FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ratcliffe, MB Wallace, AW Teerlink, JR Hong, J Salahieh, A Sung, SH Keung, EC Lee, RJ AF Ratcliffe, MB Wallace, AW Teerlink, JR Hong, J Salahieh, A Sung, SH Keung, EC Lee, RJ TI Radio frequency heating of chronic ovine infarct leads to sustained infarct area and ventricular volume reduction SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 25th Annual meeting of the Western-Thoracic-Surgical-Association CY JUN 23-26, 1999 CL LAKE TAHOE, CALIFORNIA SP Western Thorac Surg Assoc ID MYOCARDIAL-INFARCTION; COLLAGENOUS TISSUE; HEART-FAILURE; MECHANICS; SHRINKAGE; ANEURYSM; SURVIVAL; DYSFUNCTION; MORTALITY; EXERCISE AB Objective: Myocardial infarct expansion and subsequent left ventricular remodeling are associated with increased incidence of congestive failure and mortality. Collagen is known to denature and contract when heated above 65 degrees C. We therefore tested the hypothesis that radio frequency heating of myocardial infarct tissue with application of a restraining patch causes a sustained reduction in myocardial infarct area and left ventricular volume. Methods: Thirteen male Dorset sheep underwent surgical coronary artery ligation. At least 14 weeks later, animals were randomized to either radio frequency infarct heating (95 degrees C) with application of a restraining patch or a sham operation. Before treatment, after treatment, and 10 weeks later, left ventricular volume was measured with transdiaphragmatic echocardiography and myocardial infarct area was measured with an array of sonomicrometry crystals. Results: Radio frequency infarct heating causes an acute decrease of 34% (-215 +/- 82 mm(2); P = .0002) in infarct area at end-diastole that is maintained at 10 weeks (-144 +/- 79 mm(2); P = .0002). Radio frequency infarct heating causes a downward trend in end-diastolic left ventricular volume measured by echocardiography of 20% (-15.7 +/- 6.3 mt; P = no significant difference) and end-systolic left ventricular volume of 32% (-17.1 +/- 9.8 mt; P = .09), which are significantly decreased at 10 weeks (-13.6 +/- 22.3 mt; P = .007 and -15.3 +/- 21.9 mt; P = .008, respectively). Radio frequency infarct heating causes an acute improvement in systolic function (P < .001), a sustained increase in left ventricular ejection fraction (+0.11%; P = .06), and preserved stroke volume. Conclusion: Radio frequency heating of chronic left ventricular myocardial infarct causes a sustained reduction in infarct area and left ventricular volume. This technique may beneficially reverse infarct expansion and left ventricular remodeling after myocardial infarction. C1 San Francisco Vet Affairs Med Ctr, VAMC Surg 112D, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Div Cardiothorac Surg, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Div Cardiol, San Francisco, CA 94143 USA. RP Ratcliffe, MB (reprint author), San Francisco Vet Affairs Med Ctr, VAMC Surg 112D, 4150 Clement St, San Francisco, CA 94121 USA. RI Teerlink, John/D-2986-2012 NR 32 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 2000 VL 119 IS 6 BP 1194 EP 1204 DI 10.1067/mtc.2000.105826 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 323HR UT WOS:000087560400018 PM 10838539 ER PT J AU Coudret, N Oertel, LB AF Coudret, N Oertel, LB TI Workshop: Internet delivery of an Anticoagulation Therapy Management Certificate Program SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article; Proceedings Paper CT 5th National Conference on Anticoagulant Therapy CY MAY 14-15, 1999 CL VANCOUVER, CANADA SP Anticoagulat Forum C1 Univ So Indiana, Sch Nursing & Hlth Prefess, Evansville, IN 47712 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Coudret, N (reprint author), Univ So Indiana, Sch Nursing & Hlth Prefess, 8600 Univ Blvd, Evansville, IN 47712 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JUN PY 2000 VL 9 IS 1 SU S BP S57 EP S59 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 326JB UT WOS:000087730600011 PM 10859588 ER PT J AU Corless, IB Nicholas, PK AF Corless, IB Nicholas, PK TI Long-term continuum of care for people living with HIV/AIDS SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE HIV/AIDS; hospice care; palliative care AB The introduction of highly active antiretroviral therapy (HAART), has created new options for those infected and affected by human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Most HIV-infected persons no longer die within months of diagnosis. There is now a long-term continuum of care that can end in miser, or relative comfort. The introduction of palliative care in concert with curative therapies throughout the disease trajectory should be the standard of care for all persons. At the very least, the introduction of palliative care and hospice at the end of lifo is important to the holistic care of persons living with HIV/AIDS. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Nursing, Boston, MA 02114 USA. RP Corless, IB (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Nursing, Boston, MA 02114 USA. OI Corless, Inge/0000-0003-0438-2037 NR 16 TC 7 Z9 7 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD JUN PY 2000 VL 77 IS 2 BP 176 EP 186 DI 10.1007/BF02390529 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 315MP UT WOS:000087117800004 PM 10855999 ER PT J AU Barry, MJ AF Barry, MJ TI Quality of life of asymptomatic men with nonmetastatic prostate cancer on androgen deprivation therapy - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2000 VL 163 IS 6 BP 1746 EP 1746 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 313DK UT WOS:000086984900032 ER PT J AU D'Amico, AV Schultz, D Schneider, L Hurwitz, M Kantoff, PW Richie, JP AF D'Amico, AV Schultz, D Schneider, L Hurwitz, M Kantoff, PW Richie, JP TI Comparing prostate specific antigen outcomes after different types of radiotherapy management of clinically localized prostate cancer highlights the importance of controlling for established prognostic factors SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostate-specific antigen; radiotherapy; prognoses ID EXTERNAL-BEAM RADIATION; IRRADIATION AB Purpose: We evaluated the impact that the composition of prognostic factors in a patient cohort may have on prostate specific antigen (PSA) outcome following external beam radiation therapy for clinically localized prostate cancer. Materials and Methods: The distribution of PSA, biopsy Gleason score and American joint Committee on Cancer (AJCC) T stage in men with prostate cancer treated with interstitial plus external beam radiation therapy was used to select a matched cohort who underwent 3-dimensional (D) conformal external beam radiation therapy. We compared PSA outcomes after 3-D conformal external beam radiation therapy in the overall and matched cohorts of 766 and 570 patients, respectively. Results: Men treated with interstitial plus external beam radiation therapy had a significantly lower rate of PSA greater than 10 to 20 (p = 0.02) and greater than 20 ng./ml. (p <0.0001), biopsy Gleason score 7 (p = 0.02) and 8 to 10 (p <0.0001), and AJCC stage T2c disease (p <0.0001). Likewise, these men also had a significantly higher rate of PSA greater than 4 to 10 ng./ml. (p <0.0001), biopsy Gleason score 5 to 6 (p = 0.0001) and AJCC stage T1 disease (p <0.0001) than those who underwent 3-D conformal external beam radiation therapy. The 5-year estimate of PSA failure-free survival after 3-D conformal external beam radiation therapy was 45% versus 67% (p = 0.0007) for all 766 consecutively treated patients and the matched cohort of 570, respectively. Conclusions: The composition of prognostic factors in a patient cohort may impact PSA outcome. Therefore, controlling for established prognostic factors is essential when comparing PSA outcome after different forms of radiotherapy for adenocarcinoma of the prostate. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Lank Ctr Genitourinary Oncol,Dept Adult Oncol, Boston, MA 02115 USA. Millersville Univ, Dept Math, Millersville, PA 17551 USA. RP D'Amico, AV (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. NR 17 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2000 VL 163 IS 6 BP 1797 EP 1799 DI 10.1016/S0022-5347(05)67546-5 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 313DK UT WOS:000086984900051 PM 10799185 ER PT J AU Pavlovich, CP Kraling, BM Stewart, RJ Chen, XH Bochner, BH Luster, AD Poppas, DP O'Donnell, MA AF Pavlovich, CP Kraling, BM Stewart, RJ Chen, XH Bochner, BH Luster, AD Poppas, DP O'Donnell, MA TI BCG-induced urinary cytokines inhibit microvascular endothelial cell proliferation SO JOURNAL OF UROLOGY LA English DT Article DE BCG; endothelial cells; angiogenesis; urinary cytokines; IP-10; TNF-alpha ID BACILLUS-CALMETTE-GUERIN; SUPERFICIAL BLADDER-CANCER; INTERFERON-INDUCIBLE PROTEIN-10; TUMOR-NECROSIS-FACTOR; FIBROBLAST GROWTH-FACTOR; POTENT INHIBITOR; IMMUNE-RESPONSE; T-LYMPHOCYTES; IFN-GAMMA; IN-VITRO AB Purpose: Angiogenesis is thought to depend on a net balance of molecules that inhibit or stimulate microvascular endothelial cells. A variety of molecules that affect: angiogenesis are induced locally by the administration of intravesical bacille Calmette-Guerin (BCG) for superficial bladder cancer. We sought to determine whether BCG-induced urinary cytokines alter the effects of patient urine on assays of angiogenic activity. Materials and Methods: Patients undergoing BCG treatment provided urine samples before and at peak cytokine production times after BCG instillation. Fifty-four urine samples from 8 patients were analyzed by ELISA for a panel of molecules known to affect angiogenesis, and tested for angiogenic activity in human dermal microvascular endothelial cell (HDMEC) proliferation and migration assays. To assess the role of specific BOG-induced cytokines, urinary HDMEC proliferation assays were repeated in the presence of neutralizing antibodies to tumor necrosis factor-alpha (TNF-alpha), interferon-inducible protein-10 (IP-10), and/or interferon-gamma (IFN-gamma). Results: Urinary IFN-gamma, IP-10, TNF-alpha, and vascular endothelial growth factor (VEGF) were induced to nanogram/ml amounts by BCG treatment. While pre-BCG treatment urine samples minimally stimulated microvascular endothelial cell proliferation (+ 9%), post-BCG treatment urine became progressively inhibitory to endothelial cells (to -85%, p = 0.005) during weekly treatment courses. Neutralizing antibodies to TNF-alpha or to IP-10, either alone or in combination, greatly reduced this inhibitory effect. Conclusions: Intravesical BCG induces a cytokine-rich urinary microenvironment that is inhibitory to human endothelial cells. Urinary cytokine profiles and assays of angiogenic inhibition may provide prognostically important information regarding BCG treatment outcomes. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Urol, Boston, MA 02215 USA. Cornell Med Ctr, New York Hosp, Dept Urol, James Buchanan Brady Urol Inst, New York, NY USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Surg,Surg Res Lab, Boston, MA 02115 USA. Univ Toronto, Toronto Hosp, Dept Surg, Div Urol, Toronto, ON, Canada. USC Norris Comprehens Canc Ctr, Dept Urol, Los Angeles, CA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Infect Dis Unit, Charlestown, MA USA. RP O'Donnell, MA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Div Urol, 330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [R29-CA64230] NR 55 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2000 VL 163 IS 6 BP 2014 EP 2021 DI 10.1016/S0022-5347(05)67620-3 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 313DK UT WOS:000086984900139 PM 10799249 ER PT J AU Cambria, RP Davison, JK Carter, C Brewster, DC Chang, YC Clark, KA Atamian, S AF Cambria, RP Davison, JK Carter, C Brewster, DC Chang, YC Clark, KA Atamian, S TI Epidural cooling for spinal cord protection during thoracoabdominal aneurysm repair: A five-year experience SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY OCT 01-03, 1999 CL CHATHAM, MASSACHUSETTS SP New England Soc Vascular Surg ID CEREBROSPINAL-FLUID DRAINAGE; AORTIC-SURGERY; NEUROLOGIC DEFICIT; DEEP HYPOTHERMIA; RISK FACTOR; PARAPLEGIA; REPLACEMENT; ISCHEMIA; INJURY; COMPLICATIONS AB Purpose: We developed and applied a method for providing regional spinal cord hypothermia with epidural cooling (EC) during thoracoabdominal aneurysm (TAA) repair. Preliminary results indicated significant reduction in spinal cord ischemic complications (SCI), compared with historical controls, and a 5-year experience with EC was reviewed. Methods: From July 1993 to September 1998, 170 patients with thoracic aneurysms (n = 14; 8.2%) or TAAs (types I and II, n = 83 [49%]; type III, n = 66 [39%]; type N, n = 7 [4.1%]) were treated with EC. An earlier aneurysm resection was noted in 44% of patients, an emergent operation was noted in 20% of patients, and an aortic dissection was noted in 16% of patients. The EC was successful (mean cerebrospinal fluid [CSF] temperature at cross-damp, 26.4 +/- 3 degrees C) in 97% of cases, with all 170 patients included in an intention-to-treat analysis. The operation was performed with a damp/sew technique (98% patients) and selective (T-9 to L-1 region) reimplantation of intercostal vessels. Clinical and EC variables were examined for association with operative mortality and SCI by means of the Fischer exact test, and those variables with a P value less than .1 were included in multivariate logistic regression analysis. Results: The operative mortality rate was 9.5% and was weakly associated (P =.07) with SCI; postoperative cardiac complications (odds ratio [OR], 35.3; 95% CI, 5.3 to 233; P < .001) and renal failure (OR, 32.2; 95% CI, 6.6 to 157; P < .001) were the only independent predictors of postoperative death. SCI of any severity occurred in 7% of cases (type I/II, 10 of 83 [12%]; all other types, 2 of 87 [2.3%]), versus a predicted (Acher model) incidence of 18.5% for this cohort (P = .003). Half the deficits were minor, with good functional recovery, and devastating paraplegia occurred in three patients (2.0%). Independent correlates of SCI included types I and II TAA (OR, 8.0; 95% CI, 1.4 to 46.3; P = .021), nonelective operation (OR, 8.3, 95% CI, 1.8 to 37.7; P = .006), oversewn T-9 to L-2 intercostal vessels (OR, 6.1; 95% CI, 1.3 to 28.8; P = .023), and postoperative renal failure (OR, 23.6; 95% CI, 4.4 to 126; P < .001). These same clinical variables of nonelective operations (OR, 7.7; 95% CI, 1.4 to 41.4; P = .017), oversewn Tg to La intercostal arteries (OR, 9.7; 95% CI, 1.5 to 61.2; P = .016), and postoperative renal failure (OR, 20.8; 95% CI, 3.0 to 142.1; P = .002) were independent predictors of SCI in the subgroup analysis of high-risk patients, ie, patients with type I/II TAA. Conclusion: EC has been effective in reducing immediate, devastating, total paraplegia after TAA repair. A strategy that combines the neuroprotective effect of regional cord hypothermia, avoiding the sacrifice of potential spinal cord blood supply, and postoperative adjuncts (eg, avoidance of hypotension, CSF drainage) appears necessary to minimize SCI after TAA repair. C1 Massachusetts Gen Hosp, Div Vasc Surg & Vasc Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg & Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, Div Vasc Surg & Vasc Anesthesia, 15 Parkman St,WAC 458, Boston, MA 02114 USA. NR 34 TC 104 Z9 107 U1 0 U2 2 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 JUN PY 2000 VL 31 IS 6 BP 1093 EP 1101 DI 10.1067/mva.2000.106492 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 324CF UT WOS:000087603700002 PM 10842145 ER PT J AU Rehring, TF Brewster, DC Cambria, RP Kaufman, JA Geller, SC Fan, CM Gertler, JP LaMuraglia, GM Abbott, WM AF Rehring, TF Brewster, DC Cambria, RP Kaufman, JA Geller, SC Fan, CM Gertler, JP LaMuraglia, GM Abbott, WM TI Utility and reliability of endovascular aortouniiliac with femorofemoral crossover graft for aortoiliac aneurysmal disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY OCT 01-03, 1999 CL CHATHAM, MASSACHUSETTS SP New England Soc Vascular Surg ID ABDOMINAL AORTIC-ANEURYSMS; LIMB-THREATENING ISCHEMIA; LIFE TABLE METHOD; OPEN REPAIR; BYPASS; MANAGEMENT; EXPERIENCE AB Objective: The purpose of this study was to determine the early efficacy of endovascular aortouniiliac stent grafts with femorofemoral bypass graft in the treatment of aortoiliac aneurysmal disease. Methods: We analyzed 51 consecutive patients from January 1997 to March 1999 with a mean follow-up of 15.8 months. Patients ranged in age from 44 to 93 years (mean, 75 years) with a mean aortic aneurysm diameter of 6.2 cm. Technical success was achieved in 50 patients; one patient required conversion to open repair intraoperatively. We placed 28 custom-made and 22 commercial devices. The mean operative time was 223 minutes. The endograft was extended to the external iliac artery in 42% of cases. The contralateral common iliac artery was occluded using either a dosed covered stent or intraluminal coils. Results: The median hospital stay was 4 days with an average intensive care unit stay of 0.25 days. There were no operative mortalities. Two patients died during follow-up from unrelated conditions. Endoleaks occurred in 11 patients (22%); seven patients (14%) required intervention (four catheter based, three operative). Other complications occurred in 38% of patients but were largely remote or wound related. One femorofemoral bypass graft occluded immediately postoperatively as a result of an intraprocedural external iliac dissection yielding a 98% primary patency and 100% secondary patency. Clinical success was achieved in 88% of patients. Conclusions: These data suggest that this strategy represents a reliable method of repair of aortoiliac aneurysmal disease and extends the capability of an endoluminal approach to patients with complex iliac anatomy. C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Sect Vasc Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Brewster, DC (reprint author), 1 Hawthorne Pl,Suite 111, Boston, MA 02114 USA. NR 27 TC 34 Z9 34 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 JUN PY 2000 VL 31 IS 6 BP 1135 EP 1141 DI 10.1067/mva.2000.107120 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 324CF UT WOS:000087603700011 PM 10842150 ER PT J AU Heckenkamp, J Adili, F Kishimoto, J Koch, M LaMuraglia, GM AF Heckenkamp, J Adili, F Kishimoto, J Koch, M LaMuraglia, GM TI Local photodynamic action of methylene blue favorably modulates the postinterventional vascular wound healing response SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY OCT 01-03, 1999 CL CHATHAM, MASSACHUSETTS SP New England Soc Vascular Surg ID EXPERIMENTAL INTIMAL HYPERPLASIA; CHONDROITIN SULFATE PROTEOGLYCAN; FIBROBLAST GROWTH-FACTOR; SMOOTH-MUSCLE CELLS; CORONARY RESTENOSIS; INJURED ARTERIES; FACTOR-BETA; FOLLOW-UP; THERAPY; MATRIX AB Purpose: Photodynamic therapy (PDT), the light activation of photosensitizers to produce free radicals, is known to inhibit experimental intimal hyperplasia (IH). However, its clinical application has been limited by the lack of a suitable approach and a clinically appropriate photosensitizer. The aim of this study was to determine the effectiveness of a clinical approach for PDT, while testing its ability to favorably modulate the vascular wound healing response. Methods: Rat carotid arteries were balloon-injured (BI), and for PDT, the arteries were irradiated with thermoneutral laser light (lambda = 660 nm, 100 J/cm(2)) after the photosensitizer methylene blue (MB) was delivered locally. Control rats included BT alone and MB after BI alone. Arteries were analyzed after 2 weeks with morphometric evaluation (n = 6) and in situ hybridization for versican and procollagen type I gene expression (digitized image pixel analyses, n = 3). Results: No IH developed in PDT-treated arteries (0 +/- 0 mm(2); compared with BI, 0.192 +/- 0.006 mm(2); P < .0001). The diameters remained unchanged (PDT, 0.95 +/- 0.04 mm; BI, 0.94 +/- 0.05 mm; uninjured artery, 0.91 +/- 0.06 mm). Arterial injury resulted in an increase of versican and procollagen type I messenger RNA (mRNA) in the adventitia and neointima. In the repopulating cells of the adventitia after PDT, there was a significant decrease in versican mRNA (% of positive pixels per high-power field: PET, 1.13% +/- 0.39%; BI, 2.93% +/- 0.61%; P < .02), but not in procollagen type I mRNA. Conclusion: The decrease of versican mRNA expression of repopulating cells after PDT reflects favorable healing on a molecular level. Site-specific delivery of MB, a clinically appropriate photosensitizer, followed by PDT represents a suitable method to promote favorable healing after balloon intervention and further supports its role for inhibiting postinterventional restenosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cutaneous Res Ctr, Boston, MA USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Surg, ACC 464, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL02583] NR 45 TC 12 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 JUN PY 2000 VL 31 IS 6 BP 1168 EP 1176 DI 10.1067/mva.2000.106491 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 324CF UT WOS:000087603700017 PM 10842154 ER PT J AU Goulder, PJR Tang, YH Pelton, SI Walker, BD AF Goulder, PJR Tang, YH Pelton, SI Walker, BD TI HLA-B57-restricted cytotoxic T-lymphocyte activity in a single infected subject toward two optimal epitopes, one of which is entirely contained within the other SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CLASS-I; EFFECTOR FUNCTION; FINE SPECIFICITY; HLA-B; PEPTIDES; BINDING; CELLS; RESPONSES; ESCAPE AB Viral peptides are recognized by cytotoxic T lymphocytes (CTL) as a complex with major histocompatibility complex (MHC) class I molecules, but the extent to which a single HLA allele can accommodate epitope peptides of different length and sequence is not well characterized. Here we report the identification of clonal CTL responses from the same donor that independently recognize one of two HLA-B57-restricted epitopes, KAFSPEVIPMF (KF11; p24(Gag) residues 30 to 40) and KAFSPEVI (KF8; p21(Gag) residues 30 to 37). Although lysis studies indicated that the KF11 peptide stabilized the HLA-B57-peptide complex more efficiently than the K18 peptide, strong clonal responses were directed at each epitope, In samples from a second donor, the same phenomenon was observed, in which distinct CTL clones recognized peptide epitopes presented by the same HLA class I allele tin this case, HLA-A3) which were entirely overlapping. These data are relevant to the accurate characterization of CTL responses, which is fundamental to a detailed understanding of MWC class I-restricted immunity. In addition, these studies demonstrate marked differences in the length of peptides presented by HLA-B57, an allele which is associated with nonprogressive human immunodeficiency virus infection. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. Boston Med Ctr, Sect Pediat Infect Dis, Boston, MA 02118 USA. RP Goulder, PJR (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 13th St,Bldg 149,Rm 5218, Charlestown, MA 02129 USA. FU NIAID NIH HHS [AI30914, R01 AI028568, AI28568, R37 AI028568, R01 AI030914] NR 37 TC 39 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2000 VL 74 IS 11 BP 5291 EP 5299 DI 10.1128/JVI.74.11.5291-5299.2000 PG 9 WC Virology SC Virology GA 312MX UT WOS:000086948000040 PM 10799606 ER PT J AU Ishido, S Wang, CY Lee, BS Cohen, GB Jung, JU AF Ishido, S Wang, CY Lee, BS Cohen, GB Jung, JU TI Downregulation of major histocompatibility complex class I molecules by Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; DNA-SEQUENCES; HEAVY-CHAINS; MHC; VIRUS; GENE; ENCODES; CELLS; IDENTIFICATION AB The T-cell-mediated immune response plays a central role in the defense against intracellular pathogens. To avoid this immune response, viruses have evolved elaborate mechanisms that target and modulate many different aspects of the host's immune system. A target common to many of these viruses is the major histocompatibility complex (MHC) class I molecules. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes K3 and K5 zinc finger membrane proteins which remove MHC class I molecules from the cell surface. K3 and K5 exhibit 40% amino acid identity to each other and Localize primarily near the plasma membrane. While K3 and K5 dramatically downregulated class I molecules, they displayed different specificities in downregulation of HLA allotypes. K5 significantly downregulated HLA-A and -B and downregulated HLA-C only weakly, but not HLA-E, whereas K3 downregulated all four HLA allotypes. This selective downregulation of If LA allotypes by K5 was partly due to differences in amino acid sequences in their transmembrane regions. Biochemical analyses demonstrated that while K3 and K5 did not affect expression and intracellular transport of class I molecules, their expression induced rapid endocytosis of the molecules. These results demonstrate that KSHV has evolved a novel immune evasion mechanism by harboring similar but distinct genes, K3 and K5, which target MHC class I molecules in different ways. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet,Div Tumor Virol, Southborough, MA 01772 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Charleston, MA 02129 USA. RP Jung, JU (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet,Div Tumor Virol, 1 Pine Hill Dr, Southborough, MA 01772 USA. FU NCI NIH HHS [CA31363, CA82057, CA86841, R01 CA031363, R01 CA082057]; NCRR NIH HHS [K26 RR000168, P51 RR000168] NR 38 TC 288 Z9 300 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2000 VL 74 IS 11 BP 5300 EP 5309 DI 10.1128/JVI.74.11.5300-5309.2000 PG 10 WC Virology SC Virology GA 312MX UT WOS:000086948000041 PM 10799607 ER PT J AU Accola, MA Strack, B Gottlinger, HG AF Accola, MA Strack, B Gottlinger, HG TI Efficient particle production by minimal gag constructs which retain the carboxy-terminal domain of human immunodeficiency virus type 1 capsid-p2 and a late assembly domain SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; MAJOR HOMOLOGY REGION; GCN4 LEUCINE-ZIPPER; IN-VITRO; NUCLEOCAPSID PROTEIN; VIRION MORPHOGENESIS; MUTATIONAL ANALYSIS; FUNCTIONAL DOMAINS; INFECTED-CELLS; MATRIX DOMAIN AB The human immunodeficiency virus type 1 (HIV-1) Gag precursor Pr55(gag) by itself is capable of assembling into retrovirus-like particles (VLP). In the present study, we attempted to identify the minimal Gag sequences required for the formation of VLP. Our results show that about 80% of Pr55(gag) can be either deleted or replaced by heterologous sequences without significantly compromising VLP production. The smallest chimeric molecule still able to efficiently form VLP was only about 16 kDa. This minimal Gag construct contained the leucine zipper domain of the yeast transcription factor GCN4 to substitute for the assembly function of nucleocapsid (NC), followed by a P-P-P-P-Y motif to provide late budding (L) domain function, and retained only the myristylation signal and the C-terminal capsid-p2 domain of Pr55(gag). We also show that the L domain function of HIV-1 p6(gag) is not dependent on the presence of an active viral protease and that the NC domain of Pr55(gag) is dispensable for the incorporation of Vpr into VLP. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gottlinger, HG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [P30 AI028691, AI28691, AI29873, R01 AI029873, R37 AI029873] NR 62 TC 213 Z9 215 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2000 VL 74 IS 12 BP 5395 EP 5402 DI 10.1128/JVI.74.12.5395-5402.2000 PG 8 WC Virology SC Virology GA 317RL UT WOS:000087240700001 PM 10823843 ER PT J AU Goulder, PJR Brander, C Annamalai, K Mngqundaniso, N Govender, U Tang, Y He, S Hartman, KE O'Callaghan, CA Ogg, GS Altfeld, MA Rosenberg, ES Cao, H Kalams, SA Hammond, M Bunce, M Pelton, SI Burchett, SA McIntosh, K Coovadia, HM Walker, BD AF Goulder, PJR Brander, C Annamalai, K Mngqundaniso, N Govender, U Tang, Y He, S Hartman, KE O'Callaghan, CA Ogg, GS Altfeld, MA Rosenberg, ES Cao, H Kalams, SA Hammond, M Bunce, M Pelton, SI Burchett, SA McIntosh, K Coovadia, HM Walker, BD TI Differential narrow focusing of immunodominant human immunodeficiency virus Gag-specific cytotoxic T-lymphocyte responses in infected African and Caucasoid adults and children SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HLA CLASS-I; HIV TYPE-1; FINE SPECIFICITY; DISEASE PROGRESSION; EFFECTOR FUNCTION; CELL RECOGNITION; GENE-PRODUCTS; VIRAL LOAD; ESCAPE AB Cytotoxic T-lymphocyte (CTL) activity plays a central role in control of viral replication and in determining outcome in cases of human immunodeficiency virus type 1 (HIV-1) infection. Incorporation of important CTL epitope sequences into candidate vaccines is, therefore, vital. Most CTL studies have focused upon small numbers of adult Caucasoid subjects infected with clade-B virus, whereas the global epidemic is most severe in sub-Saharan African populations and predominantly involves clade-C infection in both adults and children. In this study, sensitive enzyme-linked immunospot (elispot) assays have been utilized to identify the dominant Gag-specific CTL epitopes targeted by adults and children infected with clade-B or -C virus, Cohorts evaluated included I 1 B-clade-infected Caucasoid American and African American adults and children and 37 C-clade-infected African adults and children from Durban, South Africa. The results show that 3 out of 46 peptides spanning p17(Gag) and p24(Gag) sequences tested contain two-thirds of the dominant Gag-specific epitopes, irrespective of the clade, ethnicity, or age group studied. However; there were distinctive differences between the dominant responses made by Caucasoids and Africans. Dominant responses in Caucasoids were more often within p17(Gag) peptide residues 16 to 30 (38 versus 12%; P < 0.01), while p24(Gag) peptide residues 41 to 60 contained the dominant Gag epitope more often in the African subjects tested (39 versus 4%; P < 0.005), Within this 20-mer p24(Gag), an epitope presented by both B42 and B81 is defined which represents the dominant Gag response in >30% of the total infected population in Durban. This epitope is closely homologous with dominant HIV-2 and simian immunodeficiency virus Gag-specific CTL epitopes. The fine focusing of dominant CTL responses to these few regions of high immunogenicity is of significance to vaccine design. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Childrens Hosp, Div Infect Dis, Boston, MA 02118 USA. Boston Univ, Med Ctr, Sect Pediat Infect Dis, Boston, MA 02118 USA. Univ Natal, Dept Paediat, ZA-4001 Durban, South Africa. Natal Blood Transfus Serv, Durban, South Africa. John Radcliffe Hosp, Inst Mol Med, MRC Human Immunol Unit, Oxford OX3 9DU, England. Churchill Hosp, Oxford Transplant Ctr, Oxford OX3 7LJ, England. RP Goulder, PJR (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 13th St,Bldg 149,Rm 5218, Charlestown, MA 02129 USA. FU NIAID NIH HHS [AI46995, R01 AI028568, AI28568, R01 AI030914, R01 AI046995, R37 AI028568, AI30914] NR 69 TC 99 Z9 102 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2000 VL 74 IS 12 BP 5679 EP 5690 DI 10.1128/JVI.74.12.5679-5690.2000 PG 12 WC Virology SC Virology GA 317RL UT WOS:000087240700034 PM 10823876 ER PT J AU Yang, XZ Farzan, M Wyatt, R Sodroski, J AF Yang, XZ Farzan, M Wyatt, R Sodroski, J TI Characterization of stable, soluble trimers containing complete ectodomains of human immunodeficiency virus type 1 envelope glycoproteins SO JOURNAL OF VIROLOGY LA English DT Article ID GP41 TRANSMEMBRANE GLYCOPROTEIN; MONOCLONAL-ANTIBODY; HIV-1 GP41; HTLV-III; NEUTRALIZING ANTIBODIES; CRYSTAL-STRUCTURE; IMMUNE-RESPONSES; ATOMIC-STRUCTURE; MEMBRANE-FUSION; AIDS PATIENTS AB The human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins function as a membrane-anchored trimer of three gp120 exterior glycoproteins and three gp41 transmembrane glycoproteins. Previously, we reported three approaches to stabilize soluble trimers containing parts of the gp41 ectodomains: addition of GCN4 trimeric helices, disruption of the cleavage site between gp120 and gp41, and introduction of cysteines in the gp41 coiled coil to form intersubunit disulfide bonds. Here, we applied similar approaches to stabilize soluble gp140 trimers including the complete gp120 and gp41 ectodomains. A combination of fusion with the GCN4 trimeric sequences and disruption of the gp120-gp41 cleavage site resulted in relatively homogeneous gp140 trimers with exceptional stability. The gp120 epitopes recognized by neutralizing antibodies are intact and exposed on these gp140 trimers. By contrast, the nonneutralizing antibody epitopes on the gp120 subunits of the soluble trimers are relatively occluded compared with those on monomeric gp120 preparations. This antigenic similarity to the functional HIV-1 envelope glycoproteins and the presence of the complete gp41 ectodomain should make the soluble gp140 trimers useful tools for structural and immunologic studies. C1 Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Aids, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [AI24755, AI31783, AI39420, P30 AI028691, R01 AI031783, R01 AI039420, R37 AI024755] NR 61 TC 135 Z9 140 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2000 VL 74 IS 12 BP 5716 EP 5725 DI 10.1128/JVI.74.12.5716-5725.2000 PG 10 WC Virology SC Virology GA 317RL UT WOS:000087240700039 PM 10823881 ER PT J AU Bauer, PH Cui, CQ Liu, WR Stehle, T Harrison, SC DeCaprio, JA Benjamin, TL AF Bauer, PH Cui, CQ Liu, WR Stehle, T Harrison, SC DeCaprio, JA Benjamin, TL TI Discrimination between sialic acid-containing receptors and pseudoreceptors regulates polyomavirus spread in the mouse (vol 73, pg 5826, 1999) SO JOURNAL OF VIROLOGY LA English DT Correction C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Benjamin, TL (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2000 VL 74 IS 12 BP 5746 EP 5746 DI 10.1128/JVI.74.12.5746-5746.2000 PG 1 WC Virology SC Virology GA 317RL UT WOS:000087240700044 ER PT J AU Rubenstein, LZ Josephson, KR Trueblood, PR Loy, S Harker, JO Pietruszka, FM Robbins, AS AF Rubenstein, LZ Josephson, KR Trueblood, PR Loy, S Harker, JO Pietruszka, FM Robbins, AS TI Effects of a group exercise program on strength, mobility, and falls among fall-prone elderly men SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; OLDER ADULTS; TAI-CHI; BALANCE; COMMUNITY; GAIT; PERFORMANCE; WOMEN; INTERVENTION; DISABILITY AB Objectives. This randomized controlled trial studied the effects of a low- to moderate-intensity group exercise program on strength, endurance, mobility, and fall rates in fall-prone elderly men with chronic impairments. Methods. Fifty-nine community-living men (mean age = 74 years) with specific fall risk factors (i.e., leg weakness, impaired gait or balance, previous falls) were randomly assigned to a control group (n = 28) or to a 12-week group exercise program (n = 31). Exercise sessions (90 minutes, three times per week) focused on increasing strength and endurance and improving mobility and balance. Outcome measures included isokinetic strength and endurance, five physical performance measures, and self-reported physical functioning, health perception, activity level, and falls. Results. Exercisers showed significant improvement in measures of endurance and gait. Isokinetic endurance increased 21% for right knee flexion and 26% for extension. Exercisers had a 10% increase (p < .05) in distance walked in six minutes, and improved (p < .05) scores on an observational gait scale. Isokinetic strength improved only for right knee flexion. Exercise achieved no significant effect on hip or ankle strength, balance, self-reported physical Functioning, or number of falls. Activity level increased within the exercise group. When fall rates were adjusted for activity level, the exercisers had a lower 3-month fall rate than controls (6 falls/1000 hours of activity vs 16.2 fails/1000 hours, p < .05). Discussion. These findings suggest that exercise can improve endurance, strength, gait, and function in chronically impaired, fall-prone elderly persons. In addition, increased physical activity was associated with reduced fall rates when adjusted for level of activity. C1 VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr 11E, Sepulveda, CA 91343 USA. Calif State Univ Fresno, Dept Phys Therapy, Fresno, CA 93740 USA. Calif State Univ Northridge, Dept Kinesiol, Northridge, CA 91330 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Rubenstein, LZ (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr 11E, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 26 TC 186 Z9 191 U1 11 U2 37 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2000 VL 55 IS 6 BP M317 EP M321 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XV UT WOS:000088044700011 PM 10843351 ER PT J AU Johansen, KL Chertow, GM Ng, AV Mulligan, K Carey, S Schoenfeld, PY Kent-Braun, JA AF Johansen, KL Chertow, GM Ng, AV Mulligan, K Carey, S Schoenfeld, PY Kent-Braun, JA TI Physical activity levels in patients on hemodialysis and healthy sedentary controls SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Society-of-Nephrology CY NOV 02-05, 1999 CL MIAMI, FLORIDA SP Amer Soc Nephrol DE end-stage renal disease; exercise; mortality and physical inactivity; dialysis; nutrition; uremic muscle ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; MULTIPLE-SCLEROSIS; EXERCISE CAPACITY; ACCELEROMETER; DIALYSIS; QUALITY; RECALL; LIFE AB Background. Patients on dialysis have reduced exercise tolerance compared with age-matched sedentary controls. The reasons for this debility have not been fully elucidated, but physical inactivity could be a contributing factor. The purpose of the current study was to determine whether patients on hemodialysis are less active than healthy sedentary controls and to explore clinical correlates of physical activity level in a group of hemodialysis patients. Methods. Thirty-four hemodialysis patients and 80 healthy sedentary individuals participated in the study. Physical activity was measured for seven days with a three-dimensional accelerometer and with an activity questionnaire. Results. Vector magnitude values from the accelerometer for the dialysis and control subjects were 104,718 +/- 9631 and 161,255 +/- 6792 arbitrary units per day, respectively (P < 0.0001, mean +/- SEM). The estimated energy expenditure values derived from the questionnaire were 33.6 +/- 0.5 kcal/kg/day and 36.2 +/- 0.5 kcal/kg/day (P = 0.002). The difference between patients on dialysis and controls increased with advancing age. Among the dialysis subjects, some measures of nutritional status correlated with physical activity level, including serum albumin concentration (r = 0.58, P = 0.003), serum creatinine concentration (r = 0.37, P = 0.03), and phase angle derived from bioelectrical impedance analysis (r = 0.40, P = 0.02). Conclusions. Patients on hemodialysis are less active than healthy sedentary controls, and this difference is more pronounced among older individuals. There is an association between the level of physical activity and nutritional status among patients on dialysis. These findings are of great concern, given the trend toward increasing age in incident dialysis patients and the well-known association between inactivity and increased mortality in the general population. C1 Univ Calif San Francisco, Moffitt Long Hosp, San Francisco VA Med Ctr, Div Nephrol, San Francisco, CA USA. Univ Calif San Francisco, UCSF Mt Zion Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Radiol, San Francisco, CA USA. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Physiol Nursing, San Francisco, CA USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Div Nephrol 111J, 4150 Clement St, San Francisco, CA 94121 USA. FU NCRR NIH HHS [RR00083] NR 29 TC 193 Z9 198 U1 4 U2 15 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2000 VL 57 IS 6 BP 2564 EP 2570 DI 10.1046/j.1523-1755.2000.00116.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 319MQ UT WOS:000087346100038 PM 10844626 ER PT J AU Choi, JY AF Choi, JY TI Isolation and identification of PilA homolog, strain-specific gene in Pseudomonas aeruginosa SO KOREAN JOURNAL OF GENETICS LA English DT Article DE Pseudomonas aeruginosa; pathogenicity; pilin; representational difference analysis ID ADRENAL CHROMAFFIN GRANULES; SEQUENCES; SUBUNIT; PAO; GLYCOSPHINGOLIPIDS; ORGANIZATION; ADHERENCE; CLONING; REGION AB The pilA of Pseudomonas aeruginosa plays a major role in mediating the adhesion of the bacterial cell to epithelial tissue and thus in establishing colonization. The sequence for the pilA of P. aeruginosa strain PA14 was identified from the representational difference analysis by using the P. aeruginosa strain PA01 as the driver DNA. The entire sequence of pilA was isolated from the partial inverse PCR. The pilA gene of P. aeruginosa is 179 amino acids in length which make it the longest pilA known to date in P. aeruginosa. Comparison of the amino acid sequences of pilA produced by P. aeruginosa with other strain reveals a region corresponding to the leader peptide, the conserved N-terminus with 30 hydrophobic amino acids and a hypervariable central region with several invariant amino acids. The amino acid sequence of the peptide encompassing the major antigenic determinant of P. aeruginosa differs greatly from that of the equivalent region in other strain. The presence of pilA gene specifically in the P. aeruginosa strain PA14 suggests that it is important in the horizontal cotransfer of sequence particular to this pathogen. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 23 TC 1 Z9 1 U1 0 U2 0 PU GENETICS SOC KOREA PI SEOUL PA SEOUL NATL UNIV, DEPT BIOLOGY, COLL EDUCATION, SINLIMDONG SAN 56-1, KWANAKGU, SEOUL 151-742, SOUTH KOREA SN 0254-5934 J9 KOREAN J GENETIC JI Korean J. Genet. PD JUN PY 2000 VL 22 IS 2 BP 141 EP 151 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 341ZC UT WOS:000088620000006 ER PT J AU Choi, JY AF Choi, JY TI Representational difference analysis to identify genomic differences between two related pathogenic strains of Pseudomonas aeruginosa SO KOREAN JOURNAL OF GENETICS LA English DT Article DE Pseudomonas aeruginosa; pathogenesis; representational difference analysis; subtraction hybridization ID ENDOCARDITIS; VIRULENCE; RESISTANCE; BACTERIA AB Representational difference analysis (RDA) is a recently developed technique used for amplifying genetic differences between two closely related genomes. The technique of RDA was adapted to the search for genes present in the PA14 strain but absent from the PA01 strain in Pseudomonas aeruginosa. Genes present in PA14 strain were physically subtracted from PA01 strain. The genes obtained from the second-round subtraction were tested by Southern blotting for their reactivity with the two species. The libraries achieved were comprehensive and specific in that they contain sequences corresponding to the presently identified PA14-specific genes. Of 16 randomly chosen clones specific to PA14 strain, the colony PCR confirmed that the majority of the products had the different size of genes. These results indicated that a number of unique fragments could be generated from the comparison of the two strains, that is consistent with the probable genetic differences between the two strains. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 22 TC 0 Z9 0 U1 1 U2 1 PU GENETICS SOC KOREA PI SEOUL PA SEOUL NATL UNIV, DEPT BIOLOGY, COLL EDUCATION, SINLIMDONG SAN 56-1, KWANAKGU, SEOUL 151-742, SOUTH KOREA SN 0254-5934 J9 KOREAN J GENETIC JI Korean J. Genet. PD JUN PY 2000 VL 22 IS 2 BP 153 EP 163 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 341ZC UT WOS:000088620000007 ER PT J AU Shimizu, A Meehan, SM Kozlowski, T Sablinski, T Ierino, FL Cooper, DKC Sachs, DH Colvin, RB AF Shimizu, A Meehan, SM Kozlowski, T Sablinski, T Ierino, FL Cooper, DKC Sachs, DH Colvin, RB TI Acute humoral xenograft rejection: Destruction of the microvascular capillary endothelium in pig-to-nonhuman primate renal grafts SO LABORATORY INVESTIGATION LA English DT Article ID BABOON CARDIAC TRANSPLANTS; ORGAN XENOTRANSPLANTATION; ALLOGRAFT REJECTION; TOLERANCE INDUCTION; VASCULAR REJECTION; DNA FRAGMENTATION; NUCLEAR-DNA; ACTIVATION; CELLS; ANTIBODIES AB The major cause of xenograft loss beyond hyperacute rejection is a form of injury, traditionally termed delayed xenograft rejection (DXR), whose pathogenesis is unknown. Here we analyze the immunologic and morphologic features of DXR that develops in pig kidney xenografts transplanted into nonhuman primates. Kidneys from miniature swine were transplanted into cynomolgus monkeys (n = 14) or baboons (n = 11) that received regimens aimed to induce mixed chimerism and tolerance. No kidney was rejected hyperacutely. Morphologic and immunohistochemical studies were performed on serial biopsies, and an effort was made to quantify the pathologic features seen. The early phase of DXR (Days 0-12) was characterized by focal deposition of IgM, IgG, C3, and scanty neutrophil and macrophage infiltrates. The first abnormality recognized was glomerular and peritubular capillary endothelial cell death as defined by in situ DNA nick-end labeling (TUNEL). Damaged endothelial cells underwent apoptosis and, later, frank necrosis. The progressive phase developed around Day 6 and was characterized by progressive deposition of IgM, IgG, C3, and prominent infiltration of cytotoxic T cells and macrophages, with a small number of NK cells. Thrombotic microangiopathy developed in the glomeruli and peritubular capillaries with TUNEL+ endothelial cells, platelet aggregation, and destruction of the capillary network. Only rare damaged arterial endothelial cells and tubular epithelial cells were observed, with rare endothelialitis and tubulitis. in the advanced phase of DXR, interstitia[ hemorrhage and infarction occurred. During the development of DXR, the number of TUNEL+ cells increased, and this correlated with progressive deposition of antibody. The degree of platelet aggregation correlated with the number of TUNEL+ damaged endothelial cells. We conclude that peritubular and glomerular capillary endothelia are the primary targets of renal DXR rather than tubular epithelial cells or arterial endothelium and that the earliest detectable change is endothelial cell death. DXR was characterized by progressive destruction of the microvasculature (glomeruli and peritubular capillaries) and formation of fibrin-platelet thrombi. Both cytotoxic cells and antibodies potentially mediate the endothelial damage in DXR; however, in this model, DXR is largely humorally mediated and is better termed "acute humoral xenograft rejection." C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 225, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01-HL 18646] NR 43 TC 62 Z9 65 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUN PY 2000 VL 80 IS 6 BP 815 EP 830 PG 16 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 326UK UT WOS:000087755100004 PM 10879733 ER PT J AU Busaba, NY Siegel, N Salman, SD AF Busaba, NY Siegel, N Salman, SD TI Bacteriology of nontraumatic maxillary sinus mucoceles versus chronic sinusitis 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, 2000 CL PITTSBURGH, PENNSYLVANIA SP Amer Laryngol Rhinol & Otol Soc Inc, Eastern Sect DE maxillary mucoceles; chronic sinusitis; bacteriology ID ADULTS AB Objective: To compare the bacteriology of maxillary sinus mucoceles to chronic sinusitis and understand the pathogenesis of nontraumatic maxillary sinus mucoceles (NTMSM). Study Design: Retrospective review. Methods: Review of intraoperative bacteriology culture results obtained in patients with NTMSM. Patients with history of facial trauma or previous paranasal sinus surgery were not included in the study. The results were compared to intraoperative cultures obtained from patients with chronic sinusitis (CS), Results: The study groups consisted of 16 patients with NTMSM (9 male and 7 female patients) and 211 patients with CS (86 male and 125 female patients). Cultures in the NTMSM group were positive in 7 of 16 patients (44%) (four cultures had more than one isolate). There was no growth in cultures of 9 patients (56%). On the other hand, cultures in 176 patients with CS (83%) grew organisms (42 cultures had more than one isolate); there was no growth in 36 of 211 patients (17%) (P =.0007), The cultures grew aerobic bacteria in 7 of 16 (44%) and 160 of 211 (76%) patients of the NTMSM and CS groups, respectively. Anaerobic bacteria were detected in cultures of 2 of 16 patients (12.5%) with NTMSM compared with 13 of 211 patients (6.2%) in the CS group (P =.286), The most common pathogenic aerobe in the NTMSM group was a-hemolytic Streptococcus, while Staphylococcus aureus was the most common in the CS group. Conclusion: The bacteriology of maxillary sinus mucoceles is different from that of CS, The majority of patients with mucoceles have sterile intraoperative cultures, The data do not support infection as the main origin of NTMSM. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Boston Vet Affairs Healthcare Syst, Div Otolaryngol, Boston, MA USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. NR 9 TC 9 Z9 12 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 JUN PY 2000 VL 110 IS 6 BP 969 EP 971 DI 10.1097/00005537-200006000-00016 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 322DL UT WOS:000087494900016 PM 10852515 ER PT J AU Metson, RB Cosenza, MJ Cunningham, MJ Randolph, GW AF Metson, RB Cosenza, MJ Cunningham, MJ Randolph, GW TI Physician experience with an optical image guidance system for sinus surgery SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 29, 2000 CL PITTSBURGH, PENNSYLVANIA SP Amer Laryngol Rhinol & Otol Soc Inc, Eastern Sect DE image-guided surgery; computer-aided surgery; sinus surgery; sinusitis ID ACCURACY AB Objectives/Hypothesis: Intraoperative guidance systems have been developed which use infrared tracking technology to assist with anatomical localization during sinus surgery. Although the introduction of this technology is intended to increase the safety and efficacy of sinus surgery, little is known about its actual impact in the clinical setting. The objective of this report was to study the application and utilization of an image guidance system shared by multiple sinus surgeons in a specialty hospital. Study Design: Combined prospective case study and retrospective analysis of physician surveys. Methods: An optical-based image guidance system (LandmarX, Xomed, Inc., Jacksonville, FL) was used by 34 physicians to perform 754 sinonasal surgeries over a 2.5-year period at Massachusetts Eye and Ear Infirmary. In 19 cases, system registration was repeated during surgery to measure the effect of fiducial placement on system accuracy. Results: The measured accuracy of anatomical localization at the start of surgery (mean value, 1.69 +/- 0.38 mm) was comparable to the perceived accuracy of 1 to 3 mm that was reported by 79% of surgeons surveyed. Operating room time (mean period, 130.6 +/- 41.1 min) correlated with the surgical procedure performed (P < .05), but not with the disease stage or revision rate. According to a majority of surgeons, use of the image guidance equipment increased operating room time by 15 to 30 minutes during initial cases and by 5 to 15 minutes once experience with the equipment had been acquired. More than 90% of surgeons anticipated their continued use of the image guidance equipment for sinus surgery at a similar or greater level in the future. Conclusion: An optical-based image guidance system can be successfully integrated into a multisurgeon operating room environment. Use of the system provides accurate anatomical localization during sinus surgery and results in a relatively high level of physician satisfaction. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Dept Otol & Laryngol, Sch Med, Boston, MA 02115 USA. RP Metson, RB (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. NR 11 TC 63 Z9 68 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 2000 VL 110 IS 6 BP 972 EP 976 DI 10.1097/00005537-200006000-00017 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 322DL UT WOS:000087494900017 PM 10852516 ER PT J AU Deschler, DG Gress, CD Singer, MI AF Deschler, DG Gress, CD Singer, MI TI Outpatient retrograde placement of the indwelling voice prosthesis SO LARYNGOSCOPE LA English DT Article ID REHABILITATION; LARYNGECTOMY C1 Harvard Univ, Dept Otolaryngol Head & Neck Surg, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA. RP Deschler, DG (reprint author), Harvard Univ, Dept Otolaryngol Head & Neck Surg, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 6 TC 3 Z9 3 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 JUN PY 2000 VL 110 IS 6 BP 1063 EP 1065 DI 10.1097/00005537-200006000-00032 PG 3 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 322DL UT WOS:000087494900032 PM 10852531 ER PT J AU Stone, ME AF Stone, ME TI Medicine in quotations: Views of health and disease through the ages. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD JUN 1 PY 2000 VL 125 IS 10 BP 114 EP 114 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 321QF UT WOS:000087465600064 ER PT J AU Ashton, CM Bozkurt, B Colucci, WB Kiefe, CI Mann, DL Massie, BM Slawsky, MT Tierney, WM West, JA Whellan, DJ Wray, NP AF Ashton, CM Bozkurt, B Colucci, WB Kiefe, CI Mann, DL Massie, BM Slawsky, MT Tierney, WM West, JA Whellan, DJ Wray, NP TI Veterans affairs quality enhancement research initiative in chronic heart failure SO MEDICAL CARE LA English DT Article DE chronic heart failure; quality of care; Veterans Affairs ID CONVERTING ENZYME-INHIBITORS; PRACTICE GUIDELINES; ELDERLY PATIENTS; EARLY READMISSION; CARE; MANAGEMENT; LIFE; PATTERNS; OUTCOMES; EDUCATION AB Chronic heart failure (CHF) is a highly prevalent condition associated with serious morbidity, intense levels of health services use, and shortened survival. It is also a condition for which ameliorative therapies exist. The evidence indicates that there is substantial need to change clinical practice and health care delivery for people with CHF and thereby improve their outcomes. The goal of the Veterans Affairs (VA) Quality Enhancement Research Initiative in CHF (CHF QUERI) is to create measurable, rapid, and sustainable improvements in quality of care and health outcomes of veterans with heart failure. This article describes the current state of knowledge and practice in fare for people with CHF. Using the framework of the 5 steps of the QUERI process, we point out the gaps in research and practice that must be filled if the CHF QUERI is to achieve its goal. We relate our recommendations for how the VA can put its research and administrative infrastructure to work to fill the gaps. Lessons learned about CHF in the course of the CHF QUERI will be applicable to all people with heart failure and to all health care systems-VA as well as non-VA-that care for them. C1 VA Med Ctr 152, Houston, TX 77030 USA. VA Ctr Excellence Hlth Serv Res, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Vet Affairs Med Ctr, Boston, MA USA. Vet Affairs Med Ctr, Birmingham, AL USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Vet Affairs Med Ctr, Indianapolis, IN USA. Vet Affairs Med Ctr, Palo Alto, CA 94304 USA. Vet Affairs Med Ctr, Durham, NC 27705 USA. RP Ashton, CM (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM cashton@bcm.tmc.edu NR 56 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JUN PY 2000 VL 38 IS 6 SU VA1 BP S26 EP S37 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 321NV UT WOS:000087462300004 ER PT J AU Bozzette, SA Phillips, B Asch, S Gifford, AL Lenert, L Menke, T Ortiz, E Owens, D Deyton, L AF Bozzette, SA Phillips, B Asch, S Gifford, AL Lenert, L Menke, T Ortiz, E Owens, D Deyton, L CA HIV-QUERI Executive Comm TI Quality enhancement research initiative for human immunodeficiency virus/acquired immunodeficiency syndrome - Framework and plan SO MEDICAL CARE LA English DT Article DE quality of health care; delivery of health care; acquired immunodeficiency syndrome; human immunodeficiency virus infections ID HIV-INFECTED ADULTS; UNITED-STATES; THERAPY; CARE; MEDICATIONS; SERVICES; DISEASE; COST AB The Veterans Health Administration (VHA) sees approximate to 17,000 human immunodeficiency virus (HIV)-infected patients each year, which makes it the largest provider of HIV care in the United States. HIV causes chronic progressive disease that leads to early death. Newer combination antiretroviral treatments are effective but expensive and difficult to use. The HIV Quality Enhancement Research Initiative (HIV-QUERI) uses the QUERI process to identify high-risk and high-volume populations (step 1), which includes those already under MFA care for HIV, those who do not know of their infection, and those at risk for HIV. In identifying best practices (step 2), the HIV-QUERI will benefit greatly from existing guidelines for the care of established HIV infection, but gaps in knowledge regarding adherence to medication regimens and cost-effective screening are large. To identify existing practice patterns (step 3), the HIV-QUERI will develop a clean analytic data set based on Immunology Case Registry files and expand it through a survey of veterans. Interventions to improve care (step 4) will include national, regional, and site-specific feedback on performance relative to quality standards, as well as patient-level and provider-level interventions to improve adherence and support medical decision-making. To document that best practices improve outcomes and quality of Life (steps 5 and 6), HIN-QUERI will track indicators on an ongoing