamsters if the superior colliculus is ablated bilaterally and the somatosensory and auditory lemniscal axons are transected unilaterally on the day of birth. We studied the development of those novel projections by labeling retinal axons with the fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate to examine the relative roles of intrinsic factors and axon-target interactions in the specification of retinal axon connections. Our principal findings are as follows: (1) In hamsters operated on the day of birth to produce the novel retinal projections, retinal ganglion cell axons projecting to the ventrobasal or medial geniculate nuclei develop in three morphologically distinct stages, i.e., elongation, collateralization, and arborization, as do retinal axons projecting to the dorsal lateral geniculate nucleus, the principal thalamic visual nucleus, in normal hamsters. (2) In both the ventrobasal and medial geniculate nuclei of operated hamsters, as in the dorsal lateral geniculate nucleus of normal hamsters, collateral branches were initially formed by retinal ganglion cell axons in both the superficial and internal components of the optic tract and only collaterals from the superficial component formed permanent projections. (3) The retinofugal axon terminal arbors in the ventrobasal and medial geniculate nuclei of mature, operated hamsters resemble the same three morphologic classes that are observed in the lateral geniculate nucleus of normal hamsters, although their absolute size appears to be altered. These data suggest that both superficial and internal optic tract axons can produce thalamic collaterals during development but that only superficial optic tract axons can permanently retain thalamic collaterals. Furthermore, the same morphologic types of retinofugal axone appear to contribute to normal and surgically induced retinal projections. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp E, Dev Neurobiol Lab, 149 13th St, Charlestown, MA 02129 USA. OI Bhide, Pradeep/0000-0003-4236-9415 FU NEI NIH HHS [EY03465]; NIMH NIH HHS [MH49568]; NINDS NIH HHS [NS32657] NR 47 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 16 PY 1999 VL 411 IS 1 BP 119 EP 129 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 216VY UT WOS:000081466200009 PM 10404111 ER PT J AU Aronson, D Weinrauch, LA D'Elia, JA Tofler, GH Burger, AJ AF Aronson, D Weinrauch, LA D'Elia, JA Tofler, GH Burger, AJ TI Circadian patterns of heart rate variability, fibrinolytic activity, and hemostatic factors in type I diabetes mellitus with cardiac autonomic neuropathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CARDIOVASCULAR-DISEASE; DIURNAL-VARIATION; SYMPTOM ONSET; BLOOD-COAGULATION; SYSTEM; DEATH; SUBGROUPS; FREQUENCY; TRIGGERS AB Diabetes mellitus is associated with a marked increase in the risk of coronary events but with an altered circadian distribution that demonstrates an absent morning peak and higher infarction rate during the evening hours. To elucidate the mechanism of this phenomenon, the circadian pattern of heart rate variability was evaluated in 22 type I diabetic patients with diabetic autonomic neuropathy in conjunction with circadian changes of fibrinolytic and hemostatic factors. The circadian pattern (6 A.M. to 10 P.M. vs 10 P.M. to 6 A.M.) of 3 indexes of parasympathetic tone was evaluated using 24-hour heart rate variability analysis. The high-frequency power (3.0 +/- 0.2 vs 3.3 +/- 0.2 ms(2), p = 0.08) and the percentage of RR intervals with >50 ms variation (0.47 +/- 0.18 vs 0.69 +/- 0.33 ms, p = 0.52) demonstrated no significant circadian variation. The square root of mean squared differences of successive RR intervals showed a small but significant increase during nighttime (8.5 +/- 0.7 vs 9.7 +/- 1.1 ms, p 0.02). Fibrinolytic activity wets significantly lower at 8 A.M. than at 4 P.M. (166.4 +/- 12.5 to 200.2 +/- 9.3 mm(2), p = 0.0003), but with a low amplitude. Plasminogen activator inhibitor 1 showed no circadian variation. Factor VII and fibrinogen demonstrated a significant reduction from 8 A.M. to 4 P.M., but both peak and nadir values were elevated. The von Willebrand factor wets markedly elevated with no circadian variation. Thus, diabetic autonomic neuropathy is associated with a loss of both the nocturnal predominance of parasympathetic activity and a prothrombotic state that persists throughout the day. These abnormalities may attenuate the relative protection from coronary events during the afternoon and nighttime. (C) 1999 by Excerpta Medica, Inc. C1 Beth Israel Deaconess Med Ctr, Noninvas Cardiol Lab, Joslin Diabet Ctr, Boston, MA USA. Royal N Shore Hosp, Sydney, NSW, Australia. RP Burger, AJ (reprint author), Beth Israel Deaconess Med Ctr, Noninvas Cardiol Lab, Joslin Diabet Ctr, W Campus,Baker 3,1 Deaconess Rd, Boston, MA USA. RI Aronson, Doron/F-3390-2010; OI Weinrauch, Larry/0000-0003-1357-9528 NR 30 TC 27 Z9 29 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 1999 VL 84 IS 4 BP 449 EP 453 DI 10.1016/S0002-9149(99)00331-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 225VV UT WOS:000081987400014 PM 10468085 ER PT J AU Dougherty, DD Shin, LM Alpert, NM Pitman, RK Orr, SP Lasko, M Macklin, ML Fischman, AJ Rauch, SL AF Dougherty, DD Shin, LM Alpert, NM Pitman, RK Orr, SP Lasko, M Macklin, ML Fischman, AJ Rauch, SL TI Anger in healthy men: A PET study using script-driven imagery SO BIOLOGICAL PSYCHIATRY LA English DT Article DE PET; anger; limbic system; cingulate cortex; orbitofrontal cortex; emotion ID POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; OBSESSIVE-COMPULSIVE DISORDER; CEREBRAL BLOOD-FLOW; SYMPTOM PROVOCATION; PSYCHOPHYSIOLOGICAL ASSESSMENT; FUNCTIONAL NEUROANATOMY; FLUOXETINE TREATMENT; UNIPOLAR DEPRESSION; CINGULATE CORTEX AB Background: An understanding of the neurobiological basis of normal emotional processing is useful in formulating hypotheses regarding the pathophysiology of psychiatric illnesses. Methods: This study examined the mediating functional neuroanatomy of anger in eight healthy men. Narrative scripts were developed from autobiographical information to inducer anger and neutral states. The subjects imagined the content of the narrative scripts to induce anger during positron emission tomography to measure normalized regional cerebral blood flow (rCBF), Psychophysiologic responses and subjective ratings of Emotional state were measured for each condition, Statistical parametric maps were constructed to reflect the Anger versus Neutral state contrast. Results: Anger was associated with activation of the left orbitofrontal cortex, right anterior cingulate cortex affective division, and bilateral anterior temporal poles. Conclusions: These results suggest that the subjective experience of anger is associated with rCBF increases in anterior paralimbic regions of the brain. Biol Psychiatry 1999;46:466-472 (C) 1999 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Vet Affairs Res Serv, Manchester, NH USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, ACC 812,15 Parkman St, Boston, MA 02114 USA. FU NIMH NIH HHS [MH01215] NR 47 TC 161 Z9 164 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 1999 VL 46 IS 4 BP 466 EP 472 DI 10.1016/S0006-3223(99)00063-3 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 226TA UT WOS:000082036700003 PM 10459395 ER PT J AU Bergsagel, DE Wong, O Bergsagel, PL Alexanian, R Anderson, K Kyle, RA Raabe, GK AF Bergsagel, DE Wong, O Bergsagel, PL Alexanian, R Anderson, K Kyle, RA Raabe, GK TI Benzene and multiple myeloma: Appraisal of the scientific evidence SO BLOOD LA English DT Review ID TOPOISOMERASE-II INHIBITORS; BREAKPOINT CLUSTER REGION; COLONY-STIMULATING FACTOR; INDUSTRY WIDE MORTALITY; DISTRIBUTION WORKERS; PETROLEUM REFINERY; PLIOFILM COHORT; UNITED-STATES; LEUKEMIA; EXPOSURE C1 Univ Toronto, Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M4W 2S7, Canada. Appl Hlth Sci, San Mateo, CA USA. Tulane Univ, Med Ctr, Sch Publ Hlth, Dept Epidemiol, New Orleans, LA USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Ctr Lymphoma & Myeloma, New York, NY USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Mobil Business Resources Corp, Global Med Serv, Dept Med Informat & Hlth Risk Assessment, New Hope, PA USA. RP Bergsagel, DE (reprint author), Univ Toronto, Princess Margaret Hosp, Ontario Canc Inst, 610 Univ Ave, Toronto, ON M4W 2S7, Canada. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 NR 81 TC 39 Z9 40 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1999 VL 94 IS 4 BP 1174 EP 1182 PG 9 WC Hematology SC Hematology GA 225FE UT WOS:000081947100004 PM 10438704 ER PT J AU Taub, JW Huang, X Matherly, LH Stout, ML Buck, SA Massey, GV Becton, DL Chang, MN Weinstein, HJ Ravindranath, Y AF Taub, JW Huang, X Matherly, LH Stout, ML Buck, SA Massey, GV Becton, DL Chang, MN Weinstein, HJ Ravindranath, Y TI Expression of chromosome 21-localized genes in acute myeloid leukemia: Differences between Down syndrome and non-Down syndrome blast cells and relationship to in vitro sensitivity to cytosine arabinoside and daunorubicin SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; CHILDRENS CANCER GROUP; SUPEROXIDE-DISMUTASE; CHILDHOOD; CHEMOTHERAPY; AML; MYELODYSPLASIA; TRISOMY-21 AB The high event-free survival rates of Down syndrome (DS) children with acute myeloid leukemia (AML) are due, in part, to increased in vitro sensitivity of DS myeloblasts to cytosine arabinoside (ara-C) and daunorubicin and the greater generation of ara-C triphosphate (ara-CTP) from ara-C compared with myeloblasts from non DS patients (Taub et at, Blood 87:3395, 1996). This study further explores the molecular basis of chemotherapy sensitivity of DS AML patients by examining the expression of chromosome 21-localized genes in myeloblasts from newly diagnosed AML patients. Transcript levels of two chromosome 21-localized genes, cystathionine-P-synthase (CBS) and superoxide dismutase (SOD), measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), were 12.0- and 3.8-fold higher in DS compared with non-DS myeloblasts (P < .0001 and P < .0001, respectively). Conversely, there were no significant increases in transcripts for 2 other chromosome 21-localized genes, carbonyl reductase and the reduced folate carrier. CBS transcript levels correlated with both in vitro ara-C sensitivity measured by the 3-[4,5-dimethyl-thiazol-2-yl]-2.5-diphenyltetrazolium-bromide [MTT) assay (P = .003) and the generation of H-3-ara-C triphosphate (ara-CTP) after in vitro incubations with 5 mu mol/L H-3-ara-C (P = .0003). Transcripts of deoxycytidine kinase were 2.6-fold higher in DS compared with non-DS cells and may be a factor in the enhanced metabolism of ara-C in DS cells. There was no significant correlation of SOD transcripts with in vitro ara-C and daunorubicin sensitivities. Increased CBS transcripts could result in elevated CBS activity, which modulates ara-C metabolism by altering reduced folate pools, deoxycytidine triphosphate pools, S-adenosylmethionine levels, and/or methylation of the deoxycytidine kinase gene. The further identification of the molecular mechanisms of chemotherapy sensitivity of DS AML patients may lead to significant improvements in the treatment and cure of AML. (C) 1999 by The American Society of Hematology. C1 Childrens Hosp Michigan, Div Pediat Hematol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pediat, Barbara Ann Karmanos Canc Inst,Expt & Clin Therap, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. Med Coll Virginia, Richmond, VA USA. Univ Arkansas, Little Rock, AR USA. Univ Florida, Gainesville, FL USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Pediat Oncol Grp, Chicago, IL USA. RP Taub, JW (reprint author), Childrens Hosp Michigan, Div Pediat Hematol, 3901 Beaubien Blvd, Detroit, MI 48201 USA. NR 39 TC 115 Z9 120 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1999 VL 94 IS 4 BP 1393 EP 1400 PG 8 WC Hematology SC Hematology GA 225FE UT WOS:000081947100027 PM 10438727 ER PT J AU Munoz, SJ Alter, HJ Nakatsuji, Y Shih, JWK Reddy, RK Jeffers, L Schiff, ER Reid, AE Marrone, A Rothstein, K Manzarbeitia, C Liang, TJ AF Munoz, SJ Alter, HJ Nakatsuji, Y Shih, JWK Reddy, RK Jeffers, L Schiff, ER Reid, AE Marrone, A Rothstein, K Manzarbeitia, C Liang, TJ TI The significance of hepatitis G virus in serum of patients with sporadic fulminant and subfulminant hepatitis of unknown etiology SO BLOOD LA English DT Article ID NON-B-HEPATITIS; POLYMERASE CHAIN-REACTION; GBV-C; NON-A; LIVER-FAILURE; INFECTION; JAPAN; RNA; IDENTIFICATION; ASSOCIATION AB Excluding acute hepatic failure caused by drugs, the etiology of fulminant hepatitis (FH) remains unknown in many patients, There are conflicting data about a possible pathogenic role for the hepatitis G virus (HGV) in patients with cryptogenic fulminant hepatitis (non-A-E FH). We investigated the presence of circulating HGV in 36 patients with well-documented non-A-E fulminant and 5 patients with subfulminant hepatitis from 3 geographic locations in the United States. Serum HGV RNA was determined by reverse transcriptase-polymerase chain reaction using primers from the NS5 region of the HGV genome. HGV RNA was also measured before and after liver transplantation in 5 patients and at different time points in 7 patients. Serum samples were recoded and reanalyzed for HGV RNA using different primer sets to assess the validity of the HGV RNA assay. HGV was present in serum of 14 of the 36 patients (38.8%) with non-A-E fulminant hepatitis, Twenty percent of patients from the Northeast, 11% of the patients from the Southeast, and 50% from the Mid-Atlantic regions of the United States had circulating HGV RNA. The use of therapeutic blood products was significantly associated with the presence of serum HGV RNA (P < .02). Retesting for HGV RNA with different primers was positive in all but 1 case. HGV RNA is not causally related to non-A-E fulminant hepatitis. The finding of HGV RNA in serum from these patients is likely related to the administration of blood product transfusion after the onset of fulminant hepatitis. (C) 1999 by The American Society of Hematology. C1 Albert Einstein Med Ctr, Ctr Liver Dis, Philadelphia, PA 19141 USA. NIDDK, NIH, Liver Dis Sect, Ctr Clin, Bethesda, MD USA. NIDDK, NIH, Dept Transfus Med, Bethesda, MD USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Miami, Ctr Liver Dis, Miami, FL USA. RP Munoz, SJ (reprint author), Albert Einstein Med Ctr, Ctr Liver Dis, 5401 Old York Rd,Klein Bldg,Suite 509, Philadelphia, PA 19141 USA. NR 42 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1999 VL 94 IS 4 BP 1460 EP 1464 PG 5 WC Hematology SC Hematology GA 225FE UT WOS:000081947100034 PM 10438734 ER PT J AU Jagadeeswaran, P Sheehan, JP AF Jagadeeswaran, P Sheehan, JP TI Analysis of blood coagulation in the zebrafish SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE zebrafish; blood coagulation; animal-model; hemostasis; anticoagulation ID INHERITED THROMBOPHILIA; MODEL; THROMBIN; PROTHROMBIN; HEMOSTASIS; EMBRYOS; CDNAS AB The zebrafish (Danio rerio) is a unique animal model in which saturation mutagenesis has been used to identify genes involved in vertebrate development. The relevance of the zebrafish as a genetic model for hemostasis depends, in large part, on the degree of similarity between the zebrafish and mammalian systems. The diminutive size of the zebrafish poses technical problems for analysis of coagulation. This study describes methods to obtain citrated whole blood and plasma fi om the zebrafish, analyze in vitro coagulation in small plasma volumes, obtain uniform dosing of zebrafish with oral anticoagulants, and demonstrate specific factor activities via chromogenic assays. Analysis of the zebrafish system demonstrates the presence of both the intrinsic and extrinsic pathways of coagulation, evidence for prothrombin, factor X, protein C, antithrombin, and heparin cofactor IJ activity, and a requirement for vitamin K dependent gamma-carboxylation of zebrafish hemostatic proteins. Induction of a morphologically recognizable bleeding phenotype by warfarin treatment is also demonstrated. Characterization of zebrafish coagulation provides evidence that major hemostatic pathways are conserved between zebrafish and man. These similarities indicate that the zebrafish is a relevant genetic model for identification of novel genes involved in hemostasis and thrombosis. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Jagadeeswaran, P (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NHLBI NIH HHS [HL 02923]; NIGMS NIH HHS [GM 53373] NR 19 TC 56 Z9 57 U1 4 U2 13 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD AUG 15 PY 1999 VL 25 IS 15 BP 239 EP 249 DI 10.1006/bcmd.1999.0249 PG 11 WC Hematology SC Hematology GA 228WA UT WOS:000082157800003 PM 10575549 ER PT J AU Ramanathan, RK Lipsitz, S Asbury, RF Qazi, R Greenberg, BR Haller, DG AF Ramanathan, RK Lipsitz, S Asbury, RF Qazi, R Greenberg, BR Haller, DG TI Phase II trial of trimetrexate for patients with advanced gastric carcinoma - An Eastern Cooperative Oncology Group Study (E1287) SO CANCER LA English DT Article DE antifolates; gastric carcinoma; Phase II study; trimetrexate ID CANCER; 5-FLUOROURACIL; FLUOROURACIL; CHEMOTHERAPY; COMBINATION; DOXORUBICIN; LEUCOVORIN; CISPLATIN; PHARMACOLOGY; QUINAZOLINE AB BACKGROUND. A Phase II study was conducted to evaluate the response, duration of response, and duration of survival of patients with measurable gastric carcinoma treated with trimetrexate (TMTX) who had not had prior chemotherapy. METHODS. Thirty-three patients with unresectable or metastatic gastric adenocarcinoma who had not received previous chemotherapy were treated with intravenous TMTX 12 mg/m(2) daily for 5 days. The dosage of TMTX was reduced to 8 mg/m(2) daily for 5 days for those who had received prior radiotherapy. The cycle was repeated every 3 weeks until disease progression or unacceptable toxicity occurred. RESULTS. Thirty-three patients could be analyzed with follow-up data. There was one Grade 5 (lethal) toxicity and four Grade 4 toxicities. Hematologic toxicity was the most common. The overall response rate was 21%, the overall median progression free survival was 2.7 months, and the overall median survival was 5.9 months for the entire cohort. No patients were alive at last follow-up. CONCLUSIONS. Though TMTX as a single agent has activity in gastric carcinoma with manageable toxicity, it cannot be recommended for routine use as a single agent due to the brief duration of response and median survival. Cancer 1999;86:572-6, (C) 1999 American Cancer Society. C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA USA. Interlakes Oncol & Hematol PC, New York, NY USA. Highland Hosp, Rochester, NY USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. RP Ramanathan, RK (reprint author), Univ Pittsburgh, Inst Canc, N755 MUH,200 Lothrop St, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [CA23318, CA1863, CA07190] NR 29 TC 3 Z9 3 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 15 PY 1999 VL 86 IS 4 BP 572 EP 576 DI 10.1002/(SICI)1097-0142(19990815)86:4<572::AID-CNCR5>3.0.CO;2-# PG 5 WC Oncology SC Oncology GA 223YA UT WOS:000081868100005 PM 10440684 ER PT J AU Yu, LL Flotte, TJ Tanabe, KK Gadd, MA Cosimi, AB Sober, AJ Mihm, MC Duncan, LM AF Yu, LL Flotte, TJ Tanabe, KK Gadd, MA Cosimi, AB Sober, AJ Mihm, MC Duncan, LM TI Detection of microscopic melanoma metastases in sentinel lymph nodes SO CANCER LA English DT Article DE melanoma; sentinel lymph node; MART-1; metastasis ID AXILLARY MICRO-METASTESES; POLYMERASE CHAIN-REACTION; MALIGNANT-MELANOMA; BREAST-CANCER; TUMOR-CELLS; NODAL METASTASES; STAGE-I; DISSECTION; MICROMETASTASES; MACROMETASTASES AB BACKGROUND. Sentinel lymph node biopsy following radioisotope labeling is a recently developed, minimally invasive surgical staging procedure used in the management of primary cutaneous malignant melanoma. If histologic analysis reveals melanoma metastasis in the sentinel lymph node, completion lymphadenectomy is performed and adjuvant therapy considered. The routine pathologic assessment of the sentinel lymph node consists of bisecting the lymph node along its long axis and histologic examination of one hematoxylin and eosin-stained section of each cut surface. METHODS. In this study, the authors reexamined 235 sentinel lymph nodes reported as negative for melanoma metastasis following routine histologic examination, from 94 patients with American Joint Committee on Cancer (AJCC) Stage I and II cutaneous melanoma. RESULTS. Deeper sections into the lymph node and immunohistochemical stains with antibodies to S-100, HMB-45, NK1C3, and MART-1 led to the identification of microscopic metastases in 11 sentinel lymph nodes from 11 patients and capsular nevi in 9 sentinel lymph nodes from 8 patients. CONCLUSIONS. Deeper serial sections and immunohistochemical stains detected microscopic metastases in approximately 12% of cases that would be reported as negative for metastasis by routine pathologic analysis. These techniques also allowed for the identification of capsular melanocytic nevi in the sentinel lymph nodes of 9% of patients. [See editorial on pages 551-2, this issue.] Cancer 1999;86:617-27. (C) 1999 American Cancer Society. C1 Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Transplant Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Warren 817,55 Fruit St, Boston, MA 02114 USA. NR 39 TC 140 Z9 141 U1 1 U2 2 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 1999 VL 86 IS 4 BP 617 EP 627 DI 10.1002/(SICI)1097-0142(19990815)86:4<617::AID-CNCR10>3.0.CO;2-S PG 11 WC Oncology SC Oncology GA 223YA UT WOS:000081868100010 PM 10440689 ER PT J AU Sugarman, J Regan, K Parker, B Bluman, LG Schildkraut, J AF Sugarman, J Regan, K Parker, B Bluman, LG Schildkraut, J TI Ethical ramifications of alternative means of recruiting research participants from cancer registries SO CANCER LA English DT Article DE registries; recruitment; ethics; informed consent; confidentiality ID CONFIDENTIALITY; TRIAL AB BACKGROUND. The protection of confidentiality and the extent to which voluntary and meaningful informed consent can be obtained from potential participants are critical when recruiting patients for clinical research from cancer registries. In the current study the authors describe the influence of two methods of recruitment from a cancer registry (direct contact by research staff and contact by research staff after physicians alert potential participants) on these issues. METHODS. Enrollment rates were tabulated using each recruitment method and complaints received from potential participants regarding recruitment were reviewed. RESULTS. Of 416 women approached to participate, the first 351 women were recruited by way of direct contact by research staff and the remaining 65 women were recruited by research staff after their physician had sent them an alert letter. There was no difference in the enrollment rate using the two methods. One potential participant believed that her confidentiality had been violated and another hung up the telephone when contacted directly; two potential subjects reported feeling pressure to participate because their physician sent them a letter. CONCLUSIONS, Although concerns regarding violating confidentiality clearly are justified when recruiting research participants from cancer registries, patients also may feel pressure to participate if physician notification is part of the process. It is incumbent on investigators and institutional review boards charged with overseeing this research that they respect confidentiality and avoid pressuring persons to participate in research. It also is critical that persons whose medical information will be entered into cancer registries be informed about this process as well as how the registry will be used for research. Cancer 1999;86:647-51. (C) 1999 American Cancer Society. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Dept Philosophy, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr Comprehens Canc, Durham, NC 27710 USA. Dana Farber Canc Inst, Breast Canc Program, Boston, MA 02115 USA. RP Sugarman, J (reprint author), Duke Univ, Med Ctr, Dept Med, Box 3040, Durham, NC 27710 USA. FU NCI NIH HHS [P50CA68438-05] NR 17 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1999 VL 86 IS 4 BP 647 EP 651 DI 10.1002/(SICI)1097-0142(19990815)86:4<647::AID-CNCR13>3.0.CO;2-G PG 5 WC Oncology SC Oncology GA 223YA UT WOS:000081868100013 PM 10440692 ER PT J AU Aghi, M Chou, TC Suling, K Breakefield, XO Chiocca, EA AF Aghi, M Chou, TC Suling, K Breakefield, XO Chiocca, EA TI Multimodal cancer treatment mediated by a replicating oncolytic virus that delivers the oxazaphosphorine/rat cytochrome P4502B1 and ganciclovir/herpes simplex virus thymidine kinase gene therapies SO CANCER RESEARCH LA English DT Article ID RIBONUCLEOTIDE REDUCTASE; POLYMERASE-DELTA; MUTANT; CYCLOPHOSPHAMIDE; CHEMOTHERAPY; ACTIVATION; ANALOGS; REPAIR; GROWTH; CELLS AB Multimodal therapy is generally more effective than single-agent treatment for cancer. rRp450 is an engineered herpes simplex viral mutant that replicates in and kills tumor cells in a relatively selective fashion. It also expresses, in infected cells, the cyclophosphamide (CPA)-sensitive rat cytochrome P450 2B1 (CYP2B1) and the ganciclovir (GCV)-sensitive herpes simplex virus thymidine kinase (HSV-TK) transgenes. We show that cultured rat 9L and human U87 Delta EGFR glioma cells, infected and lysed by rRp450, also exhibit supra-additive sensitivity to both CPA and GCV, as determined by Chou-Talalay synergy analysis. DNA cross-linking, assayed by ethidium bromide fluorescence, was significantly inhibited in the presence of GCV, suggesting that interactions between the CPA/CYP2B1 and GCV/HSV-TK gene therapies occurred at the level of DNA repair. In vivo, regression of 9L s.c. tumor volumes in athymic mice was achieved only by the multimodal treatment allowed by rRp450 viral oncolysis combined with CPA/CYP2B1 and GCV/HSV-TK gene therapies, whereas all other treatment combinations produced only tumor growth retardation. C1 Massachusetts Gen Hosp, Neurosurg Serv, Mol Neurooncol Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Therapeut Program, New York, NY 10001 USA. Cornell Univ, Grad Sch Med Sci, New York, NY 10001 USA. RP Chiocca, EA (reprint author), Massachusetts Gen Hosp E, Mol Neurooncol Labs, Neurosurg Serv CNY 6, Charlestown, MA 02129 USA. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU NCI NIH HHS [CA69246] NR 21 TC 97 Z9 100 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 1999 VL 59 IS 16 BP 3861 EP 3865 PG 5 WC Oncology SC Oncology GA 228KJ UT WOS:000082135400003 PM 10463570 ER PT J AU Bell, DW Wahrer, DCR Kang, DH MacMahon, MS FitzGerald, MG Ishioka, C Isselbacher, KJ Krainer, M Haber, DA AF Bell, DW Wahrer, DCR Kang, DH MacMahon, MS FitzGerald, MG Ishioka, C Isselbacher, KJ Krainer, M Haber, DA TI Common nonsense mutations in RAD52 SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER FAMILIES; HOMOLOGOUS RECOMBINATION; DNA-REPAIR; GERMLINE MUTATIONS; IONIZING-RADIATION; BRCA1 MUTATIONS; YEAST; GENE; CELLS; ASSOCIATION AB RAD51, RAD52, and RAD54 encode proteins that are critical to the repair of double-strand DNA breaks by homologous recombination, The physical interactions among the products of RAD51, BRCA1, and BRCA2 have suggested that the BRCA1 and BRCA2 breast cancer susceptibility genes may function, at least in part, in this DNA damage repair pathway. Given the observation that different genes within a common functional pathway may be targeted by mutations in human cancers, we analyzed RAD51, RAD52, and RAD54 for the presence of germ-line mutations in 100 cases with early-onset breast cancer and for somatic mutations in 15 human breast cancer cell lines. Two premature stop codons, Ser346ter and Tyr415ter, were identified in germ-line RAD52 alleles from 5% of early-onset breast cancer cases. Together, these two heterozygous mutations were also found in 8% of a healthy control population, indicating that they do not confer an increased risk for breast cancer. A rare germ-line missense mutation was identified in RAD54, whereas no sequence variants were found in RAD51. None of the three RAD genes demonstrated somatic mutations in breast cancer cell Lines. We conclude that, despite their potential functional association with the BRCA gene products, RAD51, RAD52, and RAD54 are not themselves targeted by mutations in human breast cancer. The presence of common nonsense mutations in RAD52 within the population may have significance for other conditions associated with potential alterations in DNA damage repair pathways. C1 Massachusetts Gen Hosp Ctr, Ctr Canc Risk Anal, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Tohoku Univ, Sendai, Miyagi 980, Japan. RP Haber, DA (reprint author), Massachusetts Gen Hosp Ctr, Ctr Canc Risk Anal, Bldg 149,13th St,CNY7, Charlestown, MA 02129 USA. NR 34 TC 27 Z9 29 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 1999 VL 59 IS 16 BP 3883 EP 3888 PG 6 WC Oncology SC Oncology GA 228KJ UT WOS:000082135400008 PM 10463575 ER PT J AU Nakayama, H Ishimaru, F Avitahl, N Sezaki, N Fujii, N Nakase, K Ninomiya, Y Harashima, A Minowada, J Tsuchiyama, J Imajoh, K Tsubota, T Fukuda, S Sezaki, T Kojima, K Hara, M Takimoto, H Yorimitsu, S Takahashi, I Miyata, A Taniguchi, S Tokunaga, Y Gondo, H Niho, Y Nakao, S Kyo, T Dohy, H Kamada, N Harada, M AF Nakayama, H Ishimaru, F Avitahl, N Sezaki, N Fujii, N Nakase, K Ninomiya, Y Harashima, A Minowada, J Tsuchiyama, J Imajoh, K Tsubota, T Fukuda, S Sezaki, T Kojima, K Hara, M Takimoto, H Yorimitsu, S Takahashi, I Miyata, A Taniguchi, S Tokunaga, Y Gondo, H Niho, Y Nakao, S Kyo, T Dohy, H Kamada, N Harada, M TI Decreases in Ikaros activity correlate with blast crisis in patients with chronic myelogenous leukemia SO CANCER RESEARCH LA English DT Article ID CENTROMERIC HETEROCHROMATIN; TRANSCRIPTION FACTOR; GENE; PROGENITORS; ISOFORMS; MUTATION; HELIOS; FAMILY; AIOLOS AB Gene targeting studies in mice have shown that the lack of Ikaros activity leads to T-cell hyperproliferation and T-cell neoplasia, establishing the Ikaros gene as a tumor suppressor gene in mice. This prompted us to investigate whether mutations in Ikaros play a role in human hematological malignancies. Reverse transcription-PCR was used to determine the relative expression Levels of Ikaros isoforms in a panel of human leukemia/lymphoma cell lines and human bone marrow samples from patients with hematological malignancies. Among the cell lines examined, only BV-173, which was derived from a chronic myelogenous Leukemia (CML) patient in lymphoid blast crisis, overexpressed the dominant-negative isoform, Ik-6. In 9 of 17 samples of patients in blast crisis of CML, Ikaros activity had been reduced either by drastically reducing mRNA expression (4 of 17) or by overexpressing the dominant-negative isoform Ik-6 (5 of 17). Significantly, expression of Ikaros isoforms seemed normal in chronic phase CML patients and patients with other hematological malignancies. In some cases, overexpression of the dominant-negative Ik-6 protein was confirmed by Western blot analysis, and Southern blot analysis indicated that decreases in Ikaros activity correlated with a mutation in the Ikaros Locus. In summary, these findings suggest that a reduction of Ikaros activity may be an important step in the development of blast crisis in CML and provide further evidence that mutations that alter Ikaros expression may contribute to human hematological malignancies. C1 Okayama Univ, Dept Med, Okayama 7008558, Japan. Okayama Univ, Dept Biochem & Mol Biol, Okayama 7008558, Japan. Fujisaki Cell Ctr, Okayama 70008558, Japan. Okayama Municipal Hosp, Okayama 7008558, Japan. Okayama Natl Hosp, Okayama 7008558, Japan. Ehime Prefectural Cent Hosp, Matsuyama, Ehime 7900024, Japan. Kochi Municipal Cent Hosp, Kochi 7800821, Japan. Chugoku cent Hosp Mutual Aid Assoc Publ Sch Teach, Fukuyama, Hiroshima 7210975, Japan. Kyushu Univ, Hamanoumachi Hosp, Fukuoka 8128582, Japan. Kyushu Univ, Dept Med, Fukuoka 8128582, Japan. Kanazawa Univ, Dept Med, Kanazawa, Ishikawa 9208641, Japan. Hiroshima Red Cross Hosp, Hiroshima 7348553, Japan. Atom Bomb Survivors Hosp, Hiroshima 7348553, Japan. Hiroshima Univ, Nucl Med & Biol Res Inst, Dept Canc Cytogenet, Hiroshima 7348553, Japan. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Ishimaru, F (reprint author), Okayama Univ, Dept Med, 2-5-1 Shikatacho, Okayama 7008558, Japan. RI Fujii, Nobuharu/G-2376-2011 NR 20 TC 76 Z9 79 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 15 PY 1999 VL 59 IS 16 BP 3931 EP 3934 PG 4 WC Oncology SC Oncology GA 228KJ UT WOS:000082135400019 PM 10463586 ER PT J AU Monsky, WL Fukumura, D Gohongi, T Ancukiewcz, M Weich, HA Torchilin, VP Yuan, F Jain, RK AF Monsky, WL Fukumura, D Gohongi, T Ancukiewcz, M Weich, HA Torchilin, VP Yuan, F Jain, RK TI Augmentation of transvascular transport of macromolecules and nanoparticles in tumors using vascular endothelial growth factor SO CANCER RESEARCH LA English DT Article ID HUMAN ADENOCARCINOMA LS174T; PERMEABILITY FACTOR; MICROVASCULAR PERMEABILITY; SOLID TUMORS; MOLECULAR MEDICINE; VEGF RECEPTORS; BLOOD-VESSELS; SCID MICE; IN-VIVO; ANGIOGENESIS AB The goal of this investigation was to measure changes in vascular permeability, pore cutoff size, and number of transvascular transport pathways as a function of time and in response to vascular endothelial growth factor (VEGF), placenta growth factor (PIGF-1 and PIGF-2), or basic fibroblast growth factor (bFGF). Two human and two murine tumors were implanted in the dorsal skin chamber or cranial window. Vascular permeability to BSA (approximate to 7 nm in diameter) and extravasation of polyethylene glycol-stabilized long-circulating liposomes (100-400 nm) and latex microspheres (approximate to 800 mm) were determined by intravital microscopy. Vascular permeability was found to be temporally heterogeneous. VEGF superfusion (100 ng/ml) significantly increased vascular permeability to albumin in normal s.c. vessels, whereas a 30-fold higher dose of VEGF (3000 ng/ml) was required to increase permeability in pial vessels, suggesting that different tissues exhibit different dose thresholds for VEGF activity. Furthermore, VEGF superfusion (1000 ng/ml) increased vascular permeability to albumin in a hypopermeable human glioma xenograft in cranial window, whereas VEGF superfusion (10-1000 ng/ml) failed to increase permeability in a variety of hyperpermeable tumors grown in dorsal skin chamber. Interestingly, low-dose VEGF treatment (10 ng/ml) doubled the maximum pore size (from 400 to 800 nm) and significantly increased the frequency of large (400 nm) pores in human colon carcinoma xenografts. PIGF-1, PIGF-2, or bFGF did not show any significant effect on permeability or pore size in tumors. These findings suggest that exogenous VEGF may be useful for augmenting the transvascular delivery of larger antineoplastic agents such as gene targeting vectors and encapsulated drug carriers (typical range, 100-300 nm) into tumors. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02214 USA. Massachusetts Gen Hosp, Edwin L Steele Lab, Boston, MA 02214 USA. Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Boston, MA 02214 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Radiobiol Sci, Boston, MA 02114 USA. Natl Res Ctr Biotechnol, Dept Gene Regulat & Differentiat, Branschweig, Germany. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02214 USA. RI Yuan, Fan/A-1287-2011 FU NCI NIH HHS [R35-CA56591] NR 50 TC 250 Z9 256 U1 0 U2 17 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 1999 VL 59 IS 16 BP 4129 EP 4135 PG 7 WC Oncology SC Oncology GA 228KJ UT WOS:000082135400051 PM 10463618 ER PT J AU Shintani, S Matsuo, K Crohin, CC McBride, J Tsuji, T Donoff, RB Posner, M Todd, R Wong, DTW AF Shintani, S Matsuo, K Crohin, CC McBride, J Tsuji, T Donoff, RB Posner, M Todd, R Wong, DTW TI Intragenic mutation analysis of the human epidermal growth factor receptor (EGFR) gene in malignant human oral keratinocytes SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; HUMAN ESOPHAGEAL CANCERS; HUMAN-BRAIN TUMORS; FACTOR-ALPHA; MESSENGER-RNA; C-ERBB; AMPLIFICATION; EXPRESSION; BINDING; CLONING AB Alteration in epidermal growth factor receptor (EGFR) expression is frequently associated with malignant transformation of epithelial tissues, including oral mucosa, This study examines the mutations in the coding region of the human EGFR gene in normal and malignant human oral keratinocytes, To examine the intragenic mutations in the human EGFR gene, a panel of normal and malignant human oral keratinocytes were examined by a nonisotopic RNase cleavage assay. Two consistent alterations were detected, First, a polymorphism, which generates a unique BsrI. restriction site, was detected at position 2073, This BsrI polymorphism was present only in malignant keratinocytes, Second, Southern blot hybridization of PCR products revealed that there is a truncated EGFR mRNA (similar to 1.5-kb) in oral squamous cell carcinoma cell lines. Similar analysis in normal cell lines revealed that this truncated EGFR transcript is also present, Immunoblotting revealed the presence of this truncated form of EGFR in all keratinocyte cell lines. These data permit us to conclude that there exists a novel truncated form of EGFR in human oral keratinocytes, Furthermore, there exists a tumor-associated EGFR polymorphic site at position 2073, The potential biological relevance of the truncated receptor and the utility of the BsrI polymorphic site for diagnostic applications are currently being explored. C1 Harvard Univ, Sch Dent Med, Lab Mol Pathol, Div Oral Pathol,Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Head & Neck Oncol Grp, Boston, MA 02115 USA. RP Wong, DTW (reprint author), Harvard Univ, Sch Dent Med, Lab Mol Pathol, Div Oral Pathol,Dept Oral Med & Diagnost Sci, 188 Longwood Ave, Boston, MA 02115 USA. FU NIDCR NIH HHS [P01 DE 12467, R01 DE08680] NR 44 TC 37 Z9 38 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 15 PY 1999 VL 59 IS 16 BP 4142 EP 4147 PG 6 WC Oncology SC Oncology GA 228KJ UT WOS:000082135400053 PM 10463620 ER PT J AU Moy, TI Silver, PA AF Moy, TI Silver, PA TI Nuclear export of the small ribosomal subunit requires the Ran-GTPase cycle and certain nucleoporins SO GENES & DEVELOPMENT LA English DT Review DE ribosome; nuclear export; in situ hybridization; rRNA processing ID MESSENGER-RNA EXPORT; LACKING 5'->3' EXORIBONUCLEASE-1; TEMPERATURE-SENSITIVE MUTATIONS; PORE COMPLEX PROTEINS; SACCHAROMYCES-CEREVISIAE; POLY(A)(+) RNA; BINDING-PROTEIN; NUCLEOCYTOPLASMIC TRANSPORT; YEAST NUCLEOPORIN; IMPORT RECEPTOR AB After their assembly in the nucleolus, ribosomal subunits are exported from the nucleus to the cytoplasm. After export, the 20S rRNA in the small ribosomal subunit is cleaved to yield 18S rRNA and the small 5' ITS1 fragment. The 5' ITS1 RNA is normally degraded by the cytoplasmic Xrn1 exonuclease, but in strains lacking XRN1, the 5' ITS1 fragment accumulates in the cytoplasm. Using the cytoplasmic localization of the 5' ITS1 fragment as an indicator for the export of the small ribosomal subunit, we have identified genes that are required for ribosome export. Ribosome export is dependent on the Ran-GTPase as mutations in Ran or its regulators caused 5' ITS1 to accumulate in the nucleoplasm. Mutations in the genes encoding the nucleoporin Nup82 and in the NES exporter Xpo1/Crm1 also caused the nucleoplasmic accumulation of 5' ITS1. Mutants in a subset of nucleoporins and in the nuclear transport factors Srp1, Kap95, Pse1, Cse1, and Mtr10 accumulate the 5' ITS1 in the nucleolus and affect ribosome assembly. In contrast, we did not detect nuclear accumulation of 5' ITS1 in 28 yeast strains that have mutations in other genes affecting nuclear trafficking. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 101 TC 131 Z9 134 U1 0 U2 2 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 1999 VL 13 IS 16 BP 2118 EP 2133 DI 10.1101/gad.13.16.2118 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 232HD UT WOS:000082364400007 PM 10465789 ER PT J AU Davidson, DH Ruvkun, G AF Davidson, DH Ruvkun, G TI Themes from a NASA workshop on gene regulatory processes in development and evolution SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS EMBRYOS; CENTRAL-NERVOUS-SYSTEM; SEA-URCHIN; HOX GENES; HOMEOBOX GENES; POLYCOMB GROUP; BODY PLANS; 18S RDNA; DROSOPHILA; EXPRESSION AB A memorable workshop, focused on causal mechanisms in metazoan evolution and sponsored by NASA, was held in early June 1998, at MEL. The workshop was organized by Mike Levine and Eric H. Davidson, and it included the PI and associates from 12 different laboratories, a total of about 30 people. Each laboratory had about two and one half hours in which to represent its recent research and cast up its current ideas for an often intense discussion. In the following we have tried to enunciate some of the major themes that emerged, and to reflect on their implications. The opinions voiced are our own. We would like to tender apologies over those contributions we have not been able to include, but this is not, strictly speaking, a meeting review. Rather we have focused on those topics that bear more directly on evolutionary mechanisms, and have therefore slighted some presentations (including some of our own), that were oriented mainly toward developmental processes. (C) 1999 Wiley-Liss, Inc. C1 CALTECH, Div Biol 156 29, Pasadena, CA 91125 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Davidson, DH (reprint author), CALTECH, Div Biol 156 29, Pasadena, CA 91125 USA. EM davidson@mirsky.caltech.edu NR 83 TC 8 Z9 13 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD AUG 15 PY 1999 VL 285 IS 2 BP 104 EP 115 DI 10.1002/(SICI)1097-010X(19990815)285:2<104::AID-JEZ2>3.0.CO;2-Z PG 12 WC Zoology SC Zoology GA 224CG UT WOS:000081878500002 PM 10440721 ER PT J AU Hattori, M Yamato, E Itoh, N Senpuku, H Fujisawa, T Yoshino, M Fukuda, M Matsumoto, E Toyonaga, T Nakagawa, I Petruzzelli, M McMurray, A Weiner, H Sagai, T Moriwaki, K Shiroishi, T Maron, R Lund, T AF Hattori, M Yamato, E Itoh, N Senpuku, H Fujisawa, T Yoshino, M Fukuda, M Matsumoto, E Toyonaga, T Nakagawa, I Petruzzelli, M McMurray, A Weiner, H Sagai, T Moriwaki, K Shiroishi, T Maron, R Lund, T TI Cutting edge: Homologous recombination of the MHC class IK region defines new MHC-Linked diabetogenic susceptibility gene(s) in nonobese diabetic mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; AUTOIMMUNE INSULITIS; NOD MOUSE; PREVENTION; EXPRESSION; MOLECULES; MELLITUS AB To localize the MHC-linked diabetogenic genes in the nonobese diabetic (NOD) mouse, a recombinational hotspot from the B10.A(R209) mouse was introduced to the region between the MHC class I K and class II A of the NOD mouse with the recombinational site centromeric to the Lmp2/Tap1 complex by breeding the two strains, Replacement of the NOD region centromeric to the recombinational site with the same region in R209 mice prevented the development of diabetes (from 71 to 3%) and insulitis (from 61 to 15%) in the N7 intra-MHC recombinant NOD mice. Similarly, the replacement of the NOD class II A, E and class I D region with the same region in R209 mice prevented the diseases (diabetes, from 71 to 0%; insulitis, from 61 to 3%). In addition to the MHC class II genes, there are at least two MHC-linked diabetogenic genes in the region centromeric to Lmp2. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Natl Inst Genet, Mishima, Shizuoka 411, Japan. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. UCL, London, England. RP Hattori, M (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM hattorim@joslab.harvard.edu FU NIDDK NIH HHS [DK48825, R01 DK43613, P30 DK36836] NR 18 TC 54 Z9 55 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 AUG 15 PY 1999 VL 163 IS 4 BP 1721 EP 1724 PG 4 WC Immunology SC Immunology GA 224LH UT WOS:000081900200001 PM 10438898 ER PT J AU Schneider, H Martin, M Agarraberes, FA Yin, Y Rapoport, I Kirchhausen, T Rudd, CE AF Schneider, H Martin, M Agarraberes, FA Yin, Y Rapoport, I Kirchhausen, T Rudd, CE TI Cytolytic T lymphocyte-associated antigen-4 and the TCR zeta/CD3 complex, but not CD28, interact with clathrin adaptor complexes AP-1 and AP-2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FACTOR-II RECEPTOR; KINASE PHOSPHATIDYLINOSITOL 3-KINASE; MULTIORGAN TISSUE DESTRUCTION; CYTOPLASMIC TAIL; PLASMA-MEMBRANE; CELL ACTIVATION; SORTING SIGNALS; GOLGI MEMBRANES; TYROSINE PHOSPHORYLATION; ASSEMBLY PROTEINS AB The negative signaling receptor cytolytic T lymphocyte-associated Ag-4 (CTLA-4) resides primarily in intracellular compartments such as the Golgi apparatus of T cells. However, little is known regarding the molecular mechanisms that influence this accumulation. In this study, we demonstrate binding of the clathrin adaptor complex: AP-1 with the GVYVKM motif of the cytoplasmic domain of CTLA-4 Binding occurred primarily in the Golgi compartment of T cells, unlike with AP-2 binding that occurs mostly with cell surface CTLA-4. Although evidence was not found to implicate AP-1 binding in the retention of CTLA-4 in the Golgi, AP-1 appears to play a role in shuttling of excess receptor from the Golgi to the lysosomal compartments for degradation. In support of this, increased CTLA-4 synthesis resulted in an increase in CTLA-4/AP-1 binding and a concomitant increase in the appearance of CTLA-4 in the lysosomal compartment. At the same time, the level of intracellular receptor was maintained at a constant level, suggesting that CTLA-4/AP-1 binding represents one mechanism to ensure steady state levels of intracellular CTLA-4 in T cells. Finally, we demonstrate that the TCR zeta/CD3 complex (but not CD28) also binds to AP-1 and AP-2 complexes, thus providing a possible link between these two receptors in the regulation of T cell function. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Tufts Univ, Sackler Sch Med Biomed Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM christopher_rudd@dfci.harvard.edu RI Martin, Margarita/H-2025-2015 OI Martin, Margarita/0000-0002-9245-4899 NR 68 TC 80 Z9 82 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1999 VL 163 IS 4 BP 1868 EP 1879 PG 12 WC Immunology SC Immunology GA 224LH UT WOS:000081900200024 PM 10438921 ER PT J AU Cai, DP Clayton, LK Smolyar, A Lerner, A AF Cai, DP Clayton, LK Smolyar, A Lerner, A TI AND-34, a novel p130(Cas)-binding thymic stromal cell protein regulated by adhesion and inflammatory cytokines' SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SWISS 3T3 CELLS; NUCLEOTIDE EXCHANGE FACTOR; CRK-ASSOCIATED SUBSTRATE; TYROSINE PHOSPHORYLATION; FOCAL ADHESION; DIRECT BINDING; SH3 DOMAINS; EPITHELIAL-CELLS; SRC KINASE; V-SRC AB We have characterized a novel cDNA whose steady state mRNA levels rise in the thymus 2 to 6 h following the induction of CD4(+)CD8(+) thymocyte apoptosis by in vivo cross-linking of CD3 epsilon, This cDNA, AND-34-1, contains an open reading frame (ORF) encoding a protein with an amino-terminal Src homology 2 (SH2) domain and a carboxyl-terminal domain homologous to GDP-exchange factors (GEFs), Northern analysis demonstrates widespread expression of the AND-34 gene. Anti-CD3 epsilon treatment induces up-regulation of the AND-34 mRNA levels in total thymic RNA but not in RNA from purified thymocytes, suggesting that this transcript is derived from a thymic stromal cell population. IL-1 and TNF increase AND-34 transcript le,els in thymic cortical reticular, thymic nurse, and fibroblast cell lines. In the thymic cortical reticular cell line, IL-1 and TNF induce a protein of the predicted 93-kDa size reactive with anti-AND-34 peptide antisera, Fifteen minutes of serum stimulation of vanadate-pretreated AND-34-1-transfected NIH3T3 fibroblasts induces tyrosine phosphorylation of AND-34 as well as coprecipitating 95-, 125-, and 130-kDa proteins. One of these tyrosine phosphorylated proteins is identified as p130(Cas) (Crk-associated substrate), a signaling molecule previously known to bind to a GDP-exchange factor (C3G) and inducibly associate with the focal adhesion complex, Consistent with such an association, AND-34 tyrosine phosphorylation is induced following adherence of trypsinized fibroblasts to fibronectin or poly-L-lysine-coated surfaces. C1 Boston Med Ctr, Dept Med, Sect Hematol & Oncol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Lerner, A (reprint author), Boston Med Ctr, Dept Med, Sect Hematol & Oncol, Evans 539,88 E Newton St, Boston, MA 02118 USA. NR 42 TC 46 Z9 48 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 1999 VL 163 IS 4 BP 2104 EP 2112 PG 9 WC Immunology SC Immunology GA 224LH UT WOS:000081900200053 PM 10438950 ER PT J AU Quinones-Hinojosa, A Ames, A Malek, JY Maynard, KI AF Quinones-Hinojosa, A Ames, A Malek, JY Maynard, KI TI An in vitro rabbit retina model to study electrophysiologic and metabolic function during and following ischemia SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE stroke; neuroprotection; oxygen deprivation; glucose deprivation; energy metabolism; electrophysiology; compound action potentials ID CEREBRAL BLOOD-FLOW; PATHO-PHYSIOLOGY; CELL-DEATH; CNS ISCHEMIA; REQUIREMENTS; THRESHOLDS; RECOVERY; RATS AB Most in vitro studies involving neuronal ischemia use biochemical measures and/or cell counting to assess cellular death. We describe an in vitro rabbit retina model in which we measured glucose utilization, lactate production, and light-evoked compound action potentials (CAPs) to assess metabolic and functional recovery following ischemia. Under control conditions, retinal glucose utilization and lactate production (n = 7), as well as CAPs (n = 8) remained quite constant for 6-8 h. During ischemia (glucose reduced from 6 to 1 mM and oxygen from 95 to 15%), glucose utilization and lactate production fell to 50%. CAPs fell to 50% in 3-4 min, and to 0% in 8-10 min. Recovery during 3-4 h of 'return-to-control' was dependent upon the length of ischemia. Glucose utilization recovered to 63% after 1 h (n = 4) and to 18% after 2 h of ischemia (n = 6, P < 0.001). Lactate production recovered to 77% after 1 h (n = 4) and to 54% after 2 h of ischemia (n = 6, P < 0.001). CAPs returned to 51, 15, and 0.13% of the control responses after 0.5 h (n = 7), 1 h (n = 8), and 2 h (n = 5) of ischemia, respectively (P < 0.001). This avascular, blood-brain barrier-free preparation provides an opportunity to use both metabolic and functional criteria to test protection against neuronal ischemia. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Neurosurg Serv, Neurophysiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Maynard, KI (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Neurophysiol Lab, Edwards Res Bldg,Room 414,55 Fruit St, Boston, MA 02114 USA. NR 25 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD AUG 15 PY 1999 VL 90 IS 2 BP 107 EP 115 DI 10.1016/S0165-0270(99)00068-0 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 239UQ UT WOS:000082788400003 PM 10513594 ER PT J AU Hirakura, Y Lin, MC Kagan, BL AF Hirakura, Y Lin, MC Kagan, BL TI Alzheimer amyloid A beta 1-42 channels: Effects of solvent, pH, and congo red SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE membranes; bilayers; aggregation; pores ID BETA-PROTEIN; BILAYER-MEMBRANES; CALCIUM CHANNELS; CELL-DEATH; DISEASE; PEPTIDES; NEUROTOXICITY; AGGREGATION; FRAGMENT; PLAQUES AB Substantial genetic and biochemical evidence implicates amyloid peptides (A beta) int the etiology of Alzheimer's Disease (AD), Recent evidence indicates that A beta 1-42 is the predominant species in the hallmark senile amyloid plaque of AD, Furthermore, A beta 1-42 forms aggregates inside lysosomes of cultured neurons leading to lysosomal disruption and cell death, We report here that A beta 1-42 forms slightly cation selective, voltage-independent ion channels with multiple conductance levels at neurotoxic concentrations in planar bilayer membranes. The channels show substantial irregularity of activity, and the size of conductances and the length of open lifetimes depend on solvent history, Formation of channels requires anionic lipids, is enhanced in acidic solutions, and is inhibited by Congo Red. These properties suggest that the channels are formed by aggregates of A beta 1-42, In addition, the channels are reversibly blocked by zinc in a voltage-independent manner. The properties of these channels would likely render them neurotoxic to relevant neurons in vivo. These results are consistent with the channel hypothesis of A beta neurotoxicity. Published 1999 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci,Mental Retardat Res Ctr, Inst Neuropsychiat,Brain Res Inst, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Kagan, BL (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat, Inst Neuropsychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIMH NIH HHS [MH01174] NR 40 TC 108 Z9 113 U1 2 U2 16 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 15 PY 1999 VL 57 IS 4 BP 458 EP 466 DI 10.1002/(SICI)1097-4547(19990815)57:4<458::AID-JNR5>3.0.CO;2-4 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 223LA UT WOS:000081841500005 PM 10440895 ER PT J AU Francis, A Raabe, TD Wen, DZ DeVries, GH AF Francis, A Raabe, TD Wen, DZ DeVries, GH TI Neuregulins and ErbB receptors in cultured neonatal astrocytes SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE growth factor; autocrine; neuregulin; astrocyte; erbB receptor ID NEU DIFFERENTIATION FACTOR; EPIDERMAL GROWTH-FACTOR; SECRETE NEUREGULINS; SIGNAL-TRANSDUCTION; NERVOUS-SYSTEM; SCHWANN-CELLS; GLIAL-CELLS; EXPRESSION; PROTEIN; BRAIN AB Neuregulins (NRGs) are a family of growth factors involved in signaling between neurons and glial cells of the peripheral and central nervous system, NRGs are synthesized and secreted by a number of cell types including Schwann cells, neurons, and oligodendrocytes, NRG transduction signals are mediated by the erbB family of receptor tyrosine kinases, These NRGs may be important for paracrine or autocrine signaling during development, injury, and the normal functioning of the central nervous system. In this study, we characterize the NRGs and erbB receptors expressed by cultured neonatal rat astrocytes, Using immunoblotting protocols With pan-specific antibodies, we identified eleven NRG molecular weight isoforms from approximately 16 kDa to 105 kDa in cultured neonatal rat astrocytes, Immunocyotchemistry with isoform-specific antibodies revealed the expression of both major isoform families (NRG alpha, NRG beta), Additionally, astrocyte-conditioned media contained two molecular weight isoforms of NRGs, We detected mRNA expression of NRG alpha and NRG beta in astrocytes by amplifying mRNA transcripts with reverse transcription polymerase chain reaction. Furthermore, we confirm that cultured astrocytes express all four erbB receptors as detected by immunocytochemical and immunoblotting techniques, These data indicate that astrocytes contain and secrete NRGs. (C) 1999 Wiley-Liss,Inc. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv 151, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Dept Cell Biol Neurobiol & Anat, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Grad Program Neurosci, Maywood, IL 60153 USA. St Marys Univ, Dept Biol Sci, San Antonio, TX USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP DeVries, GH (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv 151, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 34 TC 17 Z9 18 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 15 PY 1999 VL 57 IS 4 BP 487 EP 494 DI 10.1002/(SICI)1097-4547(19990815)57:4<487::AID-JNR8>3.0.CO;2-W PG 8 WC Neurosciences SC Neurosciences & Neurology GA 223LA UT WOS:000081841500008 PM 10440898 ER PT J AU Colson, YL El-Ezz, AYA Gaines, BA Ildstad, ST AF Colson, YL El-Ezz, AYA Gaines, BA Ildstad, ST TI Positive and negative selection of alpha beta TCR+ T cells in thymectomized adult radiation bone marrow chimeras SO TRANSPLANTATION LA English DT Article ID CLONAL DELETION; RECEPTOR REPERTOIRE; MICE; THYMUS; SPECIFICITY; TOLERANCE; ANTIGENS; ANERGY; H-2; MHC AB Background. The mature T-cell repertoire is characterized by the negative selection of potentially autoreactive T cells and the positive selection of T cells restricted to antigen-recognition in the context of self-MHC molecules, It is currently believed that the thymus is critical for these selection events. Although alpha beta T cell receptor (TCR)(+) T cells have been reported in thymectomized recipients, whether this represents clonal expansion of residual T cells or de novo generation of new T cells in the absence of a thymus has not been definitively evaluated. Methods. In the current study, development of the T-cell repertoire was evaluated in adult radiation bone marrow chimeras prepared after complete surgical thymectomy. Results. CD4(+) and CD8(+) T cells were present and exhibited donor-specific TCR-V beta expression and self-tolerance, indicative of negative selection. Positive selection was confirmed with the demonstration of host MHC restriction and the presence of donor-derived CD8(+) T cells after the transplantation of marrow from Class I deficient donors into normal recipients. Conclusions. These data provide evidence, for the first time, that the development of a functional T-cell repertoire can occur in adult recipients without the thymic microenvironment. C1 Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15261 USA. Univ Louisville, Inst Cellular Therapeut, Louisville, KY 40202 USA. RP Colson, YL (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 615,44 Binney St, Boston, MA 02115 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NIDDK NIH HHS [DK43901, DK46874]; PHS HHS [R01 A130615] NR 41 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 15 PY 1999 VL 68 IS 3 BP 403 EP 410 DI 10.1097/00007890-199908150-00013 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 226YK UT WOS:000082050600013 PM 10459545 ER PT J AU Rubin, DA Hellman, P Zon, LI Lobb, CJ Bergwitz, C Juppner, H AF Rubin, DA Hellman, P Zon, LI Lobb, CJ Bergwitz, C Juppner, H TI A G protein-coupled receptor from zebrafish is activated by human parathyroid hormone and not by human or teleost parathyroid hormone-related peptide - Implications for the evolutionary conservation of calcium-regulating peptide hormones SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PTH-RELATED PEPTIDE; CALCITONIN-RECEPTOR; METAPHYSEAL CHONDRODYSPLASIA; FUNCTIONAL-CHARACTERIZATION; PTH/PTHRP RECEPTOR; GROWTH-HORMONE; GENE; EXPRESSION; CLONING; ISOFORMS AB Genomic and cDNA clones encoding portions of a putative catfish parathyroid hormone (PTH) 2 receptor (PTH2R) led to the isolation of a cDNA encoding a full-length zebrafish PTH2R (zPTH2R), The zPTH2R shared 63 and 60% amino acid sequence identity with human and rat PTH2Rs, respectively, 47-52% identity with mammalian and frog PTH/PTHrP receptors (PTH1R), and less than 37% with other members of this family of G protein-coupled receptors, COS-7 cells expressing zPTH2R(43), a 5' splice variant that lacked 17 amino acids in the amino-terminal extracellular domain, showed cAMP accumulation when challenged with [Tyr(34)]hPTH(1-34)-amide (hPTH) (EC50, 1.64 +/- 0.95 nM) and [Ile(5),Trp(23),Tyr(36)]hPTHrP-(1-36)-amide ([Ile5, Trp23]hPTKrP) (EC50, 46.8 +/- 12.1 nM) but not when stimulated with [Tyr(36)]hPTHrP-(1-36)-amide (hPTHrP), [Trp(23),Tyr(36)]hPTHrP-(1-36)-amide ([Trp(23)]hPTHrP), or [Ala(29),Glu(30), Ala(34), Glu(35), Tyr(36)]fugufish PTHrP-(1-36)-amide (fuguPTHrP), FuguPTHrP also failed to activate the human PTH2R but had similar efficiency and efficacy as hPTH and hPTHrP when tested with cells expressing the human PTH1R. Agonist-dependent activation of zPTH2R was less efficient than that of zPTH2R(43), and both receptor variants showed no cAMP accumulation when stimulated with either secretin, growth hormone-releasing hormone, or calcitonin. The zPTH2R thus has ligand specificity similar to that of the human homolog, which raises the possibility that a PTH-like molecule exists in zebrafish, species which lack parathyroid glands. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Univ Mississippi, Med Ctr, Dept Microbiol, Jackson, MS 39216 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 09500, DK-11794, F32 DK09500] NR 62 TC 47 Z9 47 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 AUG 13 PY 1999 VL 274 IS 33 BP 23035 EP 23042 DI 10.1074/jbc.274.33.23035 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800021 PM 10438471 ER PT J AU Klingenspor, M Xu, P Cohen, RD Welch, C Reue, K AF Klingenspor, M Xu, P Cohen, RD Welch, C Reue, K TI Altered gene expression pattern in the fatty liver dystrophy mouse reveals impaired insulin-mediated cytoskeleton dynamics SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REPRESENTATIONAL DIFFERENCE ANALYSIS; PROTEIN-KINASE-C; LIPOPROTEIN-LIPASE; FLD MUTATION; RAT ADIPOCYTES; MUTANT MOUSE; ACTIN; BINDING; CELLS; IDENTIFICATION AB The mouse fatty liver dystrophy (fld) mutation is characterized by transient hypertriglyceridemia and fatty liver during the neonatal period, followed by development of a peripheral neuropathy, To uncover the metabolic pathway that is disrupted by the fld mutation, we analyzed the altered pattern of gene expression in the fatty liver of fld neonates by representational difference analysis of cDNk Differentially expressed genes detected include a novel member of the Ras superfamily of small GTP-binding proteins, a novel Ser/Thr kinase, and several actin cytoskeleton-associated proteins including actin, profilin, alpha-actinin, and myosin light chain. Because these proteins have a potential functional link in the propagation of hormone signals, we investigated cytoskeleton dynamics in fld cells in response to hormone treatment. These studies revealed that preadipocytes from fld mice exhibit impaired formation of actin membrane ruffles in response to insulin treatment, These findings suggest that the altered mRNA expression levels detected in fld tissue represent a compensatory response for the nonfunctional fld gene and that the fld gene product may be required for development of normal insulin response. C1 W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90045 USA. RP Reue, K (reprint author), W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, 11301 Wilshire Blvd,Bldg 113,Rm 312, Los Angeles, CA 90073 USA. RI Klingenspor, Martin/D-6930-2011; OI Klingenspor, Martin/0000-0002-4502-6664 FU NHLBI NIH HHS [HL28481] NR 39 TC 20 Z9 21 U1 1 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 AUG 13 PY 1999 VL 274 IS 33 BP 23078 EP 23084 DI 10.1074/jbc.274.33.23078 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800026 PM 10438476 ER PT J AU Moro, O Wakita, K Ohnuma, M Denda, S Lerner, EA Tajima, M AF Moro, O Wakita, K Ohnuma, M Denda, S Lerner, EA Tajima, M TI Functional characterization of structural alterations in the sequence of the vasodilatory peptide maxadilan yields a pituitary adenylate cyclase-activating peptide type 1 receptor-specific antagonist SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FLY LUTZOMYIA-LONGIPALPIS; SALIVARY-GLANDS; I RECEPTOR; POLYPEPTIDE; EXPRESSION; SECONDARY; MEMBRANES; CLONING; TISSUE; CELLS AB Maxadilan is a vasodilatory peptide derived from sand flies that is an agonist at the pituitary adenylate cyclase-activating peptide (PACAP) type 1 receptor. Surprisingly, maxadilan does not share significant sequence homology with PACAP, To examine the relationship between structure and activity of maxadilan, several amino acid substitutions and deletions were made in the peptide. These peptides were examined in vitro for binding to crude membranes derived from rabbit brain, a tissue that expresses PACAP type 1 receptors; and induction of cAMP was determined in PC12 cells, a line that expresses these receptors, The peptides were examined in vivo for their ability to induce erythema in rabbit skin. Substitution of the individual cysteines at positions 1 and 5 or deletion of this ring structure had little effect on activity. Substitution of either cysteine at position 14 or 51 eliminated activity. Deletion of the 19 amino acids between positions 24 and 42 resulted in a peptide with binding, but no functional activity. The capacity of this deletion mutant to interact with COS cells transfected with the PACAP type 1 receptor revealed that this peptide was a specific antagonist to the PACAP type 1 receptor. C1 Shiseido Basic Res Ctr, Kohoku Ku, Yokohama, Kanagawa 2238553, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Tajima, M (reprint author), Shiseido Basic Res Ctr, Kohoku Ku, 1050 Nippa, Yokohama, Kanagawa 2238553, Japan. EM tajima_masahiro@po.shiseido.co.jp FU NIAMS NIH HHS [R01 AR42005] NR 18 TC 52 Z9 54 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 13 PY 1999 VL 274 IS 33 BP 23103 EP 23110 DI 10.1074/jbc.274.33.23103 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800029 PM 10438479 ER PT J AU Cherny, RA Legg, JT McLean, CA Fairlie, DP Huang, XD Atwood, CS Beyreuther, K Tanzi, RE Masters, CL Bush, AI AF Cherny, RA Legg, JT McLean, CA Fairlie, DP Huang, XD Atwood, CS Beyreuther, K Tanzi, RE Masters, CL Bush, AI TI Aqueous dissolution of Alzheimer's disease A beta amyloid deposits by biometal depletion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SENILE PLAQUES; PROTEIN; PEPTIDES; ZINC; AGGREGATION AB Zn(II) and Cu(II) precipitate AP in vitro into insoluble aggregates that are dissolved by metal chelators. We now report evidence that these biometals also mediate the deposition of AP amyloid in Alzheimer's disease, since the solubilization of AP from post-mortem brain tissue was significantly increased by the presence of chelators, EGTA, N,N,N',N'-tetrakis(2-pyridyl-methyl) ethylene diamine, and bathocuproine. Efficient extraction of A beta also required Mg(II) and Ca(II), The chelators were more effective in extracting AP from Alzheimer's disease brain tissue than age-matched controls, suggesting that metal ions differentiate the chemical architecture of amyloid in Alzheimer's disease. Agents that specifically chelate copper and zinc ions but preserve Mg(II) and Ca(II) may be of therapeutic value in Alzheimer's disease. C1 Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Mental Hlth Res Inst, Parkville, Vic 3052, Australia. Univ Queensland, Ctr Drug Design & Drug Dev, Brisbane, Qld 4072, Australia. Harvard Univ, Lab Oxidat Biol, Genet & Aging Unit, Massachusetts Gen Hosp,Sch Med, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02129 USA. Univ Heidelberg, Ctr Mol Biol, D-69120 Heidelberg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. RP Bush, AI (reprint author), Massachusetts Gen Hosp E, Lab Oxidat Biol, Genet & Aging Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Fairlie, David/F-8865-2014; Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [5R29AG12686] NR 23 TC 373 Z9 386 U1 2 U2 29 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 13 PY 1999 VL 274 IS 33 BP 23223 EP 23228 DI 10.1074/jbc.274.33.23223 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800045 PM 10438495 ER PT J AU Zuckerman, JB Chen, XY Jacobs, JD Hu, BF Kleyman, TR Smith, PR AF Zuckerman, JB Chen, XY Jacobs, JD Hu, BF Kleyman, TR Smith, PR TI Association of the epithelial sodium channel with Apx and alpha-spectrin in A6 renal epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NA+ CHANNEL; LIDDLES-SYNDROME; APICAL MEMBRANE; XENOPUS-LAEVIS; BETA-SUBUNIT; K+ CHANNEL; STOICHIOMETRY; CYTOSKELETON; PROTEIN; NA+,K+-ATPASE AB Recent molecular cloning of the epithelial sodium channel (ENaC) provides the opportunity to identify ENaC-associated proteins that function in regulating its cell surface expression and activity. We have examined whether ENaC is associated with Apr (apical protein Xenopus) and the spectrin-based membrane cytoskeleton in Xenopus A6 renal epithelial cells. We have also addressed whether Apr is required for the expression of amiloride-sensitive Na+ currents by cloned ENaC, Sucrose density gradient centrifugation of A6 cell detergent extracts showed co-sedimentation of xENaC, alpha-spectrin, and Apr. Immunoblot analysis of proteins co-immunoprecipitating under high stringency conditions from peak Xenopus ENaC/Apx-containing gradient fractions indicate that ENaC, Apr, and alpha-spectrin are associated in a macromolecular complex. To examine whether Apr is required for the functional expression of ENaC, alpha beta gamma mENaC cRNAs were coinjected into Xenopus oocytes with Apr sense or antisense oligodeoxynucleotides. The two-electrode voltage clamp technique showed there was a marked reduction in amiloride-sensitive current in oocytes coinjected with antisense oligonucleotides when to compared with oocytes coinjected with sense oligonucleotides. These studies indicate that ENaC is associated in a macromolecular complex with Apr and alpha-spectrin in A6 cells and suggest that Apr is required for the functional expression of ENaC in Xenopus epithelia. C1 Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Med Coll Penn & Hahnemann Univ, Dept Physiol, Philadelphia, PA 19129 USA. RP Smith, PR (reprint author), Univ Alabama, Dept Physiol & Biophys, 1918 Univ Blvd, Birmingham, AL 35294 USA. OI Zuckerman, Jonathan/0000-0002-8190-9210 FU NIDDK NIH HHS [DK 51391, DK 46705, DK 59596] NR 45 TC 63 Z9 65 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 13 PY 1999 VL 274 IS 33 BP 23286 EP 23295 DI 10.1074/jbc.274.33.23286 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800054 PM 10438504 ER PT J AU Devchand, PR Hihi, AK Perroud, M Schleuning, WDD Spiegelman, BM Wahli, W AF Devchand, PR Hihi, AK Perroud, M Schleuning, WDD Spiegelman, BM Wahli, W TI Chemical probes that differentially modulate peroxisome proliferator-activated receptor alpha and BLTR, nuclear and cell surface receptors for leukotriene B-4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FATTY-ACIDS; PPAR-ALPHA; POLYMORPHONUCLEAR LEUKOCYTES; HYPOLIPIDEMIC AGENTS; TARGETED DISRUPTION; ARACHIDONIC-ACID; GAMMA; ADIPOGENESIS; METABOLISM; PATHWAY AB Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a nuclear receptor for various fatty acids, eicosanoids, and hypolipidemic drugs. In the presence of ligand, this transcription factor increases expression of target genes that are primarily associated with lipid homeostasis. We have previously reported PPAR alpha as a nuclear receptor of the inflammatory mediator leukotriene B-4 (LTB4) and demonstrated an anti-inflammatory function for PPAR alpha in vivo (Devchand, P. R., Keller, H., Peters, J. M., Vazquez, M., Gonzalez, F. J., and Wahli, W. (1996) Nature 384, 39-43). LTB4 also has a cell surface receptor (BLTR) that mediates proinflammatory events, such as chemotaxis and chemokinesis (Yokomizo, T., Izumi, T., Chang, K., Takuwa, Y., and Shimizu, T. (1997) Nature 387, 620-624). In this study, we report on chemical probes that differentially modulate activity of these two LTB4 receptors. The compounds selected were originally characterized as synthetic BLTR effecters, both agonists and antagonists. Here, we evaluate the compounds as effecters of the three PPAR isotypes (alpha, beta, and gamma) by transient transfection assays and also determine whether the compounds are ligands for these nuclear receptors by coactivator-dependent receptor ligand interaction assay, a semifunctional in vitro assay. Because the compounds are PPAR alpha selective, we further analyze their potency in a biological assay for the PPAR alpha-mediated activity of lipid accumulation. These chemical probes will prove invaluable in dissecting processes that involve nuclear and cell surface LTB4 receptors and also aid in drug discovery programs. C1 Univ Lausanne, Inst Biol Anim, CH-1015 Lausanne, Switzerland. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Schering AG, Inst Cell & Mol Biol, D-1000 Berlin, Germany. RP Wahli, W (reprint author), Univ Lausanne, Inst Biol Anim, Batiment Biol, CH-1015 Lausanne, Switzerland. RI Wahli, Walter/B-1398-2009 OI Wahli, Walter/0000-0002-5966-9089 FU NIDDK NIH HHS [R37DK31405] NR 45 TC 30 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 AUG 13 PY 1999 VL 274 IS 33 BP 23341 EP 23348 DI 10.1074/jbc.274.33.23341 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 226GV UT WOS:000082012800061 PM 10438511 ER PT J AU Vieregge, P Hagenah, J Heberlein, I Klein, C Ludin, HP AF Vieregge, P Hagenah, J Heberlein, I Klein, C Ludin, HP TI Parkinson's disease in twins - A follow-up study SO NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; F-18 DOPA PET; ALPHA-SYNUCLEIN; LEWY-BODY; DISCORDANT; DIAGNOSIS; ETIOLOGY; MUTATION; PAIRS AB Objective: To reevaluate concordance rates in 9 monozygotic (MZ) and 12 dizygotic (DZ) twin pairs with PD 8 years after the initial study. Background: Longitudinal investigations increase accuracy in clinical diagnosis of PD. Methods: Follow-up by personal interview and clinical examination. Results: Concordance rates were not different between MZ (3/9) and DZ (5/12) twin pairs at follow-up, even when PD-associated dementia and isolated postural tremor were considered diagnostic of familial Lewy body parkinsonism. Evaluation of medical history, personality traits, and blink rate did not reveal putative early or premorbid parkinsonism in 9 co-twins who were motor-asymptomatic during the follow-up interval. However, these co-twins had reduced semantic fluency in comparison with a healthy control group of similar age. None of 7 co-twins without motor signs who underwent PET investigation 6 years previously showed signs of extrapyramidal disease at follow-up, but verbal memory continued to be reduced in 5 of these co-twins. Conclusion: Based on concordance rates only, the findings in our twin sample do not support a major genetic impact for the motor expression of PD. C1 Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Kantonsspital, Dept Neurol, CH-9007 St Gallen, Switzerland. RP Vieregge, P (reprint author), Univ Lubeck, Dept Neurol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. NR 40 TC 24 Z9 25 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 11 PY 1999 VL 53 IS 3 BP 566 EP 572 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 224PA UT WOS:000081906400022 PM 10449122 ER PT J AU Triggs, WJ Menkes, D Onorato, J Yan, RSH Young, MS Newell, E Sander, HW Soto, O Chiappa, KH Cros, D AF Triggs, WJ Menkes, D Onorato, J Yan, RSH Young, MS Newell, E Sander, HW Soto, O Chiappa, KH Cros, D TI Transcranial magnetic stimulation identifies upper motor neuron involvement in motor neuron disease SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; BRAIN-STIMULATION; RESONANCE SPECTROSCOPY; CORTICAL STIMULATION; CORTEX; CONDUCTION; RESPONSES; EXCITABILITY; EXCITATION; INHIBITION AB Objective: To evaluate the sensitivity of transcranial magnetic stimulation (TMS) to identify upper motor neuron involvement in patients with motor neuron disease. Background: Diagnosis of ALS depends on upper and lower motor neuron involvement. Lower motor neuron involvement may be documented with electromyography, whereas definite evidence of upper motor neuron involvement may be elusive. A sensitive, noninvasive test of upper motor neuron function would be useful. Methods: TMS and clinical assessment in 121 patients with motor neuron disease. Results: TMS revealed evidence of upper motor neuron dysfunction in 84 of 121 (69%) patients, including 30 of 40 (75%) patients with only probable upper motor neuron signs and unsuspected upper motor neuron involvement in 6 of 22 (27%) patients who had purely lower motor neuron syndromes clinically. In selected cases, upper motor neuron involvement identified with TMS was verified in postmortem examination. Increased motor evoked potential threshold was the abnormality observed most frequently and was only weakly related to peripheral compound muscle action potential amplitude. In a subset of 12 patients reexamined after 11 +/- 6 months, TMS she-wed progression of abnormalities, including progressive inexcitability of central motor pathways and loss of the normal inhibitory cortical stimulation silent period. Conclusions: TMS provides a sensitive means for the assessment and monitoring of excitatory and inhibitory upper motor neuron function in motor neuron disease. C1 Massachusetts Gen Hosp, EMG Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Florida, Coll Med, Dept Neurol, Gainesville, FL USA. Univ Florida, Coll Med, Human Motor Lab, Gainesville, FL USA. RP Cros, D (reprint author), Massachusetts Gen Hosp, EMG Lab, Boston, MA 02114 USA. NR 34 TC 82 Z9 84 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 11 PY 1999 VL 53 IS 3 BP 605 EP 611 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 224PA UT WOS:000081906400027 PM 10449127 ER PT J AU Osterle, S AF Osterle, S TI Interventional cardiology - The trial: PACIFIC SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 10 PY 1999 VL 100 IS 6 BP 572 EP 573 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 224RV UT WOS:000081912900010 ER PT J AU Bogan, JS Lodish, HF AF Bogan, JS Lodish, HF TI Two compartments for insulin-stimulated exocytosis in 3T3-L1 adipocytes defined by endogenous ACRP30 and GLUT4 SO JOURNAL OF CELL BIOLOGY LA English DT Article DE exocytosis; monosaccharide transport proteins; insulin; adipose tissue; secretion ID GLUCOSE-TRANSPORTER GLUT4; RAT ADIPOSE-CELLS; CLATHRIN-COATED VESICLES; TRANS-GOLGI NETWORK; PHOSPHATIDYLINOSITOL 3-KINASE; BETA-COP; ENDOPLASMIC-RETICULUM; S6 KINASE; IMMUNOGLOBULIN-CHAINS; SECRETORY PATHWAY AB Insulin stimulates adipose cells both to secrete proteins and to translocate the GLUT4 glucose transporter from an intracellular compartment to the plasma membrane. We demonstrate that whereas insulin stimulation of 3T3-L1 adipocytes has no effect on secretion of the alpha 3 chain of type VI collagen, secretion of the protein hormone adipocyte complement related protein of 30 kD (ACRP30) is markedly enhanced, Like GLUT4, regulated exocytosis of ACRP30 appears to require phosphatidylinositol-3-kinase activity, since insulin-stimulated ACRP30 secretion is blocked by pharmacologic inhibitors of this enzyme. Thus, 3T3-L1 adipocytes possess a regulated secretory compartment containing ACRP30. Whether GLUT4 recycles to such a compartment has been controversial. We present deconvolution immunofluorescence microscopy data demonstrating that the subcellular distributions of ACRP30 and GLUT4 are distinct and nonoverlapping; in contrast, those of GLUT4 and the transferrin receptor overlap. Together with supporting evidence that GLUT4 does not recycle to a secretory compartment via the trans-Golgi network, we conclude that there are at least two compartments that undergo insulin-stimulated exocytosis in 3T3-L1 adipocytes: one for ACRP30 secretion and one for GLUT4 translocation. C1 Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Diabet Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Lodish, HF (reprint author), Whitehead Inst Biomed Res, Cambridge Ctr 9, Room 567F, Cambridge, MA 02142 USA. RI Bogan, Jonathan/A-1575-2010 OI Bogan, Jonathan/0000-0001-6463-8466 FU NIDDK NIH HHS [DK47618, DK02371, R37 DK047618, R01 DK047618] NR 61 TC 132 Z9 142 U1 1 U2 4 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 AUG 9 PY 1999 VL 146 IS 3 BP 609 EP 620 DI 10.1083/jcb.146.3.609 PG 12 WC Cell Biology SC Cell Biology GA 226FB UT WOS:000082008700007 PM 10444069 ER PT J AU Mitic, LL Schneeberger, EE Fanning, AS Anderson, JM AF Mitic, LL Schneeberger, EE Fanning, AS Anderson, JM TI Connexin-occludin chimeras containing the ZO-binding domain of occludin localize at MDCK tight junctions and NRK cell contacts SO JOURNAL OF CELL BIOLOGY LA English DT Article DE tight junction; occludin; connexin 32; ZO-1; MAGUK ID TUMOR-SUPPRESSOR PROTEIN; INTEGRAL MEMBRANE-PROTEINS; EPITHELIAL-CELLS; POSSIBLE INVOLVEMENT; DIRECT ASSOCIATION; CDNA CLONING; K+ CHANNELS; BARRIER; PERMEABILITY; COMPLEX AB Occludin is a transmembrane protein of the tight junction that functions in creating both an intercellular permeability barrier and an intramembrane diffusion barrier. Creation of the barrier requires the precise localization of occludin, and a distinct family of transmembrane proteins called claudins, into continuous linear fibrils visible by freeze-fracture microscopy. Conflicting evidence exists regarding the relative importance of the transmembrane and extracellular versus the cytoplasmic domains in localizing occludin in fibrils. To specifically address whether occludin's COOH-terminal cytoplasmic domain is sufficient to target it into tight junction fibrils, we created chimeras with the transmembrane portions of connexin 32, Despite the gap junction targeting information present in their transmembrane and extracellular domains, these connexin-occludin chimeras localized within fibrils when expressed in MDCK cells, as assessed by immunofluorescence and immunogold freeze-fracture ima,imaging. Localization of chimeras at tight junctions depends on the COOH-terminal ZO-binding domain and not on the membrane proximal domain of occludin. Furthermore, neither endogenous occludin nor claudin is required for targeting to ZO-1-containing cell-cell contacts, since in normal rat kidney fibroblasts targeting of chimeras again required only the ZO-binding domain. These results suggest an important role for cytoplasmic proteins, presumably ZO-1, ZO-2, and ZO-3, in localizing occludin in tight junction fibrils. Such a scaffolding and cytoskeletal coupling function for ZO MAGUKs is analogous to that of other members of the MAGUK family. C1 Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. RP Mitic, LL (reprint author), Yale Univ, Sch Med, Dept Cell Biol, 333 Cedar St,POB 208002, New Haven, CT 06520 USA. FU NCI NIH HHS [CA66263]; NHLBI NIH HHS [R01 HL025822]; NIDDK NIH HHS [R01 DK045134, DK45134, DK38979, P30 DK034989] NR 50 TC 56 Z9 57 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 AUG 9 PY 1999 VL 146 IS 3 BP 683 EP 693 DI 10.1083/jcb.146.3.683 PG 11 WC Cell Biology SC Cell Biology GA 226FB UT WOS:000082008700013 PM 10444075 ER PT J AU Ross, TS Gilliland, DG AF Ross, TS Gilliland, DG TI Transforming properties of the Huntingtin interacting protein 1/platelet-derived growth factor beta receptor fusion protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC MYELOMONOCYTIC LEUKEMIA; HEMATOPOIETIC-CELL LINES; DNA-BINDING ACTIVITY; SACCHAROMYCES-CEREVISIAE; PDGF RECEPTOR; KINASE; TEL; PHOSPHORYLATION; ACTIVATION; SIGNAL AB We have previously reported that the Huntingtin interacting protein 1 (HIP1) gene is fused to the platelet-derived growth factor beta receptor (PDGF beta R) gene in a patient with chronic myelomonocytic leukemia. We now show that HIP1/PDGF beta R oligomerizes, is constitutively tyrosine-phosphorylated, and transforms the murine hematopoietic cell line, Ba/F3, to interleukin-3-independent growth. A kinase-inactive mutant is neither tyrosine-phosphorylated nor able to transform Ba/F3 cells. Oligomerization and kinase activation required the 55-amino acid carboxyl-terminal TALIN homology region but not the leucine zipper domain. Tyrosine phosphorylation of a 130-kDa protein and STAT5 correlates with transformation in cells expressing HIP1/PDGF beta R and related mutants. A deletion mutant fusion protein that contains only the TALIN homology region of HIP1 fused to PDGF beta R is incapable of transforming Ba/F3 cells and does not tyrosine-phosphorylate p130 or STAT5, although it is itself constitutively tyrosine-phosphorylated. We have also analyzed cells expressing Tyr --> Phe mutants of HIP1/PDGF beta R in the known PDGF beta R SH2 docking sites and report that none of these sites are necessary for STAT5 activation, p130 phosphorylation, or Ba/F3 transformation. The correlation of factor-independent growth of hematopoietic cells with p130 and STAT5 phosphorylation/activation in both the HIP1/ PDGF beta R Tyr --> Phe and deletion mutational variants suggests that both STAT5 and p130 are important for transformation mediated by HIP1/PDGF beta R. C1 Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Ross, TS (reprint author), 4 Blackfan Circle Ste 418, Boston, MA 02115 USA. FU NCI NIH HHS [K08 CA76025-01]; NHLBI NIH HHS [T32 HL07623]; NIDDK NIH HHS [P01DK50654] NR 25 TC 53 Z9 54 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 6 PY 1999 VL 274 IS 32 BP 22328 EP 22336 DI 10.1074/jbc.274.32.22328 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 223YD UT WOS:000081868400032 PM 10428802 ER PT J AU Scaffidi, C Schmitz, I Zha, JP Korsmeyer, SJ Krammer, PH Peter, ME AF Scaffidi, C Schmitz, I Zha, JP Korsmeyer, SJ Krammer, PH Peter, ME TI Differential modulation of apoptosis sensitivity in CD95 type I and type II cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CERAMIDE-INDUCED APOPTOSIS; MITOCHONDRIAL RESPIRATORY-CHAIN; SIGNALING COMPLEX DISC; FAS-INDUCED APOPTOSIS; LEUKEMIC HL-60 CELLS; NITRIC-OXIDE; CYTOCHROME-C; T-CELLS; MEDIATED APOPTOSIS; PERMEABLE CERAMIDE AB We have recently identified two different pathways of CD95-mediated apoptosis (Scaffidi, C., Fulda, S., Srinivasan, A., Feng, L., Friesen, C., Tomaselli, K, J,, Debatin, K.-M,, Krammer, P. H., and Peter, M.E. (1998) EMBO J. 17, 1675-1687), CD95-mediated apoptosis in type I cells is initiated by large amounts of active caspase-8 formed at the death-inducing signaling complex (DISC) followed by direct cleavage of caspase-3, In contrast, in type II cells very little DISC and small amounts of active caspase-8 sufficient to induce the apoptogenic activity of mitochondria are formed causing a profound activation of both caspase-8 and caspase-3, Only in type II cells can apoptosis be blocked by overexpressed Bcl-2 or Bcl-x(L). We now show that a number of apoptosis-inhibiting or -inducing stimuli only affect apoptosis in type II cells, indicating that they act on the mitochondrial branch of the CD95 pathway. These stimuli include the activation of protein kinase C, which inhibits CD95-mediated apoptosis resulting in a delayed cleavage of BID, and the induction of apoptosis by the ceramide analog C-2-ceramide, In addition, we have identified the CD95 high expressing cell line Boe(R) as a CD95 apoptosis-resistant type II cell that can be sensitized by treatment with cycloheximide without affecting formation of the DISC, This also places the effects of cycloheximide in the mitochondrial branch of the type II CD95 pathway. In contrast, c-FLIP was found to block CD95-mediated apoptosis in both type I and type II cells, because it acts directly at the DISC of both types of cells. C1 German Canc Res Ctr, Tumor Immunol Program, D-69120 Heidelberg, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Peter, ME (reprint author), German Canc Res Ctr, Tumor Immunol Program, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. RI Watzl, Carsten/B-4911-2013; Schmitz, Ingo/G-2093-2013 OI Watzl, Carsten/0000-0001-5195-0995; Schmitz, Ingo/0000-0002-5360-0419 NR 69 TC 467 Z9 475 U1 1 U2 8 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 6 PY 1999 VL 274 IS 32 BP 22532 EP 22538 DI 10.1074/jbc.274.32.22532 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 223YD UT WOS:000081868400060 PM 10428830 ER PT J AU Xie, SP Wang, ZJ Okano, M Nogami, M Li, Y He, WW Okumura, K Li, E AF Xie, SP Wang, ZJ Okano, M Nogami, M Li, Y He, WW Okumura, K Li, E TI Cloning, expression and chromosome locations of the human DNMT3 gene family SO GENE LA English DT Article DE DNA methylation; DNA methyltransferase ID DNA CYTOSINE-5 METHYLTRANSFERASES; EMBRYONIC STEM-CELLS; DE-NOVO; METHYLATION; DOMAIN AB DNA methylation plays an important role in animal development and gene regulation. In mammals, several genes encoding DNA cytosine methyltransferases have been identified. DNMT1 is constitutively expressed and is required for the maintenance of global methylation after DNA replication. In contrast, the murine Dnmt3 family genes appear to be developmentally regulated and behave like de novo DNA methyltransferases in vitro. In this study, we have cloned human DNMT3A and DNMT3B that encode full-length DNMT3A and DNMT3B proteins with 98% and 94% amino acid sequence identity to their murine homologues. The DNMT3A and DNMT3B show high homology in the carboxy terminal catalytic domain and contain a conserved cysteine-rich region, which shares homology with the X-linked ATRX gene of the SNF2/SWI family. We have mapped human DNMT3A and DNMT3B to chromosomes 2p23 and 20q11.2 respectively, and determined the DNMT3B genomic structure. We further show that DNMT3A expression is ubiquitous and can be readily detected in most adult tissues, whereas DNMT3B is expressed at very low levels in most tissues except testis, thyroid and bone marrow. Significantly, both DNMT3A and DNMT3B expression is elevated in several tumor cell lines to levels comparable to DNMT1. The cloning of the human DNMT3 genes will facilitate further biochemical and genetic studies of their functions in establishment of DNA methylation patterns, regulation of gene expression and tumorigenesis. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med,Sch Med, Charlestown, MA 02129 USA. Mie Univ, Fac Bioresources, Biol Chem Lab, Tsu, Mie 5148507, Japan. OriGene Technol Inc, Rockville, MD 20850 USA. RP Li, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med,Sch Med, Charlestown, MA 02129 USA. FU NIGMS NIH HHS [GM52106] NR 26 TC 227 Z9 251 U1 2 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD AUG 5 PY 1999 VL 236 IS 1 BP 87 EP 95 DI 10.1016/S0378-1119(99)00252-8 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 225QF UT WOS:000081971700010 PM 10433969 ER PT J AU Emmons, KM Colditz, GA AF Emmons, KM Colditz, GA TI Preventing excess sun exposure: It is time for a national policy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ULTRAVIOLET INDEX; MELANOMA; CANCER C1 Ctr Community Based Res, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Canc Prevent, Dept Hlth & Social Behav, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Emmons, KM (reprint author), Ctr Community Based Res, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 13 TC 32 Z9 32 U1 0 U2 1 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 4 PY 1999 VL 91 IS 15 BP 1269 EP 1270 DI 10.1093/jnci/91.15.1269 PG 2 WC Oncology SC Oncology GA 223HZ UT WOS:000081836800002 PM 10433608 ER PT J AU Reed, GL Houng, AK Liu, L Parhami-Seren, B Matsueda, LH Wang, SG Hedstrom, L AF Reed, GL Houng, AK Liu, L Parhami-Seren, B Matsueda, LH Wang, SG Hedstrom, L TI A catalytic switch and the conversion of streptokinase to a fibrin-targeted plasminogen activator SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; THROMBOLYTIC THERAPY; BINDING REGION; COMPLEX; BIOCHEMISTRY; UROKINASE; MECHANISM; FRAGMENTS; PEPTIDES; ANTIBODY AB Plasminogen (Pg) activators such as streptokinase (SK) save lives by generating plasmin to dissolve blood clots. Some believe that the unique ability of SK to activate Pg in the absence of fibrin limits its therapeutic utility. We have found that SK contains an unusual NH2-terminal "catalytic switch" that allows Pg activation through both fibrin-independent and fibrin-dependent mechanisms. Unlike SK, a mutant (rSK Delta 59) fusion protein lacking the 59 NH2-terminal residues was no longer capable of fibrin-independent Pg activation (k(cat)/k(m) decreased by >600-fold). This activity was restored by coincubation with equimolar amounts of the NH2-terminal peptide rSK1-59. Deletion of the NH2 terminus made rSK Delta 59 a Pg activator that requires fibrin, but not fibrinogen, for efficient catalytic function. The fibrin-dependence of the rSK Delta 59 activator complex apparently resulted from selective catalytic processing of fibrin-bound Pg substrates in preference to other Pg forms. Consistent with these observations, the presence (rSK) or absence (rSK Delta 59) of the SK NH2 terminal peptide markedly altered fibrinolysis of human clots suspended in plasma. Like native SK rSk produced incomplete clot lysis and complete destruction of plasma fibrinogen; in contrast, rSK Delta 59 produced total clot lysis and minimal fibrinogen degradation. These studies indicate that structural elements in the NH2 terminus are responsible for SK's unique mechanism of fibrin-independent Pg activation. Because deletion of the NH2 terminus alters SK's mechanism of action and targets Pg activation to fibrin, there is the potential to improve SK's therapeutic efficacy. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Brandeis Univ, Grad Dept Biochem, Waltham, MA 02454 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-02348, HL-57314]; NIAID NIH HHS [AI-33175] NR 39 TC 39 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 3 PY 1999 VL 96 IS 16 BP 8879 EP 8883 DI 10.1073/pnas.96.16.8879 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500022 PM 10430864 ER PT J AU Topley, GI Okuyama, R Gonzales, JG Conti, C Dotto, GP AF Topley, GI Okuyama, R Gonzales, JG Conti, C Dotto, GP TI p21(WAF1/Cip1) functions as a suppressor of malignant skin tumor formation and a determinant of keratinocyte stem-cell potential SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DEPENDENT KINASE INHIBITOR; SENCAR MOUSE SKIN; CHEMICAL CARCINOGENESIS; EPITHELIAL-CELLS; HAIR-FOLLICLES; MICE; DIFFERENTIATION; EXPRESSION; GROWTH; P53 AB p21(WAF1/Cip1) is one of the best characterized downstream targets of p53 and the growth suppressing function of this cyclin-dependent kinase inhibitor is well established. However, whether p21 exerts a tumor-suppressing function of its own remains to be established, We report here that, similarly to loss of p53 disruption of the p21(WAF1/Cip1) gene results in a markedly increased susceptibility to chemically induced skin carcinoma formation, whereas the number of papillomas is reduced. previous evidence indicates that malignant versus benign keratinocyte tumor formation is likely to involve distinct target-cell populations with a different commitment to differentiation. In parallel with the increased susceptibility to carcinoma formation, loss of p21(WAF/Cip1) was found to promote keratinocyte subpopulations with increased growth/differentiation potential, including clonal grow th capability, reversible commitment to differentiation, and capability to generate all types of terminally differentiated keratinocytes present irt vivo, not only in the interfollicular epidermis but also in hair follicles. Thus, these findings have revealed a function of p21 as a suppressor of malignant but not benign skin-tumor formation and a determinant of the growth/differentiation potential of keratinocyte subpopulations. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Texas, MD Anderson Canc Ctr, Smithville, TX 78957 USA. Univ Turin, Dept Genet Biol & Med Chem, I-10124 Turin, Italy. RP Dotto, GP (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA073796, CA 16038, P01 CA016038]; NIAMS NIH HHS [AR 39190, R01 AR039190]; NIEHS NIH HHS [ES 07784, P30 ES007784] NR 41 TC 146 Z9 151 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 3 PY 1999 VL 96 IS 16 BP 9089 EP 9094 DI 10.1073/pnas.96.16.9089 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500058 PM 10430900 ER PT J AU Mannion, RJ Costigan, M Decosterd, I Amaya, F Ma, QP Holstege, JC Ji, RR Acheson, A Lindsay, RM Wilkinson, GA Woolf, CJ AF Mannion, RJ Costigan, M Decosterd, I Amaya, F Ma, QP Holstege, JC Ji, RR Acheson, A Lindsay, RM Wilkinson, GA Woolf, CJ TI Neurotrophins: Peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NERVE GROWTH-FACTOR; PROTEIN-TYROSINE KINASE; PRIMARY SENSORY NEURONS; MESSENGER-RNA; SECONDARY HYPERALGESIA; CENTRAL SENSITIZATION; EXPRESSION; RAT; TRKB; RECEPTORS AB Brain-derived neurotrophic factor (BDNF) is expressed in nociceptive sensory neurons and transported anterogradely to the dorsal horn of the spinal cord where it is located in dense core,vesicles in C-fiber terminals. Peripheral inflammation substantially up-regulates BDNF mRNA and protein in the dorsal root ganglion (DRG) in a nerve growth factor-dependent fashion and results in novel expression of BDNF by DRG neurons with myelinated axons. C-fiber electrical activity also increases BDNF expression in the DRG, and both inflammation and activity increase full-length TrkB receptor levels in the dorsal horn, Sequestration of endogenous BDNF/neurotrophin 4 by intraspinal TrkB-Fc fusion protein administration does not, in noninflamed animals, change basal pain sensitivity nor the mechanical hypersensitivity induced by peripheral capsaicin administration, a measure of C fiber-mediated central sensitization. TrkB-Fc administration also does not modify basal inflammatory pain hypersensitivity, but does block the progressive hypersensitivity elicited by low-intensity tactile stimulation of inflamed tissue. BDNF, by virtue of its nerve growth factor regulation in sensory neurons including novel expression in A fibers, has a role as a central modulator of tactile stimulus-induced inflammatory pain hypersensitivity. C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. Erasmus Univ, Sch Med, Dept Anat, NL-3000 DR Rotterdam, Netherlands. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. European Mol Biol Lab, D-69117 Heidelberg, Germany. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, 149 13th St,Room 4310, Charlestown, MA 02129 USA. EM woolf.clifford@mgh.harvard.edu OI Ji, Ru-Rong/0000-0002-9355-3688 FU NINDS NIH HHS [R01 NS038253]; PHS HHS [N38253-01]; Wellcome Trust NR 46 TC 281 Z9 290 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 3 PY 1999 VL 96 IS 16 BP 9385 EP 9390 DI 10.1073/pnas.96.16.9385 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500110 PM 10430952 ER PT J AU Hoge, RD Atkinson, J Gill, B Crelier, GR Marrett, S Pike, GB AF Hoge, RD Atkinson, J Gill, B Crelier, GR Marrett, S Pike, GB TI Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN VISUAL-CORTEX; MACAQUE STRIATE CORTEX; OXIDATIVE-METABOLISM; FUNCTIONAL-ANATOMY; BRAIN ACTIVATION; STIMULATION; SPECTROSCOPY; CONTRAST; MODEL; PERFUSION AB The aim of this study was to test the hypothesis that, within a specific cortical unit, fractional changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMR(O2)) are coupled through an invariant relationship during physiological stimulation. This aim was achieved by simultaneously measuring relative changes in these quantities in human primary visual cortex (V1) during graded stimulation with patterns designed to selectively activate different populations of V1 neurons. Primary visual cortex was delineated individually in each subject by using phase-encoded retinotopic mapping, Flow-sensitive alternating inversion recovery MRI, in conjunction with blood oxygenation-sensitive MRI and hypercapnic calibration, was used to monitor CBF and CMR(O2). The stimuli used included (i) diffuse isoluminant chromatic displays; (ii) high spatial-frequency achromatic luminance gratings; and (iii) radial checkerboard patterns containing both color and luminance contrast modulated at different temporal rates. Perfusion responses to each pattern were graded by varying luminance and/or color modulation amplitudes. For all stimulus types, fractional changes in blood flow and oxygen uptake were found to be linearly coupled ill a consistent ratio of approximately 2:1, The most potent stimulus produced CBF and CMR(O2) increases of 48 +/- 5% and 25 +/- 4%, respectively, with no evidence of a plateau for oxygen consumption. Estimation of aerobic ATP yields from the observed CMR(O2) increases and comparison with the maximum possible anaerobic ATP contribution indicate that elevated energy demands during brain activation are met largely through oxidative metabolism. C1 McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Hoge, RD (reprint author), McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Room WB325, Montreal, PQ H3A 2B4, Canada. EM rhoge@bic.mni.mcgill.ca RI Pike, Bruce/K-5562-2014; OI Pike, Bruce/0000-0001-8924-683X; Marrett, Sean/0000-0001-8179-6511 NR 60 TC 358 Z9 358 U1 1 U2 11 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 3 PY 1999 VL 96 IS 16 BP 9403 EP 9408 DI 10.1073/pnas.96.16.9403 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223HL UT WOS:000081835500113 PM 10430955 ER PT J AU Elman, I Breiter, HC Gollub, RL Krause, S Kantor, HL Baumgartner, WA Gastfriend, DR Rosen, BR AF Elman, I Breiter, HC Gollub, RL Krause, S Kantor, HL Baumgartner, WA Gastfriend, DR Rosen, BR TI Depressive symptomatology and cocaine-induced pituitary-adrenal axis activation in individuals with cocaine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; hypothalamic-pituitary-adrenal axis; clinical pharmacology; depression; comorbidity; endocrinology ID CORTICOTROPIN-RELEASING HORMONE; POSITRON EMISSION TOMOGRAPHY; BETA-ENDORPHIN LEVELS; MAJOR DEPRESSION; NEUROENDOCRINE FUNCTION; STIMULATION TEST; ACTH-SECRETION; PANIC DISORDER; CORTISOL; ABUSE AB The hypothalamic-pituitary-adrenal (HPA) axis plays a role in cocaine dependence and major depressive disorder. The authors examined the correlation between baseline depressive symptomatology and pituitary-adrenal axis activation induced by acute cocaine challenge. Twelve patients with cocaine dependence were administered an iv bolus of cocaine (0.6 mg/kg) and their plasma was assayed for levels of adrenocorticotropic hormone (ACTH) and cortisol. Depressive symptomatology was assessed with total Hamilton rating scale for depression (HRSD) scores and its vegetative and cognitive superfactors. Cocaine produced a mean increase from baseline of 261% for ACTH and 73% for cortisol plasma levels. Changes in ACTH (r = 0.69) and cortisol (r = 0.59) were positively and significantly correlated with total HRSD scores and its vegetative, but not cognitive, factor symptom cluster. These results suggest that the HPA axis may be involved in affective disturbances associated with the use of cocaine. Implications of these data for the pathophysiology of cocaine dependence are discussed. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Addict Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Nucl Magnet Resonance Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. Univ So Calif, Sch Pharm, Los Angeles, CA USA. RP Elman, I (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Addict Serv, 15 Parkman St WACC-812, Boston, MA 02114 USA. OI Gollub, Randy L./0000-0002-9434-4044 FU NIDA NIH HHS [DA00265-01, DA00275-01, DA09467-02] NR 49 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD AUG 2 PY 1999 VL 56 IS 1 BP 39 EP 45 DI 10.1016/S0376-8716(99)00009-5 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 221RC UT WOS:000081739200006 PM 10462091 ER PT J AU Iwata, S Morimoto, C AF Iwata, S Morimoto, C TI CD26/dipeptidyl peptidase IV in context: the different roles of a multifunctional ectoenzyme in malignant transformation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID T-CELL ACTIVATION; ADENOSINE-DEAMINASE; CD26; INHIBITION; EXPRESSION; INVITRO; TUMOR; LUNG 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. Univ Tokyo, Inst Med Sci, Dept Clin Immunol, Minato Ku, Tokyo 108, Japan. Univ Tokyo, Inst Med Sci, AIDS Res Ctr, Minato Ku, Tokyo 108, Japan. RP Morimoto, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. RI Iwata, Satoshi/A-8819-2011 FU NIAID NIH HHS [AI29530, U19 AI029530, P01 AI029530]; NIAMS NIH HHS [AR33713] NR 31 TC 60 Z9 62 U1 1 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 2 PY 1999 VL 190 IS 3 BP 301 EP 305 DI 10.1084/jem.190.3.301 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 224LT UT WOS:000081901100001 PM 10430618 ER PT J AU Reed, CR Camargo, CA AF Reed, CR Camargo, CA TI Recent trends and controversies in industry-sponsored clinical trials SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE clinical trials; industry; research support; SAEM guidelines ID CONFLICTS-OF-INTEREST; ETHICAL ISSUES; LIFE SCIENCES; AUTHORS; JOURNALS AB In recent years, industry has become an important source of funding for biomedical research. Industry-sponsored clinical trials are a particular source of controversy. In light of recent developments, the authors reevaluate the 1995 SAEM guidelines for investigator involvement in industry-sponsored clinical trials. The authors divide industry-funded clinical trials into two categories: investigator-initiated and industry-initiated, and discuss the differences between them. They examine several areas of ethical debate, including exclusivity contracts between a principal investigator and a corporate sponsor, the size of per-patient reimbursements for recruiting patients into clinical trials, and authorship criteria. Finally, the authors oppose the assumption that industry-sponsored research is automatically biased, and suggest that multiple levels of review will help to uncover bias, whatever the source. Once mutual respect for ethical guidelines and practices are established, collaboration between emergency medicine researchers and industry should be encouraged. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med,Clin 116, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med,Clin 116, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-03533] NR 37 TC 11 Z9 11 U1 1 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 AUG PY 1999 VL 6 IS 8 BP 833 EP 839 DI 10.1111/j.1553-2712.1999.tb01217.