basis by use of the Immunology Case Registry database and possible future waves of the survey. In addition, we will require that these issues be addressed in evaluations of HIV-QUERI interventions. In the present article, we present these steps within a framework and plan. C1 UCSD, VASDHS, Hlth Serv Res & Dev Unit, San Diego, CA USA. RAND Hlth, Santa Monica, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Vet Affairs Houston Healthcare Syst, Houston, TX USA. Baylor Univ, Houston, TX 77030 USA. Vet Affairs Palo Alto Healthcare Syst, Palo Alto, CA USA. Stanford Univ, Palo Alto, CA 94304 USA. Vet Hlth Adm, AIDS Serv, Washington, DC USA. RP Bozzette, SA (reprint author), UCSD, VASDHS, Hlth Serv Res & Dev Unit, Mail Code 111N1,3350 La Jolla Village Dr, San Diego, CA USA. NR 16 TC 1 Z9 1 U1 0 U2 0 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 JUN PY 2000 VL 38 IS 6 SU VA1 BP S60 EP S69 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 321NV UT WOS:000087462300007 ER PT J AU Every, NR Fihn, SD Sales, AEB Keane, A Ritchie, JR AF Every, NR Fihn, SD Sales, AEB Keane, A Ritchie, JR CA QUERI IHD Executive Comm TI Quality enhancement research initiative in ischemic heart disease - A quality initiative from the Department of Veterans Affairs SO MEDICAL CARE LA English DT Article DE ischemic heart disease; guidelines; quality of care ID ACUTE MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; PHYSICIAN PERFORMANCE; THROMBOLYTIC THERAPY; CONTROLLED TRIAL; ELDERLY PATIENTS; CARE; ASPIRIN; GUIDELINES; MORTALITY AB Despite the dramatic fall in ischemic heart disease (IHD) mortality rates over the last 3 decades, it remains the number one cause of death in the United States, and one of the most frequent indications for care by the US Department of Veterans Affairs. National practice guidelines have been developed and disseminated both by societies that specialize in cardiology and within the Veterans Health Administration. Despite these efforts, a substantial minority remains of patients with IHD who are not treated with guideline-recommended therapies. The Quality Enhancement Research Initiative in IHD is a Veterans Health Administration-sponsored initiative to address the gap between guideline-recommended therapies and actual Department of Veterans Affairs practice. Because guideline development for patients with IHD is relatively mature, the Quality Enhancement Research Initiative in Ii-ID will concentrate on measuring existing practices, implementing interventions, and evaluating outcomes in veterans with IHD. Measurement of existing practices will be evaluated through analyses of existing Veterans Affairs databases developed for the Continuous Improvement in Cardiac Surgery Program, as well as data collected at the Center for the Study of Practice Patterns in veterans with acute myocardial infarction. To measure existing practices in outpatients with IHD, we plan to develop a new database that extracts electronic data from patient laboratory and pharmacy records into a relational database. Interventions to address gaps between guideline recommendations and actual practice will be solicited and implemented at individual medical centers. We plan to emphasize point-of-care electronic reminders as well as online decision support as methods for improving guideline compliance. C1 VA Puget Sound Hlth Care Syst, NW Hlth Serv Res, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dev Field Program, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv Res, Seattle, WA 98195 USA. RP Every, NR (reprint author), VA Puget Sound Hlth Care Syst, NW Hlth Serv Res, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 49 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2000 VL 38 IS 6 SU VA1 BP S49 EP S59 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 321NV UT WOS:000087462300006 ER PT J AU Fischer, EP Marder, SR Smith, GR Owen, RR Rubenstein, L Hedrick, SC Curran, GM AF Fischer, EP Marder, SR Smith, GR Owen, RR Rubenstein, L Hedrick, SC Curran, GM TI Quality enhancement research initiative in mental health SO MEDICAL CARE LA English DT Article DE major depressive disorder; schizophrenia; quality of care; physician practice patterns; practice guidelines; patient compliance; QUERI ID EPIDEMIOLOGIC CATCHMENT-AREA; PRIMARY-CARE PRACTICE; TREATING MAJOR DEPRESSION; UNITED-STATES; ANTIDEPRESSANT MEDICATIONS; SUBSTANCE-ABUSE; HIGH UTILIZERS; DISORDERS; OUTCOMES; SCHIZOPHRENIA AB The Veterans Administration (VA) recently introduced its Quality Enhancement Research Initiative (QUERI) to facilitate the translation of best practices into usual clinical fare. The Mental Health QUERI (MHQ) was charged with developing strategic plans for major depressive disorder (MDD) and schizophrenia. Twenty percent or more of VA service users are affected by 1 of these 2 disorders, disorders that often have a devastating impact on affected individuals. Despite the increasing availability of efficacious treatments for each disorder, substantial gaps remain between best practices and routine care. In this context, the MHQ identified steps critical to the success of a sustained process of rapid-cycle health care improvement for MDD and schizophrenia, including research initiatives to close gaps in knowledge of best treatment practices, demonstration projects to close gaps in practice and to expand understanding of effective strategies for implementing clinical guidelines, targeted enhancements of the VA information system, and research and dissemination initiatives to increase the availability of resources to support the accelerated incorporation of best practices into routine care. This article presents an overview of the elements in the initial MHQ strategic plans and the rationale behind them. C1 Cent Arkansas Vet Healthcare Syst, HSR&D Mental Hlth QUERI, VA HSR&D Ctr Mental Healthcare & Outcomes Res, N Little Rock, AR 72114 USA. Univ Arkansas Med Sci, Dept Psychiat & Behav Sci, Little Rock, AR 72205 USA. W Los Angeles VA Med Ctr, Mental Illness Res Educ & Clin Ctr 22, VISN, Los Angeles, CA USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Behav Sci, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA. Sepulveda VAMC, VA HSR&D Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. VA Puget Sound Hlth Care Syst, VA HSR&D Ctr Outcomes Res Older Adults, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Fischer, EP (reprint author), Cent Arkansas Vet Healthcare Syst, HSR&D Mental Hlth QUERI, VA HSR&D Ctr Mental Healthcare & Outcomes Res, 2200 Ft Roots Dr 152-NLR, N Little Rock, AR 72114 USA. NR 78 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2000 VL 38 IS 6 SU VA1 BP S70 EP S81 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 321NV UT WOS:000087462300008 ER PT J AU Rubenstein, LV Mittman, BS Yano, EM Mulrow, CD AF Rubenstein, LV Mittman, BS Yano, EM Mulrow, CD TI From understanding health care provider behavior to improving health care - The QUERI framework for quality improvement SO MEDICAL CARE LA English DT Article DE physicians; quality of patient care; outcomes and process assessment ID PRACTICE GUIDELINES; SYSTEMATIC REVIEWS; CLINICAL DECISIONS; IMPACT; TRIAL; IMPLEMENTATION; DISSEMINATION; PERFORMANCE; MANAGEMENT; MEDICINE AB Basic science and health care research provide the evidence base for the scientific practice of medicine. Over the past 2 decades, as increasingly refined tools for improving health and health care have been developed, the health care community has attempted to bridge the gap between available tools and actual health care practices. This gap can be bridged only by influencing health care provider behavior. The VA Quality Enhancement Research Initiative (QUERI) is a program designed to systematically translate research findings into better health care practices, and thus better health outcomes for enrolled veterans. Integrating provider behavior research considerations and findings into each step of the QUERI process will enhance the effectiveness of the initiative. This article presents a provider behavior research framework for planning, implementing, and evaluating quality improvement interventions within QUERI. C1 VA Ctr Study Healthcare Provider Behav 152, HSR&D Ctr Excellence, Sepulveda Ambulatory & Nursing Home Ctr, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Audie Murphy VA Med Ctr, VA Cochrane Ctr, San Antonio, TX USA. RP Rubenstein, LV (reprint author), VA Ctr Study Healthcare Provider Behav 152, HSR&D Ctr Excellence, Sepulveda Ambulatory & Nursing Home Ctr, VA Greater Los Angeles Healthcare Syst, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 54 TC 8 Z9 8 U1 1 U2 2 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 JUN PY 2000 VL 38 IS 6 SU VA1 BP S129 EP S141 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 321NV UT WOS:000087462300013 ER PT J AU Restrepo, MI Najvar, LK Barchiesi, F Luther, MF Graybill, JR AF Restrepo, MI Najvar, LK Barchiesi, F Luther, MF Graybill, JR TI Treatment of murine cryptococcal meningitis with UR-9751 and UR-9746 SO MEDICAL MYCOLOGY LA English DT Article DE fluconazole; murine cryptococcal meningitis ID AMPHOTERICIN-B AB In these studies, we compare the efficacy of two new azole antifungals with fluconazole in a murine model of cryptococcal meningitis. Mice were infected intracranially. Beginning one day later, groups of 7-10 mice were treated through to day 10 orally with UR-9751 or UR-9746 at 0.1, 0.25, 0.5, 1 or 10 mg kg(-1) day(-1) or fluconazole at 10 mg kg(-1) day(-1). At 10 mg kg(-1) day(-1), all three drugs prolonged survival over controls, but at 1 mg kg(-1) day(-1), only UR-9746 prolonged survival. Tissue counts were more varied on mice sacrificed 8 days after infection. In general, both UR drugs were equal or more potent than fluconazole, and UR-9751 was more effective than UR-9746. C1 Audie L Murphy Mem Vet Hosp, Dept Med 111F, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. RP Graybill, JR (reprint author), Audie L Murphy Mem Vet Hosp, Dept Med 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU B I O S SCIENTIFIC PUBLISHERS LTD PI OXFORD PA 9 NEWTEC PLACE, MAGDALEN RD, OXFORD OX4 1RE, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD JUN PY 2000 VL 38 IS 3 BP 221 EP 224 PG 4 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 329PV UT WOS:000087916900006 PM 10892990 ER PT J AU de Souza, CJ Capotorto, JV Cornell-Kennon, S Wu, YJ Steil, GM Trivedi, N Weir, GC AF de Souza, CJ Capotorto, JV Cornell-Kennon, S Wu, YJ Steil, GM Trivedi, N Weir, GC TI beta-cell dysfunction in 48-hour glucose-infused rats is not a consequence of elevated plasma lipid or islet triglyceride levels SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID INDUCED INSULIN-SECRETION; DEPENDENT DIABETES-MELLITUS; CIRCULATING FATTY-ACIDS; PANCREATIC-ISLETS; CHRONIC HYPERGLYCEMIA; BIOSYNTHESIS; LIPOTOXICITY; EXPOSURE; RELEASE; IDX-1 AB The abnormal insulin secretion found in human diabetics and animal models of diabetes has been attributed to the deleterious effects of chronic hyperglycemia and/or elevated circulating levels of nonesterified fatty acids (NEFAs). In this study, abnormal glucose-induced insulin secretion (GIIS) was generated by a 48-hour infusion of glucose and assessed by the isolated perfused pancreas technique. In these hyperglycemic animals, abnormal GIIS is accompanied by a decrease in plasma NEFAs, while plasma and, more importantly, islet triglycerides remain at levels comparable to those in the controls. It is concluded that the abnormal insulin secretion in this glucose infusion model was likely caused by 48 hours of hyperglycemia and not by changes in circulating or islet lipids. Copyright (C) 2000 by W.B. Saunders Company. C1 Novartis Inst Biomed Res, Summit, NJ 07901 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02115 USA. RP de Souza, CJ (reprint author), Novartis Inst Biomed Res, 556 Morris Ave, Summit, NJ 07901 USA. FU NIDDK NIH HHS [DK-35449, DK-36836] NR 29 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUN PY 2000 VL 49 IS 6 BP 755 EP 759 DI 10.1053/meta.2000.6240 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 323KQ UT WOS:000087564900013 PM 10877202 ER PT J AU Fitzgerald, SG Morgenstern, E AF Fitzgerald, SG Morgenstern, E TI Global improvement in intellectual and neuropsychological functioning after removal of a suprasellar cystic craniopharyngioma SO MILITARY MEDICINE LA English DT Article ID INTELLIGENCE; ADULTS; WAIS AB This is a case report of a patient who presented with cognitive and behavioral decline and underwent surgery for removal of a suprasellar craniopharyngioma, Previous studies have reported memory impairments in the presence of craniopharyngioma, but information is lacking regarding the impact of craniopharyngioma on other brain functions as well as on intellectual abilities. In this study, comprehensive neuropsychological testing, including intellectual testing, was conducted 9 to 14 days before surgery and 16 to 22 days after surgery. Results before surgery demonstrated average intellectual abilities, which were decreased from premorbid estimates, and diffuse neuropsychological impairments. Postoperatively, significant improvement in both intellectual abilities and neuropsychological test scores was observed. These results suggest that craniopharyngiomas can be associated with impairments in intellectual abilities and in brain functions aside from memory. The results are contrasted with those of previous reports, and implications for future research are discussed. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Fitzgerald, SG (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 23 TC 2 Z9 2 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUN PY 2000 VL 165 IS 6 BP 496 EP 499 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 324RG UT WOS:000087634700018 PM 10870373 ER PT J AU Bilsland-Marchesan, E Arino, J Saito, H Sunnerhagen, P Posas, F AF Bilsland-Marchesan, E Arino, J Saito, H Sunnerhagen, P Posas, F TI Rck2 kinase is a substrate for the osmotic stress-activated mitogen-activated protein kinase Hog1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; SIGNAL-TRANSDUCTION PATHWAY; GLYCEROL RESPONSE PATHWAY; MAP KINASE; GENE-EXPRESSION; MAMMALIAN-CELLS; BUDDING YEAST; BZIP PROTEIN; PHOSPHATASES; SPECIFICITY AB Exposure of yeast cells to increases in extracellular osmolarity activates the Hog1 mitogen-activated protein kinase (MAPK). Activation of Hog1 MAPK results in induction of a set of osmoadaptive responses, which allow cells to survive in high-osmolarity environments. Little is known about how the MAPK activation results in induction of these responses, mainly because no direct substrates for Hog1 have been reported. We conducted a two-hybrid screening using Hog1 as a bait to identify substrates for the MAPK, and the Rck2 protein kinase was identified as an interactor for Hog1. Both two-hybrid analyses and coprecipitation assays demonstrated that Hog1 binds strongly to the C-terminal region of Rck2. Upon osmotic stress, Rck2 was phosphorylated in vivo in a Hog1-dependent manner. Furthermore, purified Hog1 was able to phosphorylate Rck2 when activated both in vivo and in vitro. Rck2 phosphorylation occurred specifically at Ser519, a residue located within the C-terminal putative autoinhibitory domain. Interestingly, phosphorylation at Ser519 by Hog1 resulted in an increase of Rck2 kinase activity. Overexpression of Rck2 partially suppressed the osmosensitive phenotype of hog1 Delta and pbs2 Delta cells, suggesting that Rck2 is acting downstream of Hog1. Consistently, growth arrest caused by hyperactivation of the Hog1 MAPK was abolished by deletion of the RCK2 gene. Furthermore, overexpression of a catalytically impaired (presumably dominant inhibitory) Rck2 kinase resulted in a decrease of osmotolerance in wild-type cells but not in hog1 Delta cells. Taken together, our data suggest that Rck2 acts downstream of Hog1, controlling a subset of the responses induced by the MAPK upon osmotic stress. C1 Univ Pompeu Fabra, Fac Ciencies Salut & Vida, Dept Ciencies Expt & Salut, Cell Signaling Unit, E-08003 Barcelona, Spain. Univ Gothenburg, Lundberg Lab, Dept Cell & Mol Biol, S-40530 Gothenburg, Sweden. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Autonoma Barcelona, Fac Vet, Dept Bioquim & Biol Mol, E-08193 Barcelona, Spain. RP Posas, F (reprint author), Univ Pompeu Fabra, Fac Ciencies Salut & Vida, Dept Ciencies Expt & Salut, Cell Signaling Unit, C Doctor Aiguader 80, E-08003 Barcelona, Spain. RI Sunnerhagen, Per/G-1696-2012; Arino, Joaquin/D-3756-2011; Posas, Francesc/K-1364-2013 OI Sunnerhagen, Per/0000-0002-0967-8729; Arino, Joaquin/0000-0002-6774-2987; Posas, Francesc/0000-0002-4164-7076 FU NIGMS NIH HHS [GM50908] NR 41 TC 106 Z9 109 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2000 VL 20 IS 11 BP 3887 EP 3895 DI 10.1128/MCB.20.11.3887-3895.2000 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 313UF UT WOS:000087017100014 PM 10805732 ER PT J AU Gebow, D Miselis, N Liber, HL AF Gebow, D Miselis, N Liber, HL TI Homologous and nonhomologous recombination resulting in deletion: Effects of p53 status, microhomology, and repetitive DNA length and orientation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID WILD-TYPE P53; MAMMALIAN-CELLS; SACCHAROMYCES-CEREVISIAE; IONIZING-RADIATION; TUMOR SUPPRESSOR; MUTANT P53; PROTEIN; REPAIR; GENE; INSTABILITY AB Repetitive DNA elements frequently are precursors to chromosomal deletions in prokaryotes and lower eukaryotes. However, little is known about the relationship between repeated sequences and deletion formation in mammalian cells. We have created a novel integrated plasmid-based recombination assay to investigate repeated sequence instability in human cells. In a control cell line, the presence of direct or inverted repeats did not appreciably influence the very low deletion frequencies (2 x 10(-7) to 9 x 10(-7)) in the region containing the repeat. Similar to what has been observed in lower eukaryotes, the majority of deletions resulted from the loss of the largest direct repeat present in the system along with the intervening sequence. Interestingly, in closely related cell lines that possess a mutant p53 gene, deletion frequencies in the control and direct-repeat plasmids were 40 to 300 times higher than in their wild-type counterparts. However, mutant p53 cells did not preferentially utilize the largest available homology in the formation of the deletion. Surprisingly, inverted repeats were approximately 10,000 times more unstable in all mutant p53 cells than in wild-type cells. Finally, several deletion junctions were marked by the addition of novel bases that were homologous to one of the preexisting DNA ends. Contrary to our expectations, only 6% of deletions in all cell lines could be classified as arising from nonhomologous recombination. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Liber, HL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 302, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA049696, CA09078, CA49696, T32 CA009078] NR 45 TC 77 Z9 80 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2000 VL 20 IS 11 BP 4028 EP 4035 DI 10.1128/MCB.20.11.4028-4035.2000 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 313UF UT WOS:000087017100027 PM 10805745 ER PT J AU Sleckman, BP Khan, WN Xu, WP Bassing, CH Malynn, BA Copeland, NG Bardon, CG Breit, TM Davidson, L Oltz, EM Jenkins, NA Berman, JE Alt, FW AF Sleckman, BP Khan, WN Xu, WP Bassing, CH Malynn, BA Copeland, NG Bardon, CG Breit, TM Davidson, L Oltz, EM Jenkins, NA Berman, JE Alt, FW TI Cloning and functional characterization of the early-lymphocyte-specific Pb99 gene SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; B-CELL; V(D)J RECOMBINATION; RECEPTOR SUPERFAMILY; SIGNAL-TRANSDUCTION; MESSENGER-RNA; T-CELLS; PROTEIN; MICE; EXPRESSION AB The Pb99 gene is specifically expressed in pre-B cells and thymocytes and not in mature B and T cells or nonlymphoid tissues, implying that it may function in early lymphoid development. We have previously described the cloning of an incomplete cDNA for Pb99. Here we report the isolation of full-length cDNAs and genomic clones for the murine Pb99 gene and the mapping of its location to mouse chromosome 8. Sequence analyses of different Pb99 cDNA clones suggest that there may be at least three forms of the Pb99 protein generated by differential processing of the Pb99 transcript. The cDNA with the longest open reading frame encodes a putative protein that has seven hydrophobic domains similar to those of seven membrane-spanning proteins, such as the classical G protein-coupled receptors. To directly address the role of the Pb99 protein in lymphoid development, Pb99-deficient mice were generated by gene targeting, and lymphocyte development in these mice was analyzed. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Univ Maryland, Ctr Med Biotechnol, Baltimore, MD 21201 USA. Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Univ Maryland, Program Mol & Cell Biol, Baltimore, MD 21201 USA. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA61009]; NIAID NIH HHS [AI01297-01, AI20047] NR 35 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2000 VL 20 IS 12 BP 4405 EP 4410 DI 10.1128/MCB.20.12.4405-4410.2000 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 318NF UT WOS:000087289700021 PM 10825203 ER PT J AU Stepanova, L Finegold, M DeMayo, F Schmidt, EV Harper, JW AF Stepanova, L Finegold, M DeMayo, F Schmidt, EV Harper, JW TI The oncoprotein kinase chaperone CDC37 functions as an oncogene in mice and collaborates with both c-myc and cyclin D1 in transformation of multiple tissues SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; CELL-FREE SYSTEM; TRANSGENIC MICE; RETINOBLASTOMA PROTEIN; INHIBITOR P27(KIP1); TYROSINE KINASE; DEPENDENT KINASES; CDK INHIBITORS; RAS; HSP90 AB CDC37 encodes a 50-kDa protein that targets intrinsically unstable oncoprotein kinases including Cdk4, Raf-1, and v-src to the molecular chaperone Hsp90, an interaction that is thought to be important for the establishment of signaling pathways. CDC37 is required for proliferation in budding yeast and is coexpressed with cyclin D1 in proliferative zones during mouse development, a finding consistent with a positive role in cell proliferation. CDC37 expression may not only be required to support proliferation in cells that are developmentally programmed to proliferate but may also be required in cells that are inappropriately induced to initiate proliferation by oncogenes. Here we report that mouse mammary tumor virus (MMTV)-CDC37 transgenic mice develop mammary gland tumors at a rate comparable to that observed previously in MMTV-cyclin D1 mice. Moreover, CDC37 was found to collaborate with MMTV-c-myc in the transformation of multiple tissues, including mammary and salivary glands in females and testis in males, and also collaborates with cyclin D1 to transform the female mammary gland. These data indicate that CDC37 can function as an oncogene in mice and suggests that the establishment of protein kinase pathways mediated by Cdc37-Hsp90 can be a rate-limiting event in epithelial cell transformation. C1 Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Ctr Canc, Dept Tumor Biol, Charlestown, MA 02129 USA. RP Harper, JW (reprint author), Baylor Coll Med, Dept Biochem, 1 Baylor Plaza, Houston, TX 77030 USA. FU NIGMS NIH HHS [GM54137, R01 GM054137] NR 73 TC 57 Z9 60 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2000 VL 20 IS 12 BP 4462 EP 4473 DI 10.1128/MCB.20.12.4462-4473.2000 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 318NF UT WOS:000087289700028 PM 10825210 ER PT J AU Frank, KM Sharpless, NE Gao, YJ Sekiguchi, JM Ferguson, DO Zhu, CM Manis, JP Horner, J DePinho, RA Alt, FW AF Frank, KM Sharpless, NE Gao, YJ Sekiguchi, JM Ferguson, DO Zhu, CM Manis, JP Horner, J DePinho, RA Alt, FW TI DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway SO MOLECULAR CELL LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; ARF TUMOR-SUPPRESSOR; V(D)J RECOMBINATION; TARGETED DISRUPTION; GENE AMPLIFICATION; MAMMALIAN-CELLS; INK4A LOCUS; IN-VIVO; REPAIR; PHOSPHORYLATION AB DNA ligase IV (LIG4) is a nonhomologous end-joining (NHEJ) protein used for V(D)J recombination and DNA repair. In mice, Lig4 deficiency causes embryonic lethality, massive neuronal apoptosis, arrested lympho-genesis, and various cellular defects. Herein, we assess potential roles in this phenotype for INK4a/ARF and p53, two proteins implicated in apoptosis and senescence. INK4a/ARF deficiency rescued proliferation/senescence defects of Lig4-deficient fibroblasts but not other phenotypic aspects. In contrast, p53 deficiency rescued embryonic lethality, neuronal apoptosis, and fibroblast proliferation/senescence defects but not lymphocyte development or radiosensitivity. Young Lig4/p53 double null mice routinely died from pro-B lymphomas. Thus, in the context of Lig4 deficiency, embryonic lethality and neuronal apoptosis likely result from a p53-dependent response to unrepaired DNA damage, and neuronal apoptosis and lymphocyte developmental defects can be mechanistically dissociated. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Adult Oncol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 FU NIAID NIH HHS [AI20047, AI35714]; NICHD NIH HHS [R01HD34880] NR 60 TC 322 Z9 326 U1 0 U2 11 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 JUN PY 2000 VL 5 IS 6 BP 993 EP 1002 DI 10.1016/S1097-2765(00)80264-6 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 328HZ UT WOS:000087845900009 PM 10911993 ER PT J AU Klein, J Fasshauer, M Benito, M Kahn, CR AF Klein, J Fasshauer, M Benito, M Kahn, CR TI Insulin and the beta 3-adrenoceptor differentially regulate uncoupling protein-1 expression SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID BROWN ADIPOCYTES; BETA(3)-ADRENERGIC RECEPTOR; ADRENERGIC-RECEPTOR; KINASE CASCADE; METABOLIC-RATE; WEIGHT-GAIN; OBESITY; ACTIVATION; HYPERINSULINEMIA; NOREPINEPHRINE AB Cross-talk between insulin and the adrenergic system is important in the regulation of energy homeostasis. In cultured, differentiated mouse brown adipocytes, beta 3-adrenergic stimulation induced a 4.5-fold increase in uncoupling protein-1 (UCP-1) expression, which was diminished by 25% in the presence of insulin. beta 3-Adrenergic stimulation also activated mitogen-activated protein (MAP) kinase by 3.5-fold and caused a decrease in basal phosphoinositide (PI) 3-kinase activity detected in p1100 gamma- and G beta-subunit-immunoprecipitates in a time-dependent manner, whereas insulin stimulated p110 alpha- and phosphotyrosine-associated PI 3-kinase activity. Inhibition of MAP kinase or PI 3-kinase potentiated the beta 3-adrenergic effect on UCP-1 expression, both alone and in the presence of insulin. Thus, insulin inhibits beta 3-adrenergic stimulation of UCP-1, and both MAP kinase and PI 3-kinase are negative regulatory elements in the beta 3-adrenergic control of UCP-1 expression. Crosstalk between the adrenergic and insulin signaling systems end impaired regulation of UCP-1 might contribute to the development of a reduced energy balance, resulting in obesity and insulin resistance. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Med Univ Lubeck, Dept Internal Med 1, D-23538 Lubeck, Germany. Univ Complutense, Fac Farm, E-28040 Madrid, Spain. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [DK-33201, DK-36836] NR 35 TC 35 Z9 35 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2000 VL 14 IS 6 BP 764 EP 773 DI 10.1210/me.14.6.764 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 320ZN UT WOS:000087430600002 PM 10847579 ER PT J AU McClatchey, AI AF McClatchey, AI TI Neurofibromatosis type II: mouse models reveal broad roles in tumorigenesis and metastasis SO MOLECULAR MEDICINE TODAY LA English DT Article ID TUMOR-SUPPRESSOR; MICE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Dept Pathol, Charlestown, MA 02129 USA. RP McClatchey, AI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Dept Pathol, 149 13th St, Charlestown, MA 02129 USA. NR 5 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD JUN PY 2000 VL 6 IS 6 BP 252 EP 253 DI 10.1016/S1357-4310(00)01696-8 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 322JQ UT WOS:000087506800011 PM 10840384 ER PT J AU Bassing, CH Alt, FW Hughes, MM D'Auteuil, M Wehrly, TD Woodman, BB Gartner, F White, JM Davidson, L Sleckman, BP AF Bassing, CH Alt, FW Hughes, MM D'Auteuil, M Wehrly, TD Woodman, BB Gartner, F White, JM Davidson, L Sleckman, BP TI Recombination signal sequences restrict chromosomal V(D)J recombination beyond the 12/23 rule SO NATURE LA English DT Article ID MEDIATE RECOMBINATION; T-CELLS; BETA; GENE; REARRANGEMENT; CHAIN; DIFFERENTIATION; INITIATION; SEGMENTS; PROMOTER AB The genes encoding the variable regions of lymphocyte antigen receptors are assembled from variable (V), diversity (D) and joining (J) gene segments(1), V(D)J recombination is initiated by the recombinase activating gene (RAG)-1 and -2 proteins, which introduce DNA double-strand breaks between the V, D and J segments and their flanking recombination signal sequences (RSSs), Generally expressed DNA repair proteins then carry out the joining reaction(2,3), The conserved heptamer and nonamer sequences of the RSSs are separated by non-conserved spacers of 12 or 23 base pairs (forming 12-RSSs and 23-RSSs). The 12/23 rule, which is mediated at the level of RAG-1/2 recognition and cutting(4,5), specifies that V(D)J recombination occurs only between a gene segment flanked by a 12-RSS and one flanked by a 23-RSS1, V beta segments are appended to DJ beta rearrangements, with little or no direct V beta to J beta joining, despite 12/23 compatibility of V beta 23-RSSs and J beta 12-RSSs(6,7). Here we use embryonic stem cells and mice with a modified T-cell receptor (TCR)beta locus containing only one D beta (D beta 1) gene segment and one J beta (J beta 1) gene cluster to show that the 5' D beta 1 12-RSS, but not the J beta 1 12-RSSs, targets rearrangement of a diverse V beta repertoire, This targeting is precise and position-independent. This additional restriction on V(D)J recombination has important implications for the regulation of variable region gene assembly and repertoire development. C1 Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Sleckman, BP (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave,Campus Box 8118, St Louis, MO 63110 USA. OI White, James Michael/0000-0001-5110-6567 NR 31 TC 113 Z9 115 U1 0 U2 9 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 1 PY 2000 VL 405 IS 6786 BP 583 EP 586 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 321HF UT WOS:000087449500054 PM 10850719 ER PT J AU Mirzabekov, T Kontos, H Farzan, M Marasco, W Sodroski, J AF Mirzabekov, T Kontos, H Farzan, M Marasco, W Sodroski, J TI Paramagnetic proteoliposomes containing a pure, native, and oriented seven-transmembrane segment protein, CCR5 SO NATURE BIOTECHNOLOGY LA English DT Article DE seven-transmembrane protein; G protein-coupled receptor; CCR5; proteoliposomes; HIV-1 gp120; magnetic bead; antibody; screening assays ID PLASMON RESONANCE SPECTROSCOPY; COUPLED RECEPTORS; CHEMOKINE RECEPTORS; HIV-1 CORECEPTOR; HEPARAN-SULFATE; ACTIVATION; INFECTION; RHODOPSIN; BINDING; GLYCOPROTEINS AB Seven-transmembrane segment, G protein-coupled receptors play central roles in a wide range of biological processes, but their characterization has been hindered by the difficulty of obtaining homogeneous preparations of native protein, We have created paramagnetic proteoliposomes containing pure and oriented CCR5, a seven-transmembrane segment protein that serves as the principal coreceptor for human immunodeficiency virus (HIV-1). The CCR5 proteoliposomes bind the HIV-1 gp120 envelope glycoprotein and conformation-dependent antibodies against CCR5, The binding of gp120 was enhanced by a soluble form of the other HIV-1 receptor, CD4, but did not require additional cellular proteins. Paramagnetic proteoliposomes are uniform in size, stable in a broad range of salt concentrations and pH, and can be used in FACS and competition assays typically applied to cells. Integral membrane proteins can be inserted in either orientation into the liposomal membrane, The magnetic properties of these proteoliposomes facilitate rapid buffer exchange useful in multiple applications, As an example, the CCR5-proteoliposomes were used to select CCR5-specific antibodies from a recombinant phage display library, Thus, paramagnetic proteoliposomes should be useful tools in the analysis of membrane protein interactions with extracellular and intracellular ligands, particularly in establishing screens for inhibitors. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIAID NIH HHS [AI 41851]; NIGMS NIH HHS [GM 56550] NR 36 TC 93 Z9 95 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 2000 VL 18 IS 6 BP 649 EP 654 DI 10.1038/76501 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 325EK UT WOS:000087663200026 PM 10835604 ER PT J AU Trojan, A Schultze, JL Witzens, M Vonderheide, RH Ladetto, M Donovan, JW Gribben, JG AF Trojan, A Schultze, JL Witzens, M Vonderheide, RH Ladetto, M Donovan, JW Gribben, JG TI Immunoglobulin framework-derived peptides function as cytotoxic T-cell epitopes commonly expressed in B-cell malignancies SO NATURE MEDICINE LA English DT Article ID CLASS-I MOLECULES; MULTIPLE-MYELOMA; ENDOGENOUS IMMUNOGLOBULIN; PROTECTIVE IMMUNITY; IDIOTYPIC PROTEIN; BINDING PEPTIDES; DENDRITIC CELLS; LEUKEMIA CELLS; TUMOR-ANTIGEN; LYMPHOMA AB Although the idiotypic structures of immunoglobulin from malignant B cells were the first tumor-specific determinants recognized, and clinical vaccination trials have demonstrated induction of tumor-specific immunity, the function of immunoglobulin-specific CD8(+) cytotoxic T lymphocytes in tumor rejection remains elusive. Here, we combined bioinformatics and a T cell-expansion system to identify human immunoglobulin-derived peptides capable of inducing cytotoxic T-lymphocyte responses. Immunogenic peptides were derived from framework regions of the variable regions of the immunoglobulin that were shared among patients. Human-leukocyte-antigen-matched and autologous cytotoxic T lymphocytes specific for these peptides killed primary malignant B cells, demonstrating that malignant B cells are capable of processing and presenting such peptides. Targeting shared peptides to induce T-cell responses might further improve current vaccination strategies in B-cell malignancies. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Trojan, A (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011; OI Schultze, Joachim/0000-0003-2812-9853; LADETTO, Marco/0000-0002-8283-2681 FU NCI NIH HHS [CA78378, CA81534, P01 CA 66996] NR 45 TC 142 Z9 151 U1 1 U2 3 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 JUN PY 2000 VL 6 IS 6 BP 667 EP 672 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 321CX UT WOS:000087438300037 PM 10835683 ER PT J AU Klein, C Kann, M Kis, B Pramstaller, PP Breakefield, XO Ozelius, LJ Vieregge, P AF Klein, C Kann, M Kis, B Pramstaller, PP Breakefield, XO Ozelius, LJ Vieregge, P TI The genetics of dystonia SO NERVENARZT LA German DT Review DE genetics; dystonia; review ID IDIOPATHIC TORSION DYSTONIA; DOPA-RESPONSIVE DYSTONIA; CYCLOHYDROLASE-I GENE; AUTOSOMAL DOMINANT INHERITANCE; EARLY-ONSET DYSTONIA; ASHKENAZI JEWS; MYOCLONIC DYSTONIA; FOCAL DYSTONIA; PAROXYSMAL CHOREOATHETOSIS; PERICENTROMERIC REGION AB To date, at least 12 types of primary dystonia can be distinguished on a genetic basis. A 3-bp deletion in the DYT1 gene causes early onset, generalized torsion dystonia (TD), and mutations in the GTP cyclohydrolase I and the tyrosine hydroxylase genes result in dopa-responsive dystonia (DYT5). A missense change in the D2 dopamine receptor in one large family (DYT11) has recently been implicated in myoclonus-dystonia. Furthermore, seven other loci for dystonia genes have been mapped to chromosomal regions, including a locus for a mixed dystonia phenotype (DYT6), one form of focal dystonia (DYT7), three types of paroxysmal dystonia (DYT8-10), X-linked dystonia-parkinsonism (DYT3),and rapid-onset dystonia-parkinsonism (DYT12). No positive linkage results have yet been obtained for autosomal recessive TD (DYT2) and several other families of different types of dominantly inherited TD (DYT4). In addition, hereditary secondary dystonia may occur as part of familiar diseases of the basal ganglia, metabolic and storage disorders, and various X-linked and other familial neurodegenerative syndromes affecting the basal ganglia. It may be anticipated that the traditional clinical and etiological classifications of dystonia will increasingly be replaced by a genetic one and that the identification of more dystonia genes may lead to a better understanding of these largely nondegenerative disorders. C1 Univ Klinikum Lubeck, Neurol Klin, D-23538 Lubeck, Germany. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Reg Hosp, Dept Neurol, Bozen, Italy. RP Klein, C (reprint author), Univ Klinikum Lubeck, Neurol Klin, Ratzeburger Allee 160, D-23538 Lubeck, Germany. RI Kis, Bernhard/A-8731-2008; Pramstaller, Peter/C-2357-2008 OI Kis, Bernhard/0000-0003-3244-9737; FU NINDS NIH HHS [NS28384] NR 111 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-2804 J9 NERVENARZT JI Nervenarzt PD JUN PY 2000 VL 71 IS 6 BP 431 EP 441 DI 10.1007/s001150050604 PG 21 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 331AU UT WOS:000087995500001 PM 10919137 ER PT J AU Barbieri, R Frank, LM Quirk, MC Wilson, MA Brown, EN AF Barbieri, R Frank, LM Quirk, MC Wilson, MA Brown, EN TI A time-dependent analysis of spatial information encoding in the rat hippocampus SO NEUROCOMPUTING LA English DT Article; Proceedings Paper CT 8th Annual Computational Neurosciences Meeting (CNS 99) CY JUL, 1999 CL PITTSBURGH, PENNSYLVANIA DE hippocampal place cells; interspike interval distributions; inhomogeneous gamma process; spatial information encoding; maximum likelihood AB The place fields of rat hippocampal pyramidal cells evolve over time as the animal moves through its environment. To study the nature of this evolution we use an inhomogeneous gamma probability model and analyze the properties of place cell spike trains in nonoverlapping windows. Although the locations and heights of the fields evolve over time for 27 of the 35 place cells studied, the temporal parameter was essentially unchanged. This result suggests that adaptive estimation methods may be useful to characterize the dynamics of hippocampal place cells for behavioral tasks executed in novel and non-novel environments. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,MIT Div Hlth Sci & Technol, Dept Anesthesia & Crit Care,Stat Res Lab,Clin 3, Boston, MA 02114 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Barbieri, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,MIT Div Hlth Sci & Technol, Dept Anesthesia & Crit Care,Stat Res Lab,Clin 3, 55 Fruit St, Boston, MA 02114 USA. OI Frank, Loren/0000-0002-1752-5677; Barbieri, Riccardo/0000-0001-9381-3833 NR 5 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-2312 J9 NEUROCOMPUTING JI Neurocomputing PD JUN PY 2000 VL 32 BP 629 EP 635 DI 10.1016/S0925-2312(00)00225-3 PG 7 WC Computer Science, Artificial Intelligence SC Computer Science GA 329GB UT WOS:000087897800087 ER PT J AU Zukerberg, LR Patrick, GN Nikolic, M Humbert, S Wu, CL Lanier, LM Gertler, FB Vidal, M Van Etten, RA Tsai, LH AF Zukerberg, LR Patrick, GN Nikolic, M Humbert, S Wu, CL Lanier, LM Gertler, FB Vidal, M Van Etten, RA Tsai, LH TI Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth SO NEURON LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; UBIQUITIN-PROTEASOME PATHWAY; NEURONAL-SPECIFIC ACTIVATOR; PROTEIN-KINASE; BOVINE BRAIN; CDC2-LIKE KINASE; IDENTIFICATION; BINDING; MOUSE; MICE AB Cyclin-dependent kinase 5 (Cdk5) is a small serine/threonine kinase that plays a pivotal role during development of the CNS. Cables, a novel protein, interacts with Cdk5 in brain lysates. Cables also binds to and is a substrate of the c-Abl tyrosine kinase. Active c-Abl kinase leads to Cdk5 tyrosine phosphorylation, and this phosphorylation is enhanced by Cables. Phosphorylation of Cdk5 by c-Abl occurs on tyrosine 15 (Y15), which is stimulatory for p35/Cdk5 kinase activity. Expression of antisense Cables in primary cortical neurons inhibited neurite outgrowth. Furthermore, expression of active Abl resulted in lengthening of neurites. The data provide evidence for a Cables-mediated interplay between the Cdk5 and c-Abl signaling pathways in the developing nervous system. C1 Harvard Univ, Sch Med, Dept Pathol, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Ctr Blood Res, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02139 USA. RP Tsai, LH (reprint author), Harvard Univ, Sch Med, Dept Pathol, Howard Hughes Med Inst, Boston, MA 02115 USA. RI Humbert, Sandrine/S-2981-2016 FU NINDS NIH HHS [R01-NS37007] NR 48 TC 248 Z9 262 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN PY 2000 VL 26 IS 3 BP 633 EP 646 DI 10.1016/S0896-6273(00)81200-3 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 330ZH UT WOS:000087991600014 PM 10896159 ER PT J AU Huisman, TAGM Brandner, S Niggli, F Betts, DR Boltshauser, E Martin, E AF Huisman, TAGM Brandner, S Niggli, F Betts, DR Boltshauser, E Martin, E TI Malignant rhabdoid tumor of the brain: Quantitative H-1 MR-spectroscopy and cytogenetics SO NEUROPEDIATRICS LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CHILDREN; INFANCY; KIDNEY C1 Univ Zurich, Childrens Hosp, Dept Diagnost Imaging & Radiol, CH-8006 Zurich, Switzerland. Univ Zurich Hosp, Inst Neuropathol, Zurich, Switzerland. Univ Zurich, Childrens Hosp, Dept Oncol, CH-8006 Zurich, Switzerland. Univ Zurich, Childrens Hosp, Dept Neurol, CH-8006 Zurich, Switzerland. RP Huisman, TAGM (reprint author), Massachusetts Gen Hosp, Neuroradiol Sect, Mailcode CNY 149-2301, Boston, MA 02119 USA. NR 12 TC 6 Z9 6 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0174-304X J9 NEUROPEDIATRICS JI Neuropediatrics PD JUN PY 2000 VL 31 IS 3 BP 159 EP 161 DI 10.1055/s-2000-7489 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 340GL UT WOS:000088524700011 PM 10963106 ER PT J AU Kokkotou, E Mastaitis, JW Qu, D Hoersch, D Slieker, L Bonter, K Tritos, NA Maratos-Flier, E AF Kokkotou, E Mastaitis, JW Qu, D Hoersch, D Slieker, L Bonter, K Tritos, NA Maratos-Flier, E TI Characterization of [Phe(13), Tyr(19)]-MCH analog binding activity to the MCH receptor SO NEUROPEPTIDES LA English DT Article ID MELANIN-CONCENTRATING-HORMONE; RAT HYPOTHALAMUS; NEUROPEPTIDE-Y; SLC-1; LIGAND; GENE; IDENTIFICATION; OBESITY; SYSTEM; BRAIN AB Melanin concentrating hormone (MCH), a hypothalamic neuropeptide, is an important regulator of energy homeostasis in mammals. Characterization of an MCH specific receptor has been hampered by the lack of a suitable radioligand. The [Phe(13), Tyr(19)]-MCH analog has been shown by different investigators to bind specifically to cell lines of epithelial or pigment cell origin. Recently, using functional assays, the MCH receptor has been characterized as a seven transmembrane G-coupled protein initially identified as SLC-1. in the present study, we used tyrosine iodinated [Phe(13), Tyr(19)]-MCH analog, which stimulates food intake in a manner similar to that of MCH, as well as native MCH to conduct binding studies. Specific binding could not be demonstrated in intact cells of several cell lines, including A431 and B16. Specific binding associated with membranes localized to the microsomal, not the plasma membrane, fraction. Message for SLC-1 was absent in these cell lines, as assessed by Northern blot analysis. We conclude that cells previously reported to express the MCH receptor do not express SLC-I and that both iodinated MCH and the [Phe(13), Tyr(19)]-MCH have a large component of non-specific binding. These ligands may be useful for binding studies in transfected cells with high levels of SLC-I expression. However they do not appear to be suitable for screening for the MCH receptor as most cells demonstrate significant low affinity non-specific binding. (C) 2000 Harcourt Publishers Ltd. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. NEN Life Sci Prod, Montreal, PQ, Canada. RP Maratos-Flier, E (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-53978-02] NR 27 TC 18 Z9 18 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD JUN-AUG PY 2000 VL 34 IS 3-4 BP 240 EP 247 DI 10.1054/npep.2000.0821 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 368NG UT WOS:000090123300015 PM 11021987 ER PT J AU Kim, L Hochberg, FH Shaeffer, P AF Kim, L Hochberg, FH Shaeffer, P TI White-matter abnormalities in unirradiated patients cured of primary central nervous system lymphoma SO NEURORADIOLOGY LA English DT Article DE lymphoma, primary central nervous system; chemotherapy; magnetic resonance imaging ID EPSTEIN-BARR-VIRUS; PRIMARY CNS LYMPHOMA; HUMAN HERPESVIRUS-6 INFECTION; PRIMARY CEREBRAL LYMPHOMA; MULTIPLE-SCLEROSIS; CHILDHOOD LEUKEMIA; METHOTREXATE ENCEPHALOPATHY; BRAIN; LEUKOENCEPHALOPATHY; CHEMOTHERAPY AB On MRI, primary brain tumors are commonly seen as contrast-enhancing masses surrounded by areas of abnormal signal on T2-weighted images. Following successful treatment tumors may no longer show contrast enhancement. The residual abnormalities are assumed to be represent "edema" and infiltrating tumor cells. We report nine patients with primary lymphoma of the central nervous system who had complete responses to intravenous methotrexate, but did not receive intrathecal chemotherapy or cranial irradiation. After complete resolution of contrast-enhancing lesions, persistent abnormalities on T2-weighted images in the region of prior tumor were initially assumed to reflect residual viable tumor. As they remained unchanged for years, however, this may not hold true in the cases in which primary central nervous system lymphoma responds to chemotherapy alone. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol Neuroradiol, Boston, MA 02115 USA. RP Hochberg, FH (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Cox 315,55 Fruit St, Boston, MA 02114 USA. NR 36 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD JUN PY 2000 VL 42 IS 6 BP 406 EP 412 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 336RR UT WOS:000088317200004 PM 10929299 ER PT J AU Carter, BS Buckley, D Ferraro, R Rordorf, G Ogilvy, CS AF Carter, BS Buckley, D Ferraro, R Rordorf, G Ogilvy, CS TI Factors associated with reintegration to normal living after subarachnoid hemorrhage SO NEUROSURGERY LA English DT Article DE barthel index; cerebral aneurysm; outcome assessment; outcome study; Reintegration to Normal Living Index; Zung Self-rating Depression Scale ID QUALITY-OF-LIFE; COGNITIVE IMPAIRMENT; NEUROLOGICAL DEFICITS; STROKE PATIENTS; EARLY OPERATION; DEPRESSION; ANEURYSM; INDEX; REHABILITATION; PERFORMANCE AB OBJECTIVE: Recent reports have suggested improvement in the last decade in global outcome measures after subarachnoid hemorrhage (SAH), particularly in patients presenting in good initial neurological status. We used a standardized self-report instrument, the Reintegration to Normal Living (RNL) Index, to assess a patient-based quality of life measure and a self-report of work status. We tested the hypothesis that several patient-based factors were related to these outcomes, including depressive symptoms, physical disability, age, and initial Hunt and Hess grade. Using these data, we report the total management morbidity and mortality at 1 to 5 years after SAH for patients initially presenting in good neurological condition. METHODS: The study population consisted of 246 consecutive patients admitted to our tertiary care center with aneurysmal SAH in good neurological condition (Hunt and Hess Grades I-III). Patients underwent either surgical (92%), endovascular (7%), or medical (1%) management of aneurysmal SAH. Eighty-three percent of surviving patients completed a written or telephone questionnaire incorporating the Barthel Index, the Zung Self-rating Depression Scale, the RNL Index, and a work status assessment. RESULTS: An aneurysm-related mortality rate of 6% was observed in the patient population. Fifty-five percent of patients reported a complete reintegration into their normal living situation, as measured by the RNL Index. Sixty-seven percent of previously full-time workers returned to a full-time status. Thirty-six percent of patients reported depressive symptoms, and 23% of patients reported physical disability. In a multivariate model, the two factors that contributed most to an impairment of reintegration were depression and physical disability, whereas a failure to return to work was related to older age and a higher-grade initial neurological status. CONCLUSION: In this series of patients undergoing multimodality management of lower-grade SAH, more than one-half of patients subsequently reported a normal reintegration into their social situation, as assessed by the RNL Index. Standardized assessments of cofactors associated with impaired reintegration revealed that depressive symptoms and physical disability played a strong role in overall reintegration. Standardized assessments, such as the RNL Index, offer the potential for improved comparison of different treatment regimens and specific therapeutic targeting of factors, such as depression, which contribute to decreased quality of life. C1 Massachusetts Gen Hosp, Neurosurg Serv, Brain Aneurysm AVM Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Occupat Therapy, Boston, MA 02114 USA. RP Carter, BS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Brain Aneurysm AVM Ctr, Wang Bldg ACC 021,15 Parkman St, Boston, MA 02114 USA. NR 39 TC 69 Z9 68 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 2000 VL 46 IS 6 BP 1326 EP 1333 DI 10.1097/00006123-200006000-00008 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 316WU UT WOS:000087191700020 PM 10834638 ER PT J AU Nishimura, RN Santos, D Fu, ST Dwyer, BE AF Nishimura, RN Santos, D Fu, ST Dwyer, BE TI Induction of cell death by L-alpha-aminoadipic acid exposure in cultured rat astrocytes: Relationship to protein synthesis SO NEUROTOXICOLOGY LA English DT Article DE astrocytes; cell death; L-alpha-aminoadipic acid; protein synthesis; heat shock proteins ID HEAT-SHOCK PROTEIN-70; LONG-TERM OBSERVATION; LYSINE METABOLISM; CORTICAL-NEURONS; HEME OXYGENASE; KAINIC ACID; AMINO-ACIDS; CARP RETINA; GLIAL-CELLS; BRAIN AB The excitotoxin, L-alpha-aminoadipic acid (L-AAA), kills primary astrocytes in the brain. The mechanism underlying the induction of cell death is not well understood although many possible mechanisms are theorized. Previous studies have reported that astrocytes die after prolonged exposure to L-AAA suggesting a delayed programmed cell death and apoptosis. In this study rat cortical astrocytes exposed to continuous 1 mM L-AAA exposure for 24-, 48-, or 72 hours demonstrated increased DNA laddering, a characteristic of apoptosis. Unexpectedly, this was not ameliorated by the presence of cycloheximide at 0.1 mu g/ml medium. Because of our interest in cytoprotective heat shock proteins induced by excitoxic stress, we studied the effect of prolonged exposure of L-AAA on the synthesis of stress proteins and protein synthesis in rat cortical astrocytes. Protein synthesis as measured by [S-35]-methionine labeling showed a marked and significant decrease in incorporation of radiolabel after 24 hours of exposure to L-AAA and prior to induction of significant cell death noted at 48- and 72 hours of L-AAA exposure. The inhibition of protein synthesis was partially reversible at 24 hours if cells were labeled in medium without L-AAA during the radiolabeling period. Heat shock or stress proteins, HSP70 and heme oxygenase-1 (HO-1), were analyzed after a 24 hour exposure to L-AAA and showed no significant induction of HSP70 or HO-1. The findings suggest that the prolonged inhibition of protein synthesis and associated lack of induction of HSP70 and HO-1 synthesis contributed to apoptotic cell death induced by the excitoxin L-AAA. (C) 2000 Intox Press, Inc. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda ACCNH, Dept Neurol, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. Vet Adm Hosp, White River Junction, VT 05009 USA. ROC, Res Serv 151, White River Junction, VT 05009 USA. RP Nishimura, RN (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda ACCNH, Dept Neurol, 111N-1,16111 Plummer St, Sepulveda, CA 91343 USA. NR 32 TC 12 Z9 12 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUN PY 2000 VL 21 IS 3 BP 313 EP 320 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 329AG UT WOS:000087883500006 PM 10894121 ER PT J AU Farokhzad, OC Teodoridis, JM Park, H Arnaout, MA Shelley, CS AF Farokhzad, OC Teodoridis, JM Park, H Arnaout, MA Shelley, CS TI CD43 gene expression is mediated by a nuclear factor which binds pyrimidine-rich single-stranded DNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID WISKOTT-ALDRICH SYNDROME; T-CELL ACTIVATION; SIALOPHORIN CD43; LEUKOSIALIN CD43; MONOCLONAL-ANTIBODY; C-MYC; TRANSCRIPTIONAL ACTIVATION; MAJOR SIALOGLYCOPROTEIN; MEMBRANE-PROTEINS; ANDROGEN RECEPTOR AB CD43 is a leukocyte-specific surface molecule which plays an important role both in adhesion and signal transduction, We have identified a site spanning nucleotides +18 to +39 within the human CD43 gene promoter which in vitro is hypersensitive to cleavage by nuclease S1. Repeats of this region are sufficient to activate expression of a heterologous promoter in CD43-positive cell lines. Two nuclear factors, PyRo1 and PyRo2, interact with the hypersensitive site. PyRo1 is a single-stranded DNA-binding protein which binds the pyrimidine-rich sense strand. Mutation analysis demonstrates that the motif TCCCCT is critical for PyRo1 interaction. Replacement of this motif with the sequence CATATA abolishes PyRo1 binding and reduces expression of the CD43 promoter by 35% in Jurkat T lymphocytic cells and by 52% in the pre-erythroid/pre-megakaryocytic cell line K562. However, this same replacement failed to affect expression in U937 monocytic cells or in CEM T lymphocytic cells. PyRo1, therefore, exhibits cell-specific differences in its functional activity. Further analysis demonstrated that PyRo1 not only interacts with the CD43 gene promoter but also motifs present within the promoters of the CD11a, CD11b, CD11c and CD11d genes. These genes encode the a subunits of the beta 2 integrin family of leukocyte adhesion receptors, Deletion of the PyRo1 binding site within the CD11c gene reduced promoter activity in T lymphocytic cells by 47%. However, consistent with our analysis of the CD43 gene, the effect of this same deletion within U937 monocytic cells was less severe. That PyRo1 binds preferentially to single-stranded DNA and sequences within the CD43 and CD11 gene promoters suggests that expression of these genes is influenced by DNA secondary structure. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit,Leukocyte Biol & Inflammat Program, Boston, MA 02115 USA. RP Shelley, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit,Leukocyte Biol & Inflammat Program, 149 13th St, Boston, MA 02115 USA. FU NIAID NIH HHS [P01 AI28465]; NIDDK NIH HHS [P30 DK043351, R29 DK50779, P01 DK43351] NR 75 TC 8 Z9 8 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 1 PY 2000 VL 28 IS 11 BP 2256 EP 2267 DI 10.1093/nar/28.11.2256 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 320UA UT WOS:000087417700008 PM 10871347 ER PT J AU Hynes, DM AF Hynes, DM TI Research as a key to promoting and sustaining innovative practice SO NURSING CLINICS OF NORTH AMERICA LA English DT Article ID EVIDENCE-BASED MEDICINE; QUALITY IMPROVEMENT; CARE AB During the past decade, we have witnessed increasing emphasis on the integration of research and clinical care with the evolution of evidence-based practice and best practices. The principles underlying evidence-based medicine and best practices are fundamental to understanding the interdependence of research and innovation. These principles helped guide the US Department of Veterans Affairs (VA) Nursing innovations Task Force to review and critique programs at VA health care facilities across the United States. This article reviews how the task force applied concepts and principles of evidence-based practice to identify innovative practices at VA health care facilities. Also described are task force recommendations to foster innovative practice through increased nursing research capacity, and strategies are suggested for applying these principles in other health care settings. C1 Dept Vet Affairs Innovat Nursing Initiat Review T, Hines, IL USA. Vet Affairs Informat Resource Ctr, Hlth Serv Res & Dev Serv Special Resource Ctr, Hines, IL USA. Midw Ctr Hlth Serv Res, Hines, IL USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL 60141 USA. Loyola Univ, Dept Med, Div Gen Internal Med, Maywood, IL 60153 USA. RP Hynes, DM (reprint author), Edward Hines Vet Adm Hosp, VA Informat Resource Ctr 151V, 5th Ave & Rossevelt Rd,Bldg 1,Room B260, Hines, IL 60141 USA. NR 15 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD JUN PY 2000 VL 35 IS 2 BP 453 EP + PG 9 WC Nursing SC Nursing GA 329RB UT WOS:000087920700017 PM 10873257 ER PT J AU Hemphill, L Kemp, J AF Hemphill, L Kemp, J TI Implementing a therapeutic massage program in a tertiary and ambulatory care va setting - The healing power of touch SO NURSING CLINICS OF NORTH AMERICA LA English DT Article AB The ancient practice of massage to promote healing has a plate in contemporary health care. This article discusses the implementation of a nurse-run therapeutic massage service at the Denver Veterans Administration Medical Center. program background, evaluation, future plans, and lessons learned are described. C1 Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Hemphill, L (reprint author), Denver Vet Affairs Med Ctr, 1055 Clermont, Denver, CO 80220 USA. NR 24 TC 4 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD JUN PY 2000 VL 35 IS 2 BP 489 EP + PG 10 WC Nursing SC Nursing GA 329RB UT WOS:000087920700021 PM 10873261 ER PT J AU Schwartz, F Genovese, L Devitt, K Gottlieb, T AF Schwartz, F Genovese, L Devitt, K Gottlieb, T TI Multisite regional telephone care SO NURSING CLINICS OF NORTH AMERICA LA English DT Article AB A multisite, regional telephone-care program staffed by advance practice and critical care nurses has improved patient care and reduced unnecessary clinic and emergency room visits. It allows patients to access the health care system and receive expert advice through the use of the telephone, 24 hours per day, 7 days per week. Computerized patient medical records from eight hospitals and 31 clinics are available to a registered nurse so that informed decisions can be made. The RN records the patient's concern and intervention directly into the patient's medical record, which is transmitted to the primary care provider in real time. C1 Bronx Vet Affairs Med Ctr, Network Telephone Care Program, Bronx, NY 10468 USA. Hudson Valley Hlth Care Syst, Montrose, NY USA. Bronx Vet Affairs Med Ctr, Med Surg Patient Care Ctr, Bronx, NY 10468 USA. RP Schwartz, F (reprint author), Bronx Vet Affairs Med Ctr, Network Telephone Care Program, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 17 TC 5 Z9 5 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 JUN PY 2000 VL 35 IS 2 BP 527 EP + PG 14 WC Nursing SC Nursing GA 329RB UT WOS:000087920700025 PM 10873265 ER PT J AU Houck, K Nikrui, N Duska, L Chang, YC Fuller, AF Bell, D Goodman, A AF Houck, K Nikrui, N Duska, L Chang, YC Fuller, AF Bell, D Goodman, A TI Borderline tumors of the ovary: Correlation of frozen and permanent histopathologic diagnosis SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID INTRAOPERATIVE CONSULTATION; STAGING LAPAROTOMY; SECTION; ACCURACY; NEOPLASMS; MALIGNANCY; CARCINOMA AB Objective: To evaluate the correlation between the diagnosis of borderline tumor of the ovary by frozen and permanent pathology. Methods: All pathology reports with diagnoses of borderline tumor of the ovary between 1980 and 1998 at Massachusetts General Hospital were reviewed. Univariate and multivariable logistic regression models were constructed for patient age, tumor size, histology, presence of bilateral or extraovarian disease, and concurrent diagnosis of endometriosis or endosalpingiosis. Results: We reviewed 140 cases. The average age of patients was 52.3 years. Eighty tumors were serous, 47 mucinous, 11 mixed, and two endometrioid. The mean diameter overall was 13.7 cm (range 1-70 cm), 10.2 cm for serous, and 20.1 cm for mucinous. Diagnoses of borderline tumors by frozen and permanent pathology were consistent in 60% of cases. Frozen section interpreted a benign lesion as malignant (overdiagnosed) in 10.7% of cases, and interpreted a malignant lesion as benign (underdiagnosed) in 29.3%. No variable was a significant predicator of overdiagnosis. In univariate analysis, underdiagnosis was more likely for other types of tumors than serous (P < .001), tumors larger than 20 cm (P = .039), and tumors confined to the ovaries (P = .009). When all variables were included in a multiple regression model, only histology was a significant predictor of underdiagnosis (P = .039). Conclusion: Frozen or permanent pathology reports of diagnoses of borderline tumor were consistent 60% of the time, whereas the positive predictive value of borderline by frozen section was 89.3%. Tumors other than serous are more likely to be misinterpreted. (Obstet Gynecol 2000;95:839-43. (C) 2000 by The American College of Obstetricians and Gynecologists). C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. RP Houck, K (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Vincent 1, Boston, MA 02114 USA. NR 20 TC 77 Z9 85 U1 0 U2 2 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 JUN PY 2000 VL 95 IS 6 BP 839 EP 843 DI 10.1016/S0029-7844(99)00656-0 PN 1 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 320KW UT WOS:000087401200011 PM 10831977 ER PT J AU Shipp, TD Zelop, CM Repke, JT Cohen, A Caughey, AB Lieberman, E AF Shipp, TD Zelop, CM Repke, JT Cohen, A Caughey, AB Lieberman, E TI Labor after previous cesarean: Influence of prior indication and parity SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID VAGINAL BIRTH; DELIVERY; TRIAL; SECTION AB Objective: To determine whether the risk of cesarean for women who had trials of labor after one prior cesarean differs from that of nulliparas overall and by indications for those cesareans. Methods: We reviewed medical records of women who had trials of labor after cesareans between July 1984 and June 1996, and of nulliparas who delivered between December 1994 and August 1995. Cesarean rates for women with prior cesareans were compared with the rates for nulliparas overall and by prior cesarean indication (breech, failure to progress, nonreassuring fetal testing, or other). Lengths of labor for women who had repeat cesareans for failure to progress in index pregnancies were compared by prior cesarean indication. Results: The cesarean rate was 28.7% (634 of 2207) for the prior cesarean group and 13.5% (219 of 1617) for nulliparas (P = .001), and varied according to the prior cesarean indication (13.9%, 37.3%, 25.4%, and 24.8% for breech, failure to progress, nonreassuring fetal testing, and other, respectively). Mean durations of labor in the index pregnancies for women who had cesareans for failure to progress were 13.9, 11.5, 13.4, and 15.1 hours for breech, failure to progress, nonreassuring fetal testing, and other, respectively. Conclusion: Overall rates of cesareans were higher for women with one prior cesarean than for nulliparas. Rates of cesareans after trials of labor were related to the prior cesarean indications. Rates were highest for women whose prior cesareans were for failure to progress and lowest for women whose prior cesareans were for breech. The latter group had a rate that was essentially identical to that of nulliparas. Among women with cesareans for failure to progress in index pregnancies, lengths of labor were shorter for those whose prior cesareans were for failure to progress than for those whose prior cesareans were for other indications, suggesting that physicians may intervene earlier in these cases. (Obstet Gynecol 2000;95:913-6. (C) 2000 by The American College of Obstetricians and Gynecologists). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Univ Nebraska, Med Ctr, Dept Obstet & Gynecol, Omaha, NE USA. Univ Chicago, Chicago Lying Hosp, Dept Obstet & Gynecol, Chicago, IL 60637 USA. RP Shipp, TD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Founders 430, Boston, MA 02114 USA. NR 9 TC 34 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2000 VL 95 IS 6 BP 913 EP 916 DI 10.1016/S0029-7844(00)00790-0 PN 1 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 320KW UT WOS:000087401200025 PM 10831991 ER PT J AU Isaacson, K AF Isaacson, K TI New developments in operative hysteroscopy SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID FLUID OVERLOAD; SURGERY; COMPLICATIONS; GLYCINE AB For the past several years, few developments have been made in operative hysteroscopy to change therapeutic procedures for the treatment of benign uterine conditions. New instrumentation, however, has recently contributed to the safety of operative hysteroscopy. This article discusses developments in fluid management systems, resectoscopes, and hysteroscopes. C1 Massachusetts Gen Hosp, Div Reprod Endocrinol & Infertil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. RP Isaacson, K (reprint author), Massachusetts Gen Hosp, Div Reprod Endocrinol & Infertil, VBK 206,55 Fruit St, Boston, MA 02114 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8545 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD JUN PY 2000 VL 27 IS 2 BP 375 EP + PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 313XW UT WOS:000087025800013 PM 10857127 ER PT J AU Baksh, S DeCaprio, JA Burakoff, SJ AF Baksh, S DeCaprio, JA Burakoff, SJ TI Calcineurin regulation of the mammalian G(0)/G(1) checkpoint element, cyclin dependent kinase 4 SO ONCOGENE LA English DT Article DE cell cycle; calcineurin; cdk4; cyclin activating kinase; Jurkat cells ID RETINOBLASTOMA PROTEIN; TRANSCRIPTION FACTORS; PHOSPHORYLATION; PHOSPHATASE; FAMILY; CELLS; NFAT; CDK4 AB Cyclin dependent kinase 4 (cdk8) activity is controlled by the binding of regulatory subunits and inhibitory factors, as well as tyrosine and serine/threonine phosphorylation, More recently the influence of calcium levels have been demonstrated. Using transient transfections in Jurkat cells, we observed specific binding between cdk4 and the calcium and calmodulin activated serine/threonine phosphatase, calcineurin. Furthermore, we demonstrated that the inhibition of the phosphatase activity of calcineurin with FK506 and cyclosporin A resulted in an overall increase in cdk4 kinase activity, suggesting that the phosphatase activity of calcineurin was inhibitory to the kinase activity of cdkA In contrast, we were not able to observe a similar effect on the kinase activity of either cdk6 or cdk2, indicating that the phosphatase activity of calcineurin was specific for cdk4, In addition, using an in vitro phosphatase assay for calcineurin, we observed that the exogenous addition of calcineurin resulted in the dephosphorylation of cdk4, an event that downregulated the kinase activity of cdk4 Calcineurin could, therefore, play an opposing role to the action of the cyclin activating kinase complex, an enzyme that upregulates the kinase activity of cdk4, an important G(0)/G(1) checkpoint element in mammalian cells. C1 Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Burakoff, SJ (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 23 TC 37 Z9 38 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 1 PY 2000 VL 19 IS 24 BP 2820 EP 2827 DI 10.1038/sj.onc.1203585 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 320LX UT WOS:000087403600003 PM 10851085 ER PT J AU Chow, MT Anderson, SF AF Chow, MT Anderson, SF TI Relapsing polychondritis SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE ocular inflammation; orbital cellulitis; orbital pseudotumor; polychondropathy; posterior scleritis; relapsing polychondritis; thyroid eye disease; HLA-DR4 ID DISEASE; COMPLICATIONS; INVOLVEMENT; CARTILAGE; ARTHRITIS AB Background: Relapsing polychondritis (RPC) is a rare, chronic, and potentially fatal multisystemic inflammatory disorder targeting cartilaginous structures. This disorder is frequently associated with rheumatoid arthritis, systemic vasculitis, connective tissue diseases, and/or hematologic disorders. RPC afflicts patients with recurrent and often progressive episodes of inflammation with the potential for destruction of the affected structures. Tissues involved include the ears, joints, nose, larynx, trachea, eyes, heart valves, kidneys,and skin. Ocular manifestations commonly include episcleritis, scleritis, conjunctivitis, iridocyclitis, chorioretinitis, and proptosis. Lid edema, orbital inflammation, muscle palsies, and corneal melting may also occur. Case report An 83-year-old man previously diagnosed with RPC presented to our clinic with acute unilateral chemosis, conjunctivitis, lid edema, proptosis, and extraocular muscle restriction. After orbital cellulitis was ruled out, further evaluation revealed posterior scleritis with choroidal detachment OS. A course of oral indomethacin and topical antibiotic-steroid combination drops was implemented in the treatment of the ocular manifestations. The quick positive response to the anti-inflammatory agents confirmed the diagnosis of ocular complications secondary to RPC. Discussion: The presenting ocular signs and symptoms of RPC often resemble other commonly encountered ocular conditions. It is important for the eye care practitioner to be familiar with the ocular manifestations of RPC because the eyes are sometimes the initial site of involvement and may be a marker of severity. Early diagnosis and intervention may significantly improve the patient's outcome. This case report with literature review will hopefully bring to light features of this disease which will help the eye care practitioner in the diagnosis and management of this condition. C1 Sepulveda Ambulatory Care Ctr, VA Greater Los Angeles Healthcare Syst, Fullerton, CA USA. RP Chow, MT (reprint author), 128 Shawnee Ave, San Francisco, CA 94112 USA. NR 46 TC 7 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD JUN PY 2000 VL 77 IS 6 BP 286 EP 292 DI 10.1097/00006324-200006000-00008 PG 7 WC Ophthalmology SC Ophthalmology GA 328XR UT WOS:000087877500011 PM 10879785 ER PT J AU Sing, NMT Anderson, SF Townsend, JC AF Sing, NMT Anderson, SF Townsend, JC TI The normal optic nerve head SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE optic nerve head; optic disc; optic cup; cup/disc ratio; neuroretinal rim; retinal nerve fiber layer; relative hypoplasia; hypoplasia; computerized image analysis ID NEURORETINAL RIM AREA; HUMAN LAMINA-CRIBROSA; OPEN-ANGLE GLAUCOMA; AGE-RELATED DECLINE; NORMAL HUMAN EYES; FIBER LAYER; DISK SIZE; DIAMETER DISTRIBUTION; REFRACTIVE ERROR; AXON DIAMETER AB Background: The normal optic nerve head varies from one person to another, and there is often intraindividual variation as well. Factors such as race and age play an important role in distinguishing what may be considered normal variations in optic nerve head appearance. Methods: A literature search and review of the latest studies on the optic nerve head was conducted. Results: Results of recent studies showed that variations in the average cup-to-disc ratio exist for different races, and with age there is a gradual loss of nerve fibers leading to an overall increase in the cup-to-disc ratio. There is also evidence that congenitally larger optic nerves have larger cup-to-disc ratios and more nerve fibers. Smaller optic nerves, in contrast, have smaller cup-to-disc ratios and fewer nerve fibers. These findings are presented along with sample photographs depicting the normal variations in optic nerve head appearance. Conclusion: Over the past 30 years, technology has allowed for changing Views about what may be considered normal in reference to the optic nerve head, This information is valuable to the eye care practitioner in helping to make appropriate patient care management decisions. C1 Sepulveda Ambulatory Care Ctr & Nursing Home, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Sing, NMT (reprint author), 6601 Tennyson St NE 10204, Albuquerque, NM 87111 USA. NR 80 TC 8 Z9 8 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD JUN PY 2000 VL 77 IS 6 BP 293 EP 301 PG 9 WC Ophthalmology SC Ophthalmology GA 328XR UT WOS:000087877500012 PM 10879786 ER PT J AU Dewhirst, FE Tamer, MA Ericson, RE Lau, CN Levanos, VA Boches, SK Galvin, JL Paster, BJ AF Dewhirst, FE Tamer, MA Ericson, RE Lau, CN Levanos, VA Boches, SK Galvin, JL Paster, BJ TI The diversity of periodontal spirochetes by 16S rRNA analysis SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE periodontal diseases; Treponema; phylogeny; 16S rRNA; spirochetes; not-yet-cultivable ID NECROTIZING ULCERATIVE GINGIVITIS; SP-NOV; TREPONEMA-DENTICOLA; PHYLOGENETIC ANALYSIS; JUVENILE PERIODONTITIS; SUBGINGIVAL PLAQUE; ORAL TREPONEMES; DENTAL PLAQUE; SITES; DISEASE AB The purpose of this study was to examine the diversity of spirochetes in the subgingival pocket of multiple subjects with a range of periodontal conditions, including two healthy, one adult periodontitis, three acute necrotizing ulcerative gingivitis, eight refractory periodontitis, and one human immunodeficiency virus (HIV) periodontitis. The 16S rRNA genes of spirochetes in plaque were amplified by polymerase chain reaction using spirochete selective primers. Over 500 clones were sequenced and subjected to phylogenetic analysis. The sequences clustered into the 10 known cultivated Treponema species and into 47 as-yet-uncultivated Treponema species. Most of these Treponema species were identified From multiple clones and subjects. The human periodontal pocket harbors a highly diverse treponeme population. Of the cultivated species, Treponema denticola, Treponema maltophilum and Treponcma sp. Smibert-3 were most commonly encountered in diseased subjects but rarely in healthy subjects. Molecular tools based on the sequence data from this study will allow determination of the prevalence of cultivable and uncultivable treponemes in oral diseases. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Harvard Sch Dent Med, Dept Oral Biol, Boston, MA USA. RP Dewhirst, FE (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-10374, DE-11443] NR 49 TC 113 Z9 117 U1 0 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD JUN PY 2000 VL 15 IS 3 BP 196 EP 202 DI 10.1034/j.1399-302x.2000.150308.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 302HB UT WOS:000086358700008 PM 11154403 ER PT J AU Hogg, RJ Portman, RJ Milliner, D Lemley, KV Eddy, A Ingelfinger, J AF Hogg, RJ Portman, RJ Milliner, D Lemley, KV Eddy, A Ingelfinger, J TI Evaluation and management of proteinuria and nephrotic syndrome in children: Recommendations from a pediatric nephrology panel established at the National Kidney Foundation Conference on Proteinuria, Albuminuria, Risk, Assessment, Detection, and Elimination (PARADE) SO PEDIATRICS LA English DT Article DE proteinuria; children; adolescents; nephrotic; nephrosis ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; ENZYME-INHIBITOR FETOPATHY; CHRONIC-RENAL-FAILURE; DIABETES-MELLITUS; DISEASE; MICROALBUMINURIA; THERAPY; PROGRESSION; DIET; HYPERLIPIDEMIA AB Objective. The development of this review article evolved from a National Kidney Foundation consensus conference on recent advances in the importance of evaluating and treating proteinuria. From this conference, a series of recommendations for the evaluation of adults with proteinuria was published. Because specific pediatric aspects of the problem were outside the scope of the original National Kidney Foundation publication, an ad hoc committee of 6 pediatric nephrologists who were active participants in the National Kidney Foundation conference was established to provide primary care physicians with a concise, up-to-date reference on this subject. Methods. The recommendations that are given represent the consensus opinions of the authors. These are based on data from controlled studies in children when available, but many of the opinions are, by necessity, based on uncontrolled series in children or controlled trials performed in adults, because controlled trials in children have not been performed to evaluate many of the treatments described. Results and Conclusions. These recommendations are intended to provide primary care physicians with a useful reference when they are faced with a young child or teenager who presents with proteinuria, whether this is mild and asymptomatic or more severe, leading to nephrotic syndrome. C1 N Texas Hosp Childrens Med City, Dallas, TX 75230 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Mayo Clin, Rochester, MN USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hogg, RJ (reprint author), N Texas Hosp Childrens Med City, 7777 Forest Ln,C-740, Dallas, TX 75230 USA. NR 43 TC 108 Z9 121 U1 0 U2 5 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 JUN PY 2000 VL 105 IS 6 BP 1242 EP 1249 DI 10.1542/peds.105.6.1242 PG 8 WC Pediatrics SC Pediatrics GA 321EA UT WOS:000087441400025 PM 10835064 ER PT J AU Matzke, GR Frye, RF Joy, MS Palevsky, PM AF Matzke, GR Frye, RF Joy, MS Palevsky, PM TI Determinants of ceftriaxone clearance by continuous venovenous hemofiltration and hemodialysis SO PHARMACOTHERAPY LA English DT Article ID RENAL REPLACEMENT THERAPIES; POLYSULFONE MEMBRANES; PHARMACOKINETICS; FAILURE AB Study Objective. To guide individual ceftriaxone dosages in patients receiving continuous renal replacement therapy Design. Prospective, outpatient study. Setting. University-affiliated general clinical research center. Patients. Eight patients receiving hemodialysis. Intervention. We performed controlled clearance studies with three hemofilters: an acrylonitrile copolymer 0.6 m(2) (AN69), polymethylmethacrylate 2.1 m(2) (PMMA), and polysulfone 0.65 m(2) (PS). Measurements and Main Results. Subjects received ceftriaxone 1000 mg intravenously before the start of a clearance study. The concentration of ceftriaxone in multiple plasma and dialysate-ultrafiltrate samples was determined by high-performance liquid chromatography. The diffusional clearances (Cl-diffusion) and sieving coefficients (SC) of ceftriaxone, urea, and creatinine were compared by a mixed-model repeated-measures analysis of variance with filter and blood, dialysate inflow or ultrafiltration rate as the main effect and patient as a random effect. The fraction of ceftriaxone bound to plasma proteins was 43 +/- 15% (range 13-92%). Concentration dependence was evident in all three groups. The fraction unbound to plasma proteins (f(up)) at the time that SCs were determined was significantly lower in the PS group (0.16 +/- 0.07) than the AN69 group (0.30 +/- 0.17, p<0.01), but similar to that in the PMMA group (0.27 +/- 0.12). Despite the higher f(up), the SC of unbound ceftriaxone with the AN69 filter (0.48 +/- 0.13) was significantly lower than values for the PMMA (0.86 +/- 0.33) and PS (0.82 +/- 0.22) groups (p<0.05). Continuous venovenous hemofiltration clearance of urea and unbound ceftriaxone increased significantly only for the PMMA (p=0.006) and PS (p=0.015) filters when the ultrafiltration rate was increased. Significant linear relationships (p<0.0001) were observed between Cl-diffusion of unbound ceftriaxone and clearance of urea for all three filters: AN69 slope = 0.57, PMMA slope = 0.90, and PS slope = 1.02. The slope of this relationship for the AN69 filter was significantly lower than for the other two filters. Conclusion. Ceftriaxone clearance was significantly increased and membrane dependent during continuous venovenous hemofiltration and continuous venovenous hemodialysis. Thus individual ceftriaxone dosages for patients receiving continuous renal replacement therapies should incorporate extracorporeal clearance. C1 Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ N Carolina, Sch Med, Div Nephrol & Hypertens, Chapel Hill, NC USA. RP Matzke, GR (reprint author), Univ Pittsburgh, Sch Pharm, 724 Salk Hall, Pittsburgh, PA 15261 USA. OI Palevsky, Paul/0000-0002-7334-5400; Frye, Reginald/0000-0002-1841-1401 FU NCRR NIH HHS [5M01 RR00056] NR 30 TC 23 Z9 24 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUN PY 2000 VL 20 IS 6 BP 635 EP 643 DI 10.1592/phco.20.7.635.35170 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 320ZX UT WOS:000087431400004 PM 10853618 ER PT J AU Thompson, SC Woods, SC Hendricks, S Bell, SM Figlewicz, DP AF Thompson, SC Woods, SC Hendricks, S Bell, SM Figlewicz, DP TI Intraventricular insulin suppresses the acoustic startle response in rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE insulin; acoustic startle response; reuptake blocker; norepinephrine ID LOCUS-COERULEUS; IN-VIVO; NOREPINEPHRINE; MODULATION; INHIBITION; DOPAMINE; NEURONS; BRAIN; ALPHA(2)-ADRENOCEPTORS; AMPHETAMINE AB We and others have previously reported that the hormone insulin alters brain noradrenergic function at the synaptic and molecular levels. In the: present study, we examined the in vivo effect of insulin (administered chronically via osmotic minipumps at a dose of 5 mU/day into the third cerebral ventricle) on thr acoustic startle response. Rats receiving chronic intraventricular insulin had a significantly reduced startle response relative to vehicle-treated controls (i.e., 47 +/- 21% of baseline control startle response). Because our previous findings suggest that on an acute basis, insulin may enhance endogenous noradrenergic activity by inhibiting norepinephrine reuptake, we speculate here that the chronic effect of insulin is similar to that of the noradrenergic reuptake blocker, desipramine, which has been reported to decrease baseline startle performance. (C) 2000 Elsevier Science Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Nebraska, Dept Psychol, Omaha, NE 68182 USA. Univ Nebraska, Dept Pharmacol, Omaha, NE 68182 USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45267 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, 151,1660 So Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK40963, DK17844] NR 29 TC 3 Z9 3 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD JUN 1 PY 2000 VL 69 IS 4-5 BP 433 EP 437 DI 10.1016/S0031-9384(99)00260-7 PG 5 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 336AY UT WOS:000088280800007 PM 10913781 ER PT J AU Diener, AC Li, HX Zhou, WX Whoriskey, WJ Nes, WD Fink, GR AF Diener, AC Li, HX Zhou, WX Whoriskey, WJ Nes, WD Fink, GR TI STEROL METHYLTRANSFERASE 1 controls the level of cholesterol in plants SO PLANT CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; METHYL TRANSFERASE; BRASSINOSTEROID BIOSYNTHESIS; ARABIDOPSIS-THALIANA; MEMBRANE-FUNCTION; 24-ETHYL STEROLS; ERG6 GENE; ZEA-MAYS; YEAST; TRANSFORMATION AB The side chain in plant sterols can have either a methyl or ethyl addition at carbon 24 that is absent in cholesterol, The ethyl addition is the product of two sequential methyl additions. Arabidopsis contains three genes-sterol methyltransferase 1 (SMT1), SMT2, and SMT3-homologous to yeast ERG6, which is known to encode an S-adenosylmethionine-dependent C-24 SMT that catalyzes a single methyl addition. The SMT1 polypeptide is the most similar of these Arabidopsis homologs to yeast Erg6p, Moreover, expression of Arabidopsis SMT1 in erg6 restores SMT activity to the yeast mutant. The smt1 plants have pleiotropic defects: poor growth and fertility, sensitivity of the root to calcium, and a loss of proper embryo morphogenesis. smt1 has an altered sterol content: it accumulates cholesterol and has less C-24 alkylated sterols content. Escherichia coli extracts, obtained from a strain expressing the Arabidopsis SMT1 protein, can perform both the methyl and ethyl additions to appropriate sterol substrates, although with different kinetics. The fact that smt1 null mutants still produce alkylated sterols and that SMT1 can catalyze both alkylation steps shows that there is considerable overlap in the substrate specificity of enzymes in sterol biosynthesis. The availability of the SMT1 gene and mutant should permit the manipulation of phytosterol composition, which will help elucidate the role of sterols in animal nutrition. C1 Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Texas Tech Univ, Dept Chem & Biochem, Lubbock, TX 79409 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Fink, GR (reprint author), Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. NR 45 TC 136 Z9 147 U1 0 U2 9 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD JUN PY 2000 VL 12 IS 6 BP 853 EP 870 DI 10.1105/tpc.12.6.853 PG 18 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 330YQ UT WOS:000087989600002 PM 10852933 ER PT J AU Netscher, DT Meade, RA Goodman, CM Brehm, BJ Friedman, JD Thornby, J AF Netscher, DT Meade, RA Goodman, CM Brehm, BJ Friedman, JD Thornby, J TI Physical and psychosocial symptoms among 88 volunteer subjects compared with patients seeking plastic surgery procedures to the breast SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID REDUCTION MAMMAPLASTY AB In an investigation of the relationship between macro-mastia and physical and psychosocial symptoms, 88 female university students, 21 augmentation mammaplasty patients, and 31 breast reduction patients graded somatic and psychosocial symptoms. The intent of the study was to discover which complaints were most common among women presenting for reduction mammaplasty and to determine whether height/weight index and brassiere chest measurement and cup size might affect their symptoms. Both the student group and the augmentation mammaplasty patients differed significantly from the breast I-eduction patients. Eighty-one percent of the reduction patients complained of neck and back pain. Seventy-seven percent complained of shoulder pain, 58 percent complained of chafing or rash; 45 percent reported significant limitation in their activity; and 52 percent were unhappy with their appearance (p < 0.001 compared with augmentation and student groups). Physical symptoms were I-elated to height/weight index and bra chest and cup sizes in each of the three participating groups. It was found that patients who present for symptom-related reduction mammaplasty have a disease-specific group of physical and psychosocial complaints that are more directly related to large breast size than to being overweight. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. NR 9 TC 18 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2000 VL 105 IS 7 BP 2366 EP 2373 DI 10.1097/00006534-200006000-00009 PG 8 WC Surgery SC Surgery GA 318HF UT WOS:000087277300009 PM 10845288 ER PT J AU Butler, PEM Lee, WPA van de Water, AP Randolph, MA AF Butler, PEM Lee, WPA van de Water, AP Randolph, MA TI Neonatal induction of tolerance to skeletal tissue allografts without immunosuppression SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Plastic-Surgery-Research-Council CY JUN 01-04, 1996 CL ST LOUIS, MISSOURI SP Plast Surg Res Council ID NONLETHAL PREPARATIVE REGIMEN; LONG-TERM SURVIVAL; LIMB ALLOGRAFTS; CYCLOSPORIN-A; TRANSPLANTATION TOLERANCE; INDEFINITE SURVIVAL; RATS; MODEL; ALLOTRANSPLANTATION; CHIMERISM AB Vascularized allogeneic skeletal tissue transplantation without the need for host immunosuppression would increase reconstructive options for treating congenital and acquired defects. Because the immune system of a fetus or neonate is immature, it may be possible to induce tolerance to allogeneic skeletal tissues by alloantigen injection during this permissive period. Within 12 hours after birth, 17 neonatal Lewis rats were injected through the superficial temporal vein with 3.5 to 5 million Brown Norway hone marrow cells in 0.1 mi normal saline. Ten weeks after the injection, peripheral blood from the Lewis rats was analyzed for the presence of Brown Norway cells to determine hemopoietic chimerism. The Lewis rats chen received a heterotopic, vascularized limb tissue transplant (consisting of the knee, the distal femur, the proximal tibia, and the surrounding muscle on a femoral vascular pedicle) from Brown Norway rat donors to determine their tolerance to the allogeneic tissue. A positive control group (n = 6) consisted of syngeneic transplants from Lewis rats into naive Lewis rats to demonstrate survival of transplants. A negative control group (n = 6) consisted of Brown Norway transplants into naive Lewis rats not receiving bone marrow or other immunosuppressive treatment. The animals were assessed for transplant viability 30 days after transplantation using histologic and bone fluorochrome analysis. All the syngeneic controls (Lewis to Lewis) remained viable throughout the experiment, whereas all the Brown Norway to Lewis controls had rejected. Ten of the 17 allografts transplanted into bone marrow recipients were viable at 30 days, with profuse bleeding from the ends of the bone graft and the surrounding graft muscle. The percent of chimerism correlated with survival, with 3.31 percent (SD = 1.9) of peripheral blood, Brown Norway chimerism present in the prolonged survival groups and 0.75 percent (SD = 0.5) of Brown Norway chimerism in the rejected graft group. This study demonstrated prolonged survival of allogeneic skeletal tissue without immunosuppression after early neonatal injection of allogeneic bone marrow in a rat model. C1 Massachusetts Gen Hosp, Div Plast Surg, Ambulatory Care Ctr 453, Boston, MA 02114 USA. RP Lee, WPA (reprint author), Massachusetts Gen Hosp, Div Plast Surg, Ambulatory Care Ctr 453, Boston, MA 02114 USA. NR 33 TC 17 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2000 VL 105 IS 7 BP 2424 EP 2430 DI 10.1097/00006534-200006000-00018 PG 7 WC Surgery SC Surgery GA 318HF UT WOS:000087277300018 PM 10845297 ER PT J AU Huber, MG Balon, R Labbate, LA Brandt-Youtz, S Hammer, JH Mufti, R AF Huber, MG Balon, R Labbate, LA Brandt-Youtz, S Hammer, JH Mufti, R TI A survey of police officers' experience with Tarasoff warnings in two states SO PSYCHIATRIC SERVICES LA English DT Article ID PROTECT; DUTY AB A desk sergeant at each of 48 Michigan police stations and 52 South Carolina police stations was surveyed about: knowledge and experience of Tarasoff warnings. Respondents at 45 stations reported receiving warnings from mental health professionals, with a mean+/-SD of 3.7+/-8.4 warnings a year. Only three respondents were familiar with the Tarasoff ruling. Twenty-four stations had a specific policy on such warnings. Twenty-seven stations would not warn a potential victim. Michigan stations were much more likely than South Carolina stations to have experience with or policies on Tarasoff warnings. Because police apparently have limited experience with Tarasoff warnings, calling them may not be the best way to protect potential victims from patients making threats. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Huber, MG (reprint author), VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. NR 8 TC 7 Z9 7 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD JUN PY 2000 VL 51 IS 6 BP 807 EP 809 DI 10.1176/appi.ps.51.6.807 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 321WN UT WOS:000087477800017 PM 10828115 ER PT J AU Mueller, PR Biswal, S Halpern, EF Kaufman, JA Lee, MJ AF Mueller, PR Biswal, S Halpern, EF Kaufman, JA Lee, MJ TI Interventional radiologic procedures: Patient anxiety, perception of pain, understanding of procedure, and satisfaction with medication - A prospective study SO RADIOLOGY LA English DT Article DE anesthesia; interventional procedures ID DOUBLE-BLIND; SEDATION; ANALGESIA; ANESTHESIA; FENTANYL; SCALES; CARE AB PURPOSE: To prospectively assess patient anxiety, understanding of the procedure being performed, perception of pain level, and satisfaction with medication given for a variety of diagnostic and therapeutic vascular and visceral (nonvascular) interventional procedures. MATERIALS AND METHODS: The authors interviewed 204 patients before and after they underwent an interventional radiologic procedure. Patients responded to a series of questions by using a visual analog scale. Patients were grouped according to (a) their level of experience with the procedure and (b) the type of procedure performed (diagnostic or therapeutic visceral procedure or diagnostic or therapeutic vascular procedure). RESULTS: Patients who had previous experience with a procedure, whether visceral or vascular, were less anxious, had more understanding, and anticipated less pain than did those who did not have experience with a procedure. Patients who had only local anesthesia for visceral biopsy experienced greater pain than did those who had both local and intravenous anesthesia. Satisfaction scores, however, were similar throughout all groups. CONCLUSION: Patients have a moderate amount of anxiety about interventional procedures and anticipate some discomfort. Most patients have a high level of satisfaction despite the amount of pain they experience during the procedure. Patients experienced with a procedure tend to have a greater understanding of the procedure and less anxiety. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Beaumont Hosp, Dept Radiol, Dublin 9, Ireland. Royal Coll Surg Ireland, Dublin 2, Ireland. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 14 TC 48 Z9 50 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2000 VL 215 IS 3 BP 684 EP 688 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 317VE UT WOS:000087247000011 PM 10831684 ER PT J AU Kruskal, JB Thomas, P Nasser, I Cay, O Kane, RA AF Kruskal, JB Thomas, P Nasser, I Cay, O Kane, RA TI Hepatic colon cancer metastases in mice: Dynamic in vivo correlation with hypoechoic rims visible at US SO RADIOLOGY LA English DT Article DE blood, flow dynamics; colon, neoplasms; liver neoplasms, blood supply; liver neoplasms, secondary; liver neoplasms, US; ultrasound (US), comparative studies ID MALIGNANT LIVER-TUMORS; HISTOLOGIC CORRELATION; MR; HALO; DOXORUBICIN; ENHANCEMENT; DIAGNOSIS; CARCINOMA; LESIONS; RING AB PURPOSE: To use videomicroscopy of tumor-bearing livers of live mice to depict tumors directly to determine the exact nature of rims seen on corresponding ultrasonographic (US) scans. MATERIALS AND METHODS: Seventy-six hepatic colorectal cancer metastases were studied in exteriorized livers of 18 mice by using intravital microscopy, US, and histologic examination of the same tumors. RESULTS: Hypoechoic rims correlated with distended sinusoidal spaces in vivo. These spaces surrounded only locally invasive tumors (mean diameter, 0.85 mm) that had obstructed the supplying terminal portal venules. These spaces, containing adherent leukocytes and tumor cells, gave rise to new tumor vasculature. Results of histologic examination of rims (portal inflammation, congested or compressed sinusoids, cell atrophy) correlated with leukocyte endothelial adherence, occluded sinusoids, and new vessel formation in vivo. CONCLUSION: Unlike results from previous studies, dynamic in vivo observations of peritumoral rims demonstrated distended sinusoidal spaces giving rise to new tumor-penetrating vessels. These sinusoids arose around locally invasive tumors and were associated with more advanced intrahepatic disease. These dynamic observations provide a pathophysiologic explanation for previous histologic correlates of peritumoral rims. C1 Beth Israel Deaconess Med Ctr W, Dept Radiol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr W, Dept Canc Biol, Boston, MA 02215 USA. RP Kruskal, JB (reprint author), Beth Israel Deaconess Med Ctr W, Dept Radiol, 1 Deaconess Rd, Boston, MA 02215 USA. NR 26 TC 11 Z9 11 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2000 VL 215 IS 3 BP 852 EP 857 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 317VE UT WOS:000087247000035 PM 10831710 ER PT J AU Regan, MM Catalano, PJ AF Regan, MM Catalano, PJ TI Regression models and risk estimation for mixed discrete and continuous outcomes in developmental toxicology SO RISK ANALYSIS LA English DT Article DE clustering; cumulative probit model; generalized estimating equations; ordinal outcome; risk assessment ID FETAL WEIGHT; CONTINUOUS RESPONSES; ESTIMATING EQUATIONS; MISSING VALUES; TOXICITY; MALFORMATION; EXPOSURE; BINARY AB Multivariate dose-response models have recently been proposed for developmental toxicity data to simultaneously model malformation incidence (a binary outcome), and reductions in fetal weight (a continuous outcome). In this and other applications, the binary outcome often represents a dichotomization of another outcome or a composite of outcomes, which facilitates analysis. For example, in Segment II developmental toxicology studies, multiple malformation types (i.e., external, visceral, skeletal) are evaluated on each fetus; malformation status may also be ordinally measured (e.g., normal, signs of variation, full malformation). A model is proposed is for fetal weight and multiple malformation variables measured on an ordinal scale, where the correlations between the outcomes and between the offspring within a litter are taken into account. Fully specifying the joint distribution of outcomes within a litter is avoided by specifying only the distribution of the multivariate outcome for each fetus and using generalized estimating equation methodology to account for correlations due to litter clustering. The correlations between the outcomes are required to characterize joint risk to the fetus, and are therefore a focus of inference. Dose-response models and their application to quantitative risk assessment are illustrated using data from a recent developmental toxicology experiment of ethylene oxide in mice. C1 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, Boston, MA 02115 USA. RP Regan, MM (reprint author), Beth Israel Deaconess Med Ctr, Biometr Ctr, E GZ-800,300 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [CA09337]; NIEHS NIH HHS [ES06900] NR 34 TC 11 Z9 11 U1 0 U2 3 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD JUN PY 2000 VL 20 IS 3 BP 363 EP 376 DI 10.1111/0272-4332.203035 PG 14 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 414LL UT WOS:000167668100012 PM 10949415 ER PT J AU Drews, R Samel, A Kadin, ME AF Drews, R Samel, A Kadin, ME TI Lymphomatoid papulosis and anaplastic large cell lymphomas of the skin SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article ID CD30-POSITIVE LYMPHOPROLIFERATIVE DISORDERS; T-CELL; CUTANEOUS PROLIFERATION; MYCOSIS-FUNGOIDES; HODGKINS-DISEASE; LESIONS; THERAPY; EXPRESSION; PROGNOSIS; PHENOTYPE AB It is now generally accepted that primary CD30+ cutaneous lymphomas comprise a clinical and morphologic spectrum in which a clear distinction between lymphomatoid papulosis (LyP) and lymphoma cannot always be made, Management varies from observation in patients who have relatively asymptomatic, spontaneously remitting disease (as in LyP) to multiagent chemotherapy regimens with or without autologous stem cell transplantation in patients whose disease has spread to involve extracutaneous sites other than regional lymph nodes (as in disseminated CD30+ lymphoma), Choosing an appropriate management strategy requires correlation of the patient's clinical history (including symptoms) with physical exam and pathologic findings. The importance of clinicopathologic correlation cannot be overemphasized, because lesions with clinically "benign" behavior may appear "malignant" by pathology, and failure to interpret pathologic findings in accordance with the patient's clinical history and physical exam can result in unnecessary, overly aggressive, and potentially harmful treatments. This review highlights integration of clinical and pathologic features of these primary cutaneous CD30+ lymphoproliferative disorders. Copyright (C) 2000 by W.B. Saunders Company. C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Kadin, ME (reprint author), YA309Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. NR 43 TC 32 Z9 35 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 1085-5629 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD JUN PY 2000 VL 19 IS 2 BP 109 EP 117 DI 10.1016/S1085-5629(00)80007-3 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA 330HV UT WOS:000087957500007 PM 10892712 ER PT J AU Harari, D Minaker, KL AF Harari, D Minaker, KL TI Megacolon in patients with chronic spinal cord injury SO SPINAL CORD LA English DT Review DE spinal cord injury; megacolon; constipation; abdominal radiograph; age; laxatives ID CHRONIC GASTROINTESTINAL PROBLEMS; COLONIC TRANSIT; CONSTIPATION; BOWEL; TIME; AGE; COMPLICATIONS; INDIVIDUALS; MANAGEMENT; DISABILITY AB Purpose: To investigate the clinical and functional correlates of megacolon in individuals with chronic spinal cold injury (SCI). Patients and methods: This is a cross-sectional study of 128 patients consecutively admitted to a SCl in-patient service in a US Veterans Administration Medical Centre (mean age 57 +/- 15 years, mean years since injury 20 +/- 13, 97% male) who underwent plain abdominal radiography for study purposes. Participants were characterised by radiological findings. 'Megacolon' was defined as colonic dilatation of >6 cms in one or more colonic segment(s). Clinical, functional, and medication data were abstracted from the medical and nursing records. Individual interviews were conducted with study participants regarding bowel-related symptoms and treatment over the previous 1-month period. Results: Seventy-three per cent of subjects (n = 94) had megacolon, and 52% of these individuals had associated radiological constipation. Subjects with megacolon were compared with those without colonic dilatation (n = 34). Factors significantly associated with megacolon were older age, longer duration of injury, symptom of abdominal distension, radiological constipation, urinary outlet surgery, laxative use at least once weekly, use of anticholinergic drugs, and use of calcium-containing antacids. These factors were simultaneously included in a multiple logistic regression model. Independent correlates of megacolon were more than 10 years elapsed since acute injury, age over 50 years, and use of 34 laxative doses per month. Conclusion: Megacolon is a highly prevalent disorder in individuals with chronic spinal cord injury. Out findings suggest that the presence of megacolon may be predicted in older individuals, and in those who are more than 10 years post-SCI. We also found that clinical constipation was frequently present in individuals with megacolon, despite their significantly greater use of laxatives. Sponsorship: This work was supported by a grant from the Claude D Pepper Geriatric Research and Training Center from the National Institute of Ageing-AG08812-05, and a grant from the Education and Training Foundation of the Paralyzed Veterans Association in the USA. Dr Harari is currently recipient of a grant from Action Research (UK). C1 St Thomas Hosp, Guys Kings St Thomas Sch Med, Dept Hlth Care Elderly, London SE1, England. Massachusetts Gen Hosp, Beacon Hill Senior Hlth, Geriatr Med Unit, Boston, MA 02114 USA. RP Harari, D (reprint author), St Thomas Hosp, Guys Kings St Thomas Sch Med, Dept Hlth Care Elderly, Lambeth Palace Rd, London SE1, England. FU NIAAA NIH HHS [AAG08812-05] NR 49 TC 13 Z9 18 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD JUN PY 2000 VL 38 IS 6 BP 331 EP 339 DI 10.1038/sj.sc.3101010 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 334QJ UT WOS:000088196900001 PM 10889561 ER PT J AU Finklestein, SP AF Finklestein, SP TI Delayed systemic administration of PACAP38 is neuroprotective in transient middle cerebral artery occlusion in the rat - Comment SO STROKE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Finklestein, SP (reprint author), Massachusetts Gen Hosp, Dept Neurol, 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 0039-2499 J9 STROKE JI Stroke PD JUN PY 2000 VL 31 IS 6 BP 1417 EP 1417 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 319HJ UT WOS:000087335200037 ER PT J AU Marino, M McCluskey, RT AF Marino, M McCluskey, RT TI Megalin-mediated transcytosis of thyroglobulin by thyroid cells is a calmodulin-dependent process SO THYROID LA English DT Article ID POLYMERIC IMMUNOGLOBULIN RECEPTOR; EPITHELIAL-CELLS; NONDIPLOID KARYOTYPE; FOLLICLE CELLS; GENE FAMILY; MDCK CELLS; PROTEIN; GP330; ENDOCYTOSIS; TRANSPORT AB Megalin, a multiligand receptor expressed on the apical surface of thyroid cells, mediates transepithelial transport (transcytosis) of thyroglobulin (Tg) across thyrocytes, resulting in diversion of Tg from the lysosomal pathway and reduction of the extent of thyroid hormone release from internalized Tg molecules. The calcium regulatory protein calmodulin facilitates some forms of transcytosis. Here we investigated the role of calmodulin in megalin-mediated transcytosis of Tg by thyroid cells. For this purpose, we studied the effect of calmodulin antagonists on Tg transcytosis by Fisher rat thyroid cells (FRTL5), an established, differentiated thyroid cell line. FRTL-5 cells were cultured on permeable filters in the upper chamber of dual chambered devices, with megalin expression exclusively on the upper surface. Unlabeled Tg was added to the upper chamber at 37 degrees C, and transcytosed Tg was detected by enzyme-linked immunosorbent assay (ELISA) in fluids collected 1 hour later from the lower chamber. To study the role of calmodulin in Tg transcytosis, cells were preincubated with one of two calmodulin antagonists, either trifluoperazine or W7. Both antagonists markedly reduced transcytosis of Tg by FRTL-5 cells. These inhibitory effects and those of a monoclonal antimegalin antibody were not additive, indicating that calmodulin acts on the megalin-mediated pathway. Furthermore, trifluoperazine increased the extent of triiodothyronine (T-3) release from exogenously added Tg by FRTL-5 cells, indicating that Tg transported in the calmodulin-dependent, megalin-mediated pathway, bypasses the lysosomal pathway. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Res Lab, Charlestown, MA USA. RP Marino, M (reprint author), Univ Pisa, Dept Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. FU PHS HHS [46301] NR 43 TC 16 Z9 17 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD JUN PY 2000 VL 10 IS 6 BP 461 EP 469 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 330PE UT WOS:000087969800003 PM 10907988 ER PT J AU Bondre, S Lewandrowski, KU Hasirci, V Cattaneo, MV Gresser, JD Wise, DL Tomford, WW Trantolo, DJ AF Bondre, S Lewandrowski, KU Hasirci, V Cattaneo, MV Gresser, JD Wise, DL Tomford, WW Trantolo, DJ TI Biodegradable foam coating of cortical allografts SO TISSUE ENGINEERING LA English DT Article ID DEMINERALIZED BONE; POLY(PROPYLENE; OSTEOINDUCTION; DEGRADATION; SCAFFOLD; CEMENT AB Clinical outcomes of bone allograft procedures may be improved by modifying the surface of the graft with an osteoconductive biopolymeric coating. In this comparative in vitro study, we evaluated the dimensional stability, mechanical strength, hydrophilicity, and water uptake of biodegradable foams of poly(propylene fumarate) (PPF) and poly(d,l-lactic-co glycolic acid) (PLGA) when applied as surface coatings to cortical bone. Cortical bone samples were divided into four groups: Type I, untreated bone; Type II, laser-perforated bone; Type III, partially demineralized bone; and Type IV, laser-perforated and partially demineralized bone. Results show that PPF wets easily, achieving 12.5% wt/wt in 30 min. Compressive tests on the PPF foam material showed that the compressive strength was 6.8 MPa prior to in vitro incubation but then gradually reduced to 1.9 MPa at 8 weeks. Push-out and pull-off strength tests showed that initially both PPF and PLGA foam coatings had comparable adherence strengths to the cortical bone samples (100-150 N). When additional geometrical surface alteration by perforation and demineralization of the bony substrate was employed, in vitro adherence of the PPF foam coating was further increased to 120 N, demonstrating a statistically significant improvement of push-out strength throughout the entire 8-week observation period (p < 0.0002 for all four data points). The pore geometry of PPF-foam coatings changed little over the 2-month evaluation period. In comparison, PLGA foam coating around the cortical bone samples rapidly lost structure with a decrease of 67% in strength seen after 1-week in vitro incubation. These new types of bone allografts may be particularly useful where the use of other replacement materials is not feasible or practical. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [AR 45062]; NIDCR NIH HHS [1 R43 DE 12290-01A1] NR 33 TC 9 Z9 9 U1 2 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JUN PY 2000 VL 6 IS 3 BP 217 EP 227 DI 10.1089/10763270050044399 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA 329BQ UT WOS:000087886600002 PM 10941216 ER PT J AU Sharifi, S Dzik, WH Sadrzadeh, SMH AF Sharifi, S Dzik, WH Sadrzadeh, SMH TI Human plasma and Tirilazad mesylate protect stored human erythrocytes against the oxidative damage of gamma-irradiation SO TRANSFUSION MEDICINE LA English DT Article DE erythrocytes; gamma-irradiation; oxidative damage; plasma; Tirilazad mesylate ID LIPID-PEROXIDATION; ANTIOXIDANTS; RADICALS; INHIBITORS; LAZAROIDS; INJURY; FLUIDS AB Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious condition that under certain circumstances can be lethal in immunosuppressed patients. The risk of TA-GVHD can be reduced in this population by gamma irradiation (gamma Rad) of blood components. gamma Rad results in production of reactive oxygen species which can damage red blood cells (RBC). Tirilazad mesylate (TM) is a member of the 21-aminosteroids (Lazaroids) family and is a powerful antioxidant. We investigated the ability of TM and human plasma (which contain powerful antioxidants) to protect stored human RBC against the oxidative damage of gamma Rad. Fresh intact packed RBC obtained from the normal donors, with and without autologous plasma or TM (0.05 mg mL(-1) RBC), were exposed to gamma Rad (50 Gy) and stored for 28 days at 4 degrees C. Oxidative damage was assessed by osmotic fragility at 65 mm NaCl concentration (expressed by percentage haemolysis in 65 mm NaCl solution) and lipid peroxidation (measured by thiobarbituric acid reactive substances, TBARS). Our results showed that storage and irradiation of untreated intact RBC increased the osmotic fragility at 65 mm NaCl concentration (65.8 +/- 1.3 vs. 51.20 +/- 0.87% haemolysis; irradiated vs. controls, respectively; P = 0.002) and lipid peroxidation (TBARS = 4.47 +/- 0.12 vs. 3.45 +/- 0.09 mu m L-1 RBC; irradiated vs. controls, respectively; P = 0.001). TM protected the intact RBC against radiation-induced haemolysis (35.8 +/- 5.0 vs. 65.8 +/- 1.3% haemolysis; treated vs. untreated irradiated RBC, respectively; P = 0.02) and lipid peroxidation (TBARS = 2.91 +/- 0.2 vs. 4.47 +/- 0.12 mu m L-1 RBC; treated vs. untreated irradiated RBC, respectively; P = 0.005). Addition of autologous plasma to packed RBC significantly reduced the extent of radiation-induced haemolysis by more than six-fold (12.45 +/- 0.26 vs. 65.8 +/- 2.2% haemolysis; irradiated RBC with versus without plasma, respectively; P = 0.0001). In conclusion, these results show that irradiation and storage of blood damages RBC via oxidative processes and addition of autologous plasma and/or TM protects RBC against such damage and possibly enhances their storage and survival. C1 Univ Arizona, Coll Med, Dept Pathol, Tucson, AZ 85724 USA. Tufts Univ, New England Med Ctr, Dept Pathol, Boston, MA 02111 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Sadrzadeh, SMH (reprint author), Univ Arizona, Coll Med, Dept Pathol, POB 245043,1501 N Campbell Ave, Tucson, AZ 85724 USA. NR 25 TC 25 Z9 27 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0958-7578 J9 TRANSFUSION MED JI Transfus. Med. PD JUN PY 2000 VL 10 IS 2 BP 125 EP 130 PG 6 WC Hematology SC Hematology GA 317LC UT WOS:000087226000007 PM 10849383 ER PT J AU Bush, G Luu, P Posner, MI AF Bush, G Luu, P Posner, MI TI Cognitive and emotional influences in anterior cingulate cortex SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID CEREBRAL BLOOD-FLOW; ERROR-DETECTION; COUNTING STROOP; HUMAN BRAIN; POSITIVE AFFECT; FUNCTIONAL MRI; NEURAL SYSTEM; ATTENTION; INTERFERENCE; PERFORMANCE AB Anterior cingulate cortex (ACC) is a part of the brain's limbic system. Classically, this region has been related to affect on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain's error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed. and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation or mental and emotional activity. C1 Cornell Univ, Weill Med Coll, Dept Psychiat, Sackler Inst, New York, NY 10021 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. Elect Geodesics, Eugene, OR 97403 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Bush, G (reprint author), Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RI Frank, David/E-8213-2012; Li, Chong/F-4265-2015 NR 66 TC 3176 Z9 3255 U1 64 U2 527 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD JUN PY 2000 VL 4 IS 6 BP 215 EP 222 DI 10.1016/S1364-6613(00)01483-2 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 321VZ UT WOS:000087476500003 ER PT J AU Benacerraf, BR AF Benacerraf, BR TI Should sonographic screening for fetal Down syndrome be applied to low risk women? SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Editorial Material ID CHOROID-PLEXUS CYSTS; 2ND-TRIMESTER FETUSES; SCORING INDEX; MATERNAL AGE; PRENATAL DETECTION; GENETIC SONOGRAM; 2ND TRIMESTER; TRISOMY-21; IDENTIFICATION; PYELECTASIS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA USA. RP Benacerraf, BR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 32 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD JUN PY 2000 VL 15 IS 6 BP 451 EP 455 DI 10.1046/j.1469-0705.2000.00141.x PG 5 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 359LW UT WOS:000089613200001 PM 11005109 ER PT J AU Shipp, TD Bromley, B Lieberman, E Benacerraf, BR AF Shipp, TD Bromley, B Lieberman, E Benacerraf, BR TI The frequency of the detection of fetal echogenic intracardiac foci with respect to maternal race SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE echogenic intracardiac foci; maternal race; Asian ID DOWN-SYNDROME; TRISOMY-21; FETUSES; HEART; AGE AB Objective To determine if there is a racial difference in the frequency of identification of echogenic intracardiac loci (EIF) seen sonographically in the hearts of second-trimester fetuses. Methods Over a 2-month period (June 1998-August 1998), all fetuses scanned between 15 and 20 completed weeks' gestation were evaluated prospectively for the presence or absence of EIF. Pregnancies specifically referred for the presence of EIF were excluded. The sonographer performing the scan indicated maternal race as Asian, black, white, or (if maternal race was not clear) unknown. Maternal race, gestational age, and the presence or absence of EIF were prospectively documented. Follow-up of those fetuses with EIF was obtained from the referring physicians' offices. The groups were compared with respect to maternal race and presence or absence of EIF. Results There Ih,ere 46, 34, 400, and nine fetuses of the Asian, black, white, and unknown mothers, respectively The mean gestational age +/- 1 SD at examination was 18.2 +/- 1.6, 17.5 +/- 1.4, 17.7 +/- 1.5, and 17.8 +/- 1.1 weeks, for the Asian, black, white, and unknown mothers, respectively The incidence of sonographically detected EIF was 30.4, 5.9, 10.5 and 11.1% for the Asian, black, white. and unknown mothers, respectively, P = 0.001. In a multivariate logistic regression model, Asian mothers had an odds ratio of 3.8 (95% CI, 1.8, 7.60 for having a fetus identified as having EIF, as compared with white mothers. Conclusions The Asian patient is more likely than patients of other races to have a fetus with identified EIF. The counseling implications for Asian mothers undergoing midtrimester sonography when EIF is identified should be tempered, due to the increased frequency of EIF as a normal finding in the Asian population. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA USA. RP Shipp, TD (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. NR 9 TC 50 Z9 52 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD JUN PY 2000 VL 15 IS 6 BP 460 EP 462 DI 10.1046/j.1469-0705.2000.00138.x PG 3 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 359LW UT WOS:000089613200003 PM 11005111 ER PT J AU Zhou, AT Assil, I Abou-Samra, AB AF Zhou, AT Assil, I Abou-Samra, AB TI Role of asparagine-linked oligosaccharides in the function of the rat PTH/PTHrP receptor SO BIOCHEMISTRY LA English DT Article ID HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; EXPRESSION CLONING; PROTEIN-RECEPTOR; GLYCOSYLATION; CALCITONIN; BINDING; CORTICOTROPIN; GLYCOPROTEIN; MUTAGENESIS AB The receptor for parathyroid hormone (PTH) and PTH-related peptide (PHrP) is a G-protein-coupled receptor with four potential sites for N-linked glycosylation. The contribution of the oligosaccharide moieties to cell surface expression, ligand binding, and signal transduction was investigated. Site-directed mutagenesis of the rat PTH/PTHrP receptor cDNA was performed at single or combination of the four potential glycosylation sites to determine the effect of the putative carbohydrate chains on the activities of the receptor. The results revealed that all four potential N-glycosylation sites in the PTH/PTHrP receptor are glycosylated. Receptors missing a single or multiple glycosylation consensus but with at least one intact glycosylation site expressed sufficiently and functioned normally. In contrast, the nonglycosylated receptor, in which all four glycosylation sites were mutated, is deficient in these functions. These data indicate important roles for N-linked glycosylation in PTH/PTHrP receptor functions. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abou-Samra, AB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 32 Fruit St,BUL-327, Boston, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [P01DK11794-31] NR 23 TC 27 Z9 27 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 30 PY 2000 VL 39 IS 21 BP 6514 EP 6520 DI 10.1021/bi992706f PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 319YP UT WOS:000087374100029 PM 10828967 ER PT J AU Huncharek, M Kupelnick, B Geschwind, JF Caubet, JF AF Huncharek, M Kupelnick, B Geschwind, JF Caubet, JF TI Prognostic significance of p53 mutations in non-small cell lung cancer: a meta-analysis of 829 cases from eight published studies SO CANCER LETTERS LA English DT Article DE meta-analysis; prognosis; clinical epidemiology; survival ID POOR-PROGNOSIS; GENE-MUTATIONS; K-RAS; SURVIVAL; PROTEIN; ACCUMULATION; IRRADIATION; CARCINOMA; INDICATOR AB Mutation of the p53 tumor suppressor gene is considered a possible marker of poor survival among patients with non-small cell lung cancer (NSCLC). This report presents the results of a meta-analysis of the available data addressing this issue. Using previously described methods, a protocol was developed for a meta-analysis examining the prognostic significance of p53 mutations in NSCLC, Two-year survival data derived from 829 patients in eight published studies were analyzed using a general variance-based method employing confidence intervals described by Greenland (Epidemiol. Rev. 9 (1986) 1-30). The outcome of interest was a summary relative risk (RRs) reflecting the risk of death at 2 years associated with p53 mutation positive versus p53 negative disease. Prior to calculation of a RRs, an analysis for homogeneity (Q) showed Q to equal 22.3, With 8 degrees of freedom, this yielded a P value corresponding to P < 0.005, This indicated substantial heterogeneity across studies in terms of their estimate of effect, Although a RRs of 1.52 was found when all eight studies were combined (favoring a negative prognostic role for p53 mutation), the validity of this estimate is questionable since the existing heterogeneity indicates that factors other than p53 mutation account for the variability in RRs across studies. Sensitivity analyses suggested that selection bias might represent an important source of variability in that p53 mutations may differ in their effects on biological behavior of NSCL tumors. Other possible confounders include smoking history, race. geographic location of study and socioeconomic status. The available data do not support a clear role for p53 mutation as a prognostic marker in NSCLC. It appears that multiple sources of bias may contribute to spurious association of p53 mutation status and survival. Future analyses must control for possible confounders in order to determine whether certain p53 mutations are truly associated with poor clinical outcome. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 St Michaels Hosp, Marshfield Clin Canc Ctr, Div Radiat Oncol, Stevens Point, WI 54481 USA. Metaanal Res Grp, Stevens Point, WI USA. Johns Hopkins Hosp, Dept Intervent Radiol, Baltimore, MD 21287 USA. Johns Hopkins Hosp, Dept Surg, Baltimore, MD 21287 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Huncharek, M (reprint author), St Michaels Hosp, Marshfield Clin Canc Ctr, Div Radiat Oncol, 900 Illinois Ave, Stevens Point, WI 54481 USA. NR 23 TC 30 Z9 32 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 29 PY 2000 VL 153 IS 1-2 BP 219 EP 226 DI 10.1016/S0304-3835(00)00381-5 PG 8 WC Oncology SC Oncology GA 396WV UT WOS:000166661600030 PM 10779652 ER PT J AU Augood, SJ Hollingsworth, ZR Standaert, DG Emson, PC Penney, JB AF Augood, SJ Hollingsworth, ZR Standaert, DG Emson, PC Penney, JB TI Localization of dopaminergic markers in the human subthalamic nucleus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE basal ganglia; Parkinson's disease; brain; dopamine receptor ID HUMAN CEREBRAL-CORTEX; RAT-BRAIN; BASAL GANGLIA; MESSENGER-RNA; SUBSTANTIA-NIGRA; RECEPTOR-BINDING; D-1 RECEPTOR; IMMUNOCYTOCHEMICAL LOCALIZATION; TYROSINE-HYDROXYLASE; PARKINSONS-DISEASE AB The potential role for dopamine in the subthalamic nucleus was investigated in human postmortem tissue sections by examining; (1) immunostaining for tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis; (2) binding of [H-3]-SCH23390 (D1-like), [H-3]-YM-09151-2 (D-2-like), and [H-3] mazindol (dopamine uptake); and (3) expression of dopamine D1 and D2 receptor mRNAs. Immunostaining for tyrosine hydroxylase was visualized in Bouin's-fixed tissue by using a monoclonal antibody and the avidin-biotin-complex method. The cellular localization of the dopamine D1 and D2 receptor mRNAs was visualized by using a cocktail of human specific oligonucleotide probes radiolabeled with S-35-dATP. Inspection of immunostained tissue revealed a fine network of tyrosine hydroxylase-immunostained fibers traversing the nucleus; no immunopositive cells were detected. Examination of emulsion-coated tissue sections processed for D1 and D2 receptor mRNA revealed, as expected, an abundance of D1 and D2 mRNA-positive cells in the caudate nucleus and putamen. However, no D1 or D2 receptor mRNA-expressing cells were detected in the subthalamic nucleus. Further, semiquantitative analysis of D1-like, D2-like and dopamine uptake ligand binding similarly revealed an enrichment of specific binding in the caudate nucleus and putamen but not within the subthalamic nucleus. However, a weak, albeit specific, signal for [H-3]-SCH23390 and [H-3]-mazindol was detected in the subthalamic nucleus, suggesting that the human subthalamic nucleus may receive a weak dopaminergic input. As weak D1-like binding is detected in the subthalamic nucleus, and subthalamic neurons do not express dopamine D1 or D2 receptor mRNAs, together these data suggest that the effects of dopaminergic agents on the activity of human subthalamic neurons may be indirect and mediated via interaction with dopamine D1-like receptors. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Babraham Inst, Dept Neurobiol, Cambridge CB2 4AT, England. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Augood, SJ (reprint author), Massachusetts Gen Hosp, Warren 408,32 Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS31579] NR 47 TC 29 Z9 30 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 MAY 29 PY 2000 VL 421 IS 2 BP 247 EP 255 PG 9 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 309TW UT WOS:000086786200009 PM 10813785 ER PT J AU Aebi, S Gelber, S Castiglione-Gertsch, M Gelber, RD Collins, J Thurlimann, B Rudenstam, CM Lindtner, J Crivellari, D Cortes-Funes, H Simoncini, E Werner, ID Coates, AS Goldhirsch, A AF Aebi, S Gelber, S Castiglione-Gertsch, M Gelber, RD Collins, J Thurlimann, B Rudenstam, CM Lindtner, J Crivellari, D Cortes-Funes, H Simoncini, E Werner, ID Coates, AS Goldhirsch, A CA IBCSG TI Is chemotherapy alone adequate for young women with oestrogen-receptor-positive breast cancer? SO LANCET LA English DT Article ID AGE; CARCINOMA; PROGNOSIS; SURVIVAL; TUMOR AB Background The prognosis of breast cancer in very young women is generally considered to be unfavourable. Therefore, the outcome of adjuvant therapy was analysed in a population of young (<35 years) premenopausal patients treated in four randomised controlled trials. Methods Between 1978 and 1993 the International Breast Cancer Study Group (IBCSG) treated 3700 premenopausal and perimenopausal patients with various timing and duration of adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF with or without low-dose prednisone and oophorectomy). 314 of these women were less than 35 years old at randomisation. Findings Relapse and death occurred earlier and more often in younger (<35 years) than in older (greater than or equal to 35) patients with a 10-year disease-free survival of 35% (SE 3) versus 47% (1) (hazard ratio 1.41 [95% CI 1.22-1.62], p<0.001) and overall survival of 49% (3) versus 62% (1) (1.50 [1.28-1.77], p<0.001). Younger patients with oestrogen-receptor positive tumours had a significantly worse disease-free survival than younger patients with oestrogen-receptor negative tumours. By contrast, among older patients the disease-free survival was similar irrespective of oestrogen-receptor status. Interpretation Young premenopausal breast cancer patients treated with adjuvant CMF chemotherapy had higher risk of relapse and death than older premenopausal patients, especially if their tumours expressed oestrogen receptors. The endocrine effects of chemotherapy alone are insufficient for the younger age group and these patients should strongly consider additional endocrine therapies (tamoxifen or ovarian ablation) if their tumours express oestrogen receptors. C1 Univ Hosp Inselspital, Bern, Switzerland. Frontier Sci & Technol Res Fdn Inc, Brookline, MA USA. IBCSG Coordinating Ctr, Bern, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Anticanc Council Victoria, Melbourne, Vic, Australia. Kantonsspital, CH-9007 St Gallen, Switzerland. SU Molndals Hosp, Dept Surg, Molndal, Sweden. Inst Oncol, Ljubljana, Slovenia. Ctr Riferimento Oncol, I-33081 Aviano, Italy. Hosp Seguridad Social 12 Octubre, Madrid, Spain. Spedali Civil Brescia, I-25125 Brescia, Italy. Fdn Beretta, Brescia, Italy. Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. Univ Sydney, Australian Canc Soc, Sydney, NSW 2006, Australia. European Inst Oncol, Milan, Italy. RP Univ Bern, Inselspital, Inst Med Oncol, CH-3010 Bern, Switzerland. EM aebi@insel.ch RI Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 FU NCI NIH HHS [CA75362] NR 32 TC 178 Z9 185 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAY 27 PY 2000 VL 355 IS 9218 BP 1869 EP 1874 DI 10.1016/S0140-6736(00)02292-3 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 318VZ UT WOS:000087306500014 PM 10866443 ER PT J AU Douek, DC Vescio, RA Betts, MR Brenchley, JM Hill, BJ Zhang, L Berenson, JR Collins, RH Koup, RA AF Douek, DC Vescio, RA Betts, MR Brenchley, JM Hill, BJ Zhang, L Berenson, JR Collins, RH Koup, RA TI Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution SO LANCET LA English DT Article ID BONE-MARROW TRANSPLANTATION; INTENSIVE CHEMOTHERAPY; IMMUNE RECONSTITUTION; AGE; EXPANSION; MEMORY; THYMOPOIESIS; REGENERATION; PROGENITORS; GENERATION AB Background The potential benefits of haematopoietic stem-cell transplantation are tempered by the depletion of T-cells accompanying this procedure. We used a new technique which quantifies the excisional DNA products of T-cell-receptor (TCR) gene rearrangement to measure thymic output directly in patients with multiple myeloma, and thus assessed the contribution of the thymus to immune recovery after transplantation. Methods We studied 40 patients, 34-66 years of age, who had been randomly assigned myeloablative chemotherapy and autologous peripheral-blood haematopoietic stem-cell transplantation with unmanipulated grafts or grafts enriched for CD34 stem cells. CD4 and CD8 T-cell counts were measured, thymic output was estimated serially until 2 years after transplantation, and percentages of naive T-cells were measured. Findings The production of substantial numbers of new naive T cells by the thymus could be detected by 100 days post-transplant; there was a significant inverse relation between age and recovery of new T cells. In the CD34-unselected group, numbers of TCR-rearrangement excision circles returned to baseline after 2 years, whereas in the CD34-selected group, numbers at 2 years were significantly higher than both baseline numbers (p=0.004), and 2-year numbers in the unselected group (p=0.046). Increased thymic output correlated with, and was predictive of, increased naive T-cell numbers and broader T-cell-receptor repertoires. Interpretation Our results provide evidence that the adult thymus contributes more substantially to immune reconstitution after haematopoietic stem-cell transplantation than was previously thought, and therefore could be a target for therapeutic intervention. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Dept Hematol Oncol, Los Angeles, CA USA. RP Douek, DC (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. FU NIAID NIH HHS [AI44758] NR 31 TC 359 Z9 371 U1 0 U2 5 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 27 PY 2000 VL 355 IS 9218 BP 1875 EP 1881 DI 10.1016/S0140-6736(00)02293-5 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 318VZ UT WOS:000087306500015 PM 10866444 ER PT J AU Gojo, S Cooper, DKC Iacomini, J LeGuern, C AF Gojo, S Cooper, DKC Iacomini, J LeGuern, C TI Gene therapy and transplantation SO TRANSPLANTATION LA English DT Editorial Material ID ADENOVIRUS-MEDIATED TRANSFER; DONOR-SPECIFIC UNRESPONSIVENESS; PROLONGS ALLOGRAFT SURVIVAL; BONE-MARROW CELLS; CLASS-I ANTIGEN; FAS LIGAND; IMMUNE-RESPONSES; LIVER ALLOGRAFTS; RETROVIRAL TRANSDUCTION; VIRAL INTERLEUKIN-10 AB Advances in molecular biology and in techniques of gene transfer have resulted in the development of practical approaches to human gene therapy. Many applications are of relevance to manipulation of the immune system and have potential in organ and cell transplantation. For example, gene therapy approaches may facilitate the induction of immunological tolerance to a donor organ or protect it locally against the host's immune response. Based on a comprehensive review of the world literature, examples of current research efforts in both allogeneic and xenogeneic transplantation are presented and discussed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP LeGuern, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [2RO1 AI31046, R01 AI3619-02, AI44268-01] NR 55 TC 21 Z9 24 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 MAY 27 PY 2000 VL 69 IS 10 BP 1995 EP 1999 DI 10.1097/00007890-200005270-00001 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 320VN UT WOS:000087421700001 PM 10852583 ER PT J AU Caumon, AS Vitale, N Gensse, M Galas, MC Casanova, JE Bader, MF AF Caumon, AS Vitale, N Gensse, M Galas, MC Casanova, JE Bader, MF TI Identification of a plasma membrane-associated guanine nucleotide exchange factor for ARF6 in chromaffin cells - Possible role in the regulated exocytotic pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLATION FACTOR; PLECKSTRIN-HOMOLOGY DOMAINS; GTP-BINDING-PROTEIN; PHOSPHOLIPASE-D; SEC7 DOMAIN; PC12 CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; CATECHOLAMINE RELEASE; POSSIBLE INVOLVEMENT; ACTIN CYTOSKELETON AB ADP-ribosylation factors (ARFs) constitute a family of structurally related proteins that forms a subset of the Ras superfamily of regulatory GTP-binding proteins. Like other GTPases, activation of ARFs is facilitated by specific guanine nucleotide exchange factors (GEFs), In chromaffin cells, ARF6 is associated with the membrane of secretory granules. Stimulation of intact cells or direct elevation of cytosolic calcium in permeabilized cells triggers the rapid translocation of ARF6 to the plasma membrane and the concomitant activation of phospholipase D (PLD) in the plasma membrane. Both calcium-evoked PLD activation and catecholamine secretion in permeabilized cells are strongly inhibited by a synthetic peptide corresponding to the N-terminal domain of ARF6, suggesting that the ARF6-dependent PLD activation near the exocytotic sites represents a key event in the exocytotic reaction in chromaffin cells. In the present study, we demonstrate the occurrence of a brefeldin A-insensitive ARF6-GEF activity in the plasma membrane and in the cytosol of chromaffin cells, Furthermore, reverse transcriptase-polymerase chain reaction and immunoreplica analysis indicate that ARNO, a member of the brefeldin A-insensitive ARF-GEF family, is expressed and predominantly localized in the cytosol and in the plasma membrane of chromaffin cells. Using permeabilized chromaffin cells, we found that the introduction of anti-ARNO antibodies into the cytosol inhibits, in a dose-dependent manner, both PLD activation and catecholamine secretion in calcium-stimulated cells. Furthermore, co-expression in PC12 cells of a catalytically inactive ARNO mutant with human growth hormone as a marker of secretory granules in transfected cells resulted in a 50% inhibition of growth hormone secretion evoked by depolarization with high K+. The possibility that the plasma membrane-associated ARNO participates in the exocytotic pathway by activating ARF6 and downstream PLD is discussed. C1 INSERM, Biol Commun Cellulaire U338, F-67084 Strasbourg, France. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. RP Bader, MF (reprint author), INSERM, Biol Commun Cellulaire U338, 5 Rue Blaise Pascal, F-67084 Strasbourg, France. RI Vitale, nicolas/G-5967-2014; Dietz-Bader, Marie-France/O-2098-2016 OI Vitale, nicolas/0000-0002-4752-4907; NR 60 TC 51 Z9 53 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 MAY 26 PY 2000 VL 275 IS 21 BP 15637 EP 15644 DI 10.1074/jbc.M908347199 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 318NX UT WOS:000087291400007 PM 10748097 ER PT J AU Reddy, VB Kounga, K Mariano, F Lerner, EA AF Reddy, VB Kounga, K Mariano, F Lerner, EA TI Chrysoptin is a potent glycoprotein IIb/IIIa fibrinogen receptor antagonist present in salivary gland extracts of the deerfly SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLATELET-AGGREGATION; PROTEIN; PEPTIDE; INHIBITOR; BINDING; APYRASE; FLY AB Salivary gland lysates of the deerfly (genus Chrysops) contain chrysoptin, an inhibitor of ADP-induced platelet aggregation, which presumably assists the fly in obtaining a blood meal. Chrysoptin has now been isolated, and its cDNA has been cloned and expressed. Chrysoptin was purified to homogeneity using anion exchange and hydrophobic interaction chromatography and found to be a protein with a molecular mass of 65 kDa as determined by gel electrophoresis, N-terminal amino acid sequencing allowed for the synthesis of degenerate oligonucleotides that led to cloning, from salivary gland specific mRNA, of the cDNA encoding this platelet inhibitor. No RGD sites are present in the predicted sequence. A search of GenBank(TM) did not reveal significant sequence homology between chrysoptin and other proteins. The molecular mass predicted from the cDNA was 59 kDa. Predicted glycosylation and phosphorylation sites may account for this difference in molecular mass, as recombinant chrysoptin expressed in Sf21 cells had a molecular mass of 65 kDa, matching that of the natural protein. Chrysoptin functions by inhibiting the binding of fibrinogen to the fibrinogen/glycoprotein IIb/IIIa receptor on platelets with an IC50 of 95 pmol. These results reveal that insect salivary glands are a source of fibrinogen receptor antagonists. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Dermatol, Charlestown, MA 02129 USA. RP Lerner, EA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, E Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIAMS NIH HHS [R01 AR44510, R01 AR42005] NR 25 TC 24 Z9 26 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 26 PY 2000 VL 275 IS 21 BP 15861 EP 15867 DI 10.1074/jbc.275.21.15861 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 318NX UT WOS:000087291400036 PM 10821849 ER PT J AU Tcherepanova, I Puigserver, P Norris, JD Spiegelman, BM McDonnell, DP AF Tcherepanova, I Puigserver, P Norris, JD Spiegelman, BM McDonnell, DP TI Modulation of estrogen receptor-alpha transcriptional activity by the coactivator PGC-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEROID-HORMONE RECEPTORS; NUCLEAR RECEPTOR; POSTMENOPAUSAL WOMEN; PEPTIDE ANTAGONISTS; PROMOTER-CONTEXT; BINDING DOMAIN; BREAST-CANCER; ER-BETA; ACTIVATION; IDENTIFICATION AB A transcriptional coactivator of the peroxisome proliferator-activated receptor-gamma (PPAR gamma), PPAR gamma-coactivator-1(PGC-1) interacts in a constitutive manner with the hinge domain of PPAR gamma and enhances its transcriptional activity. In this study we demonstrate that PGC-1 is a coactivator of estrogen receptor-alpha (ER alpha)-dependent transcriptional activity. However the mechanism by which PGC-1 interacts with ER alpha is different from that of PPAR gamma. Specifically, it was determined that the carboxyl terminus of PGC-1 interacts in a ligand-independent manner with the ER alpha hinge domain. In addition, an LXXLL motif within the amino terminus of PGC-1 was shown to interact in an agonist-dependent manner with the AF2 domain within the carboxyl terminus of ER alpha. The ability of PGC-1 to associate with and potentiate the transcriptional activity of an ER alpha-AF2 mutant that is unable to interact with the p160 class of coactivators suggests that this coactivator may have a unique role in estrogen signaling. It is concluded from these studies that PGC-1 is a bona fide ER alpha coactivator, which may serve as a convergence point between PPAR gamma and ER alpha signaling. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP McDonnell, DP (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813, Durham, NC 27710 USA. FU NIDDK NIH HHS [DK48807] NR 46 TC 148 Z9 153 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 26 PY 2000 VL 275 IS 21 BP 16302 EP 16308 DI 10.1074/jbc.M001364200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 318NX UT WOS:000087291400094 PM 10748020 ER PT J AU Wu, XH Ranganathan, V Weisman, DS Heine, WF Ciccone, DN O'Neill, TB Crick, KE Pierce, KA Lane, WS Rathbum, G Livingston, DM Weaver, DT AF Wu, XH Ranganathan, V Weisman, DS Heine, WF Ciccone, DN O'Neill, TB Crick, KE Pierce, KA Lane, WS Rathbum, G Livingston, DM Weaver, DT TI ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response SO NATURE LA English DT Article ID ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; BRCA1; COMPLEX; KINASE; REPAIR; HETEROZYGOTES; ASSOCIATION; LINKAGE; RAD51 AB Nijmegen breakage syndrome (NBS) is characterized by extreme radiation sensitivity, chromosomal instability and cancer(1). The phenotypes are similar to those of ataxia telangiectasia mutated (ATM) disease, where there is a deficiency in a protein kinase that is activated by DNA damage, indicating that the Nbs and Atm proteins may participate in common pathways. Here we report that Nbs is specifically phosphorylated in response to g-radiation, ultraviolet light and exposure to hydroxyurea. Phosphorylation of Nbs mediated by g-radiation, but not that induced by hydroxyurea or ultraviolet light, was markedly reduced in ATM cells. In vivo, Nbs was phosphorylated on many serine residues, of which S343, S397 and S615 were phosphorylated by Atm in vitro. At least two of these sites were underphosphorylated in ATM cells. Inactivation of these serines by mutation partially abrogated Atm-dependent phosphorylation. Reconstituting NBS cells with a mutant form of Nbs that cannot be phosphorylated at selected, ATM-dependent serine residues led to a specific reduction in clonogenic survival after g-radiation. Thus, phosphorylation of Nbs by Atm is critical for certain responses of human cells to DNA damage. C1 Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Harvard Microchem Facil, Cambridge, MA 02138 USA. RP Livingston, DM (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 28 TC 339 Z9 346 U1 1 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 25 PY 2000 VL 405 IS 6785 BP 477 EP 482 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 317DX UT WOS:000087212000053 PM 10839545 ER PT J AU Canto, JG Every, NR Magid, DJ Rogers, WJ Malmgren, JA Frederick, PD French, WJ Tiefenbrunn, AJ Misra, VK Kiefe, CI Barron, HV AF Canto, JG Every, NR Magid, DJ Rogers, WJ Malmgren, JA Frederick, PD French, WJ Tiefenbrunn, AJ Misra, VK Kiefe, CI Barron, HV CA Natl Registry Myocardial Infarctio TI The volume of primary angioplasty procedures and survival after acute myocardial infarction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NATIONAL REGISTRY; ASSOCIATION; HOSPITALS; CARDIOLOGY; MORTALITY; OUTCOMES; PROJECT; CARE AB Background: There is an inverse relation between mortality from cardiovascular causes and the number of elective cardiac procedures (coronary angioplasty, stenting, or coronary bypass surgery) performed by individual practitioners or hospitals. However, it is not known whether patients with acute myocardial infarction fare better at centers where more patients undergo primary angioplasty or thrombolytic therapy than at centers with lower volumes. Methods: We analyzed data from the National Registry of Myocardial Infarction to determine the relation between the number of patients receiving reperfusion therapy (primary angioplasty or thrombolytic therapy) and subsequent in-hospital mortality. A total of 450 hospitals were divided into quartiles according to the volume of primary angioplasty. Multiple logistic-regression models were used to determine whether the volume of primary angioplasty procedures was an independent predictor of in-hospital mortality among patients undergoing this procedure. Similar analyses were performed for patients receiving thrombolytic therapy at 516 hospitals. Results: In-hospital mortality was 28 percent lower among patients who underwent primary angioplasty at hospitals with the highest volume than among those who underwent angioplasty at hospitals with the lowest volume (adjusted relative risk, 0.72; 95 percent confidence interval, 0.60 to 0.87; P<0.001). This lower rate, which represented 2.0 fewer deaths per 100 patients treated, was independent of the total volume of patients with myocardial infarction at each hospital, year of admission, and use or nonuse of adjunctive pharmacologic therapies. There was no significant relation between the volume of thrombolytic interventions and in-hospital mortality among patients who received thrombolytic therapy (7.0 percent for patients in the highest-volume hospitals vs. 6.9 percent for those in the lowest-volume hospitals, P=0.36). Conclusions: Among hospitals in the United States that have full interventional capabilities, a higher volume of angioplasty procedures is associated with a lower mortality rate among patients undergoing primary angioplasty, but there is no association between volume and mortality for thrombolytic therapy. (N Engl J Med 2000;342:1573-80.) (C) 2000, Massachusetts Medical Society. C1 Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL 35294 USA. Univ Washington, Cardiovasc Outcomes Res Ctr, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Colorado Permanente Med Grp, Clin Res Unit, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Emergency Med, Denver, CO USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Genentech Inc, S San Francisco, CA 94080 USA. RP Canto, JG (reprint author), Univ Alabama, Dept Med, Div Cardiovasc Dis, 363 BDB,1808 7th Ave S, Birmingham, AL 35294 USA. FU AHRQ HHS [HS08843] NR 15 TC 227 Z9 240 U1 2 U2 5 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 MAY 25 PY 2000 VL 342 IS 21 BP 1573 EP 1580 DI 10.1056/NEJM200005253422106 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 316XJ UT WOS:000087193100006 PM 10824077 ER PT J AU Adrogue, HJ Madias, NE AF Adrogue, HJ Madias, NE TI Primary care: Hyponatremia. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CENTRAL PONTINE MYELINOLYSIS; SEVERE SYMPTOMATIC HYPONATREMIA; ANTI-DIURETIC HORMONE; RAPID CORRECTION; INAPPROPRIATE SECRETION; MAGNETIC-RESONANCE; NEUROLOGIC COMPLICATIONS; ORGANIC OSMOLYTES; MANAGEMENT; VASOPRESSIN C1 New England Med Ctr, Div Nephrol, Boston, MA 02111 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Renal Sect, Houston, TX USA. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. New England Med Ctr, Tupper Res Inst, Boston, MA 02111 USA. RP Madias, NE (reprint author), New England Med Ctr, Div Nephrol, Box 172,750 Washington St, Boston, MA 02111 USA. NR 60 TC 674 Z9 713 U1 1 U2 32 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 MAY 25 PY 2000 VL 342 IS 21 BP 1581 EP 1589 DI 10.1056/NEJM200005253422107 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 316XJ UT WOS:000087193100007 PM 10824078 ER PT J AU Martino, TA Petric, M Weingartl, H Bergelson, JM Opavsky, MA Richardson, CD Modlin, JF Finberg, RW Kain, KC Willis, N Gauntt, CJ Liu, PP AF Martino, TA Petric, M Weingartl, H Bergelson, JM Opavsky, MA Richardson, CD Modlin, JF Finberg, RW Kain, KC Willis, N Gauntt, CJ Liu, PP TI The coxsackie-adenovirus receptor (CAR) is used by reference strains and clinical isolates representing all six serotypes of coxsackievirus group B and by swine vesicular disease virus SO VIROLOGY LA English DT Article DE enterovirus; coxsackievirus B; swine vesicular disease virus; coxsackievirus adenovirus receptor (CAR); decay accelerating factor (DAF; CD55) ID DECAY-ACCELERATING FACTOR; HAMSTER OVARY CELLS; VIRAL MYOCARDITIS; FACTOR CD55; HELA-CELLS; SUBGROUP-A; INFECTION; ENTEROVIRUSES; EXPRESSION; ATTACHMENT AB Group a coxsackieviruses are etiologically linked to many human diseases, and cell surface receptors are postulated to play an important role in mediating their pathogenesis. The coxsackievirus adenovirus receptor (CAR) has been shown to function as a receptor for selected strains of coxsackievirus group B (CVB) serotypes 3, 4, and 5 and is postulated to serve as a receptor for all six serotypes. In this study, we demonstrate that CAR can serve as a receptor for laboratory reference strains and clinical isolates of all six CVB serotypes. infection of CHO cells expressing human CAR results in a 1000-fold increase in CVB progeny virus titer compared to mock transfected cells. CAR was shown to be a functional receptor for swine vesicular disease virus (SVDV), as CHO-CAR cells but not CHO mock transfected controls were susceptible to SVDV infection, produced progeny SVDV, and developed cytopathic effects. Moreover, SVDV infection could be specifically blocked by monoclonal antibody to CAR (RmcB). SVDV infection of HeLa cells was also inhibited by an anti-CD55 MAb, suggesting that this virus, like some CVB, may interact with CD55 (decay accelerating factor) in addition to CAR. Finally, pretreatment of CVB or SVDV with soluble CAR effectively blocks virus infection of HeLa cell monolayers. (C) 2000 Academic Press. C1 Univ Toronto, Heart & Stroke Richard Lewar Ctr Excellence, Toronto Gen Hosp, Toronto, ON M5G 2C4, Canada. Hosp Sick Children, Virol Lab, Dept Pediat Lab Med, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet & Microbiol, Toronto, ON, Canada. Univ Toronto, Dept Med, Toronto, ON, Canada. Natl Ctr Foreign Anim Dis, Winnipeg, MB R3E 3M4, Canada. Childrens Hosp, Div Immunol & Infect Dis, Philadelphia, PA 19104 USA. Amgen Res Inst, Toronto, ON M5G 2C1, Canada. Dartmouth Med Sch, Lebanon, NH 03756 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78284 USA. RP Liu, PP (reprint author), Univ Toronto, Heart & Stroke Richard Lewar Ctr Excellence, Toronto Gen Hosp, 200 Elizabeth St,EC12-324, Toronto, ON M5G 2C4, Canada. RI Finberg, Robert/E-3323-2010 NR 36 TC 83 Z9 93 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 25 PY 2000 VL 271 IS 1 BP 99 EP 108 DI 10.1006/viro.2000.0324 PG 10 WC Virology SC Virology GA 317XM UT WOS:000087252300012 PM 10814575 ER PT J AU Murray, DR Prabhu, SD Chandrasekar, B AF Murray, DR Prabhu, SD Chandrasekar, B TI Chronic beta-adrenergic stimulation induces myocardial proinflammatory cytokine expression SO CIRCULATION LA English DT Article DE isoproterenol; tumor necrosis factor-alpha; interleukins; sympathetic nervous system; myocardium ID TUMOR-NECROSIS-FACTOR; CARDIAC MYOCYTES; DISEASE; HEART AB Background-The sympathetic nervous system and proinflammatory cytokines are believed to play key roles in the pathophysiology of congestive heart failure. To evaluate a possible relationship between these neurohormonal systems, we studied the effects of chronic beta-adrenergic stimulation on the myocardial and systemic elaboration of tumor necrosis factor (TNF)-alpha, interleukin (LL)-1 beta, and IL-6. Methods and Results-Male rats received either L-isoproterenol (2.4 mg . kg(-1) . d(-1), n=8) or saline (n=7) via miniosmotic pumps for 7 days. Myocardial cytokine expression was analyzed by both Northern and Western blotting and localized in the tissue using immunohistochemistry. ELISA was performed to measure circulating levels of cytokines. In myocardium from control animals, neither TNF-alpha nor IL-1 beta were detected, whereas IL-6 was present at very low levels. Isoproterenol led to a significant (P<0.01) increase in mRNA and protein expression of all 3 cytokines. Immunohistochemistry did not detect immunoreactivity for either cytokine in myocardium from controls; however, all 3 cytokines were readily detected (P<0.05) throughout the myocardium, localized to resident cells and vessels, in animals treated with isoproterenol, Neither treatment group had detectable levels of cytokines in the serum. Conclusions-Chronic beta-adrenergic stimulation induces myocardial, but not systemic, elaboration of TNF-alpha, IL-1 beta, and IL-6. C1 Univ Texas, Hlth Sci Ctr, Dept Med Cardiol, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, Audie Murphy Div, San Antonio, TX USA. Univ Louisville, Louisville VA Med Ctr, Louisville, KY 40292 USA. RP Murray, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Prabhu, Sumanth/D-5223-2009 NR 13 TC 150 Z9 168 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 23 PY 2000 VL 101 IS 20 BP 2338 EP 2341 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 316EY UT WOS:000087155700003 PM 10821806 ER PT J AU Tang, W Gunn, TM McLaughlin, DF Barsh, GS Schlossman, SF Duke-Cohan, JS AF Tang, W Gunn, TM McLaughlin, DF Barsh, GS Schlossman, SF Duke-Cohan, JS TI Secreted and membrane attractin result from alternative splicing of the human ATRN gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MESSENGER-RNA; TRANSCRIPTIONAL REGULATION; T-LYMPHOCYTES; IKAROS GENE; DPPT-L; PROMOTER; ACTIVATION; PROTEINS; RECEPTOR; OBESITY AB Attractin, initially identified as a soluble human plasma protein with dipeptidyl peptidase IV activity that is expressed and released by activated T lymphocytes, also has been identified as the product of the murine mahogany gene with connections to control of pigmentation and energy metabolism. The mahogany product, however, is a transmembrane protein, raising the possibility of a human membrane attractin in addition to the secreted form. The genomic structure of human attractin reveals that soluble attractin arises from transcription of 25 sequential exons on human chromosome 20p13, where the 3' terminal exon contains sequence from a long interspersed nuclear element-1 (LINE-1) retrotransposon element that includes a stop codon and a polyadenylation signal. The mRNA isoform for membrane attractin splices over the LINE-1 exon and includes five exons encoding transmembrane and cytoplasmic domains with organization and coding potential almost identical to that of the mouse gene. The relative abundance of soluble and transmembrane isoforms measured by reverse transcription-PCR is differentially regulated in lymphoid tissues. Because activation of peripheral blood leukocytes with phytohemagglutinin induces strong expression of cell surface attractin followed by release of soluble attractin, these results suggest that a genomic event unique to mammals, LINE-1 insertion, has provided an evolutionary mechanism for regulating cell interactions during an inflammatory reaction. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Genet, Beckman Ctr B271A, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pediat, Beckman Ctr B271A, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Beckman Ctr B271A, Stanford, CA 94305 USA. RP Duke-Cohan, JS (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Gunn, Teresa/0000-0003-2688-6420; Duke-Cohan, Jonathan/0000-0002-9478-9609 FU NIAID NIH HHS [AI-12069] NR 34 TC 51 Z9 56 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 MAY 23 PY 2000 VL 97 IS 11 BP 6025 EP 6030 DI 10.1073/pnas.110139897 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319BG UT WOS:000087318700064 PM 10811918 ER PT J AU Nanthakumar, NN Fusunyan, RD Sanderson, I Walker, WA AF Nanthakumar, NN Fusunyan, RD Sanderson, I Walker, WA TI Inflammation in the developing human intestine: A possible pathophysiologic contribution to necrotizing enterocolitis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RAT SMALL-INTESTINE; EPITHELIAL-CELLS; REGULATED EXPRESSION; LIPOPOLYSACCHARIDE; RESPONSIVENESS; PATHOGENESIS; CHEMOKINES; CULTURE AB Necrotizing enterocolitis (NEC), a major cause of morbidity and mortality in premature infants, occurs after the introduction of oral feedings in conjunction with initial bacterial colonization of the gut and is hypothesized to be due to an immature (inappropriate) enterocyte response to bacterial stimuli. To test this hypothesis, we compared the enterocyte IL-8 response to inflammatory stimuli [lipopolysaccharide (LPS) and IL-1 beta] in immature vs. mature human small intestine. Initial in vitro studies comparing confluent Caco-2 cells, a model for mature human enterocytes, with a primary human fetal intestinal cell line (H4 cells) demonstrated that after inflammatory stimulation fetal cells secreted more IL-8 (LPS, 8-fold; IL-1 beta, 20-fold) than Caco-2 cells. IL-8 mRNA activity in fetal compared to Caco-2 cells was proportionately increased by the same magnitude with both stimuli. To validate the in vitro observations, small intestinal organ cultures from fetuses vs. older children were exposed to LPS and IL-1 beta. Again in human organ cultures from fetuses compared to older children, IL-8 secretion was greater (LPS, 2.5-fold; IL-1 beta, 200-fold) and mRNA activity after stimulation was comparably higher, suggesting that increased transcription of the IL-8 gene may account for the excessive response. Using immunohistochemical staining to identify the cellular source of IL-8, activity was noted predominantly in villous and crypt epithelium but also in a few immunoresponsive lymphoid cells, The observation that immature human enterocytes react with excessive pro-inflammatory cytokine production after inflammatory stimulation may help in part explain why prematures exposed to initial colonizing bacteria develop necrotizing enterocolitis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dev Gastroenterol Lab, Dept Pediat,Combined Program Pediat Gastroenterol, Charlestown, MA 02129 USA. Univ London, St Bartholomews Hosp, Acad Dept Paediat Gastroenterol & Nutr, London, England. RP Walker, WA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dev Gastroenterol Lab, Dept Pediat,Combined Program Pediat Gastroenterol, 149 13th St, Charlestown, MA 02129 USA. FU NICHD NIH HHS [R01 HD-31852, R01 HD031852, R37 HD-12437, R37 HD012437]; NIDDK NIH HHS [P30 DK040561, P01 DK-33506, P01 DK033506] NR 43 TC 243 Z9 253 U1 2 U2 18 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 MAY 23 PY 2000 VL 97 IS 11 BP 6043 EP 6048 DI 10.1073/pnas.97.11.6043 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319BG UT WOS:000087318700067 PM 10823949 ER PT J AU Preston, RA Materson, BJ Reda, DJ Williams, DW AF Preston, RA Materson, BJ Reda, DJ Williams, DW TI Placebo-associated blood pressure response and adverse effects in the treatment of hypertension - Observations from a Department of Veterans Affairs Cooperative Study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID 6 ANTIHYPERTENSIVE AGENTS; SINGLE-DRUG THERAPY; CLINICAL-TRIALS; DEVELOPING-COUNTRIES; TRANSMISSION; BENEFITS; ETHICS; MANIA AB Background: The use of placebo in clinical trials has been vigorously debated. Placebo control may be useful in disease states, such as stage 1 and stage 2 hypertension as defined by the Sixth Report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC VI), in which response rates for placebo are high or close to response rates for effective therapies, or when established interventions have significant adverse effects. Objective: To compare rates for the control of blood pressure and adverse effects of placebo vs active treatment in patients with stage 1 and stage 2 hypertension. Methods: This study is a randomized controlled trial evaluating the blood pressure response and adverse effects of placebo vs 6 active treatments administered in 15 Veterans Affairs hypertension centers. The 1292 subjects of the Veterans Affairs Cooperative Study receiving single-drug therapy for hypertension were randomly allocated to receive treatment with 1 of 6 active drugs (n=1105) or placebo (n=187). Treatment success was defined as maintaining a diastolic blood pressure of less than 95 mm Hg for at least 1 year. We compared treatment success rates for the control of blood pressure and adverse effects of placebo vs active treatment. Using the Kaplan-Meier method, we also compared rates of discontinuation from placebo vs active drug treatment over time as a result of adverse drug effects and blood pressure exceeding safety limits. Results: At the end of the titration phase, 58 patients who were treated with placebo (31%) achieved a goal diastolic blood pressure lower than 90 mm Hg and 57 (30%) achieved success at 1 year. Older white patients who received placebo had a success rate of 38% vs 23% to 27% for the other age-race subgroups. The rates of discontinuation as a result of adverse drug effects were 13% for patients receiving placebo vs 12% for patients receiving active treatment (P=.40). The rates of discontinuation for blood pressure being too high were 14% for patients receiving placebo vs 7% for patients receiving active treatment(P=.01). Conclusions: Placebo control provides an important benchmark for both efficacy and adverse effects. It continues to have an appropriate place in certain therapeutic trials, particularly those involving the treatment of stage 1 and stage 2 hypertension. C1 Univ Miami, Sch Med, Div Clin Pharmacol, Miami, FL USA. Univ Miami, Sch Med, Dept Med, Miami, FL USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program, Hines, IL 60141 USA. RP Preston, RA (reprint author), Univ Miami, Sch Med, Div Clin Pharmacol & Pharmacokinet, 1500 NW 12th Ave,15th Floor,W Tower, Miami, FL 33136 USA. NR 40 TC 53 Z9 53 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 22 PY 2000 VL 160 IS 10 BP 1449 EP 1454 DI 10.1001/archinte.160.10.1449 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 315PJ UT WOS:000087121900007 PM 10826457 ER PT J AU Luthi-Carter, R Strand, A Peters, NL Solano, SM Hollingsworth, ZR Menon, AS Frey, AS Spektor, BS Penney, EB Schilling, G Ross, CA Borchelt, DR Tapscott, SJ Young, AB Cha, JHJ Olson, JM AF Luthi-Carter, R Strand, A Peters, NL Solano, SM Hollingsworth, ZR Menon, AS Frey, AS Spektor, BS Penney, EB Schilling, G Ross, CA Borchelt, DR Tapscott, SJ Young, AB Cha, JHJ Olson, JM TI Decreased expression of striatal signaling genes in a mouse model of Huntington's disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID PROTEIN-KINASE-C; EXPANDED CAG REPEAT; MESSENGER-RNA; CYCLIC-AMP; DOPAMINE-RECEPTOR; MUTANT HUNTINGTIN; TRANSGENIC MICE; NEUROTRANSMITTER RECEPTORS; INTRANUCLEAR INCLUSIONS; BRAIN AB To understand gene expression changes mediated by a polyglutamine repeat expansion in the human huntingtin protein, we used oligonucleotide DNA arrays to profile similar to 6000 striatal mRNAs in the R6/2 mouse, a transgenic Huntington's disease (HD) model. We found diminished levels of mRNAs encoding components of the neurotransmitter, calcium and retinoid signaling pathways at both early and late symptomatic time points (6 and 12 weeks of age). We observed similar changes in gene expression in another HD mouse model (N171-82Q). These results demonstrate that mutant huntingtin directly or indirectly reduces the expression of a distinct set of genes involved in signaling pathways known to be critical to striatal neuron function. C1 Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neuropathol, Baltimore, MD 21205 USA. RP Olson, JM (reprint author), Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA. RI Ross, Christopher/H-8395-2013 FU NINDS NIH HHS [NS10800, NS16375, NS38144] NR 60 TC 501 Z9 510 U1 2 U2 22 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 MAY 22 PY 2000 VL 9 IS 9 BP 1259 EP 1271 DI 10.1093/hmg/9.9.1259 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 319RD UT WOS:000087354800001 PM 10814708 ER PT J AU Hewett, J Gonzalez-Agosti, C Slater, D Ziefer, P Li, S Bergeron, D Jacoby, DJ Ozelius, LJ Ramesh, V Breakefield, XO AF Hewett, J Gonzalez-Agosti, C Slater, D Ziefer, P Li, S Bergeron, D Jacoby, DJ Ozelius, LJ Ramesh, V Breakefield, XO TI Mutant torsinA, responsible for early-onset torsion dystonia, forms membrane inclusions in cultured neural cells SO HUMAN MOLECULAR GENETICS LA English DT Article ID ENDOPLASMIC-RETICULUM; HUMAN BRAIN; NEURODEGENERATIVE DISEASES; NEUROTRANSMITTER RELEASE; ASHKENAZI JEWS; GENE DYT1; PROTEIN; MECHANISM; EXPRESSION; TRANSPORT AB Early-onset torsion dystonia is a hereditary movement disorder thought to be caused by decreased release of dopamine into the basal ganglia, without apparent neuronal degeneration. Recent cloning of the gene responsible for this disease, TOR1 A (DYT1), identified the encoded protein, torsinA, as a member of the AAA+ superfamily of chaperone proteins and revealed highest levels of expression in dopaminergic neurons in human brain. Most cases of this disease are caused by a deletion of one glutamic acid residue in the C-terminal region of the protein. Antibodies generated against torsinA revealed expression of a predominant immunoreactive protein species similar to the predicted size of 37.8 kDa in neural, glial and fibroblastic lines by western blot analysis. This protein is N-glycosylated with high mannose content and not, apparently, phosphorylated. Overexpression of torsinA in mouse neural CAD cells followed by immunocytochemistry, revealed a dramatically different pattern of distribution for wild-type and mutant forms of the protein. The wild-type protein was found throughout the cytoplasm and neurites with a high degree of co-localization with the endoplasmic reticulum (ER) marker, protein disulfide isomerase. In contrast, the mutant protein accumulated in multiple, large inclusions in the cytoplasm around the nucleus. These inclusions were composed of membrane whorls, apparently derived from the ER. If disrupted processing of the mutant protein leads to its accumulation in multilayer membranous structures in vivo, these may interfere with membrane trafficking in neurons. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Dept Mol Neurogenet, 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS28384, NS37409, NS38372] NR 47 TC 134 Z9 137 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 22 PY 2000 VL 9 IS 9 BP 1403 EP 1413 DI 10.1093/hmg/9.9.1403 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 319RD UT WOS:000087354800015 PM 10814722 ER PT J AU Rizzuto, C Sodroski, J AF Rizzuto, C Sodroski, J TI Fine definition of a conserved CCR5-binding region on the human immunodeficiency virus type 1 glycoprotein 120 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID GP120 ENVELOPE GLYCOPROTEIN; T-LYMPHOTROPIC RETROVIRUS; SOLUBLE RECEPTOR-BINDING; HIV-1 CORECEPTOR USAGE; CHEMOKINE RECEPTORS; CD4-INDEPENDENT INFECTION; CONFORMATIONAL-CHANGES; V3 DOMAIN; INFLUENZA HEMAGGLUTININ; EXTRACELLULAR DOMAINS AB A previous study implicated a conserved surface of the human immunodeficiency virus (HIV-1) gp120 exterior envelope glycoprotein in binding the CCR5 viral coreceptor (Rizzuto C, Wyatt R, Hernandez-Ramos N, Sun Y, Kwong PD, Hendrickson WA, and Sodroski J: Science 1998;280:1949-1953). Additional mutagenesis indicates that important residues in this region for CCR5 binding are Ile-420, Lys-421, Gln-422, Pro-438, and Gly-441, These highly conserved residues are located on two strands that connect the gp120 bridging sheet and outer domain, suggesting a mechanism whereby interdomain conformational shifts induced by CD4 binding could facilitate CCR5 binding. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Jimmy Fund Bldg,Rm 824,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI40895, AI41851] NR 87 TC 139 Z9 141 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 20 PY 2000 VL 16 IS 8 BP 741 EP 749 DI 10.1089/088922200308747 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 315AF UT WOS:000087089900006 PM 10826481 ER PT J AU Padilla, PI Wada, A Yahiro, K Kimura, M Niidome, T Aoyagi, H Kumatori, A Anami, M Hayashi, T Fujisawa, J Saito, H Moss, J Hirayama, T AF Padilla, PI Wada, A Yahiro, K Kimura, M Niidome, T Aoyagi, H Kumatori, A Anami, M Hayashi, T Fujisawa, J Saito, H Moss, J Hirayama, T TI Morphologic differentiation of HL-60 cells is associated with appearance of RPTP beta and induction of Helicobacter pylori VacA sensitivity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROMYELOCYTIC LEUKEMIA-CELLS; PROTEIN-TYROSINE-PHOSPHATASE; VACUOLATING CYTOTOXIN; TERMINAL DIFFERENTIATION; RETINOIC ACID; HL60 CELLS; LINE; EXPRESSION; TOXIN; PROLIFERATION AB Phorbol la-myristate Is-acetate (PMA) induces differentiation of human leukemic HL-60 cells into cells with macrophage-like characteristics and enhances the susceptibility of HL-60 cells to the Helicobacter pylori VacA toxin (de Bernard, M., Moschioni., M., Papini, E., Telford, J. L., Rappuoli, Il., and Montecucco, C. (1998) FEES Lett. 436, 218-222). We examined the mechanism by which HL-60 cells acquire sensitivity to VacA, in particular, looking for expression of RPTP beta, a VacA-binding protein postulated to be the VacA receptor (Yahiro, K., Niidome, T., Kimura, M., Hatakeyama, T., Aoyagi, H., Kurazono, H., Imagawa, K., Wads, A, Moss, J., and Hirayama, T. (1999) J. BioL Chem, 274, 36693-36699). PMA induced expression of RPTP beta mRNA and protein as determined by RNase protection assay and indirect immunofluorescence studies, respectively. Vitamin D-3 and interferon-gamma, which stimulate differentiation of HL-60 cells into monocyte-like cells, also induced VacA sensitivity and expression of RPTP beta mRNA, whereas 1.2% Me,SO and retinoic acid, which stimulated the maturation of HL-60 into granulocyte-like cells, did not. RPTP beta antisense oligonucleotide inhibited induction of VacA sensitivity and expression of RPTP beta. Double immunostaining studies also indicated that newly expressed RPTP beta colocalized with VacA in PMA-treated HL-60 cells. In agreement with these data, BHK-21 cells, which are insensitive to VacA, when transfected with the RPTP beta cDNA, acquired VacA sensitivity. All data are consistent with the conclusion that acquisition of VacA sensitivity by PMA-treated HL-60 cells results from induction of RPTP beta, a protein that functions as the VacA receptor. C1 Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 852, Japan. Nagasaki Univ, Inst Trop Med, Dept Biochem, Nagasaki 8528523, Japan. Nagasaki Univ, Fac Engn, Dept Appl Chem, Nagasaki 8528523, Japan. Nagasaki Univ Hosp, Dept Pathol, Nagasaki 8528501, Japan. Kansai Med Univ, Dept Microbiol, Moriguchi, Osaka 5708506, Japan. Dana Farber Canc Inst, Dept Tumor Immunol, Boston, MA 02115 USA. NHKBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 852, Japan. RI Niidome, Takuro/F-1508-2010 OI Niidome, Takuro/0000-0002-8070-8708 NR 37 TC 50 Z9 55 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2000 VL 275 IS 20 BP 15200 EP 15206 DI 10.1074/jbc.275.20.15200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315TD UT WOS:000087128300059 PM 10809755 ER PT J AU Kharbanda, S Kumar, V Dhar, S Pandey, P Chen, C Majumder, P Yuan, ZM Whang, Y Strauss, W Pandita, TK Weaver, D Kufe, D AF Kharbanda, S Kumar, V Dhar, S Pandey, P Chen, C Majumder, P Yuan, ZM Whang, Y Strauss, W Pandita, TK Weaver, D Kufe, D TI Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase SO CURRENT BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; HUMAN PAPILLOMAVIRUS TYPE-16; ATAXIA-TELANGIECTASIA; DNA-DAMAGE; TUMOR-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; SACCHAROMYCES-CEREVISIAE; IONIZING-RADIATION; APOPTOTIC RESPONSE; CELLULAR-RESPONSE AB Background: Telomeres consist of repetitive (TTAGGG) DNA sequences that are maintained by the multisubunit telomerase ribonucleoprotein. Telomerase consists of an RNA, which serves as template for the sequence tracts, and a catalytic subunit that functions in reverse transcription of the RNA template. Cloning and characterization of the human catalytic subunit of telomerase (hTERT) has supported a role in cell transformation. How telomerase activity is regulated, however, is largely unknown. Results: We show here that hTERT associates directly with the c-Abl protein tyrosine kinase. We also found that c-Abl phosphorylates hTERT and inhibits hTERT activity. Moreover, our findings demonstrate that exposure of cells to ionizing radiation induces tyrosine phosphorylation of hTERT by a c-Abl-dependent mechanism. The functional significance of the c-Abl-hTERT interaction is supported by the demonstration that cells deficient in c-Abl show telomere lengthening. Conclusions: The ubiquitously expressed c-Abl tyrosine kinase is activated by DNA double-strand breaks. Our finding of telomere lengthening in c-Abl-deficient cells and the functional interactions between c-Abl and hTERT support a role for c-Abl in the regulation of telomerase function. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA 02115 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Genet & Microbiol, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. FU NCI NIH HHS [CA29431, CA55241, CA75216] NR 70 TC 103 Z9 107 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 18 PY 2000 VL 10 IS 10 BP 568 EP 575 DI 10.1016/S0960-9822(00)00483-8 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 348HA UT WOS:000088978400014 PM 10837221 ER PT J AU Duggan, A Garcia-Anoveros, J Corey, DP AF Duggan, A Garcia-Anoveros, J Corey, DP TI Insect mechanoreception: What a long, strange TRP it's been SO CURRENT BIOLOGY LA English DT Article ID NONSELECTIVE CATION CHANNEL; MECHANOSENSITIVE CHANNELS; ESCHERICHIA-COLI; HAIR-CELLS; DROSOPHILA; TRANSDUCTION; IDENTIFICATION; CONDUCTANCE; ACTIVATION; MUTATIONS AB Insect bristles are model mechanasensory organs. An ion channel of the TRP superfamily has recently been identified which is required for production of mechanoreceptor currents by insect bristles, and seems likely to represent a new kind of mechanically gated channel. 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 Duggan, A (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 23 TC 11 Z9 15 U1 1 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 18 PY 2000 VL 10 IS 10 BP R384 EP R387 DI 10.1016/S0960-9822(00)00478-4 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 348HA UT WOS:000088978400011 PM 10837217 ER PT J AU Adrogue, HJ Madias, NE AF Adrogue, HJ Madias, NE TI Primary care - Hypernatremia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SYSTEM; VOLUME C1 New England Med Ctr, Div Nephrol, Boston, MA 02111 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Renal Sect, Houston, TX USA. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. New England Med Ctr, Tupper Res Inst, Boston, MA 02111 USA. RP Madias, NE (reprint author), New England Med