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 229HD UT WOS:000082186700014 PM 10463557 ER PT J AU Weissman, DE Block, SD Blank, L Cain, J Cassem, N Danoff, D Foley, K Meier, D Schyue, P Theige, D Wheeler, HB AF Weissman, DE Block, SD Blank, L Cain, J Cassem, N Danoff, D Foley, K Meier, D Schyue, P Theige, D Wheeler, HB TI Recommendations for incorporating palliative care education into the acute care hospital setting SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT National Consensus Conference on Medical Education for Care Near the End of Life CY MAY, 1997 CL WASHINGTON, D.C. ID CANCER PAIN; MANAGEMENT; PROGRAM; MODEL AB This article presents recommendations for improving the education of physicians about end-of-life care in the acute care hospital setting. The authors, who have a variety of backgrounds and represent several types of institutions, formulated and reached consensus on these recommendations as members,of the Acute Care Hospital Working Group, one of eight working groups convened at the National Consensus Conference on Medical Education for Care Near the End of Life in May 1997. A recently published literature review on the status of palliative:care education, a summary of recent research on education about end-of-life care, and expert opinion were helpful in developing the recommendations. The authors emphasize that the acute care setting offers many opportunities for education about care at the end of life. Faculty should support learners'. appreciation of the importance of end-of-life care, and convey the meaning and privilege of attending to patients and families lies at this dificult time. Faculty should teach students and residents to provide care that embodies attention;to the control of distressing physical, physiologic and spiritual symptoms, appropriate awareness of patients' differing cultural backgrounds and their impact upon the experience of dying, excellent communication skills, the application of bioethical principles, timely referral and smooth transition to other care settings that meet patient and family goals, and the role of the interdisciplinary team in meeting the diverse needs of dying patients their families. C1 Med Coll Wisconsin, Palliat Care Program, Milwaukee, WI 53226 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA. Amer Board Internal Med, Philadelphia, PA USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Obstet & Gynecol, Hershey, PA 17033 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. AAMC, Div Med Educ, Washington, DC USA. Cornell Univ, Sch Med, Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mt Sinai Med Ctr, Dept Geriatr & Adult Dev, New York, NY 10029 USA. Joint Commiss Accrediitat Healthcare Orgn, Oak Brook Terrace, IL USA. Univ N Dakota, Sch Med & Hlth Sci, Off Med Educ, Grand Forks, ND 58201 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. RP Weissman, DE (reprint author), Froedtert Hosp E, Dept Hematol Oncol, Palliat Care Program, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 33 TC 33 Z9 33 U1 3 U2 6 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 AUG PY 1999 VL 74 IS 8 BP 871 EP 877 DI 10.1097/00001888-199908000-00009 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 227CP UT WOS:000082061000011 PM 10495725 ER PT J AU Mehta, A Dreyer, KJ Novelline, RA Schultz, TJ Bell, TV AF Mehta, A Dreyer, KJ Novelline, RA Schultz, TJ Bell, TV TI Facilitating the production of digital radiology teaching files with the radiology annotation and publishing system: A software tool for radiology educators SO ACADEMIC RADIOLOGY LA English DT Article ID INFORMATION; INTERNET C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Mehta, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 14 TC 3 Z9 3 U1 3 U2 5 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1999 VL 6 IS 8 BP 496 EP 501 DI 10.1016/S1076-6332(99)80169-X PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 296PT UT WOS:000086033400007 PM 10480046 ER PT J AU Bernt, KM Walker, WA AF Bernt, KM Walker, WA TI Human milk as a carrier of biochemical messages SO ACTA PAEDIATRICA LA English DT Article; Proceedings Paper CT Symposium on Advances in Infant Feeding - Human Milk and Formula CY MAR 20-21, 1998 CL BAVENO, ITALY DE allergy; breastfeeding; cytokines; gastrointestinal tract-growth and development; growth factors; hormones; immune system-growth and development; necrotizing enterocolitis ID EPIDERMAL GROWTH-FACTOR; COLONY-STIMULATING FACTOR; GLAND EPITHELIAL-CELLS; HUMAN BREAST-MILK; FOLLOW-UP; FACTOR-I; T-CELLS; NECROTIZING ENTEROCOLITIS; DIETARY NUCLEOTIDES; CYTOKINE PRODUCTION AB Not only does breast milk provides an ideal nutrient composition for the newborn, but it also contains a variety of substances that may actively influence growth and development of the infant and stimulate neonatal protection against gastrointestinal diseases. Hormones, growth factors, cytokines and even whole cells are present in breast milk and act to establish biochemical and immunological communication between mother and child. In addition, milk nutrients such as nucleotides, glutamine and lactoferrin have been shown to influence gastrointestinal development and host defense. The unique properties of milk as a mediator of biochemical messages will be presented and the clinical significance of breastfeeding in the prevention of neonatal gastrointestinal diseases will be discussed. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. RP Walker, WA (reprint author), Harvard Univ, Sch Med, Dev Gastroenterol Lab,Childrens Hosp, Combined Program Pediat Gastroenterol & Nutr, 300 Longwood Ave, Boston, MA 02115 USA. NR 81 TC 58 Z9 58 U1 1 U2 6 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD AUG PY 1999 VL 88 SU 430 BP 27 EP 41 PG 15 WC Pediatrics SC Pediatrics GA 248VP UT WOS:000083296700007 PM 10569221 ER PT J AU Teerlink, JR Massie, BM AF Teerlink, JR Massie, BM TI The interaction of ACE inhibitors and aspirin in heart failure: Torn between two lovers SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID CONVERTING ENZYME-INHIBITORS; ACUTE MYOCARDIAL-INFARCTION; ACETYLSALICYLIC-ACID; RENAL-FUNCTION; ENALAPRIL; RAMIPRILAT; SURVIVAL; REDUCTION; DISEASE; TRIAL C1 San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP Teerlink, JR (reprint author), San Francisco Vet Affairs Med Ctr, Cardiol Sect, 111C,4150 Clement St, San Francisco, CA 94121 USA. RI Teerlink, John/D-2986-2012 NR 33 TC 21 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 1999 VL 138 IS 2 BP 193 EP 197 DI 10.1016/S0002-8703(99)70099-2 PN 1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 224WD UT WOS:000081922200002 PM 10426826 ER PT J AU Mendes, LA Picard, MH Dec, GW Hartz, VL Palacios, IF Davidoff, R AF Mendes, LA Picard, MH Dec, GW Hartz, VL Palacios, IF Davidoff, R CA Investigators Myocarditis Treatment Trial Bosto TI Ventricular remodeling in active myocarditis SO AMERICAN HEART JOURNAL LA English DT Article ID IDIOPATHIC DILATED CARDIOMYOPATHY; ENZYME-INHIBITOR ENALAPRIL; LONG-TERM PROGRESSION; NATURAL-HISTORY; HEART-FAILURE; INFARCTION; DYSFUNCTION; AFTERLOAD; CAPTOPRIL; GEOMETRY AB Background Remodeling of the left ventricle with the development of a spherical cavity occurs in dilated cardiomyopathy and is associated with a poor long-term prognosis. The early effects of myocarditis on left ventricular geometry have not been previously described or correlated with clinical outcome. Methods The baseline echocardiograms of 35 patients with biopsy-confirmed myocarditis were compared with 20 normal controls, left ventricular end-diastolic volume, long axis length, and mid-cavity diameter were measured. The degree of sphericity was expressed as the ratio of the mid-cavity diameter to the long axis length. left ventricular ejection fraction was assessed by radionuclide angiography. Results In patients with myocarditis, mean left ventricular volume of 81 +/- 29 mL/m(2) was significantly greater than 50 +/- 8 mL/m(2) in controls (P =.001). Chamber dilatation occurred primarily along the mid-cavity diameter, which measured 5.3 +/- 0.8 cm in patients with myocarditis versus 4.2 +/- 0.4 cm in controls (P =.001). The degree of left ventricular sphericity in patients with myocarditis, 0.64 +/- 0.08, was significantly greater than that of controls, 0.54 +/- 0.04 (P =.001). When patients were stratified according to left ventricular volume, patients with increased left ventricular volume (>75 mL/m(2)) were associated with a more spherical chamber and lower left ventricular ejection fraction than patients with a more normal left ventricular volume (less than or equal to 75 mL/m(2)). Conclusions Active myocarditis is associated with early left ventricular remodeling and the development of a spherical chamber. These changes correlate with ventricular dilatation and reduced left ventricular ejection fraction. C1 Boston Med Ctr, Div Cardiol, Evans Mem Dept Clin Res, Boston, MA 02118 USA. Boston Med Ctr, Dept Med, Cardiol Sect, Boston, MA 02118 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Univ Arizona, Dept Med, Cardiol Sect, Tucson, AZ USA. RP Mendes, LA (reprint author), Boston Med Ctr, Div Cardiol, Evans Mem Dept Clin Res, 1 Boston Med Ctr Pl,E Newton St Campus, Boston, MA 02118 USA. OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [R01-HL34744] NR 22 TC 20 Z9 21 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 1999 VL 138 IS 2 BP 303 EP 308 DI 10.1016/S0002-8703(99)70116-X PN 1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 224WD UT WOS:000081922200019 PM 10426843 ER PT J AU Dominitz, JA Provenzale, D AF Dominitz, JA Provenzale, D TI Prevalence of dyspepsia, heartburn, and peptic ulcer disease in veterans SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 61st Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 21-23, 1996 CL SEATTLE, WASHINGTON SP Amer Coll Gastroenterol ID FUNCTIONAL GASTROINTESTINAL DISORDERS; ANTI-INFLAMMATORY DRUGS; CARE SEEKING BEHAVIOR; COST-BENEFIT-ANALYSIS; HELICOBACTER-PYLORI; HEALTH-CARE; MANAGEMENT STRATEGIES; BOWEL DYSFUNCTION; NON-CONSULTERS; UNITED-STATES AB OBJECTIVE: Medications used to treat gastrointestinal symptoms account for a substantial share of pharmacy expenses for veterans affairs medical centers. Prior studies have shown that the prevalence of peptic ulcer disease is higher in veterans than in nonveterans. Our aim was to determine the prevalence of upper gastrointestinal symptoms among patients seeking health care in the Department of Veterans Affairs outpatient clinics. METHODS: A total of 1582 veterans completed a previously validated bowel symptom questionnaire in the following clinics: gastroenterology (n = 693), walk-in (n = 403), general medicine (n = 379), and women's health (n = 107). RESULTS: Overall response was 78%. Dyspepsia was reported in 30%, 37%, 44%, and 53% of patients in general medicine, walk-in, women's health, and gastroenterology clinics, respectively. Heartburn, at least weekly, was reported in 21%, 21%, 28%, and 40% of patients in general medicine, walk-in, women's health, and gastroenterology clinics, respectively. Prior peptic ulcer disease (PUD) was reported in 29%, 26%, 22%, and 44% of patients in general medicine, walk-in, women's health, and gastroenterology clinics, respectively. Dyspepsia, heartburn, and PUD were significantly associated with increased physician visits and lower general health. CONCLUSIONS: Dyspepsia and heartburn are common symptoms among veterans. Lifetime prevalence of PUD is high among veterans. Gastrointestinal symptoms have a significant impact on health care utilization and general health. These prevalence estimates provide a basis for studies of resource utilization and for cost-effectiveness analyses of the treatment of gastrointestinal disorders in the veteran population. Moreover, the high prevalence of symptoms helps to explain the high utilization of gastrointestinal medications. (Am J Gastroenterol 1999;94:2086-2093. (C) 1999 by Am. Coll. of Gastroenterology). C1 VA Puget Sound Hlth Care Syst, Seattle Div 111GI, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA USA. Vet Affairs Med Ctr, Hlth Serv Res & Dev, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Med, Div Gastroenterol, Durham, NC 27710 USA. RP Dominitz, JA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div 111GI, Dept Med, Div Gastroenterol, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 42 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 1999 VL 94 IS 8 BP 2086 EP 2093 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 223YJ UT WOS:000081868900015 PM 10445532 ER PT J AU Sachdev, GP Ohlrogge, KD Johnson, CL AF Sachdev, GP Ohlrogge, KD Johnson, CL TI Review of the Fifth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy: Outpatient management for adults SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Review DE American College of Chest Physicians; anticoagulants; dosage; dosage schedules; hemorrhage; International Normalized Ratio; patients; protocols; surgery; thrombophlebitis; thrombosis; toxicity; warfarin ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; PROSTHETIC VALVE ENDOCARDITIS; INTRAVENOUS UNFRACTIONATED HEPARIN; NONRHEUMATIC ATRIAL-FIBRILLATION; ORAL ANTICOAGULANT-THERAPY; RECURRENT THROMBOEMBOLISM; CARDIOVASCULAR-DISEASE; DIFFERENT INTENSITIES; WARFARIN THERAPY AB The recommendations of the Fifth American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy are reviewed, with a focus on outpatient anticoagulation management in adults. Numerous therapeutic recommendations have changed since the Fourth ACCP Consensus Conference on Antithrombotic Therapy. The system of grading recommendations has been modified to emphasize clinically important differences and to take into account the benefit-risk ratio of each treatment option. The International Normalized Ratio (INR) goal is now expressed as a specific target value within a range rather than simply an MR range. The recommendations of the fifth conference cover initiation of warfarin therapy, hemorrhagic complications, management of excessive anticoagulation, interruption of warfarin therapy for patients requiring surgery, nonvalvular atrial fibrillation, cardioversion in patients with atrial fibrillation, valvular heart disease, mechanical and biological prosthetic heart valves, coronary artery disease, saphenous vein and internal mammary artery bypass grafts, peripheral arterial occlusive disease, prevention of venous thromboembolism, treatment of venous thromboembolism, stroke prevention in patients with cerebrovascular disease, and pregnancy. Since the fourth consensus conference, new anticoagulation therapies and indications have emerged; the recommendations of the Fifth ACCP Consensus Conference on Antithrombotic Therapy have provided practitioners with a resource of immense value. C1 Clement J Zablocki Vet Affairs Med Ctr, Milwaukee, WI 53295 USA. William S Middleton Mem Vet Hosp, Rockford Vet Affairs Primary Care Clin, Madison, WI USA. Good Samaritan Hosp, Dayton, OH USA. RP Ohlrogge, KD (reprint author), Clement J Zablocki Vet Affairs Med Ctr, 5000 W Natl Ave, Milwaukee, WI 53295 USA. NR 61 TC 20 Z9 20 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD AUG 1 PY 1999 VL 56 IS 15 BP 1505 EP 1514 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 226DR UT WOS:000082005500013 PM 10478987 ER PT J AU Trendle, MC Leong, T Kyle, RA Katzmann, JA Oken, MM Kay, NE Van Ness, BG Greipp, PR AF Trendle, MC Leong, T Kyle, RA Katzmann, JA Oken, MM Kay, NE Van Ness, BG Greipp, PR TI Prognostic significance of the S-phase fraction of light-chain-restricted cytoplasmic immunoglobulin (clg) positive plasma cells in patients with newly diagnosed multiple myeloma enrolled on Eastern Cooperative Oncology Group treatment trial E9486 SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-22, 1996 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Clin Oncol DE multiple myeloma; s-phase; flow cytometry; labeling index ID C-REACTIVE PROTEIN; LABELING INDEX; BETA-2 MICROGLOBULIN; FLOW-CYTOMETRY; DNA CONTENT; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; STAGING SYSTEM; KINETICS; BETA(2)-MICROGLOBULIN AB The bone marrow plasma cell labeling index (PCLI) as measured by bromodeoxyuridine uptake is a well-established independent prognostic factor for patients with newly diagnosed multiple myeloma, but the test is not easily done in most laboratories, The purpose of this study was to determine if the proliferative activity (% S-phase) as determined by two-color flow cytometry for cytoplasmic immunoglobulin (clg) light chain and DNA content also had prognostic significance. As part of Eastern Cooperative Oncology Group clinical trial E9486, 500 patients had successful performance of the bone marrow PCLI. Of 349 patients who had flow clg and DNA content cytometry, 210 had adequate data to reliably calculate S-phase %. Patients with low % S-phase fraction (<2%) had a significant overall survival advantage over patients high % S-phase fraction (greater than or equal to 2%), median survivals 4.1 vs. 2.9 years (P = 0.032). Measurement of the S-phase % by flow cytometry gives significant prognostic information in patients with newly diagnosed myeloma. However, in multivariate analysis, S-phase % did not add prognostic information when PCLI was in the model. S-phase % added prognostic information only when all cases with flow measurement of S-phase % were included, and when PCLI was excluded from the model, Discriminating a population of only clg positive cells proved difficult in patients with a low percentage of bone marrow plasma cells. Methodology to measure S-phase % in patients with a low percent plasma cells is needed before this technique can be used for diagnosis and prognosis in myeloma. (C) 1999 Wiley-Liss, Inc. C1 Mayo Clin, Div Hematol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN USA. RP Greipp, PR (reprint author), Mayo Clin, Div Hematol, 920 Hilton,200 1st Ave SW, Rochester, MN 55905 USA. FU NCI NIH HHS [CA 13650, CA 15947, CA 23318] NR 35 TC 14 Z9 15 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD AUG PY 1999 VL 61 IS 4 BP 232 EP 237 PG 6 WC Hematology SC Hematology GA 221KN UT WOS:000081726400002 PM 10440908 ER PT J AU Shayakul, C Breton, S Brown, D Alper, SL AF Shayakul, C Breton, S Brown, D Alper, SL TI Gene therapy of inherited renal tubular disease SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID ANHYDRASE-II DEFICIENCY; MOLECULAR-BASIS; IN-VIVO; KIDNEY; CELLS; EXPRESSION; MICE C1 Beth Israel Deaconess Med Ctr, Mol Med Unit, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Renal Unit, Boston, MA 02215 USA. Siriraj Hosp, Dept Med, Renal Unit, Bangkok, Thailand. Mahidol Univ, Bangkok 10700, Thailand. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Alper, SL (reprint author), Beth Israel Deaconess Med Ctr, Mol Med Unit, 330 Brookline Ave, Boston, MA 02215 USA. NR 23 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 1999 VL 34 IS 2 BP 374 EP 377 DI 10.1016/S0272-6386(99)70372-0 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 225JY UT WOS:000081955600030 PM 10430991 ER PT J AU Asch, DA Faber-Langendoen, K Shea, JA Christakis, NA AF Asch, DA Faber-Langendoen, K Shea, JA Christakis, NA TI The sequence of withdrawing life-sustaining treatment from patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID DECISION-MAKING; PHYSICIANS; SUPPORT; EUTHANASIA; ATTITUDES; CARE; PREFER; ILL AB PURPOSE: To describe the observed sequence of withdrawal of eight different forms of life-sustaining treatment and to determine whether aspects of those treatments determine the order of withdrawal. SUBJECTS AND METHODS: We observed 211 consecutive patients dying in four midwestern US hospitals from whom at least one of eight specific life-sustaining treatments was or could have been withdrawn. We used a parametric statistical technique to explain the order of withdrawal based on selected characteristics of the forms of life support, including cost, scarcity, and discomfort. RESULTS: The eight forms of life support were withdrawn in a distinct sequence. From earliest to latest, the order was blood products, hemodialysis, vasopressors, mechanical ventilation, total parenteral nutrition, antibiotics, intravenous fluids, and tube feedings (P <0.0001). The sequence was almost identical to that observed in a previous study based on hypothetical scenarios. Forms of life support that were perceived as more artificial, scarce, or expensive were withdrawn earlier. CONCLUSION: The preference for withdrawing some forms of life-sustaining treatments more than others is associated with intrinsic characteristics of these treatments. Once the decision has been made to forgo life-sustaining treatment, the process remains complex and appears to target many different goals simultaneously. (C) 1999 by Excerpta Medica, Inc. C1 Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. SUNY Hlth Sci Ctr, Dept Med, Program Bioeth, Syracuse, NY 13210 USA. Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. Univ Chicago, Dept Sociol, Chicago, IL 60637 USA. RP Asch, DA (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, 3641 Locust Walk, Philadelphia, PA 19104 USA. RI Christakis, Nicholas/B-6690-2008; Christakis, Nicholas/C-3205-2009 NR 21 TC 51 Z9 52 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 1999 VL 107 IS 2 BP 153 EP 156 DI 10.1016/S0002-9343(99)00198-9 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 225EE UT WOS:000081944800009 PM 10460047 ER PT J AU Rabb, H Bonventre, JV AF Rabb, H Bonventre, JV TI Leukocyte adhesion molecules in transplantation SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ISCHEMIC-REPERFUSION INJURY; ANTIGEN-1 MONOCLONAL-ANTIBODY; HUMAN KIDNEY-TRANSPLANTATION; HEART ALLOGRAFT-REJECTION; ICAM-1 PROTECT KIDNEYS; ACUTE-RENAL-FAILURE; CELL-ADHESION; P-SELECTIN; CARDIAC ALLOGRAFT; XENOGRAFT REJECTION C1 Univ Minnesota, Sch Med, Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55455 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Med Serv, Boston, MA USA. Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Boston, MA USA. RP Bonventre, JV (reprint author), Massachusetts Gen Hosp E, Suite 4002,149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK 39773, DK 38452]; NINDS NIH HHS [NS 10828] NR 81 TC 8 Z9 9 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 1999 VL 107 IS 2 BP 157 EP 165 DI 10.1016/S0002-9343(99)00199-0 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 225EE UT WOS:000081944800010 PM 10460048 ER PT J AU Huang, D Abe, T Kojima, K Tanaka, N Watauabe, M Ohkura, A Nishimura, H Hayabuchi, N Norbash, AM AF Huang, D Abe, T Kojima, K Tanaka, N Watauabe, M Ohkura, A Nishimura, H Hayabuchi, N Norbash, AM TI Intracystic hemorrhage of the middle fossa arachnoid cyst and subdural hematoma caused by ruptured middle cerebral artery aneurysm SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID SPACE; CT AB We report a case of a cerebral aneurysm arising from the bifurcation of the left middle cerebral artery that ruptured into a left middle cranial fossa arachnoid cyst, associated with acute subdural hematoma. We discuss the relationships of aneurysm, arachnoid cyst, and subdural hematoma. C1 Kurume Univ, Sch Med, Dept Radiol, Kurume, Fukuoka 8300011, Japan. Koyanagi Mem Hosp, Dept Neurosurg, Saga, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Abe, T (reprint author), Kurume Univ, Sch Med, Dept Radiol, 67 Asahimachi, Kurume, Fukuoka 8300011, Japan. NR 12 TC 15 Z9 15 U1 1 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD AUG PY 1999 VL 20 IS 7 BP 1284 EP 1286 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 232CY UT WOS:000082349200020 PM 10472987 ER PT J AU Castro, MA Fassett, MJ Reynolds, TB Shaw, KJ Goodwin, TM AF Castro, MA Fassett, MJ Reynolds, TB Shaw, KJ Goodwin, TM TI Reversible peripartum liver failure: A new perspective on the diagnosis, treatment, and cause of acute fatty liver of pregnancy, based on 28 consecutive cases SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE acute fatty liver of pregnancy; liver failure; critical care ID HEPATIC-FAILURE; TRANSPLANTATION; MANAGEMENT; RECURRENCE AB OBJECTIVE: We sought to describe our experience with the clinical diagnosis, management, and course of patients with acute fatty liver of pregnancy. STUDY DESIGN: Twenty-eight cases of acute fatty liver of pregnancy at the Los Angeles County and University of Southern California Medical Center from 1982 to June 1997 were identified, and presenting symptoms, clinical course, laboratory values, maternal complications, and neonatal outcomes were studied. RESULTS: The incidence of acute fatty liver of pregnancy was 1 in 6659 births. There were no maternal deaths. Initial presentation was at an average of 37 weeks of gestation with a characteristic prodrome of malaise, nausea, vomiting, and abdominal pain. No patient was admitted with the diagnosis of acute fatty liver of pregnancy. The condition was diagnosed most commonly on the second hospital day after laboratory results indicated coagulopathy, renal insufficiency, and liver function abnormalities. One patient underwent liver biopsy at cesarean delivery. Radiologic studies did not aid with the diagnosis. Twenty-one patients were admitted in spontaneous labor, and 16 labors were complicated by abnormal fetal heart rate patterns or meconium. There was 1 stillbirth and 1 neonatal death as a result of perinatal asphyxia. Maternal morbidity consisted of hypoglycemia, infection, renal insufficiency, coagulopathy, encephalopathy, and wound complications. All patients had evidence of disseminated intravascular coagulopathy with profoundly decreased antithrombin levels. All patients recovered normal liver function post partum. CONCLUSIONS: Reversible peripartum liver failure may be diagnosed and managed on the basis of clinical and laboratory criteria. With adequate support, these patients may have full recovery of hepatic function. C1 Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Los Angeles Cty Womens & Childrens Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Los Angeles, CA USA. Univ So Calif, Womens & Childrens Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Los Angeles, CA USA. Univ So Calif, Los Angeles Cty Med Ctr, Div Hepatol, Dept Med, Los Angeles, CA 90033 USA. Univ So Calif, Ctr Med, Dept Med, Div Hepatol, Los Angeles, CA 90033 USA. White Mem Med Ctr, Div Maternal Fetal Med, Dept Obstet & Gynecol, Los Angeles, CA USA. RP Castro, MA (reprint author), Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Founders 430, Boston, MA 02114 USA. NR 25 TC 98 Z9 107 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 1999 VL 181 IS 2 BP 389 EP 395 DI 10.1016/S0002-9378(99)70567-3 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 228WZ UT WOS:000082161300042 PM 10454689 ER PT J AU Streit, M Velasco, P Brown, LF Skobe, M Richard, L Riccardi, L Lawler, J Detmar, M AF Streit, M Velasco, P Brown, LF Skobe, M Richard, L Riccardi, L Lawler, J Detmar, M TI Overexpression of thrombospondin-1 decreases angiogenesis and inhibits the growth of human cutaneous squamous cell carcinomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; LUNG-CARCINOMA; TUMOR-GROWTH; IN-VITRO; EXPRESSION; INVASION; LINES; TUMORIGENESIS; ATTACHMENT; SUPPRESSES AB The function of the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1) in epithelial tumor development has remained controversial. We studied the in vitro growth characteristics and the in vivo tumor xenograft growth of the human squamous cell carcinoma cell lines A431 and SCC-13, stably transfected to overexpress human TSP-1. Overexpression of TSP-1 inhibited tumor growth of A431 xenotransplants, and completely abolished tumor formation by SCC-13 cells. TSP-1 overexpressing A431 tumors were characterized by extensive areas of necrosis and by decreased tumor vessel number and size. The effects of TSP-1 on tumor cell growth Fc ere indirect since tumor cell proliferation rates in vivo and in vitro, anchorage-dependent and -independent growth in vitro, and susceptibility to induction of apoptosis by serum withdrawal were unchanged in TSP-1 overexpressing tumor cells. However, TSP-1 overexpression up-regulated the TSP-1 receptor CD36, leading to enhanced adhesion of A431 cells to TSP-1. These findings establish TSP-1 as a potent inhibitor of angiogenesis and tumor growth in carcinomas of the skin. C1 Massachusetts Gen Hosp, Dept Dermatol, CBRC, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Dept Dermatol, CBRC, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69184, R01 CA069184]; NHLBI NIH HHS [HL28749] NR 47 TC 206 Z9 216 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1999 VL 155 IS 2 BP 441 EP 452 DI 10.1016/S0002-9440(10)65140-1 PG 12 WC Pathology SC Pathology GA 224LY UT WOS:000081901600014 PM 10433937 ER PT J AU Ikezu, T Yasuhara, S Granneman, JG Kraemer, FB Okamoto, T Tompkins, RG Martyn, JAJ AF Ikezu, T Yasuhara, S Granneman, JG Kraemer, FB Okamoto, T Tompkins, RG Martyn, JAJ TI A unique mechanism of desensitization to lipolysis mediated by beta(3)-adrenoceptor in rats with thermal injury SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE adrenergic receptor; burns; hormone-sensitive lipase; insulin; protein kinase A ID BETA-ADRENERGIC-RECEPTOR; HUMAN BETA-3-ADRENERGIC RECEPTOR; HORMONE-SENSITIVE LIPASE; BURN INJURY; ADIPOCYTES; PROTEIN; EXPRESSION; AGONIST; INSULIN; GENERATION AB Thermal injury causes a hypermetabolic state associated with increased levels of catabolic hormones, but the molecular bases for the metabolic abnormalities are poorly understood. We investigated the lipolytic responses after beta(3)-adrenoceptor (beta(3)-AR) agonists and evaluated the associated changes in beta-AR and its downstream signaling molecules in adipocytes isolated from rats with thermal injury. Maximal lipolytic responses to a specific beta(3)-AR agonist, BRL-37344, were significantly attenuated at post burn days (PBD) 3 and 7. Despite significant reduction of the cell surface beta(3)-AR number and its mRNA at PBD 3 and 7, BRL-37344 and forskolin-stimulated cAMP levels were not decreased. Glycerol production in response to dibutyryl cAMP, a direct stimulant of hormone-sensitive lipase (HSL) via protein kinase A (PKA), was significantly attenuated. Although immunoblot analysis indicated no differences in the expression and activity of PKA. or in the expression of HSL, HSL activity showed significant reductions. Finally, beta(3)-AR-induced insulin secretion was indeed attenuated in vivo. These studies indicate that the beta(3)-AR system is desensitized after burns, both in the adipocytes and in beta(3)-AR-induced secretion of insulin. Furthermore, these data suggest a complex and unique mechanism underlying the altered signaling of lipolysis at the level of HSL in animals after burns. C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. Wayne State Univ, Sch Med, Dept Psychiat, Detroit, MI 48207 USA. Stanford Univ, Med Ctr, Div Endocrinol Gerontol & Metab, Stanford, CA 94305 USA. RP Martyn, JAJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM-55081-3, GM-31569-17]; NIMH NIH HHS [MH-56036] NR 33 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 1999 VL 277 IS 2 BP E316 EP E324 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 222WW UT WOS:000081809200017 PM 10444428 ER PT J AU Akiba, Y Guth, PH Engel, E Nastaskin, I Kaunitz, JD AF Akiba, Y Guth, PH Engel, E Nastaskin, I Kaunitz, JD TI Acid-sensing pathways of rat duodenum SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE laser-Doppler flowmetry; vanilloid (capsaicin) receptor; capsazepine; bradykinin; indomethacin ID GENE-RELATED PEPTIDE; INDUCED MESENTERIC HYPEREMIA; SENSITIVE SENSORY NERVES; GATED CATION CHANNEL; GUINEA-PIG HEART; LOW PH; CAPSAICIN-RECEPTOR; RUTHENIUM RED; VANILLOID RECEPTOR; INDUCED RELEASE AB We tested the hypothesis that the duodenal hyperemic response to acid occurs through activation of capsaicin-sensitive afferent nerves with subsequent release of vasodilatory substances such as calcitonin gene-related peptide (CGRP) and nitric oxide (NO). Laser-Doppler flowmetry was used to measure duodenal blood flow in urethan-anesthetized rats. Duodenal mucosa was superfused with pH 7.0 buffer with capsaicin or bradykinin or was acid challenged with pH 2.2 solution, with or without vanilloid receptor antagonists, a CGRP receptor antagonist, an NO synthase (NOS) inhibitor, or a cyclooxygenase inhibitor. The selective vanilloid receptor antagonist capsazepine (CPZ) dose dependently inhibited the hyperemic response to acid and capsaicin but did not affect bradykinin-induced hyperemia. Ruthenium red was less inhibitory than capsazepine. Selective ablation of capsaicin-sensitive nerves, CGRP-(8-37), and N-G-nitro-L-arginine methyl ester inhibited acid-induced hyperemia, but indomethacin did not. We conclude that luminal acid, but not bradykinin, stimulates CPZ-sensitive receptors on capsaicin-sensitive afferent nerves of rat duodenum. Activation of these receptors produces vasodilation via the CGRP-NO pathway but not via the cyclooxygenase pathway. Acid appears to be the endogenous ligand for duodenal vanilloid receptors. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Ste 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu NR 45 TC 52 Z9 54 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 1999 VL 277 IS 2 BP G268 EP G274 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 224WB UT WOS:000081922000003 PM 10444439 ER PT J AU Kim, CD Goyal, RK Mashimo, H AF Kim, CD Goyal, RK Mashimo, H TI Neuronal NOS provides nitrergic inhibitory neurotransmitter in mouse lower esophageal sphincter SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE nitric oxide; nonadrenergic noncholinergic neurotransmission; endothelial nitric oxide synthase lacking mutant mice ID NITRIC-OXIDE SYNTHASE; INTERSTITIAL-CELLS; RELAXATION; STIMULATION; MUSCLE; CAJAL; VAGAL; MICE; GENE AB To identify the enzymatic source of nitric oxide (NO) in the lower esophageal sphincter (LES), studies were performed in wildtype and genetically engineered endothelial nitric oxide synthase [eNOS(-)] and neuronal NOS [nNOS(-)] mice. Under nonadrenergic noncholinergic (NANC) conditions, LES ring preparations developed spontaneous tone in all animals. In the wild-type mice, electrical field stimulation produced frequency-dependent intrastimulus relaxation and a poststimulus rebound contraction. NOS inhibitor N-omega-nitro-L-arginine methyl ester (100 mu M) abolished intrastimulus relaxation and rebound contraction. In nNOS(-) mice, both the intrastimulus relaxation and rebound contraction were absent. However, in eNOS(-) mice there was no significant difference in either the relaxation or rebound contraction from the wild-type animal. Both nNOS(-) and eNOS(-) tissues showed concentration-dependent relaxation to NO donor diethylenetriamine-NO and there was no difference in the sensitivity to the NO donor in nNOS(-), eNOS(-), or wild-type animals. These results indicate that in mouse LES, nNOS rather than eNOS is the enzymatic source of the NO that mediates NANC relaxation and rebound contraction. C1 Brockton W Roxbury Vet Affairs Med Ctr, Ctr Swallowing & Motil Disorders, Boston, MA 02132 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA 02132 USA. RP Mashimo, H (reprint author), Brockton W Roxbury Vet Affairs Med Ctr, Ctr Swallowing & Motil Disorders, 1400 VFW Pkwy, Boston, MA 02132 USA. EM mashimo@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK-31902, DK-02462] NR 28 TC 43 Z9 44 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD AUG PY 1999 VL 277 IS 2 BP G280 EP G284 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 224WB UT WOS:000081922000005 PM 10444441 ER PT J AU Schmidt, U Hajjar, RJ Kim, CS Lebeche, D Doye, AA Gwathmey, JK AF Schmidt, U Hajjar, RJ Kim, CS Lebeche, D Doye, AA Gwathmey, JK TI Human heart failure: cAMP stimulation of SR Ca2+-ATPase activity and phosphorylation level of phospholamban SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE human myocardium; calcium ion; sarcoplasmic reticulum; calcium ion-adenosinetriphosphatase; phospholamban; adenosine 3 ',5 '-cyclic monophosphate ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; FORCE-FREQUENCY-RELATIONSHIP; MYOCARDIAL-CONTRACTILITY; DILATED CARDIOMYOPATHY; GENE-EXPRESSION; PROTEIN-LEVELS; MESSENGER-RNA; DYSFUNCTION; HYPERTROPHY; ATPASE AB Failing human myocardium has been associated with decreased sarcoplasmic reticulum (SR) Ca2+-ATPase activity. There remains controversy as to whether the regulation of SR Ca2+-ATPase activity is altered in heart failure or whether decreased SR Ca2+-ATPase activity is due to changes in SR Ca2+-ATPase or phospholamban expression. We therefore investigated whether alterations in cAMP,dependent phosphorylation of phospholamban may be responsible for the reduced SR Ca2+-ATPase activity in human heart failure. Protein levels of phospholamban and SR Ca2+-ATPase, detected by Western blot, were unchanged in failing compared with nonfailing human myocardium. There was decreased responsiveness to the direct activation of the SR Ca2+-ATPase activity by either cAMP (0.01-100 mu mol/l) or protein kinase A (1-30 mu g) in failing myocardium. Using the backphosphorylation technique, we observed a decrease of the cAMP-dependent phosphorylation level of phospholamban by 20 +/- 2%. It is concluded that the impaired SR function in human end-stage heart failure may be due, in part, to a reduced cAMP-dependent phosphorylation of phospholamban. C1 Boston Univ, Sch Med, Integrated Physiol Labs, Dept Cardiovasc Med,Div Cardiovasc, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Integrated Physiol Labs, Evans Dept Med, Cambridge, MA 02138 USA. Whitaker Cardiovasc Inst, Cambridge, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Inst Cardiovasc Dis & Muscle Res, Cambridge, MA 02138 USA. RP Boston Univ, Sch Med, Integrated Physiol Labs, Dept Cardiovasc Med,Div Cardiovasc, 763 Bldg,E Concord Ave, Cambridge, MA 02138 USA. EM gwathmey@tiac.net FU NHLBI NIH HHS [R01-HL-49754, R43-HL-60323, R55-HL-52249] NR 34 TC 96 Z9 101 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 1999 VL 277 IS 2 BP H474 EP H480 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 223XA UT WOS:000081865800007 PM 10444471 ER PT J AU White, LT O'Donnell, JM Griffin, J Lewandowski, ED AF White, LT O'Donnell, JM Griffin, J Lewandowski, ED TI Cytosolic redox state mediates postischemic response to pyruvate dehydrogenase stimulation SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE reperfusion; lactate; nuclear magnetic resonance spectroscopy; heart; metabolism ID C-13 NMR-SPECTRA; RAT HEARTS; INFARCT SIZE; RABBIT HEART; IN-VIVO; LACTATE; MYOCARDIUM; OXIDATION; ISCHEMIA; DICHLOROACETATE AB Augmented pyruvate oxidation via pharmacological stimulation of pyruvate dehydrogenase (PDH) during reperfusion has been related to improved recovery of postischemic hearts independent of glycolytic activity. This study examined recovery of postischemic rabbit hearts during activation of PDH with dichloroacetate (DCA) in the presence of lactate, as a source of pyruvate, to determine the response to substrate-dependent changes in cytosolic redox state. After 10 min of ischemia, isolated hearts were reperfused with either 2.5 mM or 0.5 mM: pyruvate (Pyr) or 2.5 mM lactate (Lac), with or without 5 mM DCA. C-13-enriched substrates allowed NMR assessment of metabolic perturbations. During normal perfusion, Pyr and Lac supported similar mechanical work. Increasing Pyr oxidation restored postischemic rate-pressure product to 82 +/- 4 and 88 +/- 6% of preischemic values during reperfusion with 2.5 and 0.5 mM Pyr, respectively, vs. 61 +/- 6 and 45 +/- 14% for untreated 2.5 and 0.5 mM Pyr, respectively (P < 0.05). In contrast, increasing Lac oxidation did not bene fit recovery of RPP in untreated (44 +/- 7%) vs. DCA-treated 36 +/- 4% hearts. Thus the benefit of PDH activation for contractile recovery of postischemic hearts is mediated by the source of pyruvate, which also influences cytosolic redox state. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. RP Lewandowski, ED (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01-HL-49244] NR 35 TC 17 Z9 17 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD AUG PY 1999 VL 277 IS 2 BP H626 EP H634 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 223XA UT WOS:000081865800024 PM 10444488 ER PT J AU Michelson, D Amsterdam, JD Quitkin, FM Reimherr, FW Rosenbaum, JF Zajecka, J Sundell, KL Kim, Y Beasley, CM AF Michelson, D Amsterdam, JD Quitkin, FM Reimherr, FW Rosenbaum, JF Zajecka, J Sundell, KL Kim, Y Beasley, CM TI Changes in weight during a 1-year trial of fluoxetine SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BODY-WEIGHT; GAIN; ANTIDEPRESSANTS; LITHIUM; DEPRESSION; ADULTS AB Objective: Fluoxetine has been associated with weight loss during acute treatment, but no controlled studies of weight change during long-term treatment with fluoxetine or other selective serotonin reuptake inhibitors have been reported. Weights were assessed for patients whose depressive symptoms had disappeared with acute fluoxetine treatment. Patients were then randomly assigned to continuation treatment with fluoxetine or placebo. Method: Patients whose illness had remitted after 12 weeks of treatment with fluoxetine, 20 mg/day, were randomly assigned to receive up to 38 weeks of treatment with fluoxetine or placebo. Weight was assessed at each visit. Change in weight was analyzed during the initial 12 weeks of acute treatment and after 14, 26, and 38 weeks. Relationships between weight change and body mass index and between weight change and appetite change were assessed. Results: During the initial 4 weeks of therapy, a mean absolute weight decrease of 0.4 kg was observed for all patients. Among patients who completed 50 weeks of therapy, the mean absolute weight increase during continuation treatment was similar for both the placebo- and fluoxetine-treated groups. Weight increase was not related to initial body mass index but was related to both poor appetite at study entry and to improvement in appetite after recovery. No patients discontinued therapy because of weight gain. Conclusions: Acute therapy with fluoxetine is associated with modest weight loss. After remission of depressive symptoms, weight gain for patients taking fluoxetine for longer periods is not different from that for patients taking placebo and is most likely related to recovery from depression. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Penn, Med Ctr, Depress Res Unit, Philadelphia, PA 19104 USA. New York State Psychiat Inst, New York, NY 10032 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. RP Michelson, D (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, DC 2423, Indianapolis, IN 46285 USA. OI Beasley, Charles/0000-0001-8743-7691 NR 17 TC 87 Z9 89 U1 1 U2 9 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1999 VL 156 IS 8 BP 1170 EP 1176 PG 7 WC Psychiatry SC Psychiatry GA 224WQ UT WOS:000081923300007 PM 10450256 ER PT J AU Batra, RK Guttridge, DC Brenner, DA Dubinett, SM Baldwin, AS Boucher, RC AF Batra, RK Guttridge, DC Brenner, DA Dubinett, SM Baldwin, AS Boucher, RC TI I kappa B alpha gene transfer is cytotoxic to squamous-cell lung cancer cells and sensitizes them to tumor necrosis factor-alpha-mediated cell death SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID ADENOVIRAL VECTOR; INDUCED APOPTOSIS; EARLY REGION-1; ACTIVATION; PHOSPHORYLATION; SIGNAL; PROTEOLYSIS; THERAPY; PROTEIN; FAMILY AB Current paradigms in cancer therapy suggest that activation of nuclear factor-kappa B (NF-kappa B) by a variety of stimuli, including some cytoreductive agents, may inhibit apoptosis. Thus, inhibiting NF-kappa B activation may sensitize cells to anticancer therapy. thereby providing a more effective treatment for certain cancers. E-1-deleted adenoviral (Ad) vectors encoding a "superrepressor" form of the NF-kappa B inhibitor I kappa B alpha (AdI kappa B alpha SR) or beta-galactosidase (AdLacZ) were tested alone and in combination with tumor necrosis factor-alpha (TNF-alpha) in lune cancer cells for sensitization of the cells to death. Following transduction with AdI kappa B alpha SR, lung cancer cells expressed I kappa B alpha SR in a dose-dependent manner. Probing nuclear extracts of lung cancer cells with NF-kappa B-sequence-specifc oligonucleotides indicated that there was a minimal amount of NF-kappa B in the nucleus at baseline and an expected and dramatic increase in nuclear NF-kappa B following exposure of cells to TNF-alpha. Control E-1-deleted AdLacZ did not promote NF-kappa B activation. Importantly, AdI kappa B alpha SR-mediated gene transfer resulted in the complete block of nuclear translocation of NF-kappa B by specific binding of its p65/relA component with transgenic I kappa B alpha SR. At the cellular level, transduction with AdI kappa B alpha SR resulted in increased cytotoxicity in lung cancer cells as opposed to transduction with equivalent doses of AdLacZ. In addition. whereas the parental cells were resistant to TNF-alpha-mediated cytotoxicity, I kappa B alpha SR-transduced cells could be sensitized to TNF-alpha. Consequently, AdI kappa B alpha SR transduction followed by exposure to TNF-alpha uniformly resulted in the death of non-small-cell lung cancer cells. These data suggest that novel approaches incorporating I kappa B alpha. gene therapy may have a role in the treatment of lung cancer. C1 Univ Calif Los Angeles, W Los Angeles Vet Adm Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, W Los Angeles Vet Adm Med Ctr, Wadsworth Pulm Immunol Lab, Los Angeles, CA 90073 USA. Univ N Carolina, Dept Med, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC USA. Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC USA. RP Batra, RK (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Adm Med Ctr, Dept Med, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [R01 CA078654-01A1, R01-CA72771]; NHLBI NIH HHS [HL51818] NR 46 TC 39 Z9 41 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD AUG PY 1999 VL 21 IS 2 BP 238 EP 245 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 227JF UT WOS:000082076800015 PM 10423407 ER PT J AU O'Neill, MJ Yoder, IC Connolly, SA Mueller, PR AF O'Neill, MJ Yoder, IC Connolly, SA Mueller, PR TI Imaging evaluation and classification of developmental anomalies of the female reproductive system with an emphasis on MR imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Roentgen-Ray-Society CY MAY, 1997 CL BOSTON, MASSACHUSETTS SP Amer Roentgen Ray Soc ID CLEAR CELL ADENOCARCINOMA; KUSTER-HAUSER SYNDROME; UTERINE ANOMALIES; HYSTEROSCOPIC METROPLASTY; MULLERIAN ANOMALIES; DIETHYLSTILBESTROL; HYSTEROSALPINGOGRAPHY; UTERUS; CERVIX; WOMEN C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP O'Neill, MJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal & Intervent Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 38 TC 11 Z9 13 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 1999 VL 173 IS 2 BP 407 EP 416 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 219QU UT WOS:000081618900032 PM 10430146 ER PT J AU Hoch, JR Kennell, TW Hollister, MS Sproat, IA Swan, JS Acher, CW Burks, J Heisey, DM AF Hoch, JR Kennell, TW Hollister, MS Sproat, IA Swan, JS Acher, CW Burks, J Heisey, DM TI Comparison of treatment plans for lower extremity arterial occlusive disease made with electrocardiography-triggered two-dimensional time-of-flight magnetic resonance angiography and digital subtraction angiography SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-for-Clinical-Vascular-Surgery CY MAR 24-28, 1999 CL LAKE BUENA VISTA, FLORIDA SP Soc Clin Vasc Surg ID DISTAL LOWER-EXTREMITY; MR-ANGIOGRAPHY; ARTERIOGRAPHY; SURGERY AB BACKGROUND: The purpose of the study was to determine whether preoperative treatment plans for patients with lower extremity ischemia can be made with electrocardiography (EKG)-triggered two-dimensional (2D) time-of-flight (TOF) magnetic resonance angiography (MRA) as accurately as digital subtraction angiography (DSA). METHODS: Forty patients were prospectively evaluated with the combination of EKG-triggered 2D TOF MRA, DSA, and pulse volume recordings. Blinded reviewers graded arterial segments for disease severity. Accuracy of separate MRA- and DSA-based treatment plans was compared with the procedures performed based on all available information. RESULTS: There was an 86% exact match between MRA- and DSA-based plans (92% MRA and 94% DSA accuracy). The MRA-based plan accurately predicted 90% of suprainguinal and 95% of infrainguinal procedures, whereas the DSA-based plan accurately predicted 100% of suprainguinal and 85% of infrainguinal procedures. Two-year primary patency was 83% for all procedures. Radiologists' review of disease severity resulted in a mean exact correlation between studies of 81% (kappa = 0.64). The agreement between radiologists interpreting the MRA was 84% (kappa = 0.7) compared with 82% (kappa = 0.66) for the DSA. CONCLUSIONS: MRA- and DSA-based preoperative management plans were of comparable efficacy. Significant interobserver variability was seen with the interpretations of both preoperative studies. EKG-triggered 2D TOF MRA can be used to plan arterial reconstructions; however, all patients require arterial pressure measurements prior to suprainguinal repair and confirmatory intraoperative angiography during infrainguinal revascularization. Am J Surg. 1999;178:166-173. (C) 1999 by Excerpta Medica, Inc. C1 Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Dept Surg, Vasc Surg Sect, Madison, WI USA. Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Dept Radiol, Vasc Surg Sect, Madison, WI USA. RP Hoch, JR (reprint author), Univ Wisconsin, Dept Surg, H4-730 Clin Sci Ctr,600 Highland Ave, Madison, WI 53792 USA. NR 14 TC 9 Z9 9 U1 0 U2 0 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 1999 VL 178 IS 2 BP 166 EP 172 DI 10.1016/S0002-9610(99)00158-0 PG 7 WC Surgery SC Surgery GA 231DG UT WOS:000082292400018 PM 10487272 ER PT J AU Nucci, MR Clement, PB Young, RH AF Nucci, MR Clement, PB Young, RH TI Lobular endocervical glandular hyperplasia, not otherwise specified - A clinicopathologic analysis of thirteen cases of a distinctive pseudoneoplastic lesion and comparison with fourteen cases of adenoma malignum SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE uterine cervix; pseudotumor; glandular hyperplasia ID MINIMAL-DEVIATION ADENOCARCINOMA; UTERINE CERVIX; MICROGLANDULAR HYPERPLASIA; TUNNEL CLUSTERS; METAPLASIA; FEATURES; ATYPIA AB We report 13 cases of a previously undescribed pseudoneoplastic lesion of the uterine cervix, which we have designated "lobular endocervical glandular hyperplasia, not otherwise specified." The patients' ages ranged from 37 to 71 years (mean, 45 years; median, 49 years). Three (27%) patients had a history of hormone use. Seven lesions were incidental findings in hysterectomy specimens. In the six other cases, the patient came to clinical attention because of a mucoid cervical discharge (two cases), increased vaginal discharge (two cases), abdominal discomfort (one case), or a 3.5-cm cervical mass found when being examined because of ovarian carcinoma (one case); hysterectomy was performed in each of these six cases. Microscopic examination showed a distinctly lobular proliferation of small to moderately sized rounded glands often centered around a larger central gland. The lobular proliferation was well to poorly demarcated and usually confined to the inner half of the cervical wall. Glands within the lobules were usually separated from each other by unaltered or hypercellular cervical stroma and were lined by columnar mucinous cells similar to the normal endocervix. Occasional reactive atypia of the endocervical cells and mitoses were seen, but no significant cytologic atypia was identified. Neither of the two cases stained showed cytoplasmic immunoreactivity for carcinoembryonic antigen. Follow-up of seven patients showed no evidence of recurrence of the cervical lesion, with an average length of follow-up of 3.4 years; three patients were lost to follow-up and three cases are recent. The principal consideration in the differential diagnosis was adenoma malignum (minimal deviation adenocarcinoma). The features most helpful in this distinction, in addition to the orderly lobular arrangement of the glands, were a lack of the following: irregular stromal infiltration, a desmoplastic stromal response, and focal malignant cytologic features. Lobular endocervical gland hyperplasia should be added to the list of previously described pseudoneoplastic glandular lesions of the cervix and, like them, not misinterpreted as neoplastic. C1 Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Nucci, MR (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. NR 23 TC 78 Z9 85 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD AUG PY 1999 VL 23 IS 8 BP 886 EP 891 DI 10.1097/00000478-199908000-00005 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 221RQ UT WOS:000081740400005 PM 10435557 ER PT J AU Rodriguez, A Flemington, EK AF Rodriguez, A Flemington, EK TI Transfection-mediated cell-cycle signaling: Considerations for transient transfection-based cell-cycle studies SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE apoptosis; transfection; p53; cell cycle ID P53 HOMOLOG; GENE; ARREST; DEATH; DNA AB Transient transfection of recombinant genes into cells is a commonly used approach for analyzing cell-cycle- and/or apoptotic-related activities of cell-cycle control proteins. In this approach, information regarding the functional consequence of expressing a recombinant protein transiently is garnered by comparing against results obtained from cells which are transfected with either a control expression plasmid and/or with mutant expression plasmids. In general however, little attention is paid to whether the transfection procedure itself influences these experiments. Using the calcium phosphate transfection method, we show that the introduction of DNA into cells induces signaling of the cell-cycle control machinery. In Hela cells, a transient increase in G0/G1 cells is observed 8 h after transfection. Furthermore, the introduction of DNA into several cell lines induces apoptosis. Transfection-mediated apoptosis can be elicited through a p53-independent mechanism, suggesting the possible extrapolation to many tumor cell lines. Last, we show that due to a likely cell-cycle-specific entry of marker genes into the nucleus, a highly biased cell-cycle distribution is observed in successfully transfected cells at early times following transfection. The importance of these issues in the interpretation as well as the design of transient transfection-based cell-cycle experiments is discussed. (C) 1999 Academic Press. C1 Harvard Univ, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Flemington, EK (reprint author), Harvard Univ, 44 Binney St, Boston, MA 02115 USA. OI Rodriguez Marquez, Antonio Andres/0000-0003-2455-6583 FU NIGMS NIH HHS [R01 GM48045] NR 15 TC 24 Z9 25 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 1 PY 1999 VL 272 IS 2 BP 171 EP 181 DI 10.1006/abio.1999.4156 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 222CX UT WOS:000081766800008 PM 10415086 ER PT J AU Martyn, JAJ Vincent, A AF Martyn, JAJ Vincent, A TI A new twist to myopathy of critical illness SO ANESTHESIOLOGY LA English DT Editorial Material DE acetylcholine receptor; anticholine receptor antibodies; critical illness; muscle weakness; myopathy; neuromuscular ID GUILLAIN-BARRE-SYNDROME; ACETYLCHOLINE-RECEPTORS; MYASTHENIA-GRAVIS; NEUROMUSCULAR-JUNCTION; GASTROCNEMIUS-MUSCLE; D-TUBOCURARINE; SEPSIS; RESPONSES; DISEASE; INJURY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02114 USA. Univ Oxford, John Radcliffe Hosp, Inst Mol Med, Neurosci Grp, Oxford OX3 9DS, England. RP Martyn, JAJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02114 USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 1999 VL 91 IS 2 BP 337 EP 339 DI 10.1097/00000542-199908000-00003 PG 3 WC Anesthesiology SC Anesthesiology GA 221KM UT WOS:000081726300002 PM 10443592 ER PT J AU Cohen, LG Fatalo, A Thompson, BT Bergeron, GD Flood, JG Poupolo, PR AF Cohen, LG Fatalo, A Thompson, BT Bergeron, GD Flood, JG Poupolo, PR TI Olanzapine overdose with serum concentrations SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID NEUROLEPTIC MALIGNANT SYNDROME AB Olanzapine, a new atypical antipsychotic drug, has been prescribed in the treatment of schizophrenia and psychotic mood disorders for approximately 2.3 million patients worldwide. Considering the increase in olanzapine prescriptions and the increased risk of suicide in this patient population, the number of reported cases of olanzapine overdose may be expected to increase. This report describes the clinical course and serum concentrations in a patient who consumed an olanzapine overdose (800 mg). Profound central nervous system depression and tachycardia without arrhythmia occurred within 2 hours after the ingestion. Additional clinical findings (ie, fever, mutism, agitation, dystonia, akathisia, elevated creatine kinase, and increased leukocyte count) were similar to those of neuroleptic malignant syndrome. After intubation, gut decontamination, and supportive care, the patient recovered and was discharged. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, Boston, MA 02114 USA. RP Cohen, LG (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Dept Psychiat, 15 Parkman St,WACC 725, Boston, MA 02114 USA. NR 17 TC 32 Z9 32 U1 0 U2 1 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 1999 VL 34 IS 2 BP 275 EP 278 DI 10.1016/S0196-0644(99)70243-X PG 4 WC Emergency Medicine SC Emergency Medicine GA 221JA UT WOS:000081722900026 PM 10424935 ER PT J AU Simon, JA Hudes, ES AF Simon, JA Hudes, ES TI Serum ascorbic acid and cardiovascular disease prevalence in US adults: The Third National Health and Nutrition Examination Survey (NHANES III) SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE antioxidants; ascorbic acid; coronary disease; stroke ID VITAMIN-C STATUS; LOW-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; LIPID-PEROXIDATION; ETHANOL-METABOLISM; E CONSUMPTION; AORTIC RINGS; PLASMA; RISK AB PURPOSE: To examine the relation between serum ascorbic acid concentration, which reflects dietary and supplement intake, and the prevalence of cardiovascular disease. METHODS: We analyzed data from 7658 men and women enrolled in thr Third National Health and Nutrition Examination Survey (NHANES III). We calculated odds ratios and 95% confidence intervals (CI) to estimate the relative prevalence of cardiovascular disease, defined as self-reported angina, myocardial infarction, or stroke. Because we detected an interaction between serum ascorbic acid concentration and alcohol intake, we performed analyses stratified by drinking status. RESULTS: Among participants who reported no alcohol consumption, serum ascorbic acid concentrations were not independently associated with cardiovascular disease prevalence. Among participants. who consumed alcohol, serum ascorbic acid concentrations consistent with tissue saturation (1.0-3.0 mg/dl) were associated with a decreased prevalence of angina (multivariate odds ratio (OR): 0.48; 95% CI: 0.23% to 1.03; p for trend = 0.06), but were not significantly associated with myocardial infarction or stroke prevalence. CONCLUSIONS: These results suggest the possibility of a biologic interaction between ascorbic acid and alcohol and that higher intakes of ascorbic acid may be associated with a decreased risk of angina among drinkers. Published by Elsevier Science Inc. C1 San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, Med Serv, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94143 USA. RP Simon, JA (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, Med Serv, 4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [HL53479] NR 50 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 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD AUG PY 1999 VL 9 IS 6 BP 358 EP 365 DI 10.1016/S1047-2797(99)00008-3 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 229GZ UT WOS:000082186300005 PM 10475535 ER PT J AU Kramer, PL Mineta, M Klein, C Schilling, K de Leon, D Farlow, MR Breakefield, XO Bressman, SB Dobyns, WB Ozelius, LJ Brashear, A AF Kramer, PL Mineta, M Klein, C Schilling, K de Leon, D Farlow, MR Breakefield, XO Bressman, SB Dobyns, WB Ozelius, LJ Brashear, A TI Rapid-onset dystonia-parkinsonism: Linkage to chromosome 19q13 SO ANNALS OF NEUROLOGY LA English DT Article ID TORSION DYSTONIA; PHENOTYPIC-EXPRESSION; ALPHA-SYNUCLEIN; BASAL GANGLIA; GENE; DISEASE; MUTATION; FAMILY; LOCUS AB Rapid-onset dystonia-parkinsonism (RPD) is an autosomal dominant movement disorder characterized by sudden onset of persistent dystonia and parkinsonism, generally during adolescence or early adulthood. Symptoms evolve over hours or days, and generally stabilize within a few weeks, with slow or no progression. Other features include little or no response to L-dopa, and low levels of homovanillic acid in the central nervous system. Neuroimaging studies indicate no degeneration of dopaminergic nerve terminals in RDP, suggesting that this disorder results from a functional deficit, as in dystonia, rather than neuronal loss, as in Parkinson's disease. We studied 81 members of two midwestern US families with RDP, 16 of whom exhibited classic features of RDP. We found significant evidence for linkage in these two families to markers on chromosome 19q13, with the highest multipoint LOD score at D19S198 (z = 5.77 at theta = 0.0). The flanking markers D19S587 and D19S900 define a candidate region of approximately 8 cM. Although RDP itself is a rare condition, it is important because it has clinical and biochemical similarities to both Parkinson's disease and dystonia. Identification of the genetic defect in RDP holds promise for understanding the underlying disease processes of both of these more common diseases. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. RP Kramer, PL (reprint author), Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. RI Brashear, Allison/G-3853-2015; OI Dobyns, William/0000-0002-7681-2844 FU NINDS NIH HHS [NS38372] NR 41 TC 53 Z9 55 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1999 VL 46 IS 2 BP 176 EP 182 DI 10.1002/1531-8249(199908)46:2<176::AID-ANA6>3.0.CO;2-2 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 224BU UT WOS:000081876900006 PM 10443882 ER PT J AU Hochman, II Zeitels, SM Heaton, JT AF Hochman, II Zeitels, SM Heaton, JT TI Analysis of the forces and position required for direct laryngoscopic exposure of the anterior vocal folds SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Broncho-Esophagological-Association CY MAY 11-12, 1998 CL PALM BEACH, FLORIDA SP Amer Broncho Esophagol Assoc DE airway management; endotracheal anesthesia; glottis; intubation; laryngoscope; laryngoscopy; vocal cords; vocal folds ID MANAGEMENT; CARCINOMA AB The sniffing position is traditionally considered optimal for direct laryngoscopic examination of the Vocal folds. This study examined head and neck positions associated with ideal exposure of the anterior glottal commissure with a variety of laryngoscopes. A prospective investigation was done in 20 patients by comparing the force required to expose the anterior vocal folds by utilizing 3 head and neck positions with 3 different-sized tubular laryngoscopes. The completeness of anterior glottal exposure was rated and the force required to achieve this exposure was measured with a strain gauge. Three positions relating the atlanto-occipital and cervicothoracic vertebrae were analyzed: 1) extension-extension, 2) sniffing: extension-flexion, and 3) flexion-flexion. Head and neck position and laryngoscope size were both statistically significant factors for achieving complete anterior vocal fold exposure. Regardless of the laryngoscope, the number of patients in whom complete exposure could be achieved increased gradually when the position was changed from extension-extension to extension-flexion to flexion-flexion. Complete exposure was inversely related to larger laryngoscope size. According to the data herein, the flexion-flexion position provides the best glottal exposure for endotracheal intubation in those patients who are anatomically predisposed to difficulty in direct examination of the glottis. Because this places the laryngoscope lumen in a vertical position, this position is inappropriate for microlaryngoscopy. The study reinforced the concept that the sniffing position is the optimal position for microlaryngoscopy because it enables the use of the largest-lumened laryngoscope. This facilitates ideal exposure of the anterior vocal folds, which is necessary for phonomicrosurgery. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 38 TC 49 Z9 51 U1 0 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD AUG PY 1999 VL 108 IS 8 BP 715 EP 724 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 224MT UT WOS:000081903400001 PM 10453776 ER PT J AU Jacobs, ML Buckley, MJ Liberthson, RL AF Jacobs, ML Buckley, MJ Liberthson, RL TI Combined Rastelli and atrial switch procedure: A 10-year follow-up SO ANNALS OF THORACIC SURGERY LA English DT Article ID VENTRICULAR SEPTAL-DEFECT; CORRECTED TRANSPOSITION; ALTERNATIVE APPROACH; REPAIR AB We performed a combined atrial (Mustard) and ventricular (Rastelli) repair on a previously palliated patient with situs inversus, atrioventricular discordance, ventricular septal defect, and pulmonary atresia. The suitability and durability of this operative strategy is supported by the satisfactory hemodynamic and functional status of the patient 10 years later. (C) 1999 by The Society of Thoracic Surgeons. C1 Deborah Heart & Lung Ctr, Dept Surg, Browns Mills, NJ 08015 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Jacobs, ML (reprint author), St Christophers Hosp Children, Sect Cardiothorac Surg, Erie Ave Front St, Philadelphia, PA 19134 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 1999 VL 68 IS 2 BP 570 EP 571 DI 10.1016/S0003-4975(99)00573-1 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 230LT UT WOS:000082253200062 PM 10475436 ER PT J AU Dewhirst, FE Chien, CC Paster, BJ Ericson, RL Orcutt, RP Schauer, DB Fox, JG AF Dewhirst, FE Chien, CC Paster, BJ Ericson, RL Orcutt, RP Schauer, DB Fox, JG TI Phylogeny of the defined murine microbiota: Altered Schaedler flora SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID LACTIC-ACID BACTERIA; SP-NOV; HELICOBACTER-HEPATICUS; LACTOBACILLUS-ACIDOPHILUS; FLEXISTIPES-SINUSARABICI; GASTROINTESTINAL-TRACT; GENUS BACTEROIDES; RIBOSOMAL-RNA; MICE; INFECTION AB The "altered Schaedler flora" (ASF) was developed for colonizing germfree rodents with a standardized microbiota, The purpose of this study was to identify each of the eight ASF strains by 16S rRNA sequence analysis. Three strains were previously identified as Lactobacillus acidophilus (strain ASP 360), Lactobacillus salivarius (strain ASF 361), and Bacteroides distasonis (strain ASF 519) based on phenotypic criteria. 16S rRNA analysis indicated that each of the strains differed from its presumptive identity. The 16S rRNA sequence of strain ASF 361 is essentially identical to the 16S rRNA sequences of the type strains of Lactobacillus murinis and Lactobacillus animalis (both isolated from mice), and all of these strains probably belong to a single species. Strain ASF 360 is a novel lactobacillus that clusters with L. acidophilus and Lactobacillus lactis. Strain ASF 519 falls into an unnamed genus containing [Bacteroides] distasonis, [Bacteroides] merdae, [Bacteroides] forsythus, and CDC group DF-3. This unnamed genus is in the Cytophaga-Flavobacterium-Bacteroides phylum and is most closely related to the genus Porphyromonas. The spiral-shaped strain, strain ASF 457, is in the Flexistipes phylum and exhibits sequence identity with rodent isolates of Robertson. The remaining four ASF strains, which are extremely oxygen-sensitive fusiform bacteria, group phylogenetically with the low-G+C-content gram-positive bacteria (Firmicutes, Bacillus-Clostridium group). ASF 356, ASF 492, and ASP 502 fall into Clostridium cluster XIV of Collins et al. Morphologically, ASF 492 resembles members of this cluster, Roseburia cecicola, and Eubacterium plexicaudatum. The 16S rRNA sequence of ASF 492 is identical to that of E. plexicaudatum. Since the type strain and other viable original isolates of E. plexicaudatum have been lost, strain ASF 492 is a candidate for a neotype strain. Strain ASF 500 branches deeply in the low-G+C-content gram-positive phylogenetic tree but is not closely related to any organisms whose 16S rRNA sequences are currently in the GenBank database. The 16S rRNA sequence information determined in the present study should allow rapid identification of ASP strains and should permit detailed analysis of the interactions of ASF organisms during development of intestinal disease in mice that are coinfected with a variety of pathogenic microorganisms. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Dent Ctr, Dept Mol Genet, Boston, MA 02115 USA. Biomed Res Associates, Frederick, MD 21702 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Rm 825C, Cambridge, MA 02139 USA. FU NCI NIH HHS [P01 CA026731, R01 CA067529]; NIDCR NIH HHS [R01 DE011443, R01 DE010374, R01DE-10374, R01DE-11443]; NIDDK NIH HHS [R01 DK052413, R01DK52413] NR 57 TC 191 Z9 198 U1 1 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD AUG PY 1999 VL 65 IS 8 BP 3287 EP 3292 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 223WR UT WOS:000081865000004 PM 10427008 ER PT J AU Park, SS Vallar, RV Hong, CH von Gunten, S Ruoff, K D'Amico, DJ AF Park, SS Vallar, RV Hong, CH von Gunten, S Ruoff, K D'Amico, DJ TI Intravitreal dexamethasone effect on intravitreal vancomycin elimination in endophthalmitis SO ARCHIVES OF OPHTHALMOLOGY 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 STAPHYLOCOCCUS-EPIDERMIDIS ENDOPHTHALMITIS; TIME COURSE; INFLAMMATION; INJECTION; GENTAMICIN; ENDOTOXIN; RABBITS AB Objective: To determine whether intravitreal dexamethasone administration can alter the elimination of intravitreal vancomycin hydrochloride in rabbit eyes with experimental Streptococcus pneumoniae endophthalmitis. Methods: Albino rabbits were infected with an intravitreal inoculum of S pneumoniae (2 X 10(3) colony-forming units) and randomized after 24 hours to treatment with intravitreal vancomycin hydrochloride (1 mg), alone or in combination with intravitreal dexamethasone (400 mu g). For comparison, uninfected eyes were similarly treated. All eyes were enucleated 24, 48, or 72 hours after treatment, and vitreous levels of vancomycin were quantitated using a fluorescence polarizing immunoassay. Results: The half-life of intravitreal vancomycin in infected eyes was prolonged from 48 to 84 hours when eyes were treated with dexamethasone. Conversely, such treatment shortened the half-life in uninfected eyes from 56 to 42 hours. Conclusions: Intravitreal dexamethasone administration reduces the elimination of intravitreal vancomycin in rabbit eyes with pneumococcal endophthalmitis, whereas an opposite effect is noted in uninfected eyes. Clinical Relevance: In patients with eyes having endophthalmitis caused by virulent organisms, the elimination of intravitreal vancomycin may be reduced when intraocular inflammation is minimized with corticosteroid therapy. This may enhance the efficacy of intravitreal vancomycin therapy in treating the infection. C1 Univ Texas, SW Med Ctr, Dept Ophthalmol, Dallas, TX USA. Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Microbiol Lab, Boston, MA 02114 USA. RP Park, SS (reprint author), Permanente Med Grp Inc, Dept Retina, 1650 Response Rd, Sacramento, CA 95815 USA. NR 21 TC 26 Z9 27 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 1999 VL 117 IS 8 BP 1058 EP 1062 PG 5 WC Ophthalmology SC Ophthalmology GA 225DY UT WOS:000081944200009 PM 10448749 ER PT J AU Merbs, SL Harris, LL Iwamoto, MA Iliff, NT AF Merbs, SL Harris, LL Iwamoto, MA Iliff, NT TI Prevention of prolapsed silicone stents in lacrimal intubation using an intrasac fixation suture SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID COMPLICATIONS; SURGERY AB Silicone stents are routinely used for the maintenance of patent mucosal passages in patients with nasolacrimal disorders, A common complication associated with the use of silicone stents is lateral migration or displacement of the tubes, which can be difficult to correct. This report describes a modified Quickert-Dryden approach with fixation of the tubes by an intrasac suture. From 1990 to 1996, 53 patients had silicone stents placed by this method with no complications related to tube displacement. The intrasac fixation suture has distinct advantages over other fixation methods. C1 Johns Hopkins Univ, Wilmer Eye Inst, Sch Med, Oculoplast Div, Baltimore, MD 21287 USA. Coastal Carolina Eye Ctr, Wilmington, NC USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. Ophthalm Consultants Boston, Boston, MA USA. RP Iliff, NT (reprint author), Johns Hopkins Univ, Wilmer Eye Inst, Sch Med, Oculoplast Div, 600 N Wolfe St, Baltimore, MD 21287 USA. NR 11 TC 6 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 1999 VL 117 IS 8 BP 1092 EP 1095 PG 4 WC Ophthalmology SC Ophthalmology GA 225DY UT WOS:000081944200021 PM 10448761 ER PT J AU Kao, GD Devine, P Mirza, N AF Kao, GD Devine, P Mirza, N TI Oral cavity and oropharyngeal tumors in human immunodeficiency virus-positive patients - Acute response to radiation therapy SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID HIV-1 INFECTION; PROGNOSIS; AIDS AB Background: The survival of patients with human immunodeficiency virus (HIV) has improved considerably with modern medical management. However, there remains surprisingly little information on treating head and neck neoplasms in HIV-positive patients. Objective: To report our recent experience treating oral cavity and oropharyngeal tumors in HIV-positive patients. Design and Patients: Retrospective analysis of a cohort of 8 HIV-positive patients with Kaposi sarcoma (KS), lymphoma, or squamous carcinoma of the oral cavity or oropharynx who were consecutively treated during a single year with radiation therapy at a tertiary care referral center. Length of follow-up was at least 2 years (mean, 2.5 years). Results: All patients had partial and complete responses to treatment lasting until the last follow-up. However, we found that treatment was considerably better tolerated by patients with non-KS tumors, with fewer acute reactions and significantly less weight loss, despite larger treatment volumes and higher radiation doses, compared with patients with KS. Patients with non-KS tumors received a mean radiation dose of 62.6 Gy to 2636 cm(3), yet lost only a mean of 0.1 kg in weight, whereas patients with KS were treated with a mean radiation dose of 19 Gy to a mean volume of 568 cm(3), but lost a mean of 5.8 kg during treatment (P =.005) and on average sustained an additional grade of severity on a standard scale of mucosal reaction (P =.01). Conclusions: Oral cavity and oropharyngeal tumors in HIV-positive patients respond to radiation therapy, but there is a marked difference in the degree of acute reactions to treatment between patients with and without KS. Infection with HIV is not a contraindication when aggressive radiation therapy is needed in select patients. C1 Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA USA. Vet Affairs Med Ctr, Dept Otolaryngol, Philadelphia, PA USA. Vet Affairs Med Ctr, Dept Head & Neck Surg, Philadelphia, PA USA. RP Kao, GD (reprint author), Hosp Univ Penn, Dept Radiat Oncol, 2 Donner,3400 Spruce St, Philadelphia, PA 19104 USA. NR 13 TC 20 Z9 20 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 1999 VL 125 IS 8 BP 873 EP 876 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 224LV UT WOS:000081901300007 PM 10448734 ER PT J AU Bursell, JP Little, JW Stiens, SA AF Bursell, JP Little, JW Stiens, SA TI Electrodiagnosis in spinal cord injured persons with new weakness or sensory loss: Central and peripheral etiologies SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Physical-Medicine-and-Rehabilitation CY OCT-NOV -, 1995 CL ORLANDO, FLORIDA SP Amer Acad Phys Med & Rehabilitat ID POSTTRAUMATIC SYRINGOMYELIA; CYSTIC MYELOPATHY; UPPER EXTREMITY; QUADRIPLEGIA; PARAPLEGIA AB Objective: To assess the prevalence and causes of late neurologic decline of persons with spinal cord injury (SCI). Design: Retrospective review of persons with SCI over a 9-year period. Those with complaints of new weakness or sensory loss were grouped into three categories based on clinical examination, electrodiagnosis, and imaging: (1) central pathology (ie, brain, spinal cord, or nerve root); (2) peripheral pathology (plexus or peripheral nerve); or (3) no identifiable etiology. The specific diagnoses of late neurologic decline were identified. Setting: Regional Veterans Affairs Spinal Cord Injury Service. Patients: Five hundred two inpatient and outpatient adults with SCI. Results: Nineteen percent of the study population complained of new weakness and/or sensory loss. Neurologic abnormalities were noted in 13.5%, 7.2% with central and 6.4% with peripheral causes. The most common pathologies were posttraumatic syringomyelia (2.4%) and cervical (1.6%) and lumbosacral (1.2%) myelopathy/radiculopathy. A specific etiology was not determined in 6 cases (1.6%). Peripheral involvement was mostly from ulnar nerve entrapment (3.4%) and carpal tunnel syndrome (3.0%). Conclusions: Late-onset neurologic decline is common after SCI and can result from central or peripheral pathology. Regular neurologic monitoring of SCI patients is recommended, since many with neurologic decline respond favorably if diagnosed and treated early. C1 VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Bursell, JP (reprint author), VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA 98108 USA. NR 29 TC 11 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD AUG PY 1999 VL 80 IS 8 BP 904 EP 909 DI 10.1016/S0003-9993(99)90081-3 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 224VB UT WOS:000081919700007 PM 10453766 ER PT J AU Boninger, ML Cooper, RA Baldwin, MA Shimada, SD Koontz, A AF Boninger, ML Cooper, RA Baldwin, MA Shimada, SD Koontz, A TI Wheelchair Pushrim kinetics: Body weight and median nerve function SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID CARPAL-TUNNEL SYNDROME; SPINAL-CORD INJURIES; RISK-FACTORS; UPPER EXTREMITY; PROPULSION; PREVALENCE; ENTRAPMENTS; CONDUCTION; DYNAMICS; FORCES AB Objectives: Individuals who use manual wheelchairs are at high risk for median nerve injury and subsequent carpal tunnel syndrome (CTS), To gain a better understanding of the mechanism behind CTS in manual wheelchair users, this study examined the relation between (1) pushrim biomechanics and function of the median nerve, (2) pushrim biomechanics and subject characteristics, and (3) median nerve function and subject characteristics. Design: Case series. Setting: Biomechanics laboratory and an electromyography laboratory. Participants: Thirty-four randomly recruited individuals with paraplegia who use a manual wheelchair for mobility. Intervention: Subjects propelled their own wheelchair on a dynamometer at 0.9m/sec and 1.8m/sec. Bilateral biomechanical data were obtained using a force- and moment-sensing pushrim and a motion analysis system, Bilateral nerve conduction studies focusing on the median nerve were also completed. Main Outcome Measures: Pearson's correlation coefficients between subject characteristics, median nerve conduction studies, and propulsion biomechanics; a regression model of nerve conduction studies incorporating subject characteristics and pushrim biomechanics. Results: Subject weight was significantly related to median nerve latency (r = .36, p = .03) and median sensory amplitude (r = -.43, p = .01). Height was also significantly related to median sensory amplitude (r = -.58, p = .01). Subject weight was significantly related to the peak resultant force applied to the pushrim (r = .59, p < .001). Height, weight, and weight-normalized pushrim forces were successfully incorporated into a linear regression model predicting median sensory amplitude (r = .63,p < .05) and mean median latency (r = .54, p < .05), Conclusion: This study found subject weight to be related to pushrim forces and median nerve function. Independent of subject weight, pushrim biomechanics were also related to median nerve function. Through weight loss and changes in pushrim biomechanics, it may be possible to prevent median nerve injury in manual wheelchair users. (C) 1999 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Univ Pittsburgh, Div Phys Med & Rehabil, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ So Calif, Biomech Lab, Sacramento, CA USA. RP Boninger, ML (reprint author), Univ Pittsburgh, Div Phys Med & Rehabil, Suite 901 Kaufmann Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA. OI Boninger, Michael/0000-0001-6966-919X FU NICHD NIH HHS [K08 HD01122-01, 5 P01 HD33989 03] NR 32 TC 142 Z9 143 U1 1 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD AUG PY 1999 VL 80 IS 8 BP 910 EP 915 DI 10.1016/S0003-9993(99)90082-5 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 224VB UT WOS:000081919700008 PM 10453767 ER PT J AU Escalante, A Lichtenstein, MJ Hazuda, HP AF Escalante, A Lichtenstein, MJ Hazuda, HP TI Determinants of shoulder and elbow flexion range: Results from the San Antonio Longitudinal Study of Aging SO ARTHRITIS CARE AND RESEARCH LA English DT Article DE shoulder; elbow; joint range of motion; diabetes; Mexican Americans ID LIMITED JOINT MOBILITY; DIABETES-MELLITUS; MEXICAN-AMERICANS; COMPLICATIONS; PAIN; COLLAGEN; OBESITY AB Objective. To gain a knowledge of factors associated with impaired upper extremity range of motion (ROM) in order to understand pathways that lead to disability. Methods. Shoulder and elbow flexion range was measured in a cohort of 695 community-dwelling subjects aged 65 to 74 years. Associations between subjects' shoulder and elbow flexion ranges and their demographic and anthropometric characteristics, as well as the presence of diabetes mellitus or self-reported physician-diagnosed arthritis, were examined using multivariate regression models. The relationship between shoulder or elbow flexion range and subjects' functional reach was examined to explore the functional significance of ROM in these joints. Results. The flexion range for the 4 joints studied was at least 120 degrees in nearly all subjects (greater than or equal to 99% of the subjects for each of the 4 joints). Multivariate models revealed significant associations between male sex, Mexican American ethnic background, the use of oral hypoglycemic drugs or insulin to treat diabetes mellitus, and a lower shoulder flexion range. A lower elbow flexion range was associated with male sex, increasing body mass index, and the use of oral hypoglycemic drugs or insulin. A higher shoulder or elbow flexion range was associated with a lower likelihood of having a short functional reach. Conclusions. The great majority of community-dwelling elderly have a flexion range of shoulder and elbow joints that can be considered functional. Diabetes mellitus and obesity are two potentially treatable factors associated with reduced flexion range of these two functionally important joints. C1 Univ Texas, Hlth Sci Ctr, Div Clin Immunol & Rheumatol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Audie L Murphy Div, Geriatr Res & Educ Clin Ctr, San Antonio, TX USA. RP Hazuda, HP (reprint author), 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCRR NIH HHS [M01-RR-01346]; NIA NIH HHS [1-RO1-AG-10444] NR 33 TC 14 Z9 14 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-7524 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD AUG PY 1999 VL 12 IS 4 BP 277 EP 286 DI 10.1002/1529-0131(199908)12:4<277::AID-ART6>3.0.CO;2-5 PG 10 WC Rheumatology SC Rheumatology GA 225NX UT WOS:000081968600006 PM 10689992 ER PT J AU Otto, MW Pollack, MH Penava, SJ Zucker, BG AF Otto, MW Pollack, MH Penava, SJ Zucker, BG TI Group cognitive-behavior therapy for patients failing to respond to pharmacotherapy for panic disorder: a clinical case series SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article; Proceedings Paper CT Meeting of the Association-for-Advancement-of-Behavior-Therapy CY NOV 13-16, 1997 CL MIAMI BEACH, FLORIDA SP Assoc Advancement Behav Therapy DE cognitive-behavior therapy; behavior therapy; panic disorder; nonresponders; treatment-resistance; pharmacotherapy ID CONCURRENT MEDICATION TREATMENT; AGORAPHOBIA; METAANALYSIS; ALPRAZOLAM; EXPOSURE AB The last decade has brought exciting advances to the treatment of panic disorder and agoraphobia, and a variety of cognitive-behavioral and pharmacologic treatment strategies offer clear benefit to patients. Nonetheless, treatment nonresponse continues to be a chronic problem, and additional strategies are needed to aid patients who do not respond fully to initial interventions. In the present study, we use 'services' research to document the clinical response of pharmacotherapy nonresponders to a standard program of brief, group cognitive-behavioral therapy. Patients responded well, regardless of whether they had received a full, adequate trial of pharmacotherapy. In addition to its application as an initial treatment for panic disorder, routine application of cognitive-behavioral therapy in pharmacologic treatment algorithms is encouraged, with attention to referral of pharmacotherapy nonresponders to cognitive-behavioral therapy. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, 15 Parkman St, Boston, MA 02114 USA. NR 27 TC 58 Z9 59 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD AUG PY 1999 VL 37 IS 8 BP 763 EP 770 DI 10.1016/S0005-7967(98)00176-4 PG 8 WC Psychology, Clinical SC Psychology GA 220EW UT WOS:000081652400004 PM 10452176 ER PT J AU Fruman, DA Snapper, SB Yballe, CM Alt, FW Cantley, LC AF Fruman, DA Snapper, SB Yballe, CM Alt, FW Cantley, LC TI Phosphoinositide 3-kinase knockout mice: role of p85 alpha in B cell development and proliferation SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Colloquium on Phospholipids - Regulators of Membrane Traffic and Signalling CY APR 07-09, 1999 CL UNIV GLASGOW, GLASGOW, SCOTLAND SP Eschelon Res Lab, Eli Lilly & Co, Gatsby Charitable Fdn, Merck Sharpe & Dohme, Novartis, SmithKline Beecham, Unilever, Yamanouchi Res Inst, Zeneca HO UNIV GLASGOW ID X-LINKED AGAMMAGLOBULINEMIA; BRUTONS TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3'-KINASE; REGULATORY SUBUNIT; CATALYTIC SUBUNIT; FAMILY; TRANSFORMATION; ASSOCIATION; ACTIVATION; BINDING C1 Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Fruman, DA (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Transduct, HIM 1007,330 Brookline Ave, Boston, MA 02215 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM041890] NR 29 TC 21 Z9 21 U1 1 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD AUG PY 1999 VL 27 IS 4 BP 624 EP 629 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 230RF UT WOS:000082263600053 PM 10917654 ER PT J AU Muratoglu, OK Bragdon, CR O'Connor, DO Jasty, M Harris, WH Gul, R McGarry, F AF Muratoglu, OK Bragdon, CR O'Connor, DO Jasty, M Harris, WH Gul, R McGarry, F TI Unified wear model for highly crosslinked ultra-high molecular weight polyethylenes (UHMWPE) SO BIOMATERIALS LA English DT Article DE UHMWPE; total hip arthroplasty; wear; crosslinking ID CROSS-LINKING AB Crosslinking has been shown to improve the wear resistance of ultra-high molecular weight polyethylene in both in vitro and clinical in vivo studies. The molecular mechanisms and material properties that are responsible for this marked improvement in wear resistance are still not well understood. In fact, following crosslinking a number of mechanical properties of UHMWPE are decreased including toughness, modulus, ultimate tensile strength, yield strength, and hardness. In general, these changes would be expected to constitute a precursor for lower wear resistance, presenting a paradox in that wear resistance increases with crosslinking. In order to understand better and to analyze this paradoxical behaviour of crosslinked UHMWPE, we investigated the wear behavior of (i) radiation-crosslinked GUR 1050 resin, (ii) peroxide-crosslinked GUR 1050 resin and (iii) peroxide-crosslinked Himont 1900 resin using a bi-directional pin-on-disk (POD) machine. Wear behavior was analyzed as a function of crystallinity, ultimate tensile strength (UTS), yield strength (YS), and molecular weight between crosslinks (M-c). The crosslink density increased with increasing radiation dose level and initial peroxide content. The UTS, YS, and crystallinity decreased with increasing crosslink density. While these variations followed the same trend, the absolute changes as a function of crosslink density were different for the three types of crosslinked UHMWPE studied. There was no unified correlation for the wear behavior of the three types of crosslinked UHMWPE with the crystallinity, UTS and YS. However, the POD wear rate showed the identical linear dependence on M-c with all three types of crosslinked UHMWPEs studied. Therefore, we have strong evidence to propose that M-c or crosslink density is a fundamental material property that governs the lubricated adhesive and abrasive wear mechanisms of crosslinked UHMWPEs, overriding the possible effects of other material properties such as UTS, US and crystallinity on the wear behavior. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. MIT, Dept Mat Sci & Engn, Cambridge, MA 02141 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, GRJ 1206, Boston, MA 02114 USA. NR 21 TC 251 Z9 256 U1 6 U2 53 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD AUG PY 1999 VL 20 IS 16 BP 1463 EP 1470 DI 10.1016/S0142-9612(99)00039-3 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 232EB UT WOS:000082355500003 PM 10458559 ER PT J AU Makino, CL Groesbeek, M Lugtenburg, J Baylor, DA AF Makino, CL Groesbeek, M Lugtenburg, J Baylor, DA TI Spectral tuning in salamander visual pigments studied with dihydroretinal chromophores SO BIOPHYSICAL JOURNAL LA English DT Article ID MONKEY MACACA-FASCICULARIS; RESONANCE RAMAN MICROPROBE; SCHIFF-BASE COUNTERION; BOVINE RHODOPSIN; WAVELENGTH REGULATION; CONE PIGMENT; RETINAL CHROMOPHORE; BETA-IONONE; AMINO-ACIDS; SENSITIVITY AB In visual pigments, opsin proteins regulate the spectral absorption of a retinal chromophore by mechanisms that change the energy level of the excited electronic state relative to the ground state. We have studied these mechanisms by using photocurrent recording to measure the spectral sensitivities of individual red rods and red (long-wavelength-sensitive) and blue (short-wavelength-sensitive) cones of salamander before and after replacing the native 3-dehydro 11-cis retinal chromophore with retinal analogs: 11-cis retinal, 3-dehydro g-cis retinal, 9-cis retinal, and 5,6-dihydro 9-cis retinal. The protonated Schiff's bases of analogs with unsaturated bonds in the ring had broader spectra than the same chromophores bound to opsins. Saturation of the bonds in the ring reduced the spectral bandwidths of the protonated Schiff's bases and the opsin-bound chromophores and made them similar to each other. This indicates that torsion of the ring produces spectral broadening and that torsion is limited by opsin. Saturating the 5,6 double bond in retinal reduced the perturbation of the chromophore by opsin in red and in blue cones but not in red rods. Thus an interaction between opsin and the chromophoric ring shifts the spectral maxima of the red and blue cone pigments, but not that of the red rod pigment. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Leiden State Univ, Dept Chem, NL-2300 RA Leiden, Netherlands. Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA. RP Makino, CL (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY01543, EY11358, F32 EY06195] NR 90 TC 30 Z9 31 U1 0 U2 5 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 1999 VL 77 IS 2 BP 1024 EP 1035 PG 12 WC Biophysics SC Biophysics GA 224VK UT WOS:000081920500034 PM 10423447 ER PT J AU Li, JZ Xia, YP Kuter, DJ AF Li, JZ Xia, YP Kuter, DJ TI Interaction of thrombopoietin with the platelet c-mpl receptor in plasma: binding, internalization, stability and pharmacokinetics SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE thrombopoietin; c-mpl; pharmacokinetics; platelets; receptor ID HUMAN MEGAKARYOCYTE GROWTH; IN-VITRO; INDUCED THROMBOCYTOPENIA; NONHUMAN-PRIMATES; PROGENITOR CELLS; LIGAND; MICE; REGULATOR; IDENTIFICATION; CHEMOTHERAPY AB Thrombopoietin (TPQ) is the primary regulator of platelet production and acts through binding its receptor, c-mpl, found on megakaryocyte progenitor cells, megakaryocytes and platelets, Circulating levels of TPO are regulated primarily by the clearance of TPO after it binds to c-mpl receptors on circulating platelets. In this study the interaction of TPO with the platelet c-mpl receptor has been analysed under physiological conditions using radiochemical and pharmacokinetic approaches. I-125-rHuTpO was prepared using a novel method of gentle iodination that preserved its biological activity and used to demonstrate that platelets, but not endothelial cells, have a single class of binding sites (56 +/- 17 binding sites/platelet) with high affinity (K-d = 163 +/- 31 pM). Cross-linking experiments confirmed that TPO, but not erythropoietin (EPO), specifically associated with the 95 kD platelet c-mpl receptor, Upon addition of TPO to platelets, 80% of the TPO binding sites were internalized within an hour and were not recycled. TPO that was not bound by platelets was stable for up to 6d in both platelet-poor and platelet-rich plasma, Using unlabelled recombinant human TPO (rHuTPO), standard pharmacokinetic analysis demonstrated that platelets have an average TPO clearance of 1.24 +/- 0.38 ml/h/10(9) platelets and that TPO clearance was reduced by low temperature but not by a number of drugs or metabolic inhibitors. The maximal amount of TPO removed by platelets in vitro was identical to that predicted by the total number of TPO binding sites. These results provide a biochemical and pharmacokinetic basis for the clinical use of TPO and for understanding possible disorders of platelet production. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, 100 Blossom St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL54838] NR 53 TC 95 Z9 96 U1 1 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 1999 VL 106 IS 2 BP 345 EP 356 DI 10.1046/j.1365-2141.1999.01571.x PG 12 WC Hematology SC Hematology GA 227TP UT WOS:000082096300010 PM 10460590 ER PT J AU Raymond, JR Mukhin, YV Gettys, TW Garnovskaya, MN AF Raymond, JR Mukhin, YV Gettys, TW Garnovskaya, MN TI The recombinant 5-HT1A receptor: G protein coupling and signalling pathways SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Review DE 5-hydroxytryptamine; transfection; G protein; adenylyl cyclase; phospholipase; calcium; efficacy; potency ID BETA-ADRENERGIC-RECEPTOR; GAMMA-S BINDING; HUMAN 5-HYDROXYTRYPTAMINE(1A) RECEPTOR; AGONIST-INDUCED DESENSITIZATION; HAMSTER OVARY CELLS; KINASE-C; ADENYLATE-CYCLASE; RAT HIPPOCAMPUS; FUNCTIONAL EXPRESSION; SEROTONIN RECEPTOR AB The 5-hydroxytryptamine 5-HT1A receptor was one of the first G protein coupled receptors whose cDNA and gene were isolated by molecular cloning methods. Transfection of the cDNA of this receptor into cells previously bearing no 5-HT receptors has resulted in the acquisition of large amounts of information regarding potential signal transduction pathways linked to the receptor, correlations of receptor structure to its various functions, and pharmacological properties of the receptor. Transfection studies with the 5-HT1A receptor have generated critical new information that might otherwise have been elusive. This information notably includes the discovery of unsuspected novel signalling linkages, the elucidation of the mechanisms of receptor desensitization, the refinement of models of the receptor pharmacophore, and the development of silent receptor antagonists, among others. The current review summarizes the most important studies of the recombinant 5-HT1A receptor in the decade since the identificiation of its cDNA. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Gastroenterol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. RP Raymond, JR (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Room 829 CSB,171 Ashley Ave, Charleston, SC 29425 USA. OI Gettys, Thomas/0000-0001-7125-7995 FU NIDDK NIH HHS [DK53891, DK52448, R01 DK052448, R56 DK052448] NR 155 TC 163 Z9 166 U1 1 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD AUG PY 1999 VL 127 IS 8 BP 1751 EP 1764 DI 10.1038/sj.bjp.0702723 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 231LW UT WOS:000082312500001 PM 10482904 ER PT J AU Carapeti, M Aguiar, RCT Watmore, AE Goldman, JM Cross, NCP AF Carapeti, M Aguiar, RCT Watmore, AE Goldman, JM Cross, NCP TI Consistent fusion of MOZ and TIF2 in AML with inv(8)(p11q13) SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACETYLTRANSFERASE AB We have recently cloned the inv(8)(p11q13) in a patient with acute myeloid leukemia (AML), and demonstrated a fusion between the MOZ and TIF2 genes at 8p11 and 8q13, respectively. We have partially characterized a further case of AML with the same karyotypic abnormality. Rearrangements were detected by Southern blotting with a TIF2 probe that rr as close to the breakpoint in the original inv(8) case and with a MOZ probe corresponding to the breakpoint cluster region in the t(8;16) (p11;p13). These findings indicate the existence of breakpoint cluster regions within both genes and demonstrate that the MOZ-TIF2 fusion is consistently associated with the inv(8)(p11q13). (C) Elsevier Science Inc., 1999. All rights reserved. C1 Hammersmith Hosp, Imperial Coll Sch Med, Dept Haematol, London W12 0NN, England. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA USA. N Trent cytogenet Serv, Ctr Human Genet, Sheffield, S Yorkshire, England. RP Cross, NCP (reprint author), Hammersmith Hosp, Imperial Coll Sch Med, Dept Haematol, Du Cane Rd, London W12 0NN, England. RI Cross, Nicholas/B-4817-2009 OI Cross, Nicholas/0000-0001-5481-2555 NR 9 TC 41 Z9 41 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD AUG PY 1999 VL 113 IS 1 BP 70 EP 72 DI 10.1016/S0165-4608(99)00007-2 PG 3 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 226YG UT WOS:000082050300013 PM 10459350 ER PT J AU Fournier, MV Guimaraes, FC Paschoal, MEM Ronco, LV Carvalho, MDC Pardee, AB AF Fournier, MV Guimaraes, FC Paschoal, MEM Ronco, LV Carvalho, MDC Pardee, AB TI Identification of a gene encoding a human oxysterol-binding protein-homologue: A potential general molecular marker for blood dissemination of solid tumors SO CANCER RESEARCH LA English DT Article ID POLYMERASE-CHAIN-REACTION; HUMAN PAPILLOMAVIRUS TYPE-16; DIFFERENTIAL DISPLAY; EPITHELIAL-CELLS; MESSENGER-RNA; CANCER-CELLS; SUFFICIENT; CLONING; LINES; CYCLE AB This study describes a new potential role in human cancer for a gene, HLM, isolated by differential display, that bears homology to an oxysterol-binding protein. A significant association between increased expression of HLM with metastatic disease was found. HLM mRNA levels were increased in circulating tumor cells in patients' peripheral blood and in primary human epithelial cells expressing the human papillomavirus16 E6 and E7 proteins. HLM mRNA was not detected in most normal human tissues, including peripheral blood and lymph node. These findings indicate that HLM may function as a potential marker for tumor dissemination. C1 Dana Farber Canc Inst, Cell Growth & Regulat Div, Boston, MA 02115 USA. Univ Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Lab Control Gene Express, Inst Biofis Carlos Chagas Filho, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Mol Oncol Lab, Rio De Janeiro, Brazil. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Fournier, MV (reprint author), New England Med Ctr, Dept Radiat Oncol, Box 824,750 Washington St, Boston, MA 02111 USA. OI carvalho, maria da gloria/0000-0001-5890-8095 NR 27 TC 44 Z9 44 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1999 VL 59 IS 15 BP 3748 EP 3753 PG 6 WC Oncology SC Oncology GA 224GT UT WOS:000081890200037 PM 10446991 ER PT J AU Griffon-Etienne, G Boucher, Y Brekken, C Suit, HD Jain, RK AF Griffon-Etienne, G Boucher, Y Brekken, C Suit, HD Jain, RK TI Taxane-induced apoptosis decompresses blood vessels and lowers interstitial fluid pressure in solid tumors: Clinical implications SO CANCER RESEARCH LA English DT Article ID ANTITUMOR-ACTIVITY; MITOTIC ARREST; BREAST-CANCER; PHASE-II; ANGIOGENESIS; HYPERTENSION; PACLITAXEL; DOCETAXEL; TAXOL; RADIORESPONSE AB Elevated tuner interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, The etiology of tumor interstitial hypertension is poorly understood. We have postulated that the solid stress generated by tumor cells growing in a confined space compresses blood vessels and increases tumor microvascular pressure and IFP. To test the hypothesis that neoplastic cell loss would decompress blood vessels and lower IFP, we induced apoptosis in tumors with paclitaxel and docetaxel, Taxanes inhibited the growth of the murine mammary carcinoma (MCa-IV) and of the human soft tissue sarcoma (HSTS-26T), Taxanes induced apoptosis and reduced the density of intact neoplastic cells in both MCa-IV and HSTS-26T, To determine whether neoplastic cell loss decompressed blood vessels, we measured the diameter of tumor vessels in HSTS-26T tumors implanted in transparent dorsal skin fold chambers, At 48 and 96 h after paclitaxel, the diameter of tumor vessels was significantly increased. The increase in vascular diameters was associated with reductions in microvascular pressure and IFP. The changes in neoplastic cell density and IFP were also correlated. In the human glioblastoma U87, which is resistant to paclitaxel, the IFP and cellular density were not modified by paclitaxel treatment. Collectively, these results support the hypothesis that solid stress generated by neoplastic cell proliferation increases vascular resistance and IFP. The increase in vessel diameter induced by paclitaxel and docetaxel suggests that taxanes could improve tumor response by increasing the vascular surface area for delivery of therapeutic agents. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. Debiopharm SA, CH-1003 Lausanne, Switzerland. Norwegian Univ Sci & Technol, N-7034 Trondheim, Norway. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Cox-7, Boston, MA 02114 USA. FU NCI NIH HHS [CA-13311, R35-CA-56591] NR 33 TC 219 Z9 223 U1 2 U2 22 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 1999 VL 59 IS 15 BP 3776 EP 3782 PG 7 WC Oncology SC Oncology GA 224GT UT WOS:000081890200041 PM 10446995 ER PT J AU Prabhu, SD AF Prabhu, SD TI Load sensitivity of left ventricular relaxation in normal and failing hearts: evidence of a nonlinear biphasic response SO CARDIOVASCULAR RESEARCH LA English DT Article DE heart failure; ventricular function; cardiomyopathy; contractile function; hemodynamics ID TACHYCARDIA-INDUCED CARDIOMYOPATHY; END-SYSTOLIC PRESSURE; CLOSED-CHEST DOGS; CONSCIOUS DOGS; MYOCARDIAL RELAXATION; DIASTOLIC FUNCTION; VOLUME; DETERMINANTS; FAILURE; EJECTION AB Objective: This investigation sought to define the effect of heart failure (HF) on the load sensitivity of left ventricular (LV) relaxation and to correlate alterations in load sensitivity with the variables of ejection timing, systolic load profile and elastic recoil. Methods: Nine dogs instrumented with LV micromanometers and piezoelectric crystals were studied before and after HF produced by prolonged rapid LV pacing. After pharmacologic autonomic blockade and atrial pacing at 160 bpm, hemodynamic measurements were recorded at steady-state and during vena caval occlusion. LV relaxation for individual beats during caval occlusion was assessed using tau, the monoexponential time constant, and systolic load was estimated using end-systolic circumferential force (ESF). Results: The tau-ESF relation was nonlinear and biphasic, with an initial decrease in tau followed by a delayed increase, and was described by a parabolic equation with a curvilinearity coefficient a. Examination of ejection variables and systolic load profile indicated that the initial acceleration of relaxation reflected the influence of increased elastic recoil, whereas the late slowing reflected the influence of earlier end-ejection and delayed systolic loading. HF produced significant baseline prolongations of tau (P<0.005), time to relaxation onset (P<0.001) and time to peak force (P<0.015) compared to control. The curvilinearity coefficient of the tau-ESF relation was significantly increased (18.1+/-20.1.10(-5) vs. 3.99+/-2.89.10(-5) g(-2), P=0.048), indicating increased load sensitivity of relaxation. This increased load sensitivity correlated with delayed onset but increased overall magnitude of the effects of earlier end-ejection and late systolic loading on relaxation. Conclusions: The tau-ESF relationship during transient load reduction is nonlinear and biphasic with an initial acceleration of relaxation, reflecting the impact of elastic recoil, and delayed slowing, reflecting changes in ejection timing and systolic loading sequence. This relation is more curvilinear in the failing heart, indicating increased load sensitivity of LV relaxation. These changes primarily occur due to alterations in the impact of ejection timing and systolic load profile rather than increased elastic recoil. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Prabhu, SD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. RI Prabhu, Sumanth/D-5223-2009 NR 29 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD AUG 1 PY 1999 VL 43 IS 2 BP 354 EP 363 DI 10.1016/S0008-6363(99)00102-9 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 221VJ UT WOS:000081747400015 PM 10536665 ER PT J AU Kang, JX Bell, J Beard, RL Chandraratna, RAS AF Kang, JX Bell, J Beard, RL Chandraratna, RAS TI Mannose 6-phosphate/insulin-like growth factor II receptor mediates the growth-inhibitory effects of retinoids SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID PRO-CATHEPSIN-D; 6-PHOSPHATE RECEPTOR; FACTOR-BETA; HEPATOCELLULAR-CARCINOMA; EFFECTIVE ANTAGONIST; 9-CIS-RETINOIC ACID; PERINATAL LETHALITY; M6P/IGF2 RECEPTOR; CANCER CELLS; LIVER-TUMORS AB Both retinoids and the mannose 6-phosphate/insulin-like growth factor-ii receptor (M6P/IGF2R) have been shown to play an important role in controlling cell growth during embryonic development and oncogenesis. Our recent work (Kang ef al,, Proc. Natl, Acad, Sci, USA, 94: 13671-13676, 1997; Kang et al,, Proc. Natl, Acad, Sci. USA, 95: 13687-13691, 1998) revealed a direct biochemical interaction between retinoic acid (RA) and the M6P/IGF2R, thereby leading us to hypothesize that the M6P/IGF2R may mediate a growth-inhibiting effect of RA, To test this hypothesis, cell growth and apoptosis in response to RE and various receptor-selective retinoids were examined in cells that lack or overexpress the M6P/IGF2R, RA and those retinoids capable of binding to the M6P/IGF2R induced a remarkable morphological change with characteristics of round shape and reduced spreading, apoptosis, and growth inhibition in stably transfected mouse P388D1 cells overexpressing the M6P/IGF2R but not in the M6P/IGF2R-deficient P388D1 cells. These effects of RE were neither blocked by a potent RA nuclear receptor (RAR) antagonist (AGN193109), nor mimicked by a selective RAR agonist (TTNPB), suggesting that the observed effects of RA are independent of RARs, Similar effects of the retinoids were observed in cultured neonatal rat cardiac myocytes that have high levels of the M6P/IGF2R. Furthermore, overexpression of the M6P/IGF2R in a RA-resistant cancer cell line (HL-GOR) that lacked functional RARs gave the cells a susceptibility to RA-induced apoptosis. These data suggest that the M6P/IGF2R may play an important role in mediating retinoid-induced apoptosis/growth-inhibition and provide insight into the similar biological effects of RA and the M6P/IGF2R on fetal development and carcinogenesis. C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Allergan Pharmaceut Inc, Retinoid Res, Irvine, CA 92713 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, Room 4433,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA-79553] NR 58 TC 46 Z9 46 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD AUG PY 1999 VL 10 IS 8 BP 591 EP 600 PG 10 WC Cell Biology SC Cell Biology GA 228EB UT WOS:000082123200007 PM 10470859 ER PT J AU Levine, S AF Levine, S TI Tidal flow-volume analysis of ventilation during exercise - A useful approach for diagnosing the mechanism of ventilatory limitation to exercise during cardiopulmonary exercise testing SO CHEST LA English DT Editorial Material C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Hahnemann Univ, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Levine, S (reprint author), Dept Vet Affairs Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 1999 VL 116 IS 2 BP 277 EP 278 DI 10.1378/chest.116.2.277 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 225GQ UT WOS:000081950400004 PM 10453851 ER PT J AU Pilling, J Cutaia, M AF Pilling, J Cutaia, M TI Ambulatory oximetry monitoring in patients with severe COPD - A preliminary study SO CHEST LA English DT Article DE ambulatory oximetry monitoring; COPD; long-term oxygen therapy ID OBSTRUCTIVE PULMONARY-DISEASE; LONG-TERM OXYGEN; DOMICILIARY OXYGEN; PULSE OXIMETRY; MILD HYPOXEMIA; COR-PULMONALE; LUNG-DISEASE; THERAPY; SATURATION; EXERCISE AB Background: The benefits of long-term oxygen supplementation in COPD patients with hyposemia are well established, The standard approach to prescribing oxygen uses a static assessment of oxygen requirements in a hospital or clinic setting, The assumption behind this approach is that patients will maintain a "therapeutic" hemoglobin oxygen saturation (SpO(2)) in the outpatient setting, We questioned the validity of this assumption, and hypothesized that many patients may demonstrate significant oxygen desaturation during normal activities of daily living, Study design, methods, and measurements:We determined if oxygen supplementation maintained a therapeutic SpO(2) level in patients with COPD (n = 27), using the technique of ambulatory oximetry monitoring (AOM). AOM consisted of using a portable oximeter to monitor SpO(2), poise rate, and patient activity while patients were engaged in normal activities of daily living over an extended time period (similar to 18 h), The portable oximeter collected and stored these data every 15 s over the monitored time period, Each AOM recording was manually scored for desaturation events and other key variables, including average SpO(2) over the monitoring period, the average number of desaturation events per hour, and the percentage of monitored time deleted secondary to artifacts, Setting: University-affiliated Veterans Affairs Medical Center, Patients: All subjects were patients with stable COPD with no recent history of hospitalization or exacerbation of their lung disease. Results: This cohort of patients demonstrated a surprising frequency of desaturation below the recommended target SpO(2) value (90%), which averaged approximately 25% of AOM recording time. There was wide variability among patients in the percentage of time SpO(2), was below the target value (range, 3 to 67% of AOM recording time), Motion artifact on the AOM recordings was not a major problem; an average of 8% of the recording time was deleted secondary to artifacts in this patient cohort. Conclusions: The results demonstrate that AOM is feasible and accurate with an acceptable level of motion artifact, These results also suggest that the standard approach for prescribing oxygen may lend to subtherapeutic SpO(2), values in the outpatient setting, AOM holds promise as a tool to monitor the adequacy of oxygen prescriptions in the outpatient setting in patients with lung disease. C1 Univ Penn, Vet Affairs Med Ctr, Res Serv, Div Pulm Dis, Philadelphia, PA 19104 USA. Brown Univ, Sch Med, Dept Med, Vet Affairs Med Ctr,Pulm Dis Div, Providence, RI 02912 USA. RP Cutaia, M (reprint author), Univ Penn, Vet Affairs Med Ctr, Res Serv, Div Pulm Dis, Philadelphia, PA 19104 USA. NR 36 TC 23 Z9 23 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 1999 VL 116 IS 2 BP 314 EP 321 DI 10.1378/chest.116.2.314 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 225GQ UT WOS:000081950400010 PM 10453857 ER PT J AU Posner, MR Cavacini, LA Upton, MP Tillman, KC Gornstein, ER Norris, CM AF Posner, MR Cavacini, LA Upton, MP Tillman, KC Gornstein, ER Norris, CM TI Surface membrane-expressed CD40 is present on tumor cells from squamous cell cancer of the head and neck in vitro and in vivo and regulates cell growth in tumor cell lines SO CLINICAL CANCER RESEARCH LA English DT Article ID RECEPTOR MONOCLONAL-ANTIBODY; CD40-CD40 LIGAND INTERACTION; ACTIVATED PROTEIN-KINASES; EPSTEIN-BARR-VIRUS; DENDRITIC CELLS; B-CELLS; HUMAN KERATINOCYTES; IL-12 PRODUCTION; HUMAN MONOCYTES; CROSS-LINKING AB Because regional spread to lymph nodes without systemic spread is a relatively common event in squamous cell cancer of the head and neck (SCCHN), it is possible that lymphoid-related receptors or cytokines might directly impact the growth of these tumors. In the present study, we have shown by flow cytometry and Western blotting that the central lymphoid regulatory molecule, CD40, is expressed on the surface of all seven SCCHN tumor cell lines studied. Tumor cell lines also expressed epidermal growth factor (EGF) receptor, MHC class I, and CD95 (Fas) but did not uniformly express other important lymphoid regulatory molecules such as CD80, CD86, or interleukin (IL) 2 receptor components. CD40 ligation by trimeric CD40 ligand (CD40L) resulted in a 20-45% inhibition of tumor cell growth in three of seven cell lines tested. The cytokines IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-10, IL-11, and IL-15 neither inhibited nor stimulated growth in any of the cell lines tested. EGF had pleiotropic effects on cell growth; it inhibited growth in two cell lines, stimulated growth in one cell line, and had no effect in four cell lines. When coligation by EGF and CD40L was studied, additive or supra-additive growth inhibition was seen in four cell lines. Three cell lines were unaffected by EGF, CD40, or coligation with both reagents, Examination of tumor tissues from 12 previously untreated patients representing a broad spectrum of patients presenting with SCCHN demonstrated CD40 expression in all 12 tumor specimens. This study supports the notion that CD40 is a regulatory molecule for the growth of SCCHN. The important role of CD40-CD40L interactions in the regulation of immune cells in the lymph node and the unique high-level expression of CD40L by these immune cells lend support to the hypothesis that this ligand/receptor pair is an important mediator of cell growth in SCCHN. C1 Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Human Monoclonal Antibody Lab, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Otolaryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Otolaryngol, Harvard Head & Neck & Oncol Program, Boston, MA 02115 USA. RP Posner, MR (reprint author), Dana Farber Canc Inst, Head & Neck Oncol Program, 44 Binney St, Boston, MA 02115 USA. NR 57 TC 38 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 1999 VL 5 IS 8 BP 2261 EP 2270 PG 10 WC Oncology SC Oncology GA 228KL UT WOS:000082135600045 PM 10473114 ER PT J AU Welsh, GH Thompson, K Long-Krug, S AF Welsh, GH Thompson, K Long-Krug, S TI Evaluation of patient-perceived health status using the Medical Outcomes Survey Short-Form 36 in an intensive care unit population SO CRITICAL CARE MEDICINE LA English DT Article DE health status; quality of life; intensive care; outcome assessment; mortality; critical care; elderly; aged; Veterans hospitals; inpatients ID QUALITY-OF-LIFE; SURVEY SF-36; FUNCTIONAL STATUS; PROXY RATERS; APACHE-II; QUESTIONNAIRE; DISEASE; INSTRUMENT; VALIDITY; ADULTS AB Objective: Baseline patient functional status as assessed by providers is correlated with mortality after intensive care unit (ICU) admission. We wanted to see if patient self-perception of health status before admission to an ICU correlated with functional outcome, Design: Prospective survey on a convenience sample. Setting: Single urban university-affiliated Veterans Affairs Medial Center. Patients: One hundred ninety-nine patients in surgical and medical/coronary ICUs, Interventions: None. Measurements: Patient-assessed baseline health status was monitored with the Medical Outcome Survey Short-Form 36 (SF-36), consisting of 36 questions that evaluate eight health status concepts. In addition, baseline functional status (Zubrod scale) was determined and severity of illness (Acute Physiology and Chronic Health Evaluation [APACHE] II) data were collected. Zubrod functional status, which includes mortality, was determined 6 wks and 6 months after ICU admission, and correlation coefficients were calculated. Main Results: We found it feasible to collect SF-36 health status data on a 9% sample in this setting. Less than 1% of responses were completed by proxy. The SF-36 data were internally consistent, and several of its scales including general health perception and physical functioning correlated with patient Zubrod functional status (r(2) = .08, p < .001; r(2) = .14, p < .001) at 6 wks as did vitality (r(2) = .04, p < .01), social function (r(2) = .03, p < .05), and physical role function (r(2) = .02, p = .053), although to a lesser extent. Similar correlations were also found with 6-month functional status. Conclusions: We conclude that use of the SF-36 is time efficient in an ICU setting and correlates with 6-wk and 6-month functional outcome. It correlates as well with functional outcome as either the baseline Zubrod functional status or the APACHE II severity of illness measurement. The five-question general health evaluation portion correlated almost as well with outcome as the more extensive 36-item questionnaire. Use of the SF-36 may define patient populations for comparison across hospitals. It may also target individuals with needs for additional posthospitalization care, including rehabilitation services or nursing home placement. C1 Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Dept Res, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Welsh, GH (reprint author), Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80262 USA. NR 29 TC 23 Z9 25 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD AUG PY 1999 VL 27 IS 8 BP 1466 EP 1471 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 229WG UT WOS:000082218300009 PM 10470751 ER PT J AU Greene, R AF Greene, R TI Acute lobar collapse: Adults and infants differ in important ways SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE atelectasis; lobar collapse ID SURGERY C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Greene, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD AUG PY 1999 VL 27 IS 8 BP 1677 EP 1679 DI 10.1097/00003246-199908000-00064 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 229WG UT WOS:000082218300054 PM 10470796 ER PT J AU Teplick, R Rubin, R AF Teplick, R Rubin, R TI Therapy of sepsis: Why have we made such little progress? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE sepsis; systemic inflammatory response syndrome ID ANIMAL-MODELS; BACTERIA; SHOCK C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Teplick, R (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 14 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD AUG PY 1999 VL 27 IS 8 BP 1682 EP 1683 DI 10.1097/00003246-199908000-00066 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 229WG UT WOS:000082218300056 PM 10470798 ER PT J AU Brander, C Walker, B AF Brander, C Walker, B TI T lymphocyte responses in HIV-1 infection: implications for vaccine development SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; NEUTRALIZING ANTIBODY-RESPONSES; CLASS-I MOLECULES; IMMUNE-RESPONSES; CELL RESPONSES; RECOMBINANT GP120; CTL RESPONSES; DNA VACCINE; NEF PROTEIN AB Substantial progress has been made over the past year in understanding the cellular immune response in HIV pathogenesis. Cytotoxic T lymphocytes play a critical role in establishing the level of viremia and virus-specific Th cell responses appear to affect the in vivo efficacy of cytotoxic T lymphocytes. Together, these new data provide important insights to refocus efforts aimed at immunotherapeutic interventions and vaccine development. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp E, Sch Med, Charlestown, MA 02129 USA. RP Brander, C (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 5th Floor,149 13th St, Charlestown, MA 02129 USA. NR 104 TC 100 Z9 104 U1 2 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 1999 VL 11 IS 4 BP 451 EP 459 DI 10.1016/S0952-7915(99)80076-4 PG 9 WC Immunology SC Immunology GA 223EU UT WOS:000081828600016 PM 10448136 ER PT J AU Ausubel, F Bisseling, T AF Ausubel, F Bisseling, T TI Pathogenesis and symbiosis: two sides of the same coin that should be united by a common web-accessible database SO CURRENT OPINION IN PLANT BIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Wageningen Univ Agr, Mol Biol Lab, NL-6703 HA Wageningen, Netherlands. RP Ausubel, F (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RI Bisseling, Ton/A-2421-2013 NR 0 TC 2 Z9 4 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5266 J9 CURR OPIN PLANT BIOL JI Curr. Opin. Plant Biol. PD AUG PY 1999 VL 2 IS 4 BP 265 EP 267 DI 10.1016/S1369-5266(99)80047-8 PG 3 WC Plant Sciences SC Plant Sciences GA 223XG UT WOS:000081866400001 ER PT J AU Christian, MM Moy, RL AF Christian, MM Moy, RL TI Treatment or Hailey-Hailey disease (or benign familial pemphigus) using short pulsed and short dwell time carbon dioxide lasers SO DERMATOLOGIC SURGERY LA English DT Article ID DERMABRASION AB BACKGROUND. Surgical intervention of Hailey-Hailey disease (HHD) may be required to achieve prolonged remission or cure. Excisional surgery, dermabrasion, and continuous carbon dioxide (CO2) laser therapies have been utilized with success, though patients may experience considerable morbidity. OBJECTIVE. TO evaluate the use of short pulsed and short dwell time CO2 lasers in the treatment of HHD. METHOD. Case report and review of the relevant literature. RESULTS. A 26-year-old woman with refractory axillary HHD was initially treated with a short dwell time CO, laser. The right axilla was treated with two passes at a fluence of 25 J/cm(2), and the left axilla with three passes at 28 J/cm(2). Three years later, several foci within each axilla that periodically blistered were further treated with two passes of a short pulsed CO2 laser at a fluence of 15 J/cm(2). At a 3.5-year follow-up, the patient reported continued resolution of her left axilla but disease persistence in her right axilla. CONCLUSION. HHD can be effectively treated with a short dwell time CO2 laser if appropriate laser parameters are used. 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 Christian, MM (reprint author), 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. EM epidermiss@aol.com NR 17 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD AUG PY 1999 VL 25 IS 8 BP 661 EP 663 DI 10.1046/j.1524-4725.1999.99025.x PG 3 WC Dermatology; Surgery SC Dermatology; Surgery GA 225NB UT WOS:000081966700012 PM 10491050 ER PT J AU Noramly, S Freeman, A Morgan, BA AF Noramly, S Freeman, A Morgan, BA TI beta-catenin signaling can initiate feather bud development SO DEVELOPMENT LA English DT Article DE feather bud; beta-catenin; Wnt; pattern formation; ectoderm; chick ID GENE-EXPRESSION; SONIC-HEDGEHOG; CELL FATE; LIMB DEVELOPMENT; VERTEBRATE LIMB; AVIAN SKIN; WNT; INDUCTION; CHICK; MORPHOGENESIS AB Intercellular signaling by a subset of Wnts is mediated by stabilization of cytoplasmic beta-catenin and its translocation to the nucleus: Immunolocalization of beta-catenin in developing chick skin reveals that this signaling pathway is active in a dynamic pattern from the earliest stages of feather bud development. Forced activation of this pathway by expression of a stabilized beta-catenin in the ectoderm results in the ectopic formation of feather buds. This construct is sufficient to induce bud formation since it does so both within presumptive feather tracts and in normally featherless regions where tract-specific signals are absent. It is also insensitive to the lateral inhibition that mediates the normal spacing of buds and can induce ectopic buds in interfollicular skin. However, additional patterning signals cooperate with this pathway to regulate gene expression within domains of stabilized beta-catenin expression. Localized activation of this pathway within the bud as it develops is required for normal morphogenesis and ectopic activation of the pathway leads to abnormally oriented buds and growths on the feather filaments. These results suggest that activation of the beta-catenin pathway initiates follicle development in embryonic skin and plays important roles in the subsequent morphogenesis of the bud. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Cornell Univ, Grad Sch Med Sci, New York, NY 10021 USA. RP Morgan, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. NR 62 TC 109 Z9 110 U1 2 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD AUG PY 1999 VL 126 IS 16 BP 3509 EP 3521 PG 13 WC Developmental Biology SC Developmental Biology GA 234QY UT WOS:000082496900004 PM 10409498 ER PT J AU Hall, DH Winfrey, VP Blaeuer, G Hoffman, LH Furuta, T Rose, KL Hobert, O Greenstein, D AF Hall, DH Winfrey, VP Blaeuer, G Hoffman, LH Furuta, T Rose, KL Hobert, O Greenstein, D TI Ultrastructural features of the adult hermaphrodite gonad of Caenorhabditis elegans: Relations between the germ line and soma SO DEVELOPMENTAL BIOLOGY LA English DT Article DE electron microscopy; germ line; oocyte; meiosis; gap junction; cell-cell interaction; Caenorhabditis elegans ID C-KIT RECEPTOR; GAP-JUNCTIONS; YOLK PROTEINS; OOCYTE DEVELOPMENT; CELL-INTERACTIONS; SIGNALING LIGAND; MUSCLE-CELLS; UNC-52 GENE; GLP-1; FAMILY AB Genetic and embryological experiments have established the Caenorhabditis elegans adult hermaphrodite gonad as a paradigm for studying the control of germline development and the role of soma-germline interactions. We describe ultrastructural features relating to essential germline events and the soma-germline interactions upon which they depend, as revealed by electron and fluorescence microscopy. Gap junctions were observed between oocytes and proximal gonadal sheath cells that contract to ovulate the oocyte. These gap junctions must be evanescent since individual oocytes lose contact with sheath cells when they are ovulated. In addition, proximal sheath cells are coupled to each other by gap junctions. Within proximal sheath cells, actin/myosin bundles are anchored to the plasma membrane at plaque-like structures we have termed hemi-adherens junctions, which in turn are closely associated with the gonadal basal lamina. Gap junctions and hemi-adherens junctions are likely to function in the coordinated series of contractions required to ovulate the mature oocyte. Proximal sheath cells are fenestrated with multiple small pores forming conduits from the gonadal basal lamina to the surface of the oocyte, passing through the sheath eel. In most instances where pores occur, extracellular yolk particles penetrate the gonadal basal lamina to directly touch the underlying oocytes. Membrane-bounded yolk granules were generally not found in the sheath cytoplasm by either electron microscopy or fluorescence microscopy. Electron microscopic immunocytochemistry was used to confirm and characterize the appearance of yolk protein in cytoplasmic organelles within the oocyte and in free particles in the pseudocoelom. The primary route of yolk transport apparently proceeds from the intestine into the pseudocoelom, then through sheath pores to the surface of the oocyte, where endocytosis occurs. Scanning electron microscopy was used to directly visualize the distal tip cell which extends tentacle-like processes that directly contact distal germ cells. These distal tip cell processes are likely to play a critical role in promoting germline mitosis. Scanning electron microscopy also revealed thin filopodia extending from the distal sheath cells. Distal sheath filopodia were also visualized using a green fluorescent protein reporter gene fusion and confocal microscopy. Distal sheath filopodia may function to stretch the sheath over the distal arm, (C) 1999 Academic Press. C1 Vanderbilt Univ, Sch Med, Dept Cell Biol, Nashville, TN 37232 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Ctr C Elegans Anat, Bronx, NY 10461 USA. Vanderbilt Univ, Dept Cell Biol, Sch Med, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Greenstein, D (reprint author), Vanderbilt Univ, Sch Med, Dept Cell Biol, U-2224 MCN,21st & Garland, Nashville, TN 37232 USA. OI Hobert, Oliver/0000-0002-7634-2854 FU NCRR NIH HHS [R24 RR012596, RR12596]; NICHD NIH HHS [HD05797]; NIGMS NIH HHS [GM57173, R01 GM057173] NR 76 TC 177 Z9 193 U1 1 U2 4 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 1999 VL 212 IS 1 BP 101 EP 123 DI 10.1006/dbio.1999.9356 PG 23 WC Developmental Biology SC Developmental Biology GA 223MH UT WOS:000081844500009 PM 10419689 ER PT J AU Ristow, M Carlqvist, H Hebinck, J Vorgerd, M Krone, W Pfeiffer, A Muller-Wieland, D Ostenson, CG AF Ristow, M Carlqvist, H Hebinck, J Vorgerd, M Krone, W Pfeiffer, A Muller-Wieland, D Ostenson, CG TI Deficiency of phosphofructo-1-kinase/muscle subtype in humans is associated with impairment of insulin secretory oscillations SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; PANCREATIC BETA-CELLS; PHOSPHOFRUCTOKINASE DEFICIENCY; SUSTAINED OSCILLATIONS; INTRAVENOUS GLUCOSE; PLASMA-GLUCOSE; TOLERANCE; GLUCAGON; ISLETS; GENE AB In healthy humans, insulin is secreted in an oscillatory manner. While the underlying mechanisms generating these oscillations are not fully established, increasing evidence suggests a central role for phosphofructo-1-kinase/muscle subtype (PFK1-M), which also serves as the predominantly active PFK1 subtype in the pancreatic beta-cell. The fact that normal oscillatory secretion is impaired in subjects with impaired glucose tolerance and healthy relatives of patients with type 2 diabetes suggests that this defect may be involved in the secretory dysfunction. To evaluate a possible link between inherited PFK1-M deficiency in humans (Tarui's disease or glycogenosis type VII) and altered insulin oscillations, in vivo studies were performed. We determined basal insulin oscillations during 2 h of frequent plasma sampling in two related teen-aged individuals with homozygous and heterozygous PFK1-M deficiency compared with nondeficient, unrelated control subjects. As predicted by the underlying hypothesis, normal oscillations in insulin secretion were completely abolished in the individual with homozygous deficiency of PFK1-M and significantly impaired in the heterozygous individual, as shown by spectral density and autocorrelation analyses. Thus, deficiency of PFK1-M subtype in humans appears to be associated with an impaired oscillatory insulin secretion pattern and may contribute to the commonly observed secretion defects occurring in type 2 diabetes. C1 Univ Cologne, Klin & Poliklin Innere Med 2, Cologne, Germany. Ruhr Univ Bochum, Med Klin, D-4630 Bochum, Germany. Ruhr Univ Bochum, Neurol Klin, Muskelzentrum, D-4630 Bochum, Germany. Karolinska Inst, Dept Mol Med, Endocrine & Diabet Unit, Rolf Luft Ctr Diabet Res, Stockholm, Sweden. RP Ristow, M (reprint author), Harvard Univ, Sch Med, Joslin Diabetes Ctr, Div Res,Sect Cellular & Mol Physiol, Room 610,1 Joslin Pl, Boston, MA 02215 USA. RI Ristow, Michael/O-9858-2014 OI Ristow, Michael/0000-0003-2109-2453 NR 34 TC 28 Z9 28 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 1999 VL 48 IS 8 BP 1557 EP 1561 DI 10.2337/diabetes.48.8.1557 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 218XB UT WOS:000081577400009 PM 10426373 ER PT J AU Patti, ME Virkamaki, A Landaker, EJ Kahn, CR Yki-Jarvinen, H AF Patti, ME Virkamaki, A Landaker, EJ Kahn, CR Yki-Jarvinen, H TI Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle SO DIABETES LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; PROTEIN-KINASE-B; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE ACTIVITY; PORE COMPLEX GLYCOPROTEINS; LINKED N-ACETYLGLUCOSAMINE; RAT ADIPOSE-CELLS; GLYCOGEN-SYNTHASE; IN-VIVO; RECEPTOR SUBSTRATE-1; 1-PHOSPHATIDYLINOSITOL 3-KINASE AB To explore potential cellular mechanisms by which activation of the hexosamine pathway induces insulin resistance, we have evaluated insulin signaling in conscious fasted rats infused for 2-6 h with saline, insulin (18 mU.kg(-1).min(-1)), or insulin and glucosamine (30 mu mol.kg(-1).min(-1)) under euglycemic conditions. Glucosamine infusion increased muscle UDP-N-acetyl-glucosamine concentrations 3.9- and 4.3-fold over saline- or insulin-infused animals, respectively (P < 0.001), Glucosamine induced significant insulin resistance to glucose uptake both at the level of the whole body and in rectus abdominis muscle, and it blunted the insulin-induced increase in muscle glycogen content, At a cellular level, these metabolic effects were paralleled by inhibition of postreceptor insulin signaling critical for glucose transport and glycogen storage, including a 45% reduction in insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation (P = 0.02), a 44% decrease in IRS-1 association with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase (P = 0.03), a 34% reduction in IRS-1-associated PI 3-kinase activity (P = 0.03), and a 51% reduction in insulin-stimulated glycogen synthase activity (P = 0.03). These alterations in postreceptor insulin signaling were time-dependent and paralleled closely the progressive inhibition of systemic glucose disposal from 2 to 6 h of glucosamine infusion. We also demonstrated that glucosamine infusion results in O-linked N-acetyl-glucosamine modification of IRS-1 and IRS-2. These data indicate that activation of the hexosamine pathway may directly modulate early postreceptor insulin signal transduction, perhaps via posttranslation modification of IRS proteins, and thus contribute to the insulin resistance induced by chronic hyperglycemia. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Minerva Fdn, Med Res Inst, Helsinki, Finland. Univ Helsinki, Dept Med, Helsinki, Finland. Univ Helsinki, Div Endocrinol & Diabetol, Helsinki, Finland. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM pattim@joslab.harvard.edu FU NIDDK NIH HHS [K08 DK-02526-01, P30 DK-46200] NR 67 TC 179 Z9 186 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD AUG PY 1999 VL 48 IS 8 BP 1562 EP 1571 DI 10.2337/diabetes.48.8.1562 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 218XB UT WOS:000081577400010 PM 10426374 ER PT J AU Lupia, E Elliot, SJ Lenz, O Zheng, F Hattori, M Striker, GE Striker, LJ AF Lupia, E Elliot, SJ Lenz, O Zheng, F Hattori, M Striker, GE Striker, LJ TI IGF-1 decreases collagen degradation in diabetic NOD mesangial cells - Implications for diabetic nephropathy SO DIABETES LA English DT Article ID GROWTH-FACTOR-I; PROGRESSIVE GLOMERULOSCLEROSIS; MATRIX METALLOPROTEINASE-2; BINDING-PROTEINS; GENE-EXPRESSION; TRANSGENIC MICE; MESSENGER-RNA; HIGH GLUCOSE; KIDNEY; RATS AB Nonobese diabetic (NOD) mice develop glomerulosclerosis shortly after the onset of diabetes. We showed that mesangial cells (MCs) from diabetic mice exhibited a stable phenotypic switch, consisting of both increased IGF-1 synthesis and proliferation (Elliot SJ, Striker LJ, Hattori M, Yang CW, He CJ, Peten EP, Striker GE: Mesangial cells from diabetic NOD mice constitutively secrete increased amounts of insulin-like growth factor-I. Endocrinology 133:1783-1788, 1993). Because the extracellular matrix (ECM) accumulation in diabetic glomerulosclerosis may be partly due to decreased degradation, we examined the effect of excess IGF-1 on collagen turnover and the activity of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) in diabetic and nondiabetic NOD-MG. Total collagen degradation was reduced by 58 +/- 18% in diabetic NOD-MCs, which correlated with a. constitutive decrease in MMP-2 activity and mRNA levels, and nearly undetectable MMP-9 activity and mRNA. TIMP levels were slightly decreased in diabetic NOD-MG. The addition of recombinant IGF-1 to nondiabetic NOD-MG resulted in a decrease in MMP-2 and TIMP activity. Furthermore, treatment of diabetic NOD-MC with a neutralizing antibody against IGF-1 increased the latent form, and restored the active form, of MMP-2, In conclusion, the excessive production of IGF-1 contributes to the altered ECM turnover in diabetic NOD-MG, largely through a reduction of MMP-2 activity, These data suggest that IGF-1 could be a major contributor to the development of diabetic glomerulosclerosis. C1 Univ Miami, Sch Med, Dept Med, Div Nephrol,Renal Cell Biol Lab, Miami, FL 33101 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Striker, LJ (reprint author), Univ Miami, Sch Med, Dept Med, Div Nephrol,Renal Cell Biol Lab, POB 016960 R126, Miami, FL 33101 USA. RI Lenz, Oliver/M-4672-2016 OI Lenz, Oliver/0000-0003-2997-3976 NR 48 TC 72 Z9 90 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 1999 VL 48 IS 8 BP 1638 EP 1644 DI 10.2337/diabetes.48.8.1638 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 218XB UT WOS:000081577400020 PM 10426384 ER PT J AU Kurth-Kraczek, EJ Hirshman, MF Goodyear, LJ Winder, WW AF Kurth-Kraczek, EJ Hirshman, MF Goodyear, LJ Winder, WW TI 5 ' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle SO DIABETES LA English DT Article ID GLUCOSE TRANSPORTERS; PLASMA-MEMBRANE; MALONYL-COA; INSULIN; CONTRACTION; CELL; MECHANISM; OXIDATION; EXERCISE AB It has previously been reported that exercise causes an increase in glucose uptake in skeletal muscle and also an increase in 5' AMP-activated protein kinase (AMPK) activity. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICA-riboside), an analog of adenosine, is taken up into cells and phosphorylated to form AICA-riboside monophosphate (ZMP), which can also activate AMPK. This study was designed to determine whether the increase in glucose uptake observed with AMPK activation by AICA-riboside is due to GLUT4 translocation from an intracellular location to the plasma membranes, similar to that seen in response to contraction. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine erythrocytes, 8 mmol/l glucose, and +/-2 mmol/l AICA-riboside or +/-60 nmol/l insulin. Perfusion medium containing AICA-riboside was found to significantly increase AMPK activity, glucose uptake, and GLUT4 translocation in skeletal muscle above basal levels. Insulin-perfused muscles showed significant increases in glucose uptake and GLUT4 translocation, but AMPK activation was not significantly changed from basal levels. These results provide evidence that the increased glucose uptake observed with AMPK activation by AICA-riboside in perfused rat hindlimb muscles is due to an increase in the translocation of GLUT4 to surface membranes. C1 Brigham Young Univ, Dept Zool, Provo, UT 84602 USA. Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Winder, WW (reprint author), Brigham Young Univ, Dept Zool, 545 WIDB, Provo, UT 84602 USA. FU NIAMS NIH HHS [AR-41438, AR-45670] NR 33 TC 445 Z9 459 U1 1 U2 15 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 1999 VL 48 IS 8 BP 1667 EP 1671 DI 10.2337/diabetes.48.8.1667 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 218XB UT WOS:000081577400025 PM 10426389 ER PT J AU Bursell, SE Clermont, AC Aiello, LP Aiello, LM Schlossman, DK Feener, EP Laffel, L King, GL AF Bursell, SE Clermont, AC Aiello, LP Aiello, LM Schlossman, DK Feener, EP Laffel, L King, GL TI High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes SO DIABETES CARE LA English DT Article ID PROTEIN-KINASE-C; ENDOTHELIUM-DEPENDENT VASODILATION; OXIDATIVE STRESS; ALPHA-TOCOPHEROL; E CONSUMPTION; MELLITUS; DIACYLGLYCEROL; RATS; HEMODYNAMICS; RETINOPATHY AB OBJECTIVE - To determine the effectiveness of vitamin E treatment in normalizing retinal blood flow and renal function in patients with <10 years of type 1 diabetes. RESEARCH DESIGN AND METHODS - An 8-month randomized double-masked placebo-controlled crossover trial evaluated 36 type 1 diabetic and 9 nondiabetic subjects. Subjects were randomly assigned to either 1,800 IU vitamin E/day or placebo for 4- months and followed, after treatment crossover, for a further 4 months. Retinal blood flow was measured using video fluorescein angiography, and renal function was assessed using normalized creatinine clearance from timed urine collections. RESULTS - After vitamin E treatment, serum levels of vitamin E were significantly elevated (P < 0.01) in both type 1 diabetic and control patients. Hemoglobin Al, was not affected by vitamin E treatment. Diabetic patient baseline retinal blood flow (29.1 +/- 7.5 pixel(2)/s) was significantly (P = 0.030) decreased compared with that of nondiabetic subjects (35.2 +/- 7.2 pixel(2)/s). After vitamin E treatment, diabetic patient retinal blood flow (34.5 +/- 7.8 pixel(2)/s) was significantly increased (P < 0.001) and was comparable with that of nondiabetic subjects. Additionally, vitamin E treatment significantly (P = 0.039) normalized elevated baseline creatinine clearance in diabetic patients. CONCLUSIONS - Oral vitamin E treatment appears to be effective in normalizing retinal hemodynamic abnormalities and improving renal function in type 1 diabetic patients of short disease duration without inducing a significant change in glycemic control. This suggests that vitamin E supplementation may provide an additional benefit in reducing the risks for developing diabetic retinopathy or nephropathy. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Eye Res Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Eye Res Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM kingg@joslab.harvard.edu FU NIDDK NIH HHS [P30 DK036836] NR 37 TC 176 Z9 181 U1 2 U2 6 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 1999 VL 22 IS 8 BP 1245 EP 1251 DI 10.2337/diacare.22.8.1245 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 218QF UT WOS:000081562600003 PM 10480765 ER PT J AU Paradisi, G Smith, L Burtner, C Leaming, R Garvey, WT Hook, G Johnson, A Cronin, J Steinberg, HO Baron, AD AF Paradisi, G Smith, L Burtner, C Leaming, R Garvey, WT Hook, G Johnson, A Cronin, J Steinberg, HO Baron, AD TI Dual energy X-ray absorptiometry assessment of fat mass distribution and its association with the insulin resistance syndrome SO DIABETES CARE LA English DT Article ID ADIPOSE-TISSUE DISTRIBUTION; CORONARY HEART-DISEASE; NORMAL GLUCOSE-TOLERANCE; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ABDOMINAL FAT; OBESE WOMEN; REGIONAL ADIPOSITY; LIPOPROTEIN LEVELS; BODY-COMPOSITION AB OBJECTIVE - To determine which dual energy X-ray absorptiometry (DXA)-derived indices of fat mass distribution are the most informative to predict the various parameters of the metabolic syndrome. RESEARCH DESIGN AND METHODS - A total of 87 healthy men, 63 lean (% fat less than or equal to 26) and 24 obese (% fat >26), underwent DXA scanning to evaluate body composition with respect to the whole body and the trunk, leg, and abdominal regions from L1 to L4 and from L3 to L3. These regions were correlated with insulin sensitivity determined by the euglycemic-hyperinsulinemic clamp, insulin area under the curve after oral glucose tolerance test (AUC I); triglyceride; total, HDL, and LDL cholesterol; free fatty acids; and blood pressure. The analyses were performed in all subjects, as well as in lean and obese groups separately RESULTS - Among the various indices of body fat, DXA-determined adiposity in the abdominal cut at 11-4 level was the most predictive of the metabolic variables, showing significant relationships with glucose infusion rate ([GIR], mg . kg(-1) lean body mass . min(-1)), triglyceride, and cholesterol, independent of total-body mass (r = -0.267, P < 0.05; r = 0.316, P < 0.005, and r = 0.319, P < 0.005, respectively). Upon subanalysis, these correlations remained significant in lean men, whereas in obese men, only BMI and the amount of leg fat (negative relationship) showed significant correlations with triglyceride and cholesterol (r = 0.438, P < 0.05; r = 0.458, P < 0.05; r = -0.439, P < 0.05; and r = -0.414, P < 0.05, respectively). The results of a multiple regression analysis revealed that 47% of the variance in GIR among all study subjects was predicted by AUC I, fat L1-4, diastolic blood pressure (dBP), HDL, and triglyceride as independent variables. In the lean group, fat L1-4 alone accounted for 33% of the variance of GIR, whereas in obese men, AUC I and dBP explained 68% of the variance in GIR. CONCLUSIONS - The DXA technique applied for the evaluation of fat distribution can provide useful information regarding various aspects of the insulin resistance syndrome in healthy subjects. DXA can be a valid, accurate, relatively inexpensive, and safer alternative compared with other methods to investigate the role of abdominal body fat distribution on cardiovascular risk factors. C1 Indiana Univ, Sch Med, Div Endocrinol & Metab, Indianapolis, IN 46202 USA. Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Baron, AD (reprint author), Indiana Univ, Sch Med, Div Endocrinol & Metab, 541 N Clin Dr,Clin Bldg 459, Indianapolis, IN 46202 USA. FU NCRR NIH HHS [MO1-RR750-19]; NIDDK NIH HHS [DK-20452, DK-42469] NR 39 TC 92 Z9 94 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 1999 VL 22 IS 8 BP 1310 EP 1317 DI 10.2337/diacare.22.8.1310 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 218QF UT WOS:000081562600014 PM 10480776 ER PT J AU Egan, JM Clocquet, AR Elahi, D AF Egan, JM Clocquet, AR Elahi, D TI Insulinotropic effect of exendin-4 in humans SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 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 1999 VL 42 SU 1 MA 148 BP A41 EP A41 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937600148 ER PT J AU Elahi, D Stoffers, DA Clocquet, AR Muller, DC Wideman, L Chin, GA Clarke, WL Hanks, JB Habener, JF Egan, JM AF Elahi, D Stoffers, DA Clocquet, AR Muller, DC Wideman, L Chin, GA Clarke, WL Hanks, JB Habener, JF Egan, JM TI Impaired insulin secretion and sensitivity in MODY4. SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. UVA, Charlottesville, VA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1999 VL 42 SU 1 MA 279 BP A77 EP A77 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937600279 ER PT J AU Hansen, L Stanojevic, V Petersen, HV Urioste, S Stoffers, D Hansen, T Moller, MA Serup, P Habener, JF Pedersen, O AF Hansen, L Stanojevic, V Petersen, HV Urioste, S Stoffers, D Hansen, T Moller, MA Serup, P Habener, JF Pedersen, O TI Functional studies of variants of the human insulin promoter factor-1 (IPF-1) occurring in early- and late-onset type 2 diabetes SO DIABETOLOGIA LA English DT Meeting Abstract C1 Steno Diabet Ctr, Copenhagen, Denmark. Hagedorn Res Inst, Copenhagen, Denmark. Massachusetts Gen Hosp, Dept Mol Endocrinol, HHMI, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 1999 VL 42 SU 1 MA 420 BP A114 EP A114 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937600419 ER PT J AU Laviola, L Belsanti, G Logoluso, F Napoli, R Davalli, AM Weir, GC Giorgino, R Giorgino, F AF Laviola, L Belsanti, G Logoluso, F Napoli, R Davalli, AM Weir, GC Giorgino, R Giorgino, F TI Insulin signalling abnormalities in the heart of insulin-deficient diabetic rats: Effects of islet transplantation. SO DIABETOLOGIA LA English DT Meeting Abstract C1 Ist Clin Med Endocrinol & Malattie Metaboliche, Bari, Italy. Joslin Diabet Ctr, Boston, MA 02215 USA. RI Giorgino, Francesco/K-7262-2016 OI Giorgino, Francesco/0000-0001-7372-2678 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 1999 VL 42 SU 1 MA 240 BP A67 EP A67 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937600239 ER PT J AU Malecki, MT Ji, L Curtis, S Klupa, T Hanna, L Rich, SS Warram, JH Krolewski, AS AF Malecki, MT Ji, L Curtis, S Klupa, T Hanna, L Rich, SS Warram, JH Krolewski, AS TI Clinical characteristics of type 2 diabetes mellitus that is linked with chromosome 20q SO DIABETOLOGIA LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 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 1999 VL 42 SU 1 MA 449 BP A122 EP A122 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937600449 ER PT J AU Nguyen, HC Armstrong, DG Hadi, S Harkless, LB Lipsky, BA AF Nguyen, HC Armstrong, DG Hadi, S Harkless, LB Lipsky, BA TI Gram-stain for diabetic foot infections: Relevant, reliable or relic? SO DIABETOLOGIA LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Orthopaed, San Antonio, TX 78284 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 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 1999 VL 42 SU 1 MA 1172 BP A310 EP A310 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937601169 ER PT J AU Pham, HT Rosenblum, BI Lyons, TE Giurini, JM Smakowski, P Chrzan, JS Habershaw, GM Veves, A AF Pham, HT Rosenblum, BI Lyons, TE Giurini, JM Smakowski, P Chrzan, JS Habershaw, GM Veves, A TI Treatment with a human skin equivalent, Graftskin (Apligraf(R)), improves healing rate in diabetic foot ulcers 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 1 U2 2 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 1999 VL 42 SU 1 MA 104 BP A28 EP A28 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937600104 ER PT J AU Rasmussen, SK Lautier, C Hansen, L Grigorescu, F Smith, RJ Pedersen, O AF Rasmussen, SK Lautier, C Hansen, L Grigorescu, F Smith, RJ Pedersen, O TI Studies of the variability of the genes encoding IGF-1 and its receptor in relation to intrauterine growth retardation, insulin sensitivity and type II diabetes mellitus SO DIABETOLOGIA LA English DT Meeting Abstract C1 Steno Diabet Ctr, Copenhagen, Denmark. Hagedorn Res Inst, Copenhagen, Denmark. Ctr Rech Biochim Macromol, Montpellier, France. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 1999 VL 42 SU 1 MA 432 BP A118 EP A118 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937600431 ER PT J AU Roder, ME Schwartz, RS Prigeon, R Kahn, SE AF Roder, ME Schwartz, RS Prigeon, R Kahn, SE TI Reduced B-cell compensation to the insulin resistance of aging: Impact on proinsulin and insulin levels. SO DIABETOLOGIA LA English DT Meeting Abstract C1 Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. Univ Washington, Harborview Med Ctr, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 1999 VL 42 SU 1 MA 594 BP A160 EP A160 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937600593 ER PT J AU Sieradzki, J Malecki, MT Klupa, T Hanna, L Sieradzka, J Frey, J Krolewski, AS AF Sieradzki, J Malecki, MT Klupa, T Hanna, L Sieradzka, J Frey, J Krolewski, AS TI Amino acid variants of the vitamin D-binding protein are not associated with type 1 diabetes in Caucasians. SO DIABETOLOGIA LA English DT Meeting Abstract C1 Jagiellonian Univ, Dept Metab Dis, Krakow, Poland. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 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 1999 VL 42 SU 1 MA 332 BP A91 EP A91 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937600333 ER PT J AU Szanto, I Kahn, CR AF Szanto, I Kahn, CR TI Insulin and leptin activate state in Fao hepatoma cell line. 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 1999 VL 42 SU 1 MA 642 BP A172 EP A172 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937600641 ER PT J AU Valverde, AM Mur, C Kahn, CR Benito, M AF Valverde, AM Mur, C Kahn, CR Benito, M TI Insulin signalling in IRS-1-deficient brown adipocytes: Requirement of IRS-1 for mitogenesis and lipid synthesis. SO DIABETOLOGIA LA English DT Meeting Abstract C1 Univ Complutense Madrid, Fac Farm, Dept Bioquim & Biol Mol 2, E-28040 Madrid, Spain. Harvard Univ, Sch Med, 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 1999 VL 42 SU 1 MA 238 BP A67 EP A67 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225CC UT WOS:000081937600238 ER PT J AU Tache, Y AF Tache, Y TI Cyclic vomiting syndrome - The corticotropin-releasing-factor hypothesis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Symposium on Cyclic Vomiting Syndrome CY APR 17-18, 1998 CL MILWAUKEE, WISCONSIN DE corticotropin-releasing factor; gastric emptying; astressin; vagus; cyclic vomiting syndrome; brain; corticotropin-releasing-factor antagonist ID FACTOR-RECEPTOR ANTAGONIST; CRF-INDUCED INHIBITION; COLONIC MOTOR FUNCTION; RAT-BRAIN; COMPETITIVE ANTAGONISTS; PARAVENTRICULAR NUCLEUS; GASTRIC-EROSIONS; GENE-EXPRESSION; NERVOUS-SYSTEM; IN-VIVO AB The characterization of corticotropin-releasing factor (CRF) and CRF receptors and the use of specific CRF antagonists have paved the way to establish a key role of brain CRF in the coding of the stress response. CRF injected into the cerebrospinal fluid or the periphery inhibits gastric emptying in various species. The paraventricular nucleus of the hypothalamus and dorsal vagal complex are brain sites of action for CRF. Endogenous brain CRF plays a role in mediating psychological, physical, somatovisceral, and immunological stress-induced delayed gastric emptying in rats. Postoperative gastric ileus is also prevented by peripheral injection of CRF antagonists. Cyclic Vomiting syndrome (CVS) is precipitated by stimuli or states associated with stimulation of CRF release, and the resulting endocrine, autonomic, and visceral changes are indicative of central CRF activation. Moreover, empiric pharmacotherapy alleviating CVS symptoms are known experimentally to block CRF release or action. The relevance of central CRF activation in the pathophysiology of CVS deserves further consideration. C1 W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Bldg 115,Room 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 41301, DK-33061]; NIMH NIH HHS [MH0063] NR 94 TC 55 Z9 57 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 1999 VL 44 IS 8 SU S BP 79S EP 86S PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 235EG UT WOS:000082526600015 PM 10490044 ER PT J AU Perez, KT Davey, EW Moore, RH Bunn, PR Rosol, MS Cardin, JA Johnson, RL Kopans, DN AF Perez, KT Davey, EW Moore, RH Bunn, PR Rosol, MS Cardin, JA Johnson, RL Kopans, DN TI Application of computer-aided tomography (CT) to the study of estuarine benthic communities SO ECOLOGICAL APPLICATIONS LA English DT Article DE benthic community; computer-aided tomography; CT scanning; macrofaunal tubes and tunnels; marine sediments; Narragansett Bay; sediment; technology transfer ID LOWER CHESAPEAKE-BAY; BIOGENIC STRUCTURES; SEDIMENT CORES; MACROBENTHOS AB Sediment cores were imaged using a Computer-Aided Tomography (CT) scanner at Massachusetts General Hospital, Boston, Massachusetts, United States. Procedures were developed, using the attenuation of X-rays, to differentiate between sediment and the water contained in macrobenthic tubes and tunnels. The effects of sediment type on the ability to discriminate tubes as small as 1.5 mm were examined. Soft sediments with mean X-ray attenuations (SXA) from 450 to 576 CT numbers were successfully scanned in cores of 15.2 cm diameter by 30 cm depth. We demonstrated the accessibility and availability of CT technology to ecological studies by negotiating a reduced research rate ($200 per core) for sediment scanning at a nearby small hospital. Additionally, we were able to transfer these image data from the local hospital environment to a personal computer, by developing specialized computer software. These steps allowed greater opportunity for data exploration, manipulation, and statistical evaluation than would be available in a medical facility. CT analysis was applied to intact sediment cores from five stations along a 31-km pollution gradient in Narragansett Bay, Rhode Island, United States. The percentage of tube and tunnel area (PTTA) within the top 18 cm of sediment from each Station was measured and ranged from 0.07% to 1.13%. PTTA increased along this gradient with distance from the pollution sources (r(2) = 0.81, P < 0.01). The mean X-ray attenuation for sediment (excluding animals, their tubes and tunnels, and shells) was determined at each station. It also showed a highly significant relationship along this gradient (r(2) = 0.98, P < 0.01) and ranged from 271 to 576 CT numbers. The measurement of PTTA may be an effective management tool to assess and monitor the effects of organic carbon loading on benthic communities in Narragansett Bay and similarly impacted estuaries. C1 US EPA, Narragansett, RI 02882 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Suffolk Univ, Dept Biol, Boston, MA 02114 USA. RP Perez, KT (reprint author), US EPA, 27 Tarzwell Dr, Narragansett, RI 02882 USA. NR 26 TC 25 Z9 25 U1 0 U2 5 PU ECOLOGICAL SOC AMER PI WASHINGTON PA 1707 H ST NW, STE 400, WASHINGTON, DC 20006-3915 USA SN 1051-0761 J9 ECOL APPL JI Ecol. Appl. PD AUG PY 1999 VL 9 IS 3 BP 1050 EP 1058 DI 10.1890/1051-0761(1999)009[1050:AOCATC]2.0.CO;2 PG 9 WC Ecology; Environmental Sciences SC Environmental Sciences & Ecology GA 225QQ UT WOS:000081972600025 ER PT J AU Perez-Villamil, B Schwartz, PT Vallejo, M AF Perez-Villamil, B Schwartz, PT Vallejo, M TI The pancreatic homeodomain transcription factor IDX1/IPF1 is expressed in neural cells during brain development SO ENDOCRINOLOGY LA English DT Article ID SOMATOSTATIN GENE; HOMEOBOX FACTOR; FACTOR-I; DIFFERENTIATION; MICE; IPF1; DUODENUM; SEQUENCE AB Expression of the homeodomain transcription factor IDX1/IPF1 has been shown to be restricted to cells in the developing foregut that form the pancreatic primordium. In the adult, IDX1/IPF1 is expressed in the duodenum and pancreatic islets. The IDX1/IPF1 gene is required for pancreatic development, and in the human, heterozygous mutations have been linked to diabetes mellitus. In the present communication, we report that IDX1/IPF1 is expressed in discrete cells of the rat central nervous system during embryonic development. Using RT-PCR, IDX1/IPF1 mRNA was detected in neural precursor RC2.E10 cells, as well as in both forebrain and hindbrain of developing rats at embryonic day 15 (E15). The presence of IDX1/IPF1 protein was confirmed by Western immunoblotting. Immunohistochemical analyses of sagittal sections of E15 rats demonstrated the presence of scattered IDX1/IPF1-immunopositive cells in the forebrain. Finally, electrophoretic mobility shift assays using nuclear extracts from neural cells revealed the presence of IDX1/IPF1 bound to a putative homeodomain protein DNA-binding site present in the promoter of the glial fibrillary acidic protein gene. Our results suggest that IDX1/IPF1 may have previously unsuspected extrapancreatic functions during development of neural cells in the central nervous system. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Perez-Villamil, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-49670] NR 22 TC 33 Z9 34 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1999 VL 140 IS 8 BP 3857 EP 3860 DI 10.1210/en.140.8.3857 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 218CV UT WOS:000081536400057 PM 10433248 ER PT J AU Perumpanani, AJ Byrne, HM AF Perumpanani, AJ Byrne, HM TI Extracellular matrix concentration exerts selection pressure on invasive cells SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE biphasic invasion; haptotaxis; proliferation; mathematical model ID LIVER METASTASIS; CHEMOTAXIS; CANCER; PROLIFERATION; CHEMOKINESIS; HAPTOTAXIS; ADHESION; COLLAGEN; MODEL AB The mortality associated with cancer depends upon the ability of malignant cells to invade and metastasise into adjacent and distant regions. Such malignant spread is caused by the acquisition of an invasive phenotype which involves variable changes in cell-cell adhesion, proteolysis of adjoining extracellular matrix molecules, and the ability to move in a directed fashion in response to fixed and soluble gradients. Whilst the degree of variability in the pattern of metastasis is large, several cancers show regional predilections for invasion. Tumour cell heterogeneity and extracellular matrix composition have been shown to account for some regional variations. In this study, an invasion assay was used to assess the invasiveness of HT1080 tumour cells migrating through a collagen gel. Our experiments showed that, in the absence of externally imposed chemical gradients, HT1080 invasiveness was related in a biphasic manner to collagen concentration. Using a mathematical model, developed to study this phenomenon, we predicted that tumour cell proliferation may also be related in a biphasic manner to collagen concentration. This model prediction was confirmed using a combination of collagen gel invasion and proliferation assays. Investigation of the mathematical model suggests that interactions between haptotaxis and proliferation of the HT1080 cells may be responsible for the biphasic dependence of the penetration depth and proliferation on collagen gel concentration. In conclusion, we showed how mathematical methods can be combined with experimental work to provide new and valuable insight into important biological issues. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ Nottingham, Sch Math Sci, Div Theoret Mech, Nottingham NG7 2RD, England. Massachusetts Gen Hosp, Cambridge, MA USA. RP Byrne, HM (reprint author), Univ Nottingham, Sch Math Sci, Div Theoret Mech, Nottingham NG7 2RD, England. NR 19 TC 51 Z9 51 U1 0 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 1999 VL 35 IS 8 BP 1274 EP 1280 DI 10.1016/S0959-8049(99)00125-2 PG 7 WC Oncology SC Oncology GA 228UF UT WOS:000082153500029 PM 10615241 ER PT J AU Vincent, S Settleman, J AF Vincent, S Settleman, J TI Inhibition of RhoGAP activity is sufficient for the induction of Rho-mediated actin reorganization SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE GTPases; Rho; GTPase-activating proteins; fluoride; actin stress fibers ID GTPASE-ACTIVATING PROTEIN; BINDING-PROTEIN; FLUORIDE ACTIVATION; HOMOLOGY DOMAIN; EXCHANGE FACTOR; CELL-GROWTH; IN-VITRO; RAS; GAP; PHOSPHORYLATION AB It is generally believed that the induction of actin cytoskeleton rearrangements by extracellular stimuli results from the activation of guanine nucleotide exchange factors for the Rho GTPases, Here, we present evidence that the inactivation of RhoGAP (GTPase activating protein) activity is an equally effective means of promoting Rho-mediated cellular processes. We observed that exposure of cultured fibroblasts to sodium fluoride (NaF) results in a rapid and potent stimulation of actin stress fiber formation. This effect is mediated by the Rho GTPase and is associated with the inactivation of cellular RhoGAP activity. Specifically, NaF promotes formation of a high-affinity complex between Rho and the two cellular p190 RhoGAPs in vivo, apparently sequestering limiting amounts of RhoGAP activity, thereby resulting in Rho activation. p190 RhoGAP activity was found to account for approximately 60 % of the total RhoGAP activity detected in whole cell extracts, indicating that relatively small changes in cellular RhoGAP activity can have potent effects on Rho activation. We also found that sub-effective concentrations of NaF combined with sub-effective concentrations of the Rho pathway activator, lysophosphatidic acid, which stimulates guanine nucleotide exchange activity on the Rho GTPase, results in the rapid induction of actin stress fibers, Together, these results suggest that the Rho GTPase is regulated by a fine balance of nucleotide exchange and RhoGAP activities, and that inactivation of RhoGAP activity may be a physiologically important regulatory mechanism for activating the Rho GTPase. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 54 TC 59 Z9 59 U1 0 U2 2 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX NO.100 537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD AUG PY 1999 VL 78 IS 8 BP 539 EP 548 PG 10 WC Cell Biology SC Cell Biology GA 234AH UT WOS:000082460200003 PM 10494860 ER PT J AU Hussain, MA AF Hussain, MA TI Insulin begets insulin SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID ISOLATED PANCREATIC-ISLETS; BETA-CELLS; FEEDBACK INHIBITION; GENE-EXPRESSION; DIABETES-MELLITUS; MESSENGER-RNA; RAT ISLETS; B-CELLS; SECRETION; GLUCOSE C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Hussain, MA (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, 50 Blossom St,Wellman 320, Boston, MA 02114 USA. NR 31 TC 2 Z9 2 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD AUG PY 1999 VL 141 IS 2 BP 95 EP 97 DI 10.1530/eje.0.1410095 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228TW UT WOS:000082152600002 PM 10427148 ER PT J AU Hussain, MA AF Hussain, MA TI Bladerunners and telomerases SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID HUMAN FIBROBLASTS; IMMORTAL CELLS; ACTIVATION; LENGTH; CANCER; RNA C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Hussain, MA (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, 50 Blossom St Wellman 320, Boston, MA 02114 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD AUG PY 1999 VL 141 IS 2 BP 98 EP 100 DI 10.1530/eje.0.1410098 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228TW UT WOS:000082152600003 PM 10427149 ER PT J AU Pearce, EIF Margolis, HC Kent, RL AF Pearce, EIF Margolis, HC Kent, RL TI Effect of in situ plaque mineral supplementation on the state of saturation of plaque fluid during sugar-induced acidogenesis SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE plaque; calcium; phosphate; fluoride ID CARIES-SUSCEPTIBLE INDIVIDUALS; HUMAN DENTAL PLAQUE; POSITIVE INDIVIDUALS; SUCROSE EXPOSURE; CALCIUM; PH; BINDING; PHOSPHATE; CHALLENGE; SALIVA AB Dental plaque fluid is normally supersaturated with respect to enamel mineral but this may change to a state of undersaturation when plaque pH falls following sugar exposure, placing the adjacent enamel at risk of caries. We have determined the saturation status of the fluid in both resting and fermenting plaque following mineral supplementation. Eleven subjects abstained from oral hygiene and rinsed their mouth 3 times/d for 3 d with a placebo solution or with test solutions designed to enrich plaque with hydroxyapatite or fluorhydroxyapatite. On the morning of day 4, plaque samples were collected before and after exposure to 10% sucrose. Compared to the placebo, use of the test rinses resulted in significantly higher concentrations of Ca, P and F in plaque residue. In plaque fluid, higher post-sucrose Ca-free(2+) concentrations and saturation levels with respect to enamel mineral and fluorapatite were found after use of the hydroxyapatite rinse compared to the placebo, effects that probably resulted from the release of cell-bound Ca2+ as well as from the dissolution of apatite. Thus, some evidence was obtained that the test mouthrinses can counteract the fall in saturation level found when plaque is exposed briefly to sucrose. Potential long-term benefits of the test mouthrinses deserve further study. C1 Wellington Sch Med, Dept Pathol, Dent Res Grp, Wellington S, New Zealand. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Pearce, EIF (reprint author), Wellington Sch Med, Dept Pathol, Dent Res Grp, POB 7343, Wellington S, New Zealand. FU NIDCR NIH HHS [DE-07493] NR 29 TC 10 Z9 12 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD AUG PY 1999 VL 107 IS 4 BP 251 EP 259 DI 10.1046/j.0909-8836.1999.eos107404.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 226MP UT WOS:000082024000004 PM 10467940 ER PT J AU Roodman, GD AF Roodman, GD TI Cell biology of the osteoclast SO EXPERIMENTAL HEMATOLOGY LA English DT Review DE osteoclast; precursor; bone resorption ID COLONY-STIMULATING FACTOR; TRANSFORMING GROWTH-FACTOR; HUMAN MARROW CULTURES; BONE-RESORPTION INVITRO; CALCITONIN RECEPTOR ISOFORMS; HORMONE-RELATED PROTEIN; INHIBITORY FACTOR OCIF; ESTROGEN TARGET-CELLS; OSTEOBLAST-LIKE CELLS; LARGE T-ANTIGEN AB The osteoclast is a hematopoietic cell derived from CFU-GM and branches from the monocyte-macrophage lineage early during the differentiation process. The marrow microenvironment appears critical for osteoclast formation due to production of RANK ligand, a recently described osteoclast differentiation factor, by marrow stromal cells in response to a variety of osteotropic factors. In addition, factors such as osteoprotegerin, a newly described inhibitor of osteoclast formation, as well as secretory products produced by the osteoclast itself and other cells in the marrow enhance or inhibit osteoclast formation. The identification of the role of oncogenes such as c-fos and pp60 c-src in osteoclast differentiation and bone resorption have provided important insights in the regulation of normal osteoclast activity. Current research is beginning to delineate the signaling pathways involved in osteoclastic bone resorption and osteoclast formation in response to cytokines and hormones. The recent development of osteoclast cell lines may make it possible for major advances to our understanding of the biology of the osteoclast to be realized in the near future. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Audie L Murphy Mem Vet Hosp, Res Serv 151, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, San Antonio, TX USA. RP Roodman, GD (reprint author), Audie L Murphy Mem Vet Hosp, Res Serv 151, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 119 TC 336 Z9 355 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1999 VL 27 IS 8 BP 1229 EP 1241 DI 10.1016/S0301-472X(99)00061-2 PG 13 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 219NX UT WOS:000081614300001 PM 10428500 ER PT J AU Emery, DW Holley, K Sachs, DH AF Emery, DW Holley, K Sachs, DH TI Enhancement of swine progenitor chimerism in mixed swine/human bone marrow cultures with swine cytokines SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE culture; bone marrow; cytokines; xenogeneic; swine ID HEMATOPOIETIC STEM-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; DONOR-SPECIFIC TOLERANCE; IMMUNE-DEFICIENT MICE; MINIATURE SWINE; ORGAN XENOTRANSPLANTATION; ALLOGENEIC CHIMERISM; CYNOMOLGUS MONKEYS; TRANSPLANTATION; INDUCTION AB Objective: The induction of transplantation tolerance across xenogeneic barriers by bone marrow transplantation holds great promise, but engraftment of xenogeneic stem cells has been difficult to achieve. Part of this difficulty is due to species-specific differences in regulatory cytokines and elements of the stromal microenvironment, which we studied here. Materials and Methods: We developed a system where fresh bone marrow cells from swine and human are cultured on human bone marrow stroma in order to study these limiting factors in a clinically relevant species combination. Results: We report here the ability of recombinant swine interleukin (IL)-3 and c-kit ligand (KL) to specifically enhance swine hematopoietic chimerism in this system. In the absence of exogenous swine cytokines, there were about half as many swine progenitors as human progenitors at 1, 2, and 4 weeks of culture. When used alone, swine IL-3 led to a notable but transient increase in the relative ratio of swine progenitors, while addition of swine KL increased the ratio of swine progenitors only modestly and only at later time points. In contrast, when swine IL-3 and KL were added together, there was a two- to fourfold increase in the ratio of swine to human progenitors at all times tested. Conclusion: These data demonstrate that both swine IL-3 and KL are needed for prolonged enhancement of swine progenitor chimerism under these conditions, and suggest that the species specificity of either one or both of these cytokines may represent an important barrier to prolonged engraftment of swine bone marrow in humans. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH-E,Bldg 149-9019,13th St, Boston, MA 02129 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NHLBI NIH HHS [HL54038]; NIAID NIH HHS [AI39755] NR 50 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1999 VL 27 IS 8 BP 1330 EP 1337 DI 10.1016/S0301-472X(99)00058-2 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 219NX UT WOS:000081614300012 PM 10428510 ER PT J AU Cherubini, A Beal, MF Frei, B AF Cherubini, A Beal, MF Frei, B TI Black tea increases the resistance of human plasma to lipid peroxidation in vitro, but not ex vivo SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE tea; flavonoids; antioxidants; lipid peroxidation; human study; free radicals ID CORONARY-HEART-DISEASE; LOW-DENSITY-LIPOPROTEIN; HUMAN-BLOOD PLASMA; CHAIN-BREAKING ANTIOXIDANTS; GREEN TEA; FLAVONOID INTAKE; LDL OXIDATION; RADICALS; CONSUMPTION; EPICATECHIN AB A number of in vitro studies have shown that polyphenols and flavonoids in tea exert significant antioxidant activity. However, epidemiologic and experimental studies have produced conflicting results. The purpose of the present study was to compare the antioxidant activity of black tea in vitro with that ex vivo. Black tea polyphenols (BTP), black tea extract (BTE), or their major polyphenolic antioxidant constituent, epigallocatechin gallate (EGCG), were added to human plasma and lipid peroxidation was induced by the water-soluble radical generator 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Following a lag phase, lipid peroxidation was initiated and occurred at a rate that was lowered in a dose-dependent manner by BTP. Similarly, EGCG and BTE added to plasma in vitro strongly inhibited AAPH-induced lipid peroxidation. The lag phase preceding detectable Lipid peroxidation was due to the antioxidant activity of endogenous ascorbate, which was more effective at inhibiting lipid peroxidation than the tea polyphenols and was not spared by these compounds. In contrast, when eight healthy volunteers consumed the equivalent of six cups of black tea, the resistance of their plasma to lipid peroxidation ex vivo did not increase over the next 3 h. These data suggest that, despite antioxidant efficacy in vitro, black tea does not protect plasma from lipid peroxidation in vivo. The striking discrepancy between the in vitro and ex vivo data is most likely explained by the insufficient bioavailability of tea polyphenols in humans. (C) 1999 Elsevier Science Inc. C1 Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurochem Lab, Boston, MA USA. RP Frei, B (reprint author), Oregon State Univ, Linus Pauling Inst, 571 Weniger Hall, Corvallis, OR 97331 USA. OI Cherubini, Antonio/0000-0003-0261-9897 FU NHLBI NIH HHS [HL 56170] NR 54 TC 63 Z9 64 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG PY 1999 VL 27 IS 3-4 BP 381 EP 387 DI 10.1016/S0891-5849(99)00064-7 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 227YL UT WOS:000082107500018 PM 10468212 ER PT J AU Gross, A McDonnell, JM Korsmeyer, SJ AF Gross, A McDonnell, JM Korsmeyer, SJ TI BCL-2 family members and the mitochondria in apoptosis SO GENES & DEVELOPMENT LA English DT Review ID PROGRAMMED CELL-DEATH; CYTOCHROME-C RELEASE; PROAPOPTOTIC PROTEIN BAX; PERMEABILITY TRANSITION PORE; BH3 DOMAIN; X-L; MAMMALIAN-CELLS; SCHIZOSACCHAROMYCES-POMBE; SUBCELLULAR-DISTRIBUTION; SEQUENCE SIMILARITY C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Rockefeller Univ, New York, NY 10021 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. NR 122 TC 2624 Z9 2728 U1 19 U2 159 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 1999 VL 13 IS 15 BP 1899 EP 1911 DI 10.1101/gad.13.15.1899 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 225QH UT WOS:000081971900001 PM 10444588 ER PT J AU Krebber, H Taura, T Lee, MS Silver, PA AF Krebber, H Taura, T Lee, MS Silver, PA TI Uncoupling of the hnRNP Npl3p from mRNAs during the stress-induced block in mRNA export SO GENES & DEVELOPMENT LA English DT Article DE hnRNP; Npl3p; mRNA export; S. cerevisiae; stress ID RNA-BINDING PROTEIN; MESSENGER-RNA; NUCLEAR EXPORT; SACCHAROMYCES-CEREVISIAE; IMPORTIN-ALPHA; NUCLEOCYTOPLASMIC TRANSPORT; YEAST; SIGNAL; CYTOPLASM; CRM1 AB Npl3p, the major mRNA binding protein of the yeast Saccharomyces cerevisiae shuttles between the nucleus and the cytoplasm. A single amino acid change in the carboxyl terminus of Npl3p (E409 --> K) renders the mutant protein largely cytoplasmic because of a delay in its import into the nucleus. This import defect can be reversed by increasing the intracellular concentration of Mtr10p, the nuclear import receptor for Npl3p. Conversely, using this mutant, we show that Npl3p and mRNA export out of the nucleus is significantly slowed in cells bearing mutations in XPO1/CRM1, which encodes the export receptor for NES-containing proteins and in RAT7, which encodes an essential nucleoporin. Interestingly, following induction of stress by heat shock, high salt, or ethanol, conditions under which most mRNA export is blocked, Npl3p is still exported from the nucleus. The stress-induced export of Npl3p is independent of both the activity of Xpo1p and the continued selective export of heat-shock mRNAs that occurs following stress. UV-cross-linking experiments show that Npl3p is bound to mRNA under normal conditions, but is no longer RNA associated in stressed cells. Taken together, we suggest that;the uncoupling of Npl3p and possibly other mRNA-binding proteins from mRNAs in the nucleus provides a general switch that regulates mRNA export. By this model, under normal conditions Npl3p is a major component of an export-competent RNP complex. However, under conditions of stress, Npl3p no longer associates with the export complex, rendering it export incompetent and thus nuclear. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 43 TC 61 Z9 61 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 1 PY 1999 VL 13 IS 15 BP 1994 EP 2004 DI 10.1101/gad.13.15.1994 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 225QH UT WOS:000081971900010 PM 10444597 ER PT J AU Biener, L Glanz, K McLerran, D Sorensen, G Thompson, B Basen-Engquist, K Linnan, L Varnes, J AF Biener, L Glanz, K McLerran, D Sorensen, G Thompson, B Basen-Engquist, K Linnan, L Varnes, J TI Impact of the Working Well Trial on the worksite smoking and nutrition environment SO HEALTH EDUCATION & BEHAVIOR LA English DT Article ID HEALTH PROMOTION; DRINKING NORMS; INTERVENTION; CAFETERIA; ORGANIZATIONS AB This article reports the effect of a worksite cancer control intervention on aspects of the physical and social environment related to dietary and smoking behaviors of employees. Data are from 111 intervention and control worksites that participated in the Working Well Trial. Employee surveys and interviews with key organizational informants assessed environmental and normative changes relevant to nutrition and tobacco use. Results indicated significant effects of the intervention on all nutrition outcomes: access to healthy food, nutritional information at work, and social norms regarding dietary choice. Significant benefits were not found for smoking norms or smoking policies. However, changes occurred in both the control and intervention sites on these variables. This first large analysis of environmental and normative effects of a worksite intervention is consistent with the employee behavior change findings for the trial and serves as a model for future analyses of multilevel worksite health promotion programs. C1 Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Univ Hawaii, Ctr Canc Res, Honolulu, HI 96822 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. Miriam Hosp, Providence, RI 02906 USA. Univ Florida, Coll Hlth & Human Performance, Gainesville, FL USA. RP Biener, L (reprint author), Univ Massachusetts, Survey Res Ctr, 100 Morrissey Blvd, Boston, MA 02125 USA. OI Biener, Lois/0000-0002-4130-8138 FU NCI NIH HHS [U01 CA51686, U01 CA51687, U01 CA61771] NR 24 TC 44 Z9 44 U1 2 U2 6 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 1999 VL 26 IS 4 BP 478 EP 494 DI 10.1177/109019819902600407 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 217VJ UT WOS:000081519300006 PM 10435233 ER PT J AU Derby, ML Sena-Esteves, M Breakefield, XO Corey, DP AF Derby, ML Sena-Esteves, M Breakefield, XO Corey, DP TI Gene transfer into the mammalian inner ear using HSV-1 and vaccinia virus vectors SO HEARING RESEARCH LA English DT Article DE gene transfer; gene therapy; viral vector; herpes simplex virus; vaccinia virus; cochlea; inner ear ID HERPES-SIMPLEX VIRUS; GUINEA-PIG COCHLEA; IN-VIVO; RIBONUCLEOTIDE REDUCTASE; ADENOASSOCIATED VIRUS; THYMIDINE KINASE; NEUROTROPHIC FACTOR; IMMUNE-RESPONSES; MESSENGER-RNAS; NERVOUS-SYSTEM AB The introduction of foreign genes into cells has become an effective means of achieving intracellular expression of foreign proteins, both for therapeutic purposes and for experimental manipulation. Gene delivery to the nervous system has been extensively studied, primarily using viral vectors. However, to date less work has focused on gene delivery to the inner ear, and existing studies have primarily used adenovirus and adeno-associated virus. Using two recombinant viral vectors, herpes simplex type 1 (HSV-1), and vaccinia virus, bearing the Escherichia coli lacZ gene, we tested gene delivery to the guinea pig cochlea in vivo with beta-galactosidase staining as an assay. The HSV-1 and vaccinia virus vectors were both found to infect and elicit transgene expression successfully in many cells in the guinea pig cochlea, including cells in the organ of Corti. These data demonstrate the feasibility of gene delivery to the inner ear using these two viral vectors. Such techniques may facilitate study of the auditory systems, and might be used to develop gene therapy strategies for some forms of hearing loss, (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. RP Corey, DP (reprint author), Massachusetts Gen Hosp, WEL414, Boston, MA 02114 USA. OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [DC02355, DC02281]; NINDS NIH HHS [NS24279] NR 52 TC 67 Z9 74 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD AUG PY 1999 VL 134 IS 1-2 BP 1 EP 8 DI 10.1016/S0378-5955(99)00045-3 PG 8 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 223BY UT WOS:000081820900001 PM 10452370 ER PT J AU Jarmukli, NF Ahn, J Iranmanesh, A Russell, DC AF Jarmukli, NF Ahn, J Iranmanesh, A Russell, DC TI Effect of raised plasma beta endorphin concentrations on peripheral pain and angina thresholds in patients with stable angina SO HEART LA English DT Article DE beta endorphin; angina; pain ID SILENT-MYOCARDIAL-ISCHEMIA; CORONARY-ARTERY DISEASE; EXERCISE; PECTORIS; STIMULATION; PERCEPTION; MECHANISMS; THALAMUS; NUCLEUS; STRESS AB Objective-To determine whether changes in plasma concentrations of beta endorphins alter angina threshold and peripheral pain threshold in patients with stable angina. Design-Latin square design comparison of angina thresholds by exercise treadmill test and peripheral pain thresholds using a radiant heat source in eight patients with stable angina under control conditions, after stimulation of pituitary beta endorphin release by ketoconazole, after suppression of pituitary beta endorphin release by dexamethasone, and after blockade of opioid receptors by intravenous naloxone. Results-An approximately fivefold increase in circulating concentrations of beta endorphins was found after administration of ketoconazole (mean (SEM): 13.9 (1.2) v 73.8 (6.2) pg/ml; p < 0.05), which was associated with an increase in peripheral pain threshold to a radiant heat source (time to onset of pain perception 72 (19) v 123 (40) seconds; p < 0.05), but no significant difference in angina threshold. A reduction in circulating concentrations of beta endorphins after pretreatment with dexamethasone was statistically nonsignificant (13.9 (1.2) v 9.0 (1.5) pg/ml; NS) and was not associated with any change in either peripheral pain or angina thresholds. No effects were seen after blockade of opioid receptors by previous administration of intravenous naloxone. Conclusions-Increased plasma concentrations of beta endorphins alter peripheral pain threshold but not angina threshold in patients with stable angina pectoris. C1 Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Vet Adm Med Ctr, Cardiol Sect, Salem, VA USA. RP Russell, DC (reprint author), William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. NR 36 TC 13 Z9 15 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD AUG PY 1999 VL 82 IS 2 BP 204 EP 209 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 223BL UT WOS:000081819800021 PM 10409537 ER PT J AU Thornton, AF Laramore, GE AF Thornton, AF Laramore, GE TI Technical advances in radiotherapy of head and neck tumors SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID RADIATION-THERAPY; LOCAL-CONTROL; EYE-VIEW; SKULL; BASE; IRRADIATION; INTEGRATION; EXPERIENCE; CARCINOMAS; IR-192 AB Technical advances in the irradiation of head and neck neoplasia have included increased energies for photon delivery, three-dimensional treatment planning, and the routine incorporation of both CT and magnetic resonance imaging into the planning process. Teletherapy has taken these advances further with the refinement of stereotactic radiosurgical techniques, making possible very precise (millimeter-accuracy) irradiation, both on a single and fractionated basis. particle (largely proton or neutron) radiotherapy improves on conventional photon irradiation by increasing targeting accuracy (proton) or radiobiologic Efficacy (neutron). Radioimmunotherapy and brachytherapy seek to also improve accuracy through the direct installation of radioactive isotopes into tissues or surgically placed sources. With these modalities delivering increased doses, local control of head and neck neoplasia is being increased and systemic toxicities remain equal or decline. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. RP Massachusetts Gen Hosp, Dept Radiat Oncol, Cox-3,32 Fruit St, Boston, MA 02114 USA. NR 37 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 1999 VL 13 IS 4 BP 811 EP + DI 10.1016/S0889-8588(05)70094-0 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 231WT UT WOS:000082334900012 PM 10494515 ER PT J AU Forsch, RA Wright, JE Rosowsky, A AF Forsch, RA Wright, JE Rosowsky, A TI Synthesis of the gamma-sulfinic acid and gamma-nitro analogues of 5-deazatetrahydrofolic acid SO HETEROCYCLES LA English DT Article ID FOLYLPOLYGLUTAMATE SYNTHETASE-ACTIVITY; CCRF-CEM; CYTOTOXICITY; INHIBITORS; TRANSPORT; LEUKEMIA; INVITRO; FOLATE; ROUTE; CELLS AB Analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid with a gamma-sulfinic acid group or gamma-nitro group in place of the gamma-carboxyl group of the glutamate side chain were synthesized as diastereomeric mixtures, and were tested for their ability to inhibit the growth of CCRF-CEM human leukemia cells in culture. The concentration of the gamma-sulfinic acid analogue (7) giving 50% inhibition of growth during 120 h of continuous drug treatment was 21 mu M versus 93 mu M for the gamma-nitro analogue (8). The Ki of 7 as a competitive inhibitor of the influx of [H-3]methotrexate into CCRF-CEM cells via the reduced folate carrier (RFC) was 5.0 mu M, a value close to the K-m, values typically cited in the literature for MTX and natural reduced folates. Thus, apart from any other mechanistic targets this compound might have, 7 has the potential to deplete endogenous pools of reduced folates in dividing cells by interfering with RFC function. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Forsch, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 19 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 0385-5414 J9 HETEROCYCLES JI Heterocycles PD AUG 1 PY 1999 VL 51 IS 8 BP 1789 EP 1805 PG 17 WC Chemistry, Organic SC Chemistry GA 227KQ UT WOS:000082079900004 ER PT J AU Marsh, DJ Kum, JB Lunetta, KL Bennett, MJ Gorlin, RJ Ahmed, SF Bodurtha, J Crowe, C Curtis, MA Dasouki, M Dunn, T Feit, H Geraghty, MT Graham, JM Hodgson, SV Hunter, A Korf, BR Manchester, D Miesfeldt, S Murday, VA Nathanson, KL Parisi, M Pober, B Romano, C Tolmie, JL Trembath, R Winter, RM Zackai, EH Zori, RT Weng, LP Dahia, PLM Eng, C AF Marsh, DJ Kum, JB Lunetta, KL Bennett, MJ Gorlin, RJ Ahmed, SF Bodurtha, J Crowe, C Curtis, MA Dasouki, M Dunn, T Feit, H Geraghty, MT Graham, JM Hodgson, SV Hunter, A Korf, BR Manchester, D Miesfeldt, S Murday, VA Nathanson, KL Parisi, M Pober, B Romano, C Tolmie, JL Trembath, R Winter, RM Zackai, EH Zori, RT Weng, LP Dahia, PLM Eng, C TI PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID LHERMITTE-DUCLOS DISEASE; ENDOCRINE NEOPLASIA TYPE-2; TUMOR-SUPPRESSOR GENE; PHOSPHATASE-ACTIVITY; GERMLINE MUTATIONS; JUVENILE POLYPOSIS; PROSTATE-CANCER; PTEN/MMAC1; DELETION; BREAST AB Germline mutations in the tumour suppressor gene PTEN have been implicated in two hamartoma syndromes that exhibit some clinical overlap, Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR). PTEN maps to 10q23 and encodes a dual specificity phosphatase, a substrate of which is phosphatidylinositol 3,4,5-triphosphate, a phospholipid in the phosphatidylinositol 3-kinase pathway. CS is characterized by multiple hamartomas and an increased risk of benign and malignant disease of the breast, thyroid and central nervous system, whilst the presence of cancer has not been formally documented in ERR. The partial clinical overlap in these two syndromes is exemplified by the hallmark features of ERR: macrocephaly and multiple lipomas, the latter of which occur in a minority of individuals with CS. Additional features observed in ERR, which may also occur in a minority of CS patients, include Hashimoto's thyroiditis, vascular malformations and mental retardation. Pigmented macules of the glans penis, delayed motor development and neonatal or infant onset are noted only in ERR. In this study, constitutive DNA samples from 43 ERR individuals comprising 16 sporadic and 27 familial cases, 11 of which were families with both CS and ERR, were screened for PTEN mutations. Mutations were identified in 26 of 43 (60%) ERR cases. Genotype-phenotype analyses within the ERR group suggested a number of correlations, including the association of PTEN mutation and cancer or breast fibroadenoma in any given CS, ERR or BRR/CS overlap family (P = 0.014), and, in particular, truncating mutations were associated with the presence of cancer and breast fibroadenoma in a given family (P = 0.024). Additionally, the presence of lipomas was correlated with the presence of PTEN mutation in ERR patients (P = 0.028). In contrast to a prior report, no significant difference in mutation status was found in familial versus sporadic cases of ERR (P = 0.113). Comparisons between ERR and a previously studied group of 37 CS families suggested an increased likelihood of identifying a germline PTEN mutation in families with either CS alone or both CS and ERR when compared with ERR alone (P = 0.002). Among CS, ERR and BRR/CS overlap families that are PTEN mutation positive, the mutation spectra appear similar. Thus, PTEN mutation-positive CS and ERR may be different presentations of a single syndrome and, hence, both should receive equal attention with respect to cancer surveillance. C1 Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Pathol & Pediat, Dallas, TX 75235 USA. Univ Minnesota, Dept Oral Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Med Genet, Minneapolis, MN 55455 USA. Univ Cambridge, Sch Clin, Dept Paediat, Cambridge CB2 2QQ, England. Childrens Hosp, Richmond, VA 23220 USA. Metrohlth Med Ctr, Dept Pediat, Cleveland, OH 44109 USA. Arkansas Childrens Hosp, Clin Genet Program, Little Rock, AR 72202 USA. Vanderbilt Univ, Med Ctr, Div Genet, Nashville, TN 37232 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Henry Ford Hosp, Dept Med Genet, Detroit, MI 48202 USA. Johns Hopkins Univ, Sch Med, Dept Med Genet, Baltimore, MD 21287 USA. Cedars Sinai Med Ctr, Clin Genet & Dysmorphol Serv, Los Angeles, CA 90048 USA. United Med & Dent Sch Guys & St Thomas Hosp, St Thomas Hosp, London SE1 7EH, England. United Med & Dent Sch Guys & St Thomas Hosp, Kings Hosp, London SE1 7EH, England. Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. Childrens Hosp, Boston, MA 02114 USA. Univ Colorado, Sch Med, Clin Genet Serv, Denver, CO USA. Univ Virginia, Sch Med, Canc Genet Program, Richmond, VA USA. St George Hosp, Sch Med, London SW17 0RE, England. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Med Genet, Philadelphia, PA 19104 USA. Childrens Hosp & Reg Med Ctr, Div Med Genet, Seattle, WA 98105 USA. Yale Univ, Sch Med, New Haven, CT USA. Oasi Inst, Dept Paediat & Genet Counseling Serv, Troina, Italy. Duncan Guthrie Inst Med Genet, Glasgow G3 8SJ, Lanark, Scotland. Univ Leicester, Sch Med, Leicester, Leics, England. Great Ormond St Hosp Children NHS Trust, London WC1N 1EH, England. Inst Child Hlth, London WC1N 1EH, England. Univ Florida, Gainesville, FL USA. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, 690C Med Res Facil,420 W 12th Ave, Columbus, OH 43210 USA. RI Romano, Corrado/B-9695-2008; Marsh, Deborah/I-1491-2014; OI Romano, Corrado/0000-0003-1049-0683; Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [P30 CA16058] NR 46 TC 330 Z9 334 U1 1 U2 7 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 1999 VL 8 IS 8 BP 1461 EP 1472 DI 10.1093/hmg/8.8.1461 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 223RF UT WOS:000081853500012 PM 10400993 ER PT J AU Kamide, K Hori, MT Barrett, JD Eggena, P Tuck, ML AF Kamide, K Hori, MT Barrett, JD Eggena, P Tuck, ML TI Insulin like growth factor-1 promotes angiotensinogen production and growth in cultured rat vascular smooth muscle cells SO HYPERTENSION LA English DT Meeting Abstract C1 VA Greater Los Angeles Hlth Care Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD AUG PY 1999 VL 34 IS 2 MA P133 BP 363 EP 363 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 227YW UT WOS:000082108500235 ER PT J AU Kamide, K Hori, MT Barrett, JD Eggena, P Tuck, ML AF Kamide, K Hori, MT Barrett, JD Eggena, P Tuck, ML TI Insulin attenuates vascular renin-angiotensin system in cultured human aortic vascular endothelial cells SO HYPERTENSION LA English DT Meeting Abstract C1 VA Greater Los Angeles Hlth Care Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD AUG PY 1999 VL 34 IS 2 MA P169 BP 370 EP 370 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 227YW UT WOS:000082108500276 ER PT J AU Monroe, RJ Seidl, KJ Gaertner, F Han, SH Chen, F Sekiguchi, J Wang, JY Ferrini, R Davidson, L Kelsoe, G Alt, FW AF Monroe, RJ Seidl, KJ Gaertner, F Han, SH Chen, F Sekiguchi, J Wang, JY Ferrini, R Davidson, L Kelsoe, G Alt, FW TI RAG2 : GFP knockin mice reveal novel aspects of RAG2 expression in primary and peripheral lymphoid tissues SO IMMUNITY LA English DT Article ID HEAT-STABLE ANTIGEN(HI); B-CELL DIFFERENTIATION; V(D)J RECOMBINATION; GENE-EXPRESSION; BONE-MARROW; DEVELOPMENTAL REGULATION; LYMPHOCYTES-B; T-CELLS; RECEPTOR; REARRANGEMENT AB We generated mice in which a functional RAG2:GFP fusion gene is knocked in to the endogenous RAG2 locus. In bone marrow and thymus, RAG2:GFP expression occurs in appropriate stages of developing B and T cells as well as in immature bone marrow IgM(+) B cells. RAGS:GFP also is expressed in IgD(+) B cells following cross-linking of IgM on immature IgM(+)IgD(+) B cells generated in vitro. RAG2:GFP expression is undetectable in most immature splenic B cells; however, in young RAG2:GFP mice, there are substantial numbers of splenic RAG2:GFP(+) cells that mostly resemble pre-B cells. The tatter population decreases in size with age but reappears following immunization of older RAG2:GFP mice. We discuss the implications of these findings for current models of receptor assembly and diversification. C1 Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Duke Univ, Sch Med, Dept Immunol, Durham, NC 27710 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, 300 Longwood Ave, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 FU NIAID NIH HHS [AI24335, AI20047] NR 49 TC 134 Z9 137 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 1999 VL 11 IS 2 BP 201 EP 212 DI 10.1016/S1074-7613(00)80095-3 PG 12 WC Immunology SC Immunology GA 232RH UT WOS:000082383400009 PM 10485655 ER PT J AU Ruprecht, RM AF Ruprecht, RM TI Live attenuated AIDS viruses as vaccines: promise or peril? SO IMMUNOLOGICAL REVIEWS LA English DT Review ID SIMIAN IMMUNODEFICIENCY VIRUS; LONG-TERM SURVIVOR; RHESUS MACAQUES; IMMUNE-RESPONSES; SIV VACCINE; NEF GENE; ANTIBODY-RESPONSES; DELETION MUTANT; HIV-1 INFECTION; IN-VIVO AB Live attenuated viruses can provide vaccine protection against various viral illnesses. A number of live attenuated strains of the simian immunodeficiency virus (SIV) or related lentiviruses have been evaluated in primate models as vaccine candidates against AIDS. Impressive efficacy was observed for some viruses, most notably SIV strains with deletions in the nef gene. Sterilizing immunity was seen against homologous and heterologous virus challenge, against cell-free and cell-associated challenge, against intravenous and mucosal challenge, and against challenge as early as 3 weeks and as late as 2.25 years after just one immunization. However, these promising efficacy results are overshadowed by safety problems, such as reversion of the vaccine strain to a pathogenic virus encoding full-length nef or residual virulence of multiply deleted vaccine strains. Strategies aimed at decreasing the replicative capacity of nef-deleted vaccine strains to increase the safety profile have significantly curtailed vaccine efficacy. Nevertheless. studies of live attenuated vaccine strains should proceed and should focus on determining the correlates of vaccine protection and the molecular determinants for virulence and attenuation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCRR NIH HHS [R01-RR14180]; NIAID NIH HHS [R01-AI32330, R01-AI35533] NR 72 TC 57 Z9 60 U1 0 U2 0 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 1999 VL 170 BP 135 EP 149 DI 10.1111/j.1600-065X.1999.tb01335.x PG 15 WC Immunology SC Immunology GA 249GZ UT WOS:000083326100012 PM 10566148 ER PT J AU Lupher, ML Rao, N Eck, MJ Band, H AF Lupher, ML Rao, N Eck, MJ Band, H TI The Cbl protooncoprotein: a negative regulator of immune receptor signal transduction SO IMMUNOLOGY TODAY LA English DT Review ID CELL ANTIGEN RECEPTOR; PHOSPHOTYROSINE-BINDING DOMAIN; PROTEIN-TYROSINE KINASE; PROTOONCOGENE C-CBL; T-CELLS; PHOSPHORYLATION SITES; ACTIVATION; SYK; ZAP-70; PRODUCT AB The Cbl protooncoprotein has recently emerged as a component of tyrosine kinase-mediated signal transduction in a variety of cell types. Here, we discuss evidence that supports a role for Cbl as a novel negative regulator of immune receptor signaling, and present models for its mode of function. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Massachusetts Dept Publ Hlth, Boston, MA 02111 USA. RP Lupher, ML (reprint author), ICOS Corp, Bothell, WA 98021 USA. NR 62 TC 112 Z9 114 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD AUG PY 1999 VL 20 IS 8 BP 375 EP 382 DI 10.1016/S0167-5699(99)01484-X PG 8 WC Immunology SC Immunology GA 223TJ UT WOS:000081856700008 PM 10431158 ER PT J AU Way, SS Borczuk, AC Goldberg, MB AF Way, SS Borczuk, AC Goldberg, MB TI Thymic independence of adaptive immunity to the intracellular pathogen Shigella flexneri serotype 2a SO INFECTION AND IMMUNITY LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS INFECTION; DELAYED-TYPE HYPERSENSITIVITY; TRANSFER PROTECTIVE IMMUNITY; LYT-2+ T-CELLS; LISTERIA-MONOCYTOGENES; IMMUNOGLOBULIN-A; LEISHMANIA-MAJOR; ADOPTIVE TRANSFER; GAMMA-INTERFERON; RECTAL MUCOSA AB Shigella flexneri is a facultative intracellular pathogen. While immunity to several intracellular pathogens is mediated by T lymphocytes, it is unknown whether cellular immune responses are important to adaptive immunity to S. flexneri. We show that vaccination with S. flexneri serotype 2a confers protection to mice that lack T lymphocytes or gamma interferon (IFN-gamma), specific depletion of T lymphocytes does not alter the protection, and adoptive transfer of splenocytes from vaccinated mice does not confer protection to naive mice. In contrast, vaccination conferred no protection to mice that lack B lymphocytes and adoptive transfer of immune sera conferred partial protection to naive mice. These data demonstrate that in the mouse bronchopulmonary model, adaptive immunity to S. flexneri 2a is an antibody-mediated, B-lymphocyte-dependent process and can be generated in the absence of T lymphocytes or IFN-gamma. C1 Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. FU CSAP SAMHSA HHS [SP30-CA13330]; NCI NIH HHS [P30 CA013330]; NIAID NIH HHS [AI35817, R01 AI035817] NR 68 TC 17 Z9 17 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 AUG PY 1999 VL 67 IS 8 BP 3970 EP 3979 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 219ZA UT WOS:000081637400037 PM 10417163 ER PT J AU Zhong, Z Burns, T Chang, Q Carroll, M Pirofski, L AF Zhong, Z Burns, T Chang, Q Carroll, M Pirofski, L TI Molecular and functional characteristics of a protective human monoclonal antibody to serotype 8 Streptococcus pneumoniae capsular polysaccharide SO INFECTION AND IMMUNITY LA English DT Article ID ALTERNATIVE COMPLEMENT PATHWAY; STAPHYLOCOCCAL PROTEIN-A; SICKLE-CELL DISEASE; HUMAN-IMMUNOGLOBULIN; B-CELLS; SOMATIC HYPERMUTATION; CRYPTOCOCCUS-NEOFORMANS; PNEUMOCOCCAL ANTIBODY; GENE REPERTOIRE; HUMAN-SERUM AB The structural characteristics and biological activity of human antibodies that are reactive with the capsular polysaccharides of most serotypes of Streptococcus pneumoniae, including serotype 8, are unknown. This paper describes the generation, molecular structure, and protective efficacy of a human monoclonal antibody (MAb) reactive with the capsular polysaccharide of serotype 8 Streptococcus pneumoniae. We generated the immunoglobulin M(kappa) [IgM(kappa)] MAb D11 by Epstein-Barr virus transformation of peripheral lymphocytes from a Pneumovax recipient. Nucleic acid sequence analysis revealed that MAb D11 uses V3-15/V(H)3 and A20/V-kappa gene segments with evidence of somatic mutation. In vitro studies revealed MAb D11-dependent complement deposition on the capsule of serotype 8 organisms via either the classical or the alternative complement pathway. In vivo, MAb D11 prolonged the survival of both normal and C4-deficient mice with lethal serotype 8 S. pneumoniae infection. Our findings demonstrate that a serotype-specific human IgM with certain structural and functional characteristics was protective in mice lacking a functional classical complement pathway and show that alternative complement pathway activation is an important determinant of pneumococcal protection. C1 Yeshiva Univ Albert Einstein Coll Med, Div Infect Dis, Dept Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. RP Pirofski, L (reprint author), Yeshiva Univ Albert Einstein Coll Med, Div Infect Dis, Dept Med, Room 402 Forchheimer,1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NIAID NIH HHS [AI 35370, R01 AI035370, AI 07576] NR 56 TC 32 Z9 33 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1999 VL 67 IS 8 BP 4119 EP 4127 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 219ZA UT WOS:000081637400056 PM 10417182 ER PT J AU Nau, GJ Liaw, L Chupp, GL Berman, JS Hogan, BLM Young, RA AF Nau, GJ Liaw, L Chupp, GL Berman, JS Hogan, BLM Young, RA TI Attenuated host resistance against Mycobacterium bovis BCG infection in mice lacking osteopontin SO INFECTION AND IMMUNITY LA English DT Article ID NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; PROTECTIVE IMMUNE-RESPONSE; MUSCLE CELL-MIGRATION; INTERFERON-GAMMA; ATHEROSCLEROTIC PLAQUES; BACTERIAL-INFECTION; MURINE MACROPHAGES; GENETIC-RESISTANCE; GROWTH-INHIBITION AB Expression of the cytokine osteopontin (OPN) is elevated in granulomas caused by Mycobacterium tuberculosis. We tested the hypothesis that OPN contributes to host protection in a mouse model of mycobacterial infection. When infected with Mycobacterium bovis BCG, mice lacking a functional OPN gene had more severe infections characterized by heavier bacterial loads and a delayed clearance of the bacteria. The OPN-null mice had greater granuloma burdens consistent with the elevated bacterial load. The ability of osteopontin to facilitate the clearance of mycobacteria was most pronounced early after infection and appeared to be independent of known mediators of resistance to infection by mycobacteria: antigen-specific T-cell immunity, gamma interferon production, and nitric oxide production. BCG grew more rapidly in macrophages derived from OPN-null mice than in those from wild-type mice, demonstrating that the null phenotype was due to an intrinsic macrophage defect. These results indicate that osteopontin augments the host response against a mycobacterial infection and that it acts independently from other antimycobacterial resistance mechanisms. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Vanderbilt Univ, Med Ctr, Howard Hughes Med Inst, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Cell Biol, Nashville, TN 37232 USA. Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02188 USA. Vet Adm Med Ctr, Boston, MA 02130 USA. RP Young, RA (reprint author), MIT, Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Young, Richard/F-6495-2012; OI Young, Richard/0000-0001-8855-8647; Nau, Gerard/0000-0001-7921-8317 FU NIAID NIH HHS [AI01305, AI37869] NR 51 TC 114 Z9 119 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1999 VL 67 IS 8 BP 4223 EP 4230 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 219ZA UT WOS:000081637400069 PM 10417195 ER PT J AU McLaughlin, TJ Soumerai, SB Weinrib, D Aupont, O Cotton, D AF McLaughlin, TJ Soumerai, SB Weinrib, D Aupont, O Cotton, D TI The association between primary source of ambulatory care and access to and outcomes of treatment among AIDS patients SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE primary source of care; AIDS; access to treatment; outcomes ID ANTIRETROVIRAL THERAPY; ZIDOVUDINE USE; UNITED-STATES; DRUG-THERAPY; SURVIVAL; HIV; SEVERITY; INFECTION; DIAGNOSIS; SERVICES AB Objectives. To examine the relationship between having a primary source of ambulatory care (PSAC), access to AIDS treatment and prophylaxis for opportunistic infection, and hospital and mortality) outcomes among heterosexual men and women with AIDS. Methods. Using a linked AIDS Registry-Medicaid database, 366 adults were identified (1989-1991) with at least 1 year of continuous Medicaid enrollment before AIDS diagnosis, who survived 2 weeks after diagnosis, and with no antiretroviral use or Pnezumocystis carinii pneumonia (PCP) prophlaxis during the pre-diagnosis year. Outcomes included times to zidovudine treatment, PCP prophylaxis, hospitalization and death following diagnosis. Multivariate proportional hazards models were used to estimate the effects of patients' PSAC status in the 12-month post-diagnosis period on outcomes, controlling for demographic and case-mis variables. Results. Study criteria preferentially included females, non-whites and enrollees eligible on the basis of aid to families with dependent children. A total of 49% of the patients had no PSAC. Patients with a PSAC were more likely to have received zidovudine [relative risk RR) = 1.75, 95% confidence interval (CI) = 1.2, 2.2] or PCP prophylaxis (RR= 2.22, 95% CI = 1.5, 3.3). Regression models simultaneously examining association of the propensity to use zidovudine and PCP prophylaxis agents with death indicated that zidovudine-treated and PCP-prophylaxed patients were 64% and 51% less likely to die, respectively (RRdeath,zidovudine = 0.36, 95% CI = 0.2, 0.4; RRdeath,PCP prophylasis = 0.49, 95% CI = 0.3, 0.8). Conclusions. Patients' underuse of zidovudine and PCP prophylaxis was systematically associated with not having a PSAC. Lack of PSAC, in turn, predicted shorter survival but not increased hospitalization. Female gender, injecting drug use, nonwhite race and earlier diagnosis year also predicted poorer outcomes. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Univ, Pilgrim Hlth Care, Boston, MA 02215 USA. Beth Israel Hosp, Dept Med, Boston, MA 02215 USA. Brandeis Univ, Heller Sch, Waltham, MA 02254 USA. Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. RP McLaughlin, TJ (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 126 Brookline Ave,Suite 200, Boston, MA 02215 USA. FU AHRQ HHS [R01 HS06893]; NIAID NIH HHS [T32 AI 07433] NR 39 TC 7 Z9 7 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD AUG PY 1999 VL 11 IS 4 BP 293 EP 300 DI 10.1093/intqhc/11.4.293 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 230AC UT WOS:000082227900004 PM 10501599 ER PT J AU Chakrabarti, S Mahmood, A Makrigiorgos, GM AF Chakrabarti, S Mahmood, A Makrigiorgos, GM TI Fluorescent labelling of closely-spaced aldehydes induced in DNA by bleomycin-Fe(III) SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID MULTIPLY DAMAGED SITES; COLI ENDONUCLEASE-III; ABASIC SITES; DEOXYRIBONUCLEIC-ACID; IONIZING-RADIATION; REPAIR; CLEAVAGE; ASSAY; NEOCARZINOSTATIN; DEPURINATION AB Purpose: To test the ability of FARP(hc) and FARP, two novel fluorescent reagents, to label aldehyde-containing sites (principally abasic sites) generated in DNA by the radiomimetic drug bleomycin, and to use fluorescent energy transfer from FARP(hc) (donor) to FARP (acceptor) to quantitate such closely-spaced sites. Materials and methods: FARP(hc), 7-hydroxycoumarin-3-carboxylic acid (((((amino-oxymethyl) carbonyl) hydrazino) carbonylethyl) amide) was synthesized with a protocol similar to the one recently reported for FARP (a fluorescein-based probe). Results: Both FARP(hc) and FARP form stable oxime bonds with the open-chain aldehydes generated upon acidic depurination of DNA. Plasmid DNA exposed to bleomycin-Fe(III)-ascorbate undergoes extensive strand breakage, and upon subsequent reaction with FARP(hc) and/or FARP it becomes fluorescently labelled, indicating the generation of aldehyde-containing sites. The binding of the probes to calf thymus or plasmid DNA results in significant fluorescent energy transfer among closely-spaced fluorophores, as revealed by the fluorescence increase following digestion of fluorescently labelled samples with nuclease P1. The fluorescent quenching is most evident when both FARP(hc) and FARP are used simultaneously to trap aldehyde sites. When single-stranded oligonucleotides engineered to contain either one or two closely spaced bleomycin binding sites are exposed to bleomycin and then fluorescently labelled, the oligonucleotides demonstrate significantly increased fluorescent energy transfer with two binding sites indicating a dependence of aldehyde site generation and clustering on the local sequence of a single strand. Conclusions: A new detection method for DNA damage induced by bleomycin following fluorescent labelling of aldehyde group-containing sites (FLAGS) and their clustering via fluorescent energy transfer is demonstrated. The method is applicable to any form of DNA. This work may lead to a general approach for the quantification of multiply damaged sites in DNA, a subset of DNA lesions that may have major biological significance. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02215 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [R01 CA72046, K04 CA69296, R29 CA63334] NR 34 TC 4 Z9 5 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD AUG PY 1999 VL 75 IS 8 BP 1055 EP 1065 PG 11 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 225HW UT WOS:000081953200015 PM 10465372 ER PT J AU Hardenbergh, PH Recht, A Gollamudi, S Come, SE Hayes, DF Shulman, LN O'Neill, A Gelman, RS Silver, B Harris, JR AF Hardenbergh, PH Recht, A Gollamudi, S Come, SE Hayes, DF Shulman, LN O'Neill, A Gelman, RS Silver, B Harris, JR TI Treatment-related toxicity from a randomized trial of the sequencing of doxorubicin and radiation therapy in patients treated for early stage breast cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 38th Annual Meeting of American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 26-30, 1996 CL LOS ANGELES, CALIFORNIA SP Amer Soc Therapeut Radiol & Oncol DE late effects; cardiac toxicity; doxorubicin; radiation therapy; brachial plexopathy; arm edema; cellulitis; breast cancer ID ADJUVANT RADIOTHERAPY; HEART; CHEMOTHERAPY; SURGERY; IRRADIATION; MORTALITY; DISEASE AB Purpose: There is concern that breast cancer patients treated with left-sided radiation therapy (XRT) and doxorubicin (DOX) may have an increased risk of cardiac toxicity. In addition, the effect of different sequencing of XRT and chemotherapy (CT) on the likelihood of cardiotoxicity, as well as cellulitis, arm edema, or brachial plexopathy, is not well understood. We reviewed the records of patients treated on a randomized trial testing the sequencing of CT and XRT to determine if there was an increase in cardiac events or other complications in patients treated with a total dose of DOS of 180 mg/m(2) and XRT, comparing patients with treatment to the left breast and the right breast, and comparing patients treated with initial CT and initial RT, Materials and Methods: From June 1984 to December 1992, 244 patients with clinical stage I or II breast cancer were randomized following conservative surgery to receive CT (4 cycles of CAMFP at 3 week intervals) either before or after XRT (45 Gy to the entire breast, followed by a boost of 16 Gy; nodal radiation therapy was optional). Two hundred thirty-one patients were evaluable for the development of cardiac toxicity. The median age at diagnosis was 45 years (range, 20-68), CT doses were: doxorubicin, 45 mg/m(2) IV bolus, d 3; methotrexate, 200 mg/m(2) IV, d I and 15; 5-fluorouracil, 500 mg/m(2) IV, d 1; cyclophosphamide, 500 mg/m2 IV, d 1; prednisone 40 mg p.o., d 1-5, A cardiac event was defined as a myocardial infarction or clinical evidence of congestive heart failure. Median follow-up time was 53 months. Results: No cardiac events were observed for patients with either left- or right-sided breast cancer. The sequencing of CT and XRT had no significant effect on the risk of cardiac toxicity, cellulitis, arm edema or brachial plexopathy. Conclusions: We observed no evidence of an increased risk of cardiac toxicity from the addition of left breast tangential irradiation to DOX at a total dose of 180 mg/m(2). Additional follow-up is needed to exclude possible late events. In addition, the sequencing of CT and XRT does not appear to affect the risk of cellulitis, arm edema, or brachial plexopathy. (C) 1999 Elsevier Science Inc. C1 Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Breast Evaluat Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Sch Publ Hlth, Boston, MA USA. RP Recht, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Joint Ctr Radiat Therapy, East Campus,Finard Bldg B25,330 Brookline Ave, Boston, MA 02115 USA. NR 16 TC 24 Z9 24 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD AUG 1 PY 1999 VL 45 IS 1 BP 69 EP 72 DI 10.1016/S0360-3016(99)00127-3 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 225AZ UT WOS:000081934500011 PM 10477008 ER PT J AU Reid, P Kantoff, P Oh, W AF Reid, P Kantoff, P Oh, W TI Antiandrogens in prostate cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE antiandrogens; androgen receptor; prostate cancer; hormonal therapy ID ANDROGEN-RECEPTOR GENE; PURE NONSTEROIDAL ANTIANDROGEN; HIGH-DOSE BICALUTAMIDE; WITHDRAWAL SYNDROME; CYPROTERONE-ACETATE; CONTROLLED TRIAL; MEDROXYPROGESTERONE ACETATE; UNTREATED PATIENTS; MEGESTROL-ACETATE; RADIATION-THERAPY AB Antiandrogens competitively inhibit ligand binding to the androgen receptor (AR), and are used therapeutically in prostate cancer patients. The AR functions as a ligand dependent transcription factor that transduces androgen binding into increased transcription of androgen dependent genes. AR blockade induces programmed cell death in the vast majority of malignant and benign prostate cancer cells that have not previously been exposed to androgen ablation. The antiandrogens are divided structurally into the steroidal and non steroidal agents. The biological effects of the steroidal versus nonsteroidal agents are distinguished by differences in their effects on serum testosterone levels, and by their activity at receptors other than the androgen receptor. There is extensive clinical experience in the palliative and curative therapy of prostate cancer using antiandrogens as monotherapy or antiandrogens in combination with luteinizing hormone agonists or surgical castration. Prolonged therapy with antiandrogens selects for mutations in the AR that change the AR ligand specificity and permits stimulation by ligands that are usually inhibitory. These mutations give insight into one of the means by which prostate cancer progresses despite antiandrogen therapy, and also helps to explain the antiandrogen withdrawal syndrome. Areas of active research that may affect the future use of antiandrogens include the ongoing evaluation of antiandrogens in combination with 5 alpha reductase inhibitors to achieve AR blockade without inducing castrate testosterone levels. There is also interest in developing selective androgen receptor modulators (SARM) that can achieve AR blockade without causing the increased testosterone levels produced by the nonsteroidal antiandrogens currently in use. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Reid, P (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 94 TC 43 Z9 45 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD AUG PY 1999 VL 17 IS 3 BP 271 EP 284 DI 10.1023/A:1006344807086 PG 14 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 269LH UT WOS:000084478300006 PM 10665479 ER PT J AU Kim, I Ryan, AM Rohan, R Amano, S Agular, S Miller, JW Adamis, AP AF Kim, I Ryan, AM Rohan, R Amano, S Agular, S Miller, JW Adamis, AP TI Constitutive expression of VEGF, VEGFR-1, and VEGFR-2 in normal eyes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; PROLIFERATIVE DIABETIC-RETINOPATHY; FACTOR MESSENGER-RNA; IRIS NEOVASCULARIZATION; EPITHELIAL-CELLS; RETINAL ISCHEMIA; NONHUMAN PRIMATE; TYROSINE KINASE; FACTOR FAMILY AB PURPOSE. The expression of vascular endothelial growth factor (VEGF) and its high-affinity receptors VEGFR-1 and VEGFR-2 was investigated in normal eyes. METHODS. Monkey and rat eyes were surgically removed in animals under deep anesthesia and immediately prepared for study. Ocular VEGF, VEGFR-1, and VEGFR-2 expression was studied using a combination of in situ hybridization, northern blot analysis, immunohistochemistry, immunoassay, and reverse transcription-polymerase chain reaction. RESULTS. Steady state VEGF mRNA levels were detected in the normal vascularized ocular tissues of the monkey: the conjunctiva, iris, retina, and the choroid-retinal pigment epithelial complex. VEGF(121) and VEGF(165) were the major isoforms identified. VEGF protein was detected in the conjunctiva, retina, and the choroid-retinal pigment epithelial complex. Retinal VEGF mRNA localized to the ganglion, inner nuclear, and retinal pigment epithelial cell layers. VEGF protein localized to these same layers and to the cones of monkey retina. VEGFR-1 and VEGFR-2 mRNAs were detected in normal monkey iris, retina, and the choroid-retinal pigment epithelial complex. In both monkey and rat eyes, VEGFR-1 and VEGFR-2 mRNAs were localized to the inner nuclear layer of the retina. CONCLUSIONS. VEGF, VEGFR-1, and VEGFR-2 are constitutively expressed in the vascularized tissues of normal eyes. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Childrens Hosp, Surg Res Lab, Boston, MA 02115 USA. Genentech Inc, Dept Pathol, S San Francisco, CA 94080 USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [R01 EY11627] NR 50 TC 151 Z9 160 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 1999 VL 40 IS 9 BP 2115 EP 2121 PG 7 WC Ophthalmology SC Ophthalmology GA 221XY UT WOS:000081754000030 PM 10440268 ER PT J AU Arabi, Y Morgan, BJ Goodman, B Puleo, DS Xie, AL Skatrud, JB AF Arabi, Y Morgan, BJ Goodman, B Puleo, DS Xie, AL Skatrud, JB TI Daytime blood pressure elevation after nocturnal hypoxia SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE high altitude; hypobaric chamber ID OBSTRUCTIVE SLEEP-APNEA; POSITIVE AIRWAY PRESSURE; SYSTEMIC HYPERTENSION; SYMPATHETIC ACTIVITY; RISK; COMPONENT; RESPONSES; HUMANS AB The purpose of this study was to investigate whether nocturnal hypoxia causes daytime blood pressure (BP) elevation. We hypothesized that overnight exposure to hypoxia leads the next morning to elevation in BP that outlasts the hypoxia stimulus. We studied the effect on BP of two consecutive night exposures to hypobaric hypoxia in 10 healthy normotensive subjects. During the hypoxia nights, subjects slept for 8 h in a hypobaric chamber at a simulated altitude of 4,000 m (barometric pressure = 462 mmHg). Arterial O-2 saturation and electrocardiogram were monitored throughout the night. For 30 min before the nocturnal simulated ascent and for 4 h after return to baseline altitude the next morning, BP was measured every 5 min while the subject was awake. The same measurements were made before and after 2 normoxic nights of sleep in the hypobaric chamber at ambient barometric pressure (745 mmHg). Principal components analysis was applied to evaluate patterns of BP response after the second night of hypoxia and normoxia. A distinct pattern of diastolic BP (DBP) elevation was observed after the hypoxia night in 9 of the 10 subjects but in none after the normoxia night. This pattern showed a mean increase of 4 mmHg in DBP compared with the presleep-awake baseline in the first 60 min and a return to baseline by 90 min. We conclude that nocturnal hypoxia leads to a carryover elevation of daytime DBP. C1 William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53792 USA. Univ Wisconsin, Dept Surg, Madison, WI 53792 USA. RP Skatrud, JB (reprint author), William S Middleton Mem Vet Hosp, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 36 TC 35 Z9 36 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 1999 VL 87 IS 2 BP 689 EP 698 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 223WQ UT WOS:000081864900029 PM 10444629 ER PT J AU Hartwig, W Carter, EA Jimenez, RE Werner, J Fischman, AJ Fernandez-Del Castillo, C Warshaw, AL AF Hartwig, W Carter, EA Jimenez, RE Werner, J Fischman, AJ Fernandez-Del Castillo, C Warshaw, AL TI Chemotactic peptide uptake in acute pancreatitis: correlation with tissue accumulation of leukocytes SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE chemotactic factors; inflammation; leukocytes; N-formyl-methionyl-leucyl-phenylalanine ID IMAGING FOCAL SITES; TRYPSINOGEN-ACTIVATION PEPTIDES; BACTERIAL-INFECTION; RAT; ANALOGS; INFLAMMATION; MECHANISM; THERAPY; MODEL AB Chemotactic peptides bind specifically to receptors on leukocyte membranes. This property makes them prospective vehicles to evaluate inflammation and infection. We used two well-established models of acute pancreatitis to quantitate the binding of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine-lysine (fMLFK) to leukocytes and its correlation to degree of organ inflammation. Uptake of the Tc-99m-labeled nicotinyl hydrazine-derivatized chemotactic peptide analog fMLFK-HYNIC was measured in blood, pancreas, lung, and muscle specimens in rats with edematous or necrotizing pancreatitis and was compared with neutrophil sequestration assessed by myeloperoxidase activity and histology. Chemotactic peptide uptake in the pancreas was increased in mild and severe pancreatitis compared with controls, with higher levels in severe than in mild disease, and correlated with tissue myeloperoxidase activity (r = 0.7395, P < 0.001). Increased pulmonary uptake only in severe pancreatitis reflected pancreatitis-induced neutrophil sequestration in the lungs. Muscle uptake was unchanged compared with controls. Edema formation did not affect chemotactic peptide uptake. The data suggest that uptake of chemotactic peptides can contribute to quantitative assessment of neutrophils in localized inflammatory processes and is independent of associated edema formation or microcirculatory compromise. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, WHT 506, Boston, MA 02114 USA. NR 26 TC 24 Z9 24 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 1999 VL 87 IS 2 BP 743 EP 749 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 223WQ UT WOS:000081864900035 PM 10444635 ER PT J AU Herndon, JH AF Herndon, JH TI Five rings of Musashi SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Herndon, JH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Gray 624,55 Fruit St, Boston, MA 02114 USA. NR 20 TC 1 Z9 1 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 AUG PY 1999 VL 81A IS 8 BP 1053 EP 1062 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 228ER UT WOS:000082124600001 PM 10466638 ER PT J AU Body, SC Birmingham, J Parks, P Ley, C Maddi, R Shernan, SK Siegel, LC Stover, EP D'Ambra, MN Levin, J Mangano, DT Spiess, BD AF Body, SC Birmingham, J Parks, P Ley, C Maddi, R Shernan, SK Siegel, LC Stover, EP D'Ambra, MN Levin, J Mangano, DT Spiess, BD CA Inst Multictr Study Perioperative Ischemia Res TI Safety and efficacy of shed mediastinal blood transfusion after cardiac surgery: A multicenter observational study SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE blood; transfusion; autotransfusion; autologous blood; blood conservation; blood saving; retransfusion; shed mediastinal blood; surgery; cardiac surgery; postoperative complications; cardiopulmonary bypass ID ARTERY BYPASS-SURGERY; AUTO-TRANSFUSION; CARDIOPULMONARY BYPASS; AUTOTRANSFUSION; OPERATIONS; RETRANSFUSION; VARIABILITY; ACTIVATION; IMPACT AB Objective: To examine the efficacy and safety of shed mediastinal blood (SMB) transfusion in preventing allogenic red blood cell(RBC) transfusion. Design: An observational clinical study. Setting: Twelve US academic medical centers. Participants: Six hundred seventeen patients undergoing elective primary coronary artery bypass grafting. Interventions: Patients were administered SMB transfusion or not, according to institutional and individual practice, without random assignment. Measurements and Results: The independent effect of SMB transfusion on postoperative RBC transfusion was examined by multivariable modeling. Potential complications of SMB transfusion, such as bleeding and infection, were examined. Three hundred twelve of the study patients (51%) received postoperative SMB transfusion (mean volume, 554 +/- 359 mt). Patients transfused with SMB had significantly lower volumes of RBC transfusion than those not receiving SMB (0.86 +/- 1.50 v 1.08 +/- 1.65 units; p < 0.05). However, multivariable analysis showed that SMB transfusion was not predictive of postoperative RBC transfusion. Demographic factors (older age, female sex), institution, and postoperative events (greater chest tube drainage, lower hemoglobin level on arrival to the intensive care unit, and use of inotropes) were significant predictors of RBC transfusion. The volume of chest tube drainage on the operative day (707 +/- 392 v 673 +/- 460 mt; p = 0.30), reoperation for hemorrhage (3.1% v 2.5%; p = 0.68), and overall frequency of infection (5.8% v 6.6%; p = 0.81) were similar between patients receiving and not receiving SMB, respectively. However, in patients who did not receive allogenic RBC transfusion, there was a significantly greater frequency of wound infection in the SMB group (3.6% v 0%; p = 0.02). Conclusion: These data suggest that SMB is ineffective as a blood conservation method and may be associated with a greater frequency of wound infection. Copyright (C) 1999 by W.B. Saunders Company. C1 Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA USA. Stanford Univ, Dept Anesthesia, Stanford, CA 94305 USA. Ischemia Res & Educ Fdn, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, Dept Lab Med, San Francisco, CA 94143 USA. Vet Adm Med Ctr, San Francisco, CA 94121 USA. Univ Washington, Sch Med, Dept Anesthesia, Seattle, WA USA. RP Body, SC (reprint author), Brigham & Womens Hosp, Dept Anesthesia, 75 Francis St,CWN L118, Boston, MA 02115 USA. RI Body, Simon/O-2605-2013; OI Body, Simon/0000-0001-6721-7050; Siegel, Lawrence/0000-0002-8456-7551 NR 33 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD AUG PY 1999 VL 13 IS 4 BP 410 EP 416 DI 10.1016/S1053-0770(99)90212-4 PG 7 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 226VD UT WOS:000082042400007 PM 10468253 ER PT J AU Sharabani-Yosef, O Bak, A Langzam, L Lui, Z Nir, U Braiman, L Sweadner, KJ Sampson, SR AF Sharabani-Yosef, O Bak, A Langzam, L Lui, Z Nir, U Braiman, L Sweadner, KJ Sampson, SR TI Rat skeletal muscle in culture expresses the alpha 1 but not the alpha 2 protein subunit isoform of the Na+/K+ pump SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID BETA-SUBUNIT; ELECTROPHYSIOLOGICAL PROPERTIES; ELECTRICAL-ACTIVITY; SODIUM-CHANNELS; K+-ATPASE; NA,K-ATPASE; MYOTUBES; CELLS; DIFFERENTIATION; NA+,K+-ATPASE AB Studies from this laboratory have shown that the physiological expression of the Na+/K+ pump in primary cultures of rat skeletal muscle increases with development. The molecular mechanisms underlying these changes are not known. Therefore, we have examined the expression of alpha and beta subunits of the Na+/K+ pump at both the protein and mRNA levels during myogenesis of primary skeletal muscle cell cultures obtained from newborn rats. Protein isoforms were identified by Western blotting techniques with specific monoclonal and polyclonal antibodies and subunit mRNA was studied with specific cDNA probes. Freshly isolated skeletal muscle from newborn rats expressed both alpha 1 and alpha 2 protein subunits. From day 1 after plating, primary cultures expressed only the al protein isoform. In contrast, both beta 1 and beta 2 isoforms were expressed in freshly isolated muscle and in primary cultures, with beta 1 expression being stronger in both preparations. Studies on RNA expression showed that mRNA for alpha 1, alpha 2, beta 1, and beta 2 isoforms was identified both in freshly isolated muscle and after plating of cells in culture. These findings indicate that the lack of alpha 2 protein expression in primary muscle cell cultures reflects a form of posttranscriptional regulation. There did not appear to be a quantitative difference in isoform expression as a function of age or of fusion in spite of developmental increases in Na+/K+ pump activity and its dependence on cell fusion. The lack of expression of the alpha 2 subunit isoform suggests that the developmental changes in physiological expression of the Na+/K+ pump in primary cultures of skeletal muscle may be attributable Either to the changes in activity of the alpha 1 subunit or to differential activities of alpha beta complexes involving either of the beta subunits. (C) 1999 Wiley-Liss, Inc. C1 Bar Ilan Univ, Dept Life Sci, Otto Meyerhoff Ctr, IL-52900 Ramat Gan, Israel. Bar Ilan Univ, Dept Life Sci, Hlth Sci Res Ctr, IL-52900 Ramat Gan, Israel. Hosp Sick Children, Div Cell Biol, Toronto, ON M5G 1X8, Canada. Massachusetts Gen Hosp, Lab Membrane Biol, Ctr Neurosci, Charlestown, MA USA. RP Sampson, SR (reprint author), Bar Ilan Univ, Dept Life Sci, Otto Meyerhoff Ctr, IL-52900 Ramat Gan, Israel. NR 30 TC 22 Z9 22 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 1999 VL 180 IS 2 BP 236 EP 244 DI 10.1002/(SICI)1097-4652(199908)180:2<236::AID-JCP11>3.0.CO;2-W PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 210YF UT WOS:000081132600011 PM 10395293 ER PT J AU Musch, G Lipesky, J AF Musch, G Lipesky, J TI Dysphagia following intrathecal local anesthetic opioid administration SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE anesthesia, spinal; cesarean section; dysphagia; opioids ID LABOR ANALGESIA; SUFENTANIL; FENTANYL AB We describe the case of a parturient who developed dysphagia shortly after the intrathecal injection of a local anesthetic-opioid combination for cesarean section. Dysphagia was the only symptom of cephalad spread of the spinal anesthetic, and it was not associated with a "high" motor or sensory block. Although it resolved spontaneously, the dysphagia was extremely distressing to the patient. We conclude that dysphagia, even in the absence of an overtly "high spinal." should be added to the possible side effects of intrathecal local anesthetic-opioid administration in parturients. (C) 1999 by Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Musch, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. NR 9 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 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD AUG PY 1999 VL 11 IS 5 BP 413 EP 415 PG 3 WC Anesthesiology SC Anesthesiology GA 241ZT UT WOS:000082914300011 PM 10526813 ER PT J AU Mitsiades, N Poulaki, V Mastorakos, G Tseleni-Balafouta, S Kotoula, V Koutras, DA Tsokos, M AF Mitsiades, N Poulaki, V Mastorakos, G Tseleni-Balafouta, S Kotoula, V Koutras, DA Tsokos, M TI Fas ligand expression in thyroid carcinomas: A potential mechanism of immune evasion SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID OCCULT PAPILLARY CARCINOMA; HASHIMOTOS-THYROIDITIS; SEQUENTIAL AUTOPSIES; MOLECULAR-CLONING; INDUCED APOPTOSIS; CANCER; GLAND; TUMORS; CELLS; PATHOGENESIS AB Fas ligand (FasL) induces apoptosis by cross-linking the Fas receptor and is expressed by cells of the immune system. Recently, Fast was found in malignant tumors, suggesting that it helps them escape immune surveillance by eliminating infiltrating lymphocytes. We investigated the presence of Fast immunohistochemically in 48 thyroid carcinomas and by Western blotting and RT-PCR in 5 thyroid carcinoma cell lines. We found that in contrast to normal thyroid tissue, Fast was highly expressed in all papillary, follicular, and Huerthle carcinomas. Medullary carcinomas lacked or had minimal Fast expression. In papillary carcinomas, high levels of expression correlated independently with aggressive histology and unfavorable clinical presentation. Fast was also present in all thyroid cell lines. Thyroid carcinoma cells killed Fas-sensitive targets in a FasL-dependent manner in a coculture experiment. Cross-linking of Fas induced apoptosis in thyroid carcinoma cells only in the presence of cycloheximide. We conclude that Fast is specifically expressed in thyroid carcinomas of follicular epithelial origin, may help them evade the immune system, and may have prognostic implications in papillary carcinoma, as it is associated with a more aggressive phenotype. Thyroid carcinoma cells avoid Fas-mediated suicide possibly by expressing an inhibitor of the Fas apoptotic pathway. C1 NIH, Pathol Lab, Bethesda, MD 20892 USA. Evgenid Hosp, Endocrine Unit, Athens, Greece. Univ Athens, Athens, Greece. RP Mitsiades, N (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 7th Floor,149 13th St, Charlestown, MA 02129 USA. NR 49 TC 50 Z9 54 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 1999 VL 84 IS 8 BP 2924 EP 2932 DI 10.1210/jc.84.8.2924 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 223KL UT WOS:000081840200057 PM 10443700 ER PT J AU McGill, G Fisher, DE AF McGill, G Fisher, DE TI p53 and cancer therapy: a double-edged sword SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID P53-DEPENDENT APOPTOSIS; FIBROBLASTS; HYPOXIA; AGENTS; MODEL; CELLS; GENE C1 Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Grad Program Biol & Biomed Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Div Pediat Hematol Oncol, Dana 630,44 Binney St, Boston, MA 02115 USA. NR 20 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1999 VL 104 IS 3 BP 223 EP 225 DI 10.1172/JCI7861 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WC UT WOS:000083468500001 PM 10430602 ER PT J AU Ohdan, H Yang, YG Shimizu, A Swenson, KG Sykes, M AF Ohdan, H Yang, YG Shimizu, A Swenson, KG Sykes, M TI Mixed chimerism induced without lethal conditioning prevents T cell- and anti-Gal alpha 1,3Gal-mediated graft rejection SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; REACTIVE LYMPHOCYTES-B; ANTI-GAL ANTIBODY; NONMYELOABLATIVE REGIMEN; HYPERACUTE REJECTION; NATURAL ANTIBODIES; MEDIATED CYTOLYSIS; XENOGENEIC BARRIER; HEART XENOGRAFTS; TRANSGENIC PIGS AB Gal alpha 1,3Gal-reactive (Gal-reactive) antibodies are a major impediment to pig-to-human xenotransplantation. We investigated the potential to induce tolerance of anti-Gal-producing cells and prevent rejection of vascularized grafts in the combination of alpha 1,3-galactosyltransferase wild-type (GdT+/+) and deficient (GalT(-/-)) mice. Allogeneic (H-2 mismatched) GalT(+/+) bone marrow transplantation (BMT) to GalT(-/-) mice conditioned with a nonmyeloablative regimen, consisting of depleting CD4 and CD8 mAb's and 3 Gy whole-body irradiation and 7 Gy thymic irradiation, led to lasting multilineage H-2(bxd) GalT(+/+) + H-2(d) GalT(-/-) mixed chimerism. Induction of mixed chimerism was associated with a rapid reduction of serum anti-Gal naturally occurring antibody levels. Anti-Gal-producing cells were undetectable by 2 weeks after BMT, suggesting that anti-Gal-producing cells preexisting at the time of BMT are rapidly tolerized. Even after immunization with Gal-bearing xenogeneic cells, mixed chimeras were devoid of anti-Gal-producing cells and permanently accepted donor-type GalT(+/+) heart grafts (>150 days), whereas non-BMT control animals rejected these hearts within 1-7 days. B cells bearing receptors for Gal were completely absent from the spleens of mixed chimeras, suggesting that clonal deletion and/or receptor editing may maintain B-cell tolerance to Gal. These findings demonstrate the principle that induction of mixed hematopoietic chimerism with a potentially relevant nonmyeloablative regimen can simultaneously lead to tolerance among both T cells and Gal-reactive B cells, thus preventing vascularized xenograft rejection. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH E,Surg Serv, Transplantat Biol Res Ctr,Bone Marrow Transplanta, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,MGH E,Surg Serv, Transplantat Biol Res Ctr,Bone Marrow Transplanta, Bldg 149,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL049915, P01 HL018646, P0I HL-18646, R0I HL-49915] NR 52 TC 92 Z9 92 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1999 VL 104 IS 3 BP 281 EP 290 DI 10.1172/JCI6656 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WC UT WOS:000083468500008 PM 10430609 ER PT J AU Abel, ED Boers, ME Pazos-Moura, C Moura, E Kaulbach, H Zakaria, M Lowell, B Radovick, S Liberman, MC Wondisford, F AF Abel, ED Boers, ME Pazos-Moura, C Moura, E Kaulbach, H Zakaria, M Lowell, B Radovick, S Liberman, MC Wondisford, F TI Divergent roles for thyroid hormone receptor beta isoforms in the endocrine axis and auditory system SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; THYROTROPIN-RELEASING-HORMONE; GENE-EXPRESSION; GROWTH-HORMONE; RESPONSE ELEMENTS; RESISTANCE; CELLS; RATS; MICE; HYPOTHYROIDISM AB Thyroid hormone receptors (TRs) modulate various physiological functions in many organ systems. The TR alpha and TR beta isoforms are products of 2 distinct genes, and, the beta 1 and beta 2 isoforms are splice variants of the same gene. Whereas TR alpha 1 and TR beta 1 are widely expressed, expression of the TR beta 2 isoform is mainly limited to the pituitary, triiodothyronine-responsive TRH neurons, the developing inner ear, and the retina. Mice with targeted disruption of the entire TR beta locus (TR beta-null) exhibit elevated thyroid hormone levels as a result of abnormal central regulation of thyrotropin, and also develop profound hearing loss. To clarify the contribution of the TR beta 2 isoform to the function of the endocrine and auditory systems in vivo, we have generated mice with targeted disruption of the TR beta 2 isoform. TR beta 2-null mice have preserved expression of the TR alpha and TR beta 1 isoforms. They develop a similar degree of central resistance to thyroid hormone as TR beta-null mice, indicating the important role of TR beta 2 in the regulation of the hypothalarnic-pituitary-thyroid axis. Growth hormone gene expression is marginally reduced. In contrast, TR beta 2-null mice exhibit no evidence of hearing impairment, indicating that TR beta 1 and TR beta 2 subserve divergent roles in the regulation of auditory function. C1 Beth Israel Deaconess Med Ctr, Thyroid Unit, Dept Med, Boston, MA 02215 USA. Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Fisiol Endocrina, BR-21000000 Rio De Janeiro, Brazil. Univ Estado Rio de Janeiro, Inst Biol, Dept Ciencias Fisiol, BR-20550030 Rio De Janeiro, Brazil. Harvard Univ, Sch Med, Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Wondisford, F (reprint author), Beth Israel Deaconess Med Ctr, Thyroid Unit, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. RI Pazos Moura, Carmen/M-9256-2014 OI Pazos Moura, Carmen/0000-0003-3944-6491 FU NIDCD NIH HHS [F32 DC000188, R01 DC000188]; NIDDK NIH HHS [DK-49126, DK-02485, DK-50564, R01 DK049126] NR 46 TC 114 Z9 115 U1 1 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1999 VL 104 IS 3 BP 291 EP 300 DI 10.1172/JCI6397 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WC UT WOS:000083468500009 PM 10430610 ER PT J AU Chiang, N Gronert, K Clish, CB O'Brien, JA Freeman, MW Serhan, CN AF Chiang, N Gronert, K Clish, CB O'Brien, JA Freeman, MW Serhan, CN TI Leukotriene B-4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirin-triggered lipoxins in reperfusion SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CELLS; NEUTROPHILS; RELEASE; ATL AB Polymorphonuclear neutrophil (PMN) activation is pivotal in acute inflammation and injury from reperfusion. To elucidate components controlling PMNs in vivo, we prepared novel transgenic mice with the human leukotriene (LT) B-4 receptor (BLTR) for functional characterization. Overexpression of BLTR in leukocytes dramatically increased PMN trafficking to skin microabscesses and lungs after ischemia-reperfusion, whereas mice deficient in 5-lipoxygenase (5-LO) showed diminished PMN accumulation in reperfused lungs. Hence, both BLTR expression and LT biosynthesis are critical for PMN infiltration in reperfusion-initiated second-organ injury. Also, in BLTR transgenic mice, 5-LO expression and product formation were selectively increased in exudates, demonstrating that receptor overexpression amplifies proinflammatory circuits. Endogenous lipoxin (LX) A(4) was produced in ischemic lungs and elevated by reperfusion. Because LXA(4) and aspirin-triggered 15-epimeric LXA4 (ATL) selectively regulate leukocyte responses, they were tested in BLTR transgenic mice. Despite excessive PMN recruitment in BLTR transgenic mice, intravenous injection of ATL sharply diminished reperfusion-initiated PMN trafficking to remote organs, and topical application of LX was protective in acute dermal inflammation. These results demonstrate a direct role for BLTR with positive feedback, involving BLTR and 5-LO signaling in controlling PMNs. Moreover, LXA(4) and ATL counter BLTR-amplified networks, revealing a novel protective role for LX and ATL in stress responses that has applications in perioperative medicine. C1 Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Lipid Metab Unit, Boston, MA 02114 USA. RP Serhan, CN (reprint author), Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK-50305, P01 DK050305]; NIGMS NIH HHS [R37 GM038765, GM-38765, R01 GM038765] NR 22 TC 156 Z9 163 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1999 VL 104 IS 3 BP 309 EP 316 DI 10.1172/JCI7016 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WC UT WOS:000083468500011 PM 10430612 ER PT J AU Teshima, T Hill, GR Pan, LY Brinson, YS van den Brink, MRM Cooke, KR Ferrara, JLM AF Teshima, T Hill, GR Pan, LY Brinson, YS van den Brink, MRM Cooke, KR Ferrara, JLM TI IL-11 separates graft-versus-leukemia effects from graft-versus-host disease after bone marrow transplantation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-11; PERFORIN-DEFICIENT MICE; NECROSIS-FACTOR-ALPHA; II H-2 DIFFERENCES; T-CELLS; FAS LIGAND; ANTI-FAS; KILLER-CELLS; APOPTOSIS; CYTOTOXICITY AB We recently showed that IL-11 prevents lethal graft-versus-host disease (GVHD) in a murine bone marrow transplantation (BMT) model of GVHD directed against MHC and minor antigens. In this study, we have investigated whether IL-11. can maintain a graft-versus-leukemia (GVL) effect. Lethally irradiated B6D2F1 mice were transplanted with either T cell-depleted (TCD) bone marrow (BM) alone or with BM and splenic T cells from allogeneic BG donors. Animals also received host-type P815 mastocytoma cells at the time of BMT. Recipients were injected subcutaneously with recombinant human IL-11 or control diluent twice daily, from 2 days before BMT to 7 days after BMT TCD recipients all died from leukemia by day 23. All control- and IL-11 treated allogeneic animals effectively rejected their leukemia, but IL-11 also reduced GVHD-related mortality. Examination of the cellular mechanisms of GVL and GVHD in this system showed that IL-11 selectively inhibited CD4-mediated GVHD, while retaining both CD4- and CD8-mediated GVL. In addition, IL-11 treatment did not affect cyolytic effector functions of T cells after BMT either in vivo or in vitro. Studies with perforin-deficient donor T cells demonstrated that the GVL effect was perforin dependent. These data demonstrated that IL-11 can significantly reduce CD4-dependent GVHD without impairing cytolytic function or subsequent GVL activity of CD8(+) T cells. Brief treatment with IL-11 shortly after BMT may therefore represent a novel strategy for separating GVHD and GVL. C1 Univ Michigan, Ctr Canc, Bone Marrow Transplantat Program, Dept Internal Med & Pediat, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Hematol Oncol, Boston, MA 02215 USA. RP Ferrara, JLM (reprint author), Univ Michigan, Ctr Canc, Bone Marrow Transplantat Program, Dept Internal Med & Pediat, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI teshima, takanori/G-1671-2012; Hill, Geoffrey/O-2630-2016; OI Hill, Geoffrey/0000-0003-2994-0429; teshima, takanori/0000-0002-0941-271X FU NCI NIH HHS [CA-39542, P01 CA039542]; NHLBI NIH HHS [HL-55162] NR 49 TC 124 Z9 130 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1999 VL 104 IS 3 BP 317 EP 325 DI 10.1172/JCI7111 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WC UT WOS:000083468500012 PM 10430613 ER PT J AU Choukroun, G Hajjar, R Fry, S del Monte, F Haq, S Guerrero, JL Picard, M Rosenzweig, A Force, T AF Choukroun, G Hajjar, R Fry, S del Monte, F Haq, S Guerrero, JL Picard, M Rosenzweig, A Force, T TI Regulation of cardiac hypertrophy in vivo by the stress-activated protein kinases/c-Jun NH2-terminal kinases SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MUSCLE CELL HYPERTROPHY; N-TERMINAL KINASES; C-JUN; IN-VIVO; CARDIOMYOCYTE HYPERTROPHY; MYOCYTE HYPERTROPHY; SIGNALING PATHWAY; COUPLED RECEPTORS; P38; MICE AB Cardiac hypertrophy often presages the development of heart failure. Numerous cytosolic signaling pathways have been implicated in the hypertrophic response in cardiomyocytes in culture, but their roles in the hypertrophic response to physiologically relevant stimuli in vivo is unclear. We previously reported that adenovirus-mediated gene transfer of SEK-1(KR), a dominant inhibitory mutant of the immediate upstream activator of the stress-activated protein kinases (SAPKs), abrogates the hypertrophic response of neonatal rat cardiomyocytes to endothelin-l in culture. We now report that gene transfer of SEK-1(KR) to the adult rat heart blocks SAPK activation by pressure overload, demonstrating that the activity of cytosolic signaling pathways can be inhibited by gene transfer of loss-of-function mutants in vivo. Furthermore, gene transfer of SEK-1(KR) inhibited pressure overload-induced cardiac hypertrophy, as determined by echocardiography and several postmortem measures including left ventricular (LV) wall thickness, the ratio of LV weight to body weight, cardiomyocyte diameter, and inhibition of atrial natriuretic factor expression. Our data suggest that the SAPKs are critical regulators of cardiac hypertrophy in vivo, and therefore may serve as novel drug targets in the treatment of hypertrophy and heart failure. C1 Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Force, T (reprint author), Massachusetts Gen Hosp E, Med Serv, 149-4002 13th St, Charlestown, MA 02129 USA. OI Force, Thomas/0000-0002-0450-8659; Picard, Michael/0000-0002-9264-3243 NR 52 TC 131 Z9 136 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1999 VL 104 IS 4 BP 391 EP 398 DI 10.1172/JCI6350 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WE UT WOS:000083468700006 PM 10449431 ER PT J AU Lanske, B Amling, M Neff, L Guiducci, J Baron, R Kronenberg, HM AF Lanske, B Amling, M Neff, L Guiducci, J Baron, R Kronenberg, HM TI Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HORMONE-RELATED PEPTIDE; MESSENGER RIBONUCLEIC-ACIDS; PARATHYROID-HORMONE; PRIMARY HYPERPARATHYROIDISM; OSTEOPROGENITOR CELLS; ALKALINE-PHOSPHATASE; OSTEOSARCOMA CELLS; INDIAN HEDGEHOG; DIFFERENTIATION; EXPRESSION AB Parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) bind to and activate the same PTH/PTHrP receptor. Deletion of either the PTHrP gene or the PTH/PTHrP receptor gene leads to acceleration of differentiation of growth plate chondrocytes. To explore further the functional relationships of PTHrP and the PTH/PTHrP receptor, bones of knockout mice were analyzed early in development, and the phenotypes of double-knockout mice were characterized. One early phenotype is shared by both knockouts. Normally, the first chondrocytes to become hypertrophic are located in the centers of long bones; this polarity is greatly diminished in both these knockouts. The PTH/PTHrP receptor-deficient (PTH/PTHrP-R-/-) mice exhibited 2 unique phenotypes not shared by the PTHrP(-/-) mice. During intramembranous bone formation in the shafts of long bones, only the PTH/PTHrP-R-/- bones exhibit a striking increase in osteoblast number and matrix accumulation. Furthermore, the PTH/PTHrP-R-/- mice showed a dramatic decrease in trabecular bone formation in the primary spongiosa and a delay in vascular invasion of the early cartilage model. In the double-homozygous knockout mice, the delay in vascular invasion did not occur. Thus, PTHrP must slow vascular invasion by a mechanism independent of the PTH/PTHrP receptor. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Hamburg, Dept Bone Pathol, D-20146 Hamburg, Germany. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 501,50 Blossom St, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR-4445354]; NIDDK NIH HHS [DK-47038] NR 33 TC 141 Z9 147 U1 0 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1999 VL 104 IS 4 BP 399 EP 407 DI 10.1172/JCI6629 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WE UT WOS:000083468700007 PM 10449432 ER PT J AU Jiang, ZY Lin, YW Clemont, A Feener, EP Hein, KD Igarashi, M Yamauchi, T White, MF King, GL AF Jiang, ZY Lin, YW Clemont, A Feener, EP Hein, KD Igarashi, M Yamauchi, T White, MF King, GL TI Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SMOOTH-MUSCLE CELLS; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVATION; TYROSINE-PHOSPHATASE ACTIVITY; NITRIC-OXIDE RELEASE; PROTEIN-KINASE-C; GROWTH FACTOR-I; SKELETAL-MUSCLE; RECEPTOR SUBSTRATE-1; DNA-SYNTHESIS; GLYCOGEN-SYNTHESIS AB Both insulin resistance and hyperinsulinemia have been reported to be independent risk factors for cardiovascular diseases. However, little is known regarding insulin signaling in the vascular tissues in insulin-resistant states. In this report, insulin signaling on the phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein (MAP) kinase pathways were compared in vascular tissues of lean and obese Zucker (fa/fa) rats in both ex vivo and in vivo studies. Ex vivo, insulin-stimulated tyrosine phosphorylation of insulin receptor beta subunits (IR beta) in the aorta and microvessels of obese rats was significantly decreased compared with lean rats, although the protein levels of IR beta in the 2 groups were not different. Insulin-induced tyrosine phosphorylation of insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) and their protein levels were decreased in the aorta of obese rats compared with lean rats. The association of p85 subunit to the IRS proteins and the IRS-associated PI 3-kinase activities stimulated by insulin in the aorta of obese rats were significantly decreased compared with the lean rats. In addition, insulin-stimulated serine phosphorylation of Akt, a downstream kinase of PI 3-kinase pathway, was also reduced significantly in isolated microvessels from obese rats compared with the lean rats. In euglycemic clamp studies, insulin infusion greatly increased tyrosine phosphorylation of IR beta- and IRS-2-associated PI 3-kinase activity in the aorta of lean rats, but only slight increases were observed in obese rats. In contrast, insulin stimulated tyrosine phosphorylation of MAP kinase (ERK-1/2) equally in isolated microvessels of lean and obese rats, although basal tyrosine phosphorylation of ERK-1/2 was higher in the obese rats. To our knowledge, these data provided the first direct measurements of insulin signaling in the vascular tissues, and documented a selective resistance to PI 3-kinase (but not to MAP kinase pathway) in the vascular tissues of obese Zucker rats. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP King, GL (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK053105, DK-36836, DK-53105, P30 DK036836] NR 56 TC 385 Z9 408 U1 3 U2 16 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1999 VL 104 IS 4 BP 447 EP 457 DI 10.1172/JCI5971 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WE UT WOS:000083468700012 PM 10449437 ER PT J AU Hill, GR Teshima, T Gerbitz, A Pan, LY Cooke, KR Brinson, YS Crawford, JM Ferrara, JLM AF Hill, GR Teshima, T Gerbitz, A Pan, LY Cooke, KR Brinson, YS Crawford, JM Ferrara, JLM TI Differential roles of IL-1 and TNF-alpha on graft-versus-host disease and graft versus leukemia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; BONE-MARROW TRANSPLANTATION; TOTAL-BODY IRRADIATION; NATURAL-KILLER CELLS; CYTOTOXIC T-CELLS; IMMUNE-RESPONSES; CYTOKINE DYSREGULATION; RECEPTOR ANTAGONIST; MYELOID-LEUKEMIA; HEPATIC GRAFT AB We demonstrate an increase in graft-versus-host disease (GVHD) after experimental bone marrow transplant (BMT) when cyclophosphamide (Cy) is added to an otherwise well-tolerated dose (900 cGy) of total body irradiation (TBI). Donor T cell expansion on day +13 was increased after conditioning with Cy/TBI compared with Cy or TBI alone, although cytotoxic T lymphocyte (CTL) function was not altered. Histological analysis of the gastrointestinal tract demonstrated synergistic damage by Cy/TBI and allogeneic donor cells, which permitted increased translocation of LPS into the systemic circulation. TNF-alpha and IL-1 production in response to LIPS was increased in BMT recipients after Cy/TBI conditioning. Neutralization of IL-1 significantly reduced serum LPS levels and GVHD mortality, but it did not affect donor CTL activity. By contrast, neutralization of TNF-alpha did not prevent GVHD mortality but did impair CTL activity after BMT. When P815 leukemia cells were added to the bone marrow inoculum, allogeneic BMT recipients given the TNF-alpha inhibitor relapsed at a significantly faster rate than those given the IL-1 inhibitor. To confirm that the role of TNF-alpha in graft versus leukemia (GVL) was due to effects on donor T cells, cohorts of animals were transplanted with T cells from either wild-type mice or p55 TNF-alpha receptor-deficient mice. Recipients of TNF-alpha p55 receptor-deficient T cells demonstrated a significant impairment in donor CTL activity after BMT and an increased rate of leukemic relapse compared with recipients of wild-type T cells. These data highlight the importance of conditioning in GVHD pathophysiology, and demonstrate that TNF-alpha is critical to GVL mediated by donor T cells, whereas IL-1 is not. C1 Univ Michigan, Ctr Canc, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Canc, Dept Pediat, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. RP Ferrara, JLM (reprint author), Univ Michigan, Ctr Canc, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. RI teshima, takanori/G-1671-2012; Hill, Geoffrey/O-2630-2016 OI Hill, Geoffrey/0000-0003-2994-0429 NR 53 TC 163 Z9 168 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1999 VL 104 IS 4 BP 459 EP 467 DI 10.1172/JCI6896 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WE UT WOS:000083468700013 PM 10449438 ER PT J AU Kantoff, PW Halabi, S Conaway, M Picus, J Kirshner, J Hars, V Trump, D Winer, EP Vogelzang, NJ AF Kantoff, PW Halabi, S Conaway, M Picus, J Kirshner, J Hars, V Trump, D Winer, EP Vogelzang, NJ TI Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: Results of the Cancer and Leukemia Group B 9182 study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROGNOSTIC FACTORS; CLINICAL-TRIALS; ANTIGEN; CHEMOTHERAPY; QUALITY; THERAPY; MARKER; LIFE AB Purpose: Approximately 40,000 men die each year of hormone-refractory prostate cancer (HRPC). The results of treatment with chemotherapy have been disappointing to date, with no trials demonstrating a benefit with respect to survival duration. Corticosteroids and mitoxantrone each have been shown to be active agents in this disease. The purpose of this study was to demonstrate an advantage of mitoxantrone and hydrocortisone (M+H) over hydrocortisone alone with respect to survival duration. Patients and Methods: Two hundred forty-two patients with HRPC were randomized to receive either M+H or hydrocortisone alone. patients were monitored for survival, time to disease progression, time to treatment failure, response, and quality-of-life (QOL) parameters. Results: Treatment in both arms was well tolerated, Although there wets a delay in time to treatment failure and disease progression in favor of M+H over hydrocortisone alone, there war no difference in overall survival (12.3 months for M+H v 12.6 months for hydrocortisone alone). There was an indication that QOL was better with M+H, in particular with respect to pain control. Conclusion: M+H generated more frequent responses and a delay in both time to treatment failure and disease progression compared with hydrocortisone alone. In addition, there wets a possible benefit of M+H with respect to pain control over hydrocortisone alone. No improvement in survival was observed. Although M+H could be viewed as a palliative option for patients with HRPC, new drugs and novel strategies are needed to improve survival for this disease. (C) 1999 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Breast Oncol Ctr, Boston, MA 02115 USA. Duke Univ, Med Ctr, Can & Leukemia Grp, B Stat Ctr, Durham, NC USA. Univ Virginia, Hlth Sci Ctr, Div Biostat & Epidemiol, Charlottesville, VA USA. Washington Univ, Med Ctr, Div Med Oncol, St Louis, MO USA. Hematol Oncol Assoc Cent New York, Syracuse Hematol Oncol Community Clin Oncol Progr, Syracuse, NY USA. Univ Pittsburgh, Med Ctr, Div Med Oncol, Pittsburgh, PA USA. Univ Chicago, Med Ctr, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 25 TC 612 Z9 627 U1 0 U2 12 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 1999 VL 17 IS 8 BP 2506 EP 2513 PG 8 WC Oncology SC Oncology GA 223HJ UT WOS:000081835300027 PM 10561316 ER PT J AU Stadler, WM Kuzel, T Shapiro, C Sosman, J Clark, J Vogelzang, NJ AF Stadler, WM Kuzel, T Shapiro, C Sosman, J Clark, J Vogelzang, NJ TI Multi-institutional study of the angiogenesis inhibitor TNP-470 in metastatic renal carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL CARCINOMA; FUMAGILLOL TNP-470; DRUG-RESISTANCE; TUMOR-GROWTH; PHASE-I; AGM-1470; PHARMACOKINETICS; INTERLEUKIN-2; EXPRESSION; CANCER AB Purpose: Renal cell carcinoma is resistant to most chemotherapy, and only a minority of patients respond to immunotherapy. Its highly vascular nature suggests that antiangiogenesis therapy might be useful. We thus performed a phase II study of the fumigillin analog TNP-470 in previously treated patients with metastatic renal cell carcinoma. Patients and Methods: Metastatic renal cell carcinoma patients with good organ function were entered onto the study through five separate institutions. There were no exclusion criteria for prior therapy All patients were treated at a dose of 60 mg/m(2) of TNP-470 infused over 1 hour three times per week. Results: Thirty-three patients were enrolled. Therapy was generally well tolerated, but asthenia, fatigue, vertigo, dizziness, sense of imbalance, and loss of concentration were common and severe enough to lead to therapy discontinuation in five patients. There was only one partial response of short duration (response rate, 3%, 95% confidence interval, 0% to 16%), but six patients (18%) remained on study for 6 or more months without toxicity or disease progression. Conclusion: Long-term therapy with TNP-470 has manageable toxicities and is feasible in patients with metastatic renal cell carcinoma but does not lead to any significant objective responses. further studies in this population using TNP-470 schedules that produce mare prolonged drug levels and clinical trial end points other than objective tumor regression may be indicated. (C) 1999 by American Society of Clinical Oncology. C1 Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. Northwestern Univ, Chicago, IL 60611 USA. Loyola Univ, Chicago, IL 60611 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stadler, WM (reprint author), Univ Chicago, Hematol Oncol Sect, 5841 S Maryland,MC2115, Chicago, IL 60637 USA. NR 21 TC 99 Z9 104 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1999 VL 17 IS 8 BP 2541 EP 2545 PG 5 WC Oncology SC Oncology GA 223HJ UT WOS:000081835300031 PM 10561320 ER PT J AU Salazar, DE Fischman, AJ AF Salazar, DE Fischman, AJ TI Central nervous system pharmacokinetics of psychiatric drugs SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT Symposium on the Use of Imaging in Drug Research and Development CY SEP 11-13, 1998 CL NIH, BETHESDA, MARYLAND SP Soc Nucl Imaging Drug Dev HO NIH ID ANTIDEPRESSANT; BMS-181101 C1 Bristol Myers Squibb, Pharmaceut Res Inst, Clin Pharmacol, Princeton, NJ 08543 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. RP Salazar, DE (reprint author), Bristol Myers Squibb, Pharmaceut Res Inst, Clin Pharmacol, POB 4000, Princeton, NJ 08543 USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD AUG PY 1999 VL 39 SU S BP 10S EP 12S PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 222RQ UT WOS:000081798900003 ER PT J AU Bachofen, M Nakagawa, A Marks, IM Park, JM Greist, JH Baer, L Wenzel, KW Parkin, JR Dottl, SL AF Bachofen, M Nakagawa, A Marks, IM Park, JM Greist, JH Baer, L Wenzel, KW Parkin, JR Dottl, SL TI Home self-assessment and self-treatment of obsessive-compulsive disorder using a manual and a computer-conducted telephone interview: Replication of a UK-US study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEPRESSION; SCALE; EXPOSURE; THERAPY AB Background: This open study replicates and extends previous pilot work with BT STEPS, a self-therapy system to assess and treat obsessive-compulsive disorder (OCD) through exposure and ritual prevention. Method: 21 OCD patients entered this open trial, using a self-guiding manual and any Touch-Tone telephone to access computer-driven interviews via an Interactive Voice Response system. The patients also used the system to rate progress on rating scales. Results: The results support those of the previous open study. Of the 21 patients, 16 (76%) completed self-assessment over a mean of 21 days. Of these, 10 patients (48%) went on to do 2 or more exposure and ritual prevention sessions over a mean of 64 days: they improved significantly on OCD symptoms, as much as is usual with serotonin reuptake inhibitor medication, and in mood and work/social adjustment. Improvement was predicted by baseline motivation and by rapid completion of self-assessment with BT STEPS, even though self-assessment alone was not therapeutic. Conclusion: The significant improvement in the intent-to-treat analysis was due to the subgroup of patients (48% of those who began BT STEPS) who went beyond self-assessment to do exposure and ritual prevention self-therapy at home guided by BT STEPS. A controlled trial is now needed. C1 Univ London, Bethlem Royal & Maudsley Hosp, Inst Psychiat, London SE5 8AF, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dean Fdn Hlth Res & Educ Inc, Middletown, WI USA. RP Marks, IM (reprint author), Univ London, Bethlem Royal & Maudsley Hosp, Inst Psychiat, De Crespigny Pk, London SE5 8AF, England. NR 18 TC 55 Z9 55 U1 1 U2 6 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 1999 VL 60 IS 8 BP 545 EP 549 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 230WR UT WOS:000082275100007 PM 10485637 ER PT J AU Fava, M Rosenbaum, JF Kolsky, AR Alpert, JE Nierenberg, AA Spillmann, M Moore, C Renshaw, P Bottiglieri, T Moroz, G Magni, G AF Fava, M Rosenbaum, JF Kolsky, AR Alpert, JE Nierenberg, AA Spillmann, M Moore, C Renshaw, P Bottiglieri, T Moroz, G Magni, G TI Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PARKINSONS-DISEASE; COMT INHIBITOR; LEVODOPA AB Tolcapone is a catechol-O-methyltransferase (COMT) inhibitor that has shown efficacy in the treatment of Parkinson's disease. The authors undertook the first study on the efficacy of this COMT inhibitor in the treatment of major depressive disorder (MDD). The authors also wanted to assess the effects of tolcapone on the choline and myoinositol resonances in the left caudate and dorsolateral frontal lobe through proton magnetic resonance spectroscopy and on whole blood levels of S-adenosyl-L-methionine (SAMe). The study enrolled 21 adults (10 men and 11 women; mean age, 42.6 +/- 9.6 years) with MDD, which was diagnosed using the Structured Clinical Interview for DSM-IV, and an initial score of greater than or equal to 16 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17). Patients were then treated openly for 8 weeks with tolcapone 400 mg twice daily. Treatment efficacy was assessed with the HAM-D-17, the Clinical Global Impressions Severity (CGI-S) scale, and the Beck Depression Inventory (BDI). Among all subjects (N = 21), there were significant (p < .0001) decreases at endpoint in HAM-D-17 scores (from 19.4 +/- 2.9 to 10.7 +/- 5.5), CGI-S scores (from 3.9 +/- 0.6 to 2.4 +/- 1.1), and BDI scores (from 21.6 +/- 8.1 to 12.3 +/- 8.6). Eight patients (38%) dropped out before completing the 8-week open study because of diarrhea, elevated liver function tests, increased anxiety, and noncompliance. No significant effects were noted on choline and myoinositol resonance or on SAMe levels in whole blood before and after 2 weeks of tolcapone treatment. The preliminary results suggest that tolcapone may be a promising agent in the treatment of MDD. Furthermore, double-blind, placebo-controlled studies are necessary to confirm this impression. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. McLean Hosp, Imaging Ctr, Belmont, MA 02178 USA. Baylor Univ, Med Ctr, Inst Metab Dis, Dallas, TX USA. Hoffmann La Roche Pharmaceut, Nutley, NJ USA. Hoffmann La Roche Pharmaceut, Basel, Switzerland. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 21 TC 36 Z9 36 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1999 VL 19 IS 4 BP 329 EP 335 DI 10.1097/00004714-199908000-00008 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 219JA UT WOS:000081603100007 PM 10440460 ER PT J AU Ghaemi, SN Goodwin, FK AF Ghaemi, SN Goodwin, FK TI Use of atypical antipsychotic agents in bipolar and schizoaffective disorders: Review of the empirical literature SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PSYCHOTIC MOOD DISORDERS; TARDIVE-DYSKINESIA; MAINTENANCE TREATMENT; LITHIUM-CARBONATE; DIVALPROEX SODIUM; AFFECTIVE-ILLNESS; LONG-TERM; CLOZAPINE; RISPERIDONE; MANIA AB Atypical antipsychotic agents seem to be effective treatments for bipolar disorder, especially as adjunctive treatments. They may be a safer and more effective alternative to the common practice of maintenance adjunctive treatment with traditional antipsychotic agents in patients with bipolar disorder. However, currently available research studies are limited methodologically mainly to open-label, uncontrolled designs. Further research is required before the definitive efficacy of these agents in bipolar disorder is established. if randomized or double-blind data support the open-label data reviewed here, atypical antipsychotic agents may possess an important role in the adjunctive treatment of bipolar disorder. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. George Washington Univ, Ctr Neurosci Med Progress & Soc, Dept Psychiat, Washington, DC USA. RP Ghaemi, SN (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC-812,15 Parkman St, Boston, MA 02114 USA. NR 72 TC 33 Z9 34 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1999 VL 19 IS 4 BP 354 EP 361 DI 10.1097/00004714-199908000-00012 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 219JA UT WOS:000081603100011 PM 10440464 ER PT J AU Wolfe, J Erickson, DJ Sharkansky, EJ King, DW King, LA AF Wolfe, J Erickson, DJ Sharkansky, EJ King, DW King, LA TI Course and predictors of posttraumatic stress disorder among Gulf War veterans: A prospective analysis SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID TRAUMA-RELATED SYMPTOMS; OPERATION DESERT-STORM; RISK-FACTORS; VIETNAM VETERANS; FOLLOW-UP; PTSD; SYMPTOMATOLOGY; RESERVISTS; PERSONNEL; EXPOSURE AB Rates and predictors of posttraumatic stress disorder (PTSD) over time are not well understood. This study is the first to look at the rates of PTSD immediately following war and 2 years later using a large cohort (N = 2.949) of Gulf War veterans. Using a cut score to indicate presumptive PTSD, 3% of participants exceeded the cutoff at Time 1 compared with 8% at Time 2. Those who exceeded the cutpoint at Time 1 were up to 20 times more likely to exceed the cutpoint at Time 2 than those who did not exceed the cutpoint at Time 1. Women and those with high levels of combat exposure were at increased risk for PTSD at both times. Being young, being single, and having previous combat experience were associated with increased risk at Time 1 only, whereas reservists and enlisted personnel were at increased risk at Time 2 only. These findings indicate that, although low initially, rates of PTSD increased substantially over time. C1 Vet Affairs Med Ctr, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div 116B3, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Wolfe, J (reprint author), Vet Affairs Med Ctr, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div 116B3, 150 S Huntington Ave, Boston, MA 02130 USA. NR 36 TC 125 Z9 125 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 1999 VL 67 IS 4 BP 520 EP 528 DI 10.1037//0022-006X.67.4.520 PG 9 WC Psychology, Clinical SC Psychology GA 224DN UT WOS:000081881900008 PM 10450622 ER PT J AU Silver-Isenstadt, A Ubel, PA AF Silver-Isenstadt, A Ubel, PA TI Erosion in medical students' attitudes about telling patients they are students SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE informed consent; education; medical ethics; survey; patients; medical students ID CONSENT AB OBJECTIVE: To study the attitudes of preclinical and clinical medical students toward the importance of telling patients they are students, and to compare their attitudes with those of patients. METHODS: We conducted a cross-sectional survey of medical students from five Philadelphia medical schools, and a longitudinal follow-up in one medical school, to assess the importance students place on telling patients they are medical students before interacting with them. We asked similar questions of 100 general medical outpatients from two academically affiliated hospitals. MAIN RESULTS: In total, 2,603 students (58%) responded to the cross-sectional survey, 74 (50%) responded to the longitudinal survey, and 100 patients responded to our interview survey (94% response rate). In the cross-sectional survey, there were negligible differences in the importance that patients and medical students placed on informing alert patients that they are interacting with students in nonsurgical settings. In surgical settings involving anesthetized patients, patients placed significantly more importance on being informed of students' roles in their surgery than did students, and preclinical students placed more importance on this:his than did clinical students. Results from the cross-sectional survey were supported by the longitudinal survey, in which fourth-year medical students placed significantly less importance on informing patients of their student status than the same cohort had done 2 years previously. CONCLUSIONS: Medical students place less importance on informing patients about their student status than patients desire, especially in surgical settings in which the patient is to be anesthetized. Medical students already having completed a clinical rotation stray further from patient ideals than preclinical medical students. These findings suggest that, as medical students advance in their training, they suffer an erosion in their attitudes about telling patients they are students. C1 Univ Maryland, Dept Med, Baltimore, MD 21201 USA. RP Ubel, PA (reprint author), Univ Penn, Sch Med, Div Gen Internal Med, Vet Affairs Med Ctr, 1223 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 15 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 1999 VL 14 IS 8 BP 481 EP 487 DI 10.1046/j.1525-1497.1999.09298.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 230DV UT WOS:000082237300004 PM 10491232 ER PT J AU Di Rosa, F Ramaswamy, S Ridge, JP Matzinger, P AF Di Rosa, F Ramaswamy, S Ridge, JP Matzinger, P TI On the lifespan of virgin T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL REPERTOIRE; PERIPHERAL SELECTION; MEMORY; NAIVE; ANTIGEN; MICE; PHENOTYPE; RECOGNITION; RESPONSES; SURVIVAL AB To study the lifespan of virgin T lymphocytes, we removed the thymus from adult female mice and then, at various times afterward, tested their ability to mount an immune response to a newly encountered Ag, the male Ag H-Y, We found that unprimed thymectomized mice were able to generate a primary response to H-Y for some time after thymectomy but lost this ability at similar to 6 mo. In contrast, mice that were primed to H-Y just after thymectomy continued to display immunological memory to H-Y for >1 year. These experiments show that primary immune responses disappear in the absence of a thymus. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Di Rosa, F (reprint author), Ist Regina Elena, Ctr Ric Sperimentale, Lab Fisiopatol, Via Messi Oro 156, I-00158 Rome, Italy. RI Di Rosa, Francesca/J-8116-2014 NR 38 TC 48 Z9 48 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 1 PY 1999 VL 163 IS 3 BP 1253 EP 1257 PG 5 WC Immunology SC Immunology GA 219ZX UT WOS:000081640000021 PM 10415021 ER PT J AU Morales, VM Christ, A Watt, SM Kim, HS Johnson, KW Utku, N Texieira, AM Mizoguchi, A Mizoguchi, E Russell, GJ Russell, SE Bhan, AK Freeman, GJ Blumberg, RS AF Morales, VM Christ, A Watt, SM Kim, HS Johnson, KW Utku, N Texieira, AM Mizoguchi, A Mizoguchi, E Russell, GJ Russell, SE Bhan, AK Freeman, GJ Blumberg, RS TI Regulation of human intestinal intraepithelial lymphocyte cytolytic function by biliary glycoprotein (CD66a) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CARCINOEMBRYONIC ANTIGEN FAMILY; BGP ADHESION MOLECULE; T-CELL ACTIVATION; IMMUNOGLOBULIN SUPERFAMILY; IG SUPERFAMILY; RECEPTOR; EXPRESSION; MEMBER; CLONING; EPITOPE AB Human small intestinal intraepithelial lymphocytes (iIEL) are a unique population of CD8 alpha beta(+) TCR-alpha beta(+) but CD28(-) T lymphocytes that may function in intestinal epithelial cell immunosurveillance. In an attempt to define novel cell surface molecules involved in iIEL function, we raised several mAbs against activated iIELs derived from the small intestine that recognized an Ag on activated, but not resting, iIELs, Using expression cloning and binding studies with Fc fusion proteins and transfectants, the cognate Ag of these mAbs was identified as the N domain of biliary glycoprotein (CD66a), a carcinoembryonic Ag-related molecule that contains an immune receptor tyrosine-based inhibitory motif. Functionally, these mAbs inhibited the anti-CD3-directed and lymphokine-activated killer activity of the P815 cell line by iIELs derived from the human small intestine. These studies indicate that the expression of biliary glycoprotein on activated human iIELs and, potentially, other mucosal T lymphocytes is involved in the down-regulation of cytolytic function. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. John Radcliffe Hosp, MRC, Mol Haematol Unit, Oxford OX3 9DU, England. Charite Humboldt Univ, Inst Med Immunol, Berlin, Germany. St Bartholomews Hosp, Coll Med, Imperial Canc Res Fund, Med Oncol Unit, London, England. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. RP Blumberg, RS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI33911]; NIDDK NIH HHS [DK44319, DK51362] NR 46 TC 74 Z9 75 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 AUG 1 PY 1999 VL 163 IS 3 BP 1363 EP 1370 PG 8 WC Immunology SC Immunology GA 219ZX UT WOS:000081640000036 PM 10415036 ER PT J AU Shieh, CC Sadasivan, BK Russell, GJ Schon, MP Parker, CM Brenner, MB AF Shieh, CC Sadasivan, BK Russell, GJ Schon, MP Parker, CM Brenner, MB TI Lymphocyte adhesion to epithelia and endothelia mediated by the lymphocyte endothelial-epithelial cell adhesion molecule (LEEP-CAM) glycoprotein SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL; VASCULAR ADDRESSIN; HOMING RECEPTOR; GROWTH-FACTOR; L-SELECTIN; ALPHA(E)BETA(7) INTEGRIN; MONOCLONAL-ANTIBODIES; MUCOSAL LYMPHOCYTES; E-CADHERIN; BINDING AB Upon encountering the relevant vascular bed, lymphocytes attach to endothelial adhesion molecules, transmigrate out of circulation, and localize within tissues. Lymphocytes may then be retained at microanatomic sites, as in tissues, or they may continue to migrate to the lymphatics and recirculate in the blood. Lymphocytes also interact transiently, but with high avidity, with target cells or APC that are infected with microbes or hare taken up exogenous foreign Ags, This array of adhesive capabilities is mediated by the selective expression of lymphocyte adhesion molecules. Here, we developed the 6F10 mAb, which recognizes a cell surface glycoprotein designated lymphocyte endothelial-epithelial cell adhesion molecule (LEEP-CAM), that is distinct in biochemical characteristics and distribution of expression from other molecules known to play a role in lymphocyte adhesion. LEEP-CAM is expressed on particular epithelia, including the suprabasal region of the epidermis, the basal layer of bronchial and breast epithelia, and throughout the tonsillar and vaginal epithelia, Yet, it is absent from intestinal and renal epithelia, Interestingly, it is expressed also on vascular endothelium, especially high endothelial venules (HEV) in lymphoid organs, such as tonsil and appendix, The anti-LEEP-CAM: mAb specifically blocked T and B lymphocyte adhesion to monolayers of epithelial cells and to vascular endothelial cells in static cell-to-cell binding assays by similar to 40-60% when compared with control mAbs, These data suggest a role for this newly identified molecule in lymphocyte binding to endothelium, as well as adhesive interactions within selected epithelia. C1 Brigham & Womens Hosp, Dept Med, Lymphocyte Biol Sect, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Natl Cheng Kung Univ, Dept Pediat, Tainan 70101, Taiwan. RP Brenner, MB (reprint author), Smith Bldg,Room 522,1 Jimmy Fund Way, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK 43351]; NIGMS NIH HHS [GM 49342] NR 67 TC 16 Z9 16 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 AUG 1 PY 1999 VL 163 IS 3 BP 1592 EP 1601 PG 10 WC Immunology SC Immunology GA 219ZX UT WOS:000081640000064 PM 10415064 ER PT J AU Klein, RS Williams, KC Alvarez-Hernandez, X Westmoreland, S Force, T Lackner, AA Luster, AD AF Klein, RS Williams, KC Alvarez-Hernandez, X Westmoreland, S Force, T Lackner, AA Luster, AD TI Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: Implications for the neuropathogenesis of AIDS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; IN-SITU HYBRIDIZATION; MONOCYTE CHEMOATTRACTANT PROTEIN-1; MULTIPLE-SCLEROSIS LESIONS; CENTRAL-NERVOUS-SYSTEM; HIV-1 INFECTION; INFLAMMATORY CELLS; BETA-CHEMOKINES; MESSENGER-RNA; CO-RECEPTORS AB Chemokines are believed to play a role in the neuropathogenesis of AIDS through their recruitment of neurotoxin-secreting, virally infected leukocytes into the CNS, Levels of chemokines are elevated in brains of patients and macaques with HIV/SIV-induced encephalitis. The chemokine receptors CCR3, CCR5, and CXCR4 are found on subpopulations of neurons in the cortex of human and macaque brain. We have developed an in vitro system using both macaque and human fetal neurons and astrocytes to further investigate the roles of these receptors in neuronal response to inflammation. Here we report the presence of functional HIV/SIV coreceptors CCR3, CCR5, and CXCR4 on fetal human and macaque neurons and CCR5 and CXCR4 on astrocytes immediately ex vivo and after several weeks in culture. Confocal imaging of immunostained neurons demonstrated different patterns of distribution for these receptors, which may have functional implications. Chemokine receptors were shown to respond to their appropriate chemokine ligands with increases in intracellular calcium that, in the case of neurons, required predepolarization with KCl. These responses were blocked by neutralizing chemokine receptor in mAbs, Pretreatment of neural cells with pertussis toxin abolished responses to stromal-derived factor-1 alpha, macrophage inflammatory protein 1 beta, and RANTES, indicating coupling of CCR5 and CXCR4 to a G(i)alpha protein, as in leukocytes, Cultured macaque neurons demonstrated calcium flux response to treatment with recombinant SIVmac239 envelope protein, suggesting a mechanism by which viral envelope could affect neuronal function in SIV infection. The presence of functional chemokine receptors on neurons and astrocytes suggests that chemokines could serve to link inflammatory and neuronal responses. C1 Univ Hartford, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Unit, Charlestown, MA 02129 USA. RP Klein, RS (reprint author), Univ Hartford, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, 149 13th St,Room 5212D, Charlestown, MA 02129 USA. OI Force, Thomas/0000-0002-0450-8659 FU NCI NIH HHS [CA69212]; NIAID NIH HHS [AI40618, AI01519] NR 61 TC 162 Z9 163 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 AUG 1 PY 1999 VL 163 IS 3 BP 1636 EP 1646 PG 11 WC Immunology SC Immunology GA 219ZX UT WOS:000081640000069 PM 10415069 ER PT J AU Schapira, MM Lawrence, WF Katz, DA McAulliffe, TL Nattinger, AB AF Schapira, MM Lawrence, WF Katz, DA McAulliffe, TL Nattinger, AB TI Change in utility values between hypothetical and experienced impotence and incontinence health states in prostate cancer patients. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. Zablocki Vet Adm Med Ctr, Milwaukee, WI 53295 USA. Univ Wisconsin, William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Georgetown Univ, Washington, DC 20057 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD AUG PY 1999 VL 47 IS 7 SU S BP 250A EP 250A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 231AW UT WOS:000082284700193 ER PT J AU Sjak-Shie, NN Vescio, RA Berenson, JR AF Sjak-Shie, NN Vescio, RA Berenson, JR TI HHV-8 infection and multiple myeloma SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT 5th International Symposium on Dendritic Cells in Fundamental and Clinical Immunology CY SEP 23-28, 1998 CL PITTSBURGH, PENNSYLVANIA DE Kaposi's sarcoma herpes virus; pathophysiology; monoclonal gammopathy of undetermined significance ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; BONE-MARROW; DENDRITIC CELLS; PROGENITOR CELLS; HUMAN-HERPESVIRUS-8; BLOOD; KSHV; INDIVIDUALS; ONCOGENE AB Human herpes virus 8 (HHV-8) also known as Kaposi's sarcoma-associated herpes virus has been strongly implicated in the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. Recently, this gamma-herpes virus was also found in the nonmalignant bone marrow dendritic cells of the majority of myeloma patients. In addition, HHV-8 is also detectable in the peripheral blood of most myeloma patients. In contrast, this virus is rarely detected in close contacts of myeloma patients or healthy subjects. Furthermore, only about one-third of patients with monoclonal gammopathy of undetermined significance (MGUS) are infected with HHV-8, Sequencing of HHV-8 DNA isolated from myeloma patients shows both interpatient differences and conserved differences unique to myeloma compared to HHV-8 in other malignancies. Consistent expression of both the viral homologs of interferon regulatory factor and interleukin-8 receptor in myeloma suggests a possible role for these transforming viral genes in the pathogenesis of this disease. C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Div Hematol & Oncol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA USA. RP Berenson, JR (reprint author), Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,111H, Los Angeles, CA 90073 USA. NR 30 TC 9 Z9 9 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 1999 VL 66 IS 2 BP 357 EP 360 PG 4 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 225FF UT WOS:000081947200029 PM 10449181 ER PT J AU Zhou, DJ Kou, ZC Ibegbu, C Shen, Y Lee-Parritz, D Shen, L Sehgal, PK McClure, HM Morrison, P Bogle, C Sehgal, N Nahmias, AJ Chen, ZW AF Zhou, DJ Kou, ZC Ibegbu, C Shen, Y Lee-Parritz, D Shen, L Sehgal, PK McClure, HM Morrison, P Bogle, C Sehgal, N Nahmias, AJ Chen, ZW TI The disruption of macaque CD4+T-cell repertoires during the early simian immunodeficiency virus infection SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 16th Annual Symposium on Nonhuman Primate Models for AIDS CY OCT 07-10, 1998 CL ATLAND, GEORGIA SP Natl Ctr Res Resources, Natl Inst Allergy & Infect Dis, Yerkes Reg Primate Res Ctr, Pharmingen, BioTech Imaging Inc, Cosh Healthcare Ltd, Gilead Sci, Merck Res Lab, Surburban Surgical Co Inc DE monkey; SIU; TCR; rhesus ID RHESUS-MONKEYS; T-LYMPHOCYTES; HIV-INFECTION; ANTIGEN; REPLICATION; VACCINATION; EXPRESSION; RECEPTORS; CD4(+) AB T-cell receptor (TCR) complementarily determining region 3 (CDR3) spetratyping analysis was employed to assess the ability of an AIDS virus to disrupt CD4+ T-cell repertoires during the primary infection. Rhesus and pig-tailed macaques infected with simian immunodeficiency virus (SIV)mac 251 and SIVsmmFGb, respectively, were evaluated. Following SIV infection, the macaques exhibited an apparent decline of CD4+ peripheral blood lymphocyte (PBL) counts, which was associated with a change in CDR3 profiles from multiple-length distribution to one- or two-length dominance in the selected TCR V beta-expressing CD4+ PBL subpopulations. Molecular analysis of the perturbed cell subpopulations suggested that the CD4+ T cells bearing the dominant CDR3 length were clonally expanded. These results indicate that SIV infection can induce a disruption of macaque CD4+ T-cell repertoires during the primary infection. The finding in this study, therefore, suggests that the virus-induced clonal dominance can contribute to the disruption of CD4+ T-cell repertoires. C1 Oklahoma State Univ, Stillwater, OK 74078 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Emory Univ, Sch Med, Atlanta, GA 30303 USA. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. RP Chen, ZW (reprint author), Oklahoma State Univ, 166 Vet Med, Stillwater, OK 74078 USA. FU NCRR NIH HHS [RR13601, RR00165]; NIAID NIH HHS [AI33628] NR 22 TC 7 Z9 7 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG-OCT PY 1999 VL 28 IS 4-5 BP 174 EP 180 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 254YW UT WOS:000083642800006 PM 10593483 ER PT J AU Gauduin, MC Glickman, RL Ahmad, S Yilma, T Johnson, RP AF Gauduin, MC Glickman, RL Ahmad, S Yilma, T Johnson, RP TI Characterization of SIV-specific CD4(+) T-helper proliferative responses in macaques immunized with live-attenuated SIV SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 16th Annual Symposium on Nonhuman Primate Models for AIDS CY OCT 07-10, 1998 CL ATLAND, GEORGIA SP Natl Ctr Res Resources, Natl Inst Allergy & Infect Dis, Yerkes Reg Primate Res Ctr, Pharmingen, BioTech Imaging Inc, Cosh Healthcare Ltd, Gilead Sci, Merck Res Lab, Surburban Surgical Co Inc DE simian immunodeficiency virus; AIDS vaccines; CD4(+) T-helper responses ID SIMIAN IMMUNODEFICIENCY VIRUS; RHESUS MACAQUES; DELETION MUTANT; INFECTED CELLS; NEF GENE; INDUCTION; MONKEYS; PROTECTION; CHALLENGE; VACCINE AB Analysis of immune responses generated by live-attenuated simian immunodeficiency virus (SIV) strains may provide clues to the mechanisms of protective immunity induced by this approach. We examined SIV-specific T-helper responses in macaques immunized with the live-attenuated SIV strains SIVmac239 Delta nef and SIVmac239 Delta 3. Optimization of the concentration and duration of antigenic stimulation resulted in the detection of relatively strong SIV-specific proliferative responses, with peak stimulation indices of up to 84. SIV-specific pro liferative responses were mediated by CD4(+) T cells and were major histocompatibility (MHC) class II restricted. Limiting dilution analysis revealed SIV-specific T-helper precursor frequencies of up to 96 per 10(6) peripheral blood mononuclear cells (PBMC). Intracellular flow-cytometric analysis demonstrated the production of interleukin (IL)-2. interferon (IFN)-gamma, RANTES and macrophage inhibitory protein-1 alpha (MIP-1 alpha) by T lymphocytes from SIVmac239 Delta nef-vaccinated animals following SIV p55 stimulation. Induction of strong SIV-specific T-helper responses by live-attenuated SIV vaccines may play a role in their ability to induce protective immunity. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. Univ Calif Davis, Int Lab Mol Biol Trop Dis, Davis, CA 95616 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, New England Reg Primate Res Ctr, Sch Med, Div Immunol, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. FU NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI43044, AI36197] NR 32 TC 15 Z9 15 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG-OCT PY 1999 VL 28 IS 4-5 BP 233 EP 241 PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 254YW UT WOS:000083642800013 PM 10593490 ER PT J AU Chung, RT Monto, A Dienstag, JL Kaplan, LM AF Chung, RT Monto, A Dienstag, JL Kaplan, LM TI Mutations in the NS5A region do not predict interferon-responsiveness in American patients infected with genotype 1b hepatitis C virus SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY MAY 10-11, 1997 CL WASHINGTON, D.C. SP Amer Assoc Study Liver Dis DE hepatitis C virus; NS5a; interferon sensitivity determining region; genotype 1b ID SENSITIVITY-DETERMINING REGION; AMINO-ACID SUBSTITUTIONS; NONSTRUCTURAL 5A PROTEIN; VIRAL-HEPATITIS; NON-A; THERAPY; GENE; GENOME; ALFA; RESISTANCE AB A striking association has been demonstrated recently between mutations in amino acid residues 2209-2248 of the nonstructural protein 5a (NS5a) region of hepatitis C virus (HCV) and sustained responses to interferon in Japanese patients infected with genotype 1b. Therefore, analysis of this sequence has been suggested as a predictor of treatment response. We sought to determine whether mutations in this region predict outcome in U.S. patients infected with genotype Ib hepatitis C virus (HCV-1b). We analyzed stored pretreatment sera retrospectively from 22 patients with HCV-1b infection who had received interferon alpha-2b (IFN alpha-2b) as part of a controlled trial. Two patients were sustained responders (SR), 7 were transient responders (TR), and 13 were nonresponders (NR). We performed nested reverse transcription-polymerase chain reaction (RT-PCR) on extracted RNA using primers flanking HCV amino acids 2209-2248 and sequenced the PCR products directly. The deduced amino acid sequences were compared with the prototype HCV-J. Isolates with four or more deviations from the prototype were defined as "mutant" type, those with one to three substitutions as "intermediate" type, and those matching the prototype as "wildtype." Of the 22 HCV-1b isolates, 6 were wildtype, 11 intermediate type, and 5 mutant type. Both of the SRs were intermediate type. The 20 TRs and NRs were distributed among mutant (5), intermediate (9), and wildtype (6). Of the five patients with mutant virus, four were NR and one a TR. Variation in NS5a(2209-2248) fails to predict interferon responsiveness in this cohort of American patients infected with HCV-1b. Thus, the utility of this sequence as a predictor of interferon responsiveness appears to be specific to Japanese patients and may reflect differences between patient groups in treatment regimens, host genetic background, or alterations in the interferon signaling pathway induced by surrounding sequences within or outside NS5a. Overall, NS5a is not as integral a determinant of interferon responsiveness as previously suggested. J.Med. Virol. 58:353-358, 1999. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ-724, Boston, MA 02114 USA. FU NIAID NIH HHS [R01-AI33455]; NIDDK NIH HHS [K08-DK02209, P30-DK43351] NR 23 TC 58 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD AUG PY 1999 VL 58 IS 4 BP 353 EP 358 DI 10.1002/(SICI)1096-9071(199908)58:4<353::AID-JMV6>3.0.CO;2-C PG 6 WC Virology SC Virology GA 211XU UT WOS:000081187800006 PM 10421401 ER PT J AU Wilson, JC Zhu, JJ Black, PM AF Wilson, JC Zhu, JJ Black, PM TI The p27/Kip1 locus shows no loss of heterozygosity in human pituitary adenomas SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE p27; Kip1; pituitary adenomas; loss of heterozygosity; microsatellite markers; chromosome 12p; cyclin-dependent kinase inhibitors ID DEPENDENT KINASE INHIBITOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; GROWTH-FACTOR-BETA; CELL-CYCLE ARREST; MOLECULAR ANALYSIS; P27(KIP1) EXPRESSION; MUTATIONAL ANALYSIS; MICE LACKING; GENE LOCUS; P27 C1 Brigham & Womens Hosp, Neurosurg Labs, Boston, MA 02115 USA. Brigham & Womens Hosp, Brain Tumor Ctr, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. RP Wilson, JC (reprint author), Brigham & Womens Hosp, Neurosurg Labs, Boston, MA 02115 USA. NR 30 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD AUG PY 1999 VL 44 IS 1 BP 35 EP 39 DI 10.1023/A:1006242118541 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 248PJ UT WOS:000083283700005 PM 10582666 ER PT J AU Albers, DS Augood, SJ Martin, DM Standaert, DG Vonsattel, JPG Beal, MF AF Albers, DS Augood, SJ Martin, DM Standaert, DG Vonsattel, JPG Beal, MF TI Evidence for oxidative stress in the subthalamic nucleus in progressive supranuclear palsy SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE neurodegenerative disorders; free radicals; lipid peroxidation; malondialdehyde; subthalamic nucleus; progressive supranuclear palsy ID PARKINSONS-DISEASE; GLUTAMATE-LIKE; DAMAGE; BRAIN; IMMUNOREACTIVITY; 2-DEOXYGLUCOSE; STIMULATION; REVERSAL; MONKEYS AB Increased free radical production and oxidative stress have been proposed as pathogenic mechanisms in several neurodegenerative disorders. Free radicals interact with biological macromolecules, such as lipids, which can lead to lipid peroxidation. A well-established marker of oxidative damage to lipids is malondialdehyde (MDA). We measured tissue MDA levels in the subthalamic nucleus (STN) and cerebellum from 11 progressive supranuclear palsy (PSP) cases and 11 age-matched control cases using sensitive HPLC techniques. In PSP, a significant increase in tissue MDA levels was observed in the STN when compared with the age-matched control group. By contrast, no significant difference between tissue MDA content was observed in cerebellar tissue from the same PSP and age-matched control cases. These results indicate that lipid peroxidation may play a role in the pathogenesis of PSP. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Cornell Univ, Coll Med, Dept Neurol, New York, NY USA. RP Albers, DS (reprint author), Massachusetts Gen Hosp, Neurol Serv, Warren 408,Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NIMH NIH HHS [MH/NS 31862] NR 27 TC 40 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1999 VL 73 IS 2 BP 881 EP 884 DI 10.1046/j.1471-4159.1999.0730881.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CG UT WOS:000081535200051 PM 10428088 ER PT J AU Kraft, E Trenkwalder, C Bergh, FT Auer, DP AF Kraft, E Trenkwalder, C Bergh, FT Auer, DP TI Magnetic resonance proton spectroscopy of the brain in Wilson's disease SO JOURNAL OF NEUROLOGY LA English DT Article DE Wilson's disease; proton spectroscopy; subclinical hepatic encephalopathy ID SUBCLINICAL HEPATIC-ENCEPHALOPATHY; H-1 MR SPECTROSCOPY; H-1-NMR SPECTROSCOPY; NMR-SPECTRA; DIAGNOSIS; ABNORMALITIES; CIRRHOSIS; IDENTIFICATION; MITOCHONDRIA; DISORDERS AB We studied 13 patients with Wilson's disease (WD) using localized magnetic resonance proton spectroscopy to test whether hepatic encephalopathy or impaired energy metabolism contributes to neurological dysfunction. Levels of myoinositol (MI), choline-containing compounds (Cho), creatine (Cr), N-acetyl-aspartate (NAA), Glx (unresolved resonances of glutamate, glutamine, and gamma-aminobutyric acid) and lactate were measured using a relative quantitative approach. Results were compared with those from 12 healthy controls. In one patient with de novo WD and acute hepatic disease but no neurological symptoms we found a marked decrease in the Cho/Cr and MI/Cr ratios. However, proton spectroscopy in the white matter, gray matter, and putamen of patients with treated WD showed no significant differences compared to healthy controls. Ln none of the subjects studied was the lactate/Cr ratio elevated. The spectroscopic findings were compatible with subclinical hepatic encephalopathy in the one patient with de novo WD and acute hepatic disease, but this does not play a major role in brain dysfunction in patients with treated WD. Additionally, there was no evidence of increased lactate concentration, indicating that cerebral energy metabolism was not grossly impaired. C1 Max Planck Inst Psychiat, D-80804 Munich, Germany. RP Kraft, E (reprint author), Massachusetts Gen Hosp, MGH NMR Ctr, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM eduard@nmr.mgh.harvard.edu NR 31 TC 17 Z9 22 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD AUG PY 1999 VL 246 IS 8 BP 693 EP 699 DI 10.1007/s004150050434 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 233NY UT WOS:000082434000011 PM 10460447 ER PT J AU Ino, Y Silver, JS Blazejewski, L Nishikawa, R Matsutani, M von Deimling, A Louis, DN AF Ino, Y Silver, JS Blazejewski, L Nishikawa, R Matsutani, M von Deimling, A Louis, DN TI Common regions of deletion on chromosome 22q12.3-q13.1 and 22q13.2 in human astrocytomas appear related to malignancy grade SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE astrocytoma; chromosome 22q; glioblastoma; tumor suppressor gene ID TUMOR-SUPPRESSOR GENE; CENTRAL-NERVOUS-SYSTEM; FREQUENT LOSS; ALLELIC LOSS; HETEROZYGOSITY; CANCER; 22Q; GLIOMAS; LOCI; CHILDHOOD AB Approximately 30% of human astrocytomas have been reported to display allelic loss of the long arm of chromosome 22, suggesting the presence of a chromosome 22q astrocytoma suppressor gene. To define the most likely location for this putative tumor suppressor, we performed deletion mapping on 141 tumors using 16 chromosome 22q microsatellite markers. Allelic loss of 22q was observed in 2/12 (17%) of astrocytomas, 9/29 (31%) of anaplastic astrocytomas, and 38/100 (38%) of glioblastomas, consistent with a role for chromosome 22q loss in astrocytoma progression as well as formation. Twenty-two tumors exhibited allelic loss at every informative locus, consistent with loss of the entire arm of 22q. Twenty-seven tumors showed partial deletions, with one common region of deletion at 22q12.3-q13.1 between markers D22S280 and D22S282, and a second candidate region at 22q13.2 near the marker D22S1170. For the proximal candidate region, the incidence of allelic loss was similar between grades; for the distal locus, the incidence increased with grade, raising the possibility that the distal locus is involved in a later stage of astrocytoma tumorigenesis. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Saitama Med Univ, Sch Med, Dept Neurosurg, Saitama, Japan. Humboldt Univ, Charite, Dept Neuropathol, Berlin, Germany. RP Louis, DN (reprint author), Massachusetts Gen Hosp East, Mol Neurooncol Lab, CNY6,149 13th St, Boston, MA 02129 USA. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [CA 57683] NR 21 TC 48 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD AUG PY 1999 VL 58 IS 8 BP 881 EP 885 DI 10.1097/00005072-199908000-00010 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 225XA UT WOS:000081990200011 PM 10446812 ER PT J AU Lewis, RF Zee, DS Goldstein, HP Guthrie, BL AF Lewis, RF Zee, DS Goldstein, HP Guthrie, BL TI Proprioceptive and retinal afference modify postsaccadic ocular drift SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID EXTRAOCULAR-MUSCLE PROPRIOCEPTION; SACCADIC EYE-MOVEMENTS; DISCONJUGATE ADAPTATION; OCULOMOTOR SYSTEM; ADAPTIVE-CONTROL; PURKINJE-CELLS; MONKEY; ALIGNMENT; SIGNALS; NEURONS AB Drift of the eyes after saccades produces motion of images on the retina (retinal slip) that degrades visual acuity. In this study, we examined the contributions of proprioceptive and retinal afference to the suppression of postsaccadic drift induced by a unilateral ocular muscle paresis. Eye movements were recorded in three rhesus monkeys with a unilateral weakness of one vertical extraocular muscle before and after proprioceptive deafferentation of the paretic eye. Postsaccadic drift was examined in four visual states: monocular viewing with the normal eye (4-wk period), binocular viewing (2-wk period): binocular viewing with a disparity-reducing prism (2-wk period); and monocular viewing with the paretic eye (2-wk period). The muscle paresis produced vertical postsaccadic drift in the paretic eye, and this drift was suppressed in the binocular viewing condition even when the animals could not fuse. When the animals viewed binocularly with a disparity-reducing prism, the drift in the paretic eye was suppressed in two monkeys (with superior oblique pareses) but generally was enhance in one animal (with a tenotomy of the inferior rectus). When drift movements were enhanced, they reduced the retinal disparity that was present at the end of the saccade. In the paretic-eye-viewing condition, postsaccadic drift was suppressed in the paretic eye and was induced in the normal eye. After deafferentation in the normal-eye-viewing state, there was a change in the vertical postsaccadic drift of the paretic eye. This change in drift was idiosyncratic and variably affected the amplitude and velocity of the postsaccadic drift movements of the paretic eye. Deafferentation of the paretic eye did not affect the postsaccadic drift of the normal eye nor did it impair visually mediated adaptation of postsaccadic drift. The results demonstrate several new findings concerning the roles of visual and proprioceptive afference in the control of postsaccadic drift: disconjugate adaptation of postsaccadic drift does not require binocular fusion; sloe, postsaccadic drift movements that reduce retinal disparity but concurrently increase retinal slip can be induced in the binocular viewing state; postsaccadic drift is modified by proprioception from the extraocular muscles, but these modifications do not serve to minimize retinal slip or to correct errors in saccade amplitude; and visually mediated adaptation of postsaccadic drift does not require proprioceptive afference from the paretic eye. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. Thomas Jefferson Univ, Wills Eye Hosp, Philadelphia, PA 19107 USA. Univ Alabama, Dept Neurosurg, Birmingham, AL 35294 USA. RP Lewis, RF (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY-01849, EY-06273]; NINDS NIH HHS [NS-01656] NR 49 TC 10 Z9 11 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1999 VL 82 IS 2 BP 551 EP 563 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 226TM UT WOS:000082038000005 PM 10444655 ER PT J AU Kujawa, SG Liberman, MC AF Kujawa, SG Liberman, MC TI Long-term sound conditioning enhances cochlear sensitivity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PRODUCT OTOACOUSTIC EMISSIONS; INDUCED HEARING-LOSS; OUTER HAIR-CELLS; MIDDLE-EAR MUSCLES; TEMPORARY THRESHOLD SHIFTS; SINGLE OLIVOCOCHLEAR NEURONS; INTERRUPTED NOISE EXPOSURES; LEVEL ACOUSTIC STIMULATION; GUINEA-PIG; ELECTRICAL-STIMULATION AB Sound conditioning, by chronic exposure to moderate-level sound, can protect the inner ear (reduce threshold shifts and hair cell damage) from subsequent high-level sound exposure. To investigate the mechanisms underlying this protective effect, the present study focuses on the physiological changes brought on by the conditioning exposure itself. In our guinea-pig model, 6-h daily conditioning exposure to an octave-band noise at 85 dB SPL reduces the permanent threshold shifts (PTSs) from a subsequent 4-h traumatic exposure to the same noise band at 109 dB SPL, as assessed by both compound action potentials (CAPs) and distortion product otoacoustic emissions (DPOAEs). The frequency region of maximum threshold protection is approximately one-half octave above the upper frequency cutoff of the exposure band. Protection is also evident in the magnitude of suprathreshold CAPs and DPOAEs, where effects are more robust and extend to higher frequencies than those evident at or near threshold. The conditioning exposure also enhanced cochlear sensitivity, when evaluated at the same postconditioning time at which the traumatic exposure would be delivered in a protection study. Response enhancements were seen in both threshold and suprathreshold CAPs and DPOAEs. The frequency dependence of the enhancement effects differed, however, by these two metrics. For CAPs, effects were maximum in the same frequency reg lon as those most protected by the conditioning. For DPOAEs, enhancements were shifted to lower frequencies. The conditioning exposure also enhanced both ipsilaterally and contralaterally evoked olivocochlear (OC) reflex strength, as assessed using DPOAEs. The frequency and level dependence of the reflex enhancements were consistent with changes seen in sound-evoked discharge rates in OC fibers after conditioning. However, comparison with the frequency range and magnitude of conditioning-related protection suggests that the protection cannot be completely explained by amplification of the OC reflex and the known protective effects of OC feedback. Rather, the present results suggest that sound conditioning leads to changes in the physiology of the outer hair cells themselves, che peripheral targets of the OC reflex. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Kujawa, SG (reprint author), Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Bloedel Hearing Res Ctr, Bldg CHDD, Seattle, WA 98195 USA. FU NIDCD NIH HHS [F32 DC-00180, R01 DC-00188] NR 59 TC 27 Z9 29 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1999 VL 82 IS 2 BP 863 EP 873 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 226TM UT WOS:000082038000033 PM 10444683 ER PT J AU Rajadhyaksha, A Barczak, A Macias, W Leveque, JC Lewis, SE Konradi, C AF Rajadhyaksha, A Barczak, A Macias, W Leveque, JC Lewis, SE Konradi, C TI L-type Ca2+ channels are essential for glutamate-mediated CREB phosphorylation and c-fos gene expression in striatal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Review DE glutamate; NMDA; AMPA; kainate; L-type Ca2+ channels; CREB; c-fos ID METHYL-D-ASPARTATE; SENSITIVE CALCIUM CHANNELS; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; NMDA-RECEPTOR ACTIVATION; ELEMENT-BINDING PROTEIN; SPINAL-CORD NEURONS; HIPPOCAMPAL-NEURONS; RAT-BRAIN; MESSENGER-RNA AB The second messenger pathways linking receptor activation at the membrane to changes in the nucleus are just beginning to be unraveled in neurons. The work presented here attempts to identify in striatal neurons the pathways that mediate cAMP response element-binding protein (CREB) phosphorylation and gene expression in response to NMDA receptor activation. We investigated the phosphorylation of the transcription factor CREB, the expression of the immediate early gene c-fos, and the induction of a transfected reporter gene under the transcriptional control of CREB after stimulation of ionotropic glutamate receptors. We found that neither AMPA/kainate receptors nor NMDA receptors were able to stimulate independently a second messenger pathway that led to CREB phosphorylation or c-fos gene expression. instead, we saw a consecutive pathway from AMPA/kainate receptors to NMDA receptors and from NMDA receptors to L-type Ca2+ channels. AMPA/kainate receptors were involved in relieving the Mg2+ block of NMDA receptors, and NMDA receptors triggered the opening of L-type Ca2+ channels. The second messenger pathway that activates CREB phosphorylation and c-fos gene expression is likely activated by Ca2+ entry through L-type Ca2+ channels. We conclude that in primary striatal neurons glutamate-mediated signal transduction is dependent on functional L-type Ca2+ channels. C1 Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Konradi, C (reprint author), Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, CNY 2510,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIDA NIH HHS [DA07134, R01 DA007134, R01 DA007134-14] NR 102 TC 131 Z9 133 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 1999 VL 19 IS 15 BP 6348 EP 6359 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 220DC UT WOS:000081648400014 PM 10414964 ER PT J AU Wyszynski, M Valtschanoff, JG Naisbitt, S Dunah, AW Kim, E Standaert, DG Weinberg, R Sheng, M AF Wyszynski, M Valtschanoff, JG Naisbitt, S Dunah, AW Kim, E Standaert, DG Weinberg, R Sheng, M TI Association of AMPA receptors with a subset of glutamate receptor-interacting protein in vivo SO JOURNAL OF NEUROSCIENCE LA English DT Article DE AMPA receptor; GRIP; excitatory synapse; PDZ domain; immunoprecipitation; postsynaptic density ID NMDA RECEPTOR; POSTSYNAPTIC DENSITY; HIPPOCAMPAL-NEURONS; IMMUNOCYTOCHEMICAL CHARACTERIZATION; GUANYLATE KINASES; FASCICLIN-II; SUBUNIT NR1; RAT-BRAIN; IN-VIVO; PSD-95 AB The NMDA and AMPA classes of ionotropic glutamate receptors are concentrated at postsynaptic sites in excitatory synapses. NMDA receptors interact via their NR2 subunits with PSD-95/SAP90 family proteins, whereas AMPA receptors bind via their GluR2/3 subunits to glutamate receptor-interacting protein (GRIP), AMPA receptor-binding protein (ABP), and protein interacting with C kinase 1 (PICK1). We report here a novel cDNA (termed ABP-L/GRIP2) that is virtually identical to ABP except for additional GRIP-like sequences at the N-terminal and G-terminal ends. Like GRIP (which we now term GR(PI), AEP-L/GRIP2 contains a seventh PDZ domain at its C terminus. Using antibodies that recognize both these proteins, we examined the subcellular localization of GRIP1 and ABP-L/GRIP2 (collectively termed GRIP) and their biochemical association with AMPA receptors. Immunogold electron microscopy revealed the presence of GRIP at excitatory synapses and also at nonsynaptic membranes and within intracellular compartments. The association of native GRIP and AMPA receptors was confirmed biochemically by coimmunoprecipitation from rat brain extracts. A majority of detergent-extractable GluR2/3 was complexed with GRIP in the brain. However, only approximately half of GRIP was associated with AMPA receptors. Unexpectedly, immunocytochemistry of cultured hippocampal neurons and rat brain at the light microscopic level showed enrichment of GRIP in GABAergic neurons and in GABAergic nerve terminals. Thus GRIP is associated with inhibitory as well as excitatory synapses. Collectively, these findings support a role for GRIP in the synaptic anchoring of AMPA receptors but also suggest that GRIP has additional functions unrelated to the binding of AMPA receptors. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. Pusan Natl Univ, Dept Pharmacol, Pusan 609735, South Korea. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 423,50 Blossom St, Boston, MA 02114 USA. RI Kim, Eunjoon/C-1566-2011; OI Standaert, David/0000-0003-2921-8348 FU NCI NIH HHS [CA66268]; NINDS NIH HHS [NS35050, NS35527] NR 36 TC 133 Z9 142 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 1999 VL 19 IS 15 BP 6528 EP 6537 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 220DC UT WOS:000081648400031 PM 10414981 ER PT J AU Fitzek, MM Thornton, AF Rabinov, JD Lev, MH Pardo, FS Munzenrider, JE Okunieff, P Bussiere, M Braun, I Hochberg, FH Hedley-Whyte, ET Liebsch, NJ Harsh, GR AF Fitzek, MM Thornton, AF Rabinov, JD Lev, MH Pardo, FS Munzenrider, JE Okunieff, P Bussiere, M Braun, I Hochberg, FH Hedley-Whyte, ET Liebsch, NJ Harsh, GR TI Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a phase II prospective trial SO JOURNAL OF NEUROSURGERY LA English DT Article DE glioblastoma multiforme; dose escalation; radiation therapy; proton ID RADIATION-THERAPY; MALIGNANT GLIOMAS; INTERSTITIAL BRACHYTHERAPY; ANAPLASTIC ASTROCYTOMA; TOPOGRAPHIC ANATOMY; INITIAL MANAGEMENT; CT CORRELATIONS; IMPLANT BOOST; RADIOTHERAPY; PATTERNS AB Object. After conventional doses of 55 to 65 Gy of fractionated irradiation, glioblastoma multiforme (GBM) usually recurs at its original location. This institutional phase II study was designed to assess whether dose escalation to 90 cobalt gray equivalent (CGE) with conformal protons and photons in accelerated fractionation would improve local tumor control and patient survival. Methods. Twenty-three patients were enrolled in this study. Eligibility criteria included age between 18 and 70 years, Karnofsky Performance Scale score of greater than or equal to 70, residual tumor volume of less than 60 mi, and a supratentorial, unilateral tumor. Actuarial survival rates at 2 and 3 years were 34% and 18%, respectively. The median survival time was 20 months, with four patients alive 22 to 60 months postdiagnosis. Analysis by Radiation Therapy Oncology Group prognostic criteria or Medical Research Council indices showed a 5- to 11-month increase in median survival time over those of comparable conventionally treated patients. All patients developed new areas of gadolinium enhancement during the follow-up period. Histological examination of tissues obtained at biopsy, resection, or autopsy was conducted in 15 of 23 patients. Radiation necrosis only was demonstrated in seven patients, and their survival was significantly longer than that of patients with recurrent tumor (p = 0.01). Tumor regrowth occurred most commonly in areas that received doses of 60 to 70 CGE or less; recurrent tumor was found in only one case in the 90-CGE volume. Conclusions. A dose of 90 CGE in accelerated fractionation prevented central recurrence in almost all cases. The median survival time was extended to 20 months, likely as a result of central control. Tumors will usually recur in areas immediately peripheral to this 90-CGE volume, but attempts to extend local control by enlarging the central volume are likely to be limited by difficulties with radiation necrosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. RP Fitzek, MM (reprint author), Humboldt Univ, Dept Radiat Oncol, Charite, Schumannstr 20-21, D-10117 Berlin, Germany. FU NCI NIH HHS [P01 CA 21239] NR 32 TC 136 Z9 138 U1 0 U2 6 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 1999 VL 91 IS 2 BP 251 EP 260 DI 10.3171/jns.1999.91.2.0251 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 220RT UT WOS:000081681800011 PM 10433313 ER PT J AU Nikas, DC De Girolami, U Zamani, AA Pinkus, GS Bello, L Kirsch, M Black, PM AF Nikas, DC De Girolami, U Zamani, AA Pinkus, GS Bello, L Kirsch, M Black, PM TI Idiopathic pinealitis - Case report SO JOURNAL OF NEUROSURGERY LA English DT Article DE idiopathic pinealitis; pineal gland; pineal inflammation ID RECURRENT UVEITIS; GLAND; GERMINOMA AB This 63-year-old man presented with complaints of "having a feeling of falling backward" over a 3-month period. Results of his general physical examination, laboratory studies, and neurological examination were unremarkable. A magnetic resonance image revealed a 1.8 X 1.4 X 1.2-cm enhancing mass in the posterior third ventricle just above the corpora quadrigemina. The pineal gland was found to be diffusely enlarged at operation and separable from the posterior thalamus and was totally resected. The patient had an uneventful postoperative course but continues to be somewhat confused. The lesion consisted of a remarkable chronic inflammatory cell infiltrate permeating the pineal lobules and was composed of T and B lymphocytes, macrophages, eosinophils, and mast cells. Immunoperoxidase studies did not demonstrate Langerhans cells, and a search for microoganisms was unrevealing. There was no evidence of neoplasia; results of immunostaining for germ cell markers and other tumor-associated antigens were negative. C1 Brigham & Womens Hosp, Neurosurg Labs, Boston, MA 02115 USA. Childrens Hosp, Brigham & Womens Hosp, Brain Tumor Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Neuropathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Neuroradiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Nikas, DC (reprint author), Brigham & Womens Hosp, Neurosurg Labs, 221 Longwood Ave,LMRC-121, Boston, MA 02115 USA. RI Kirsch, Matthias/F-2824-2014 NR 19 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 1999 VL 91 IS 2 BP 330 EP 334 DI 10.3171/jns.1999.91.2.0330 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 220RT UT WOS:000081681800023 PM 10433325 ER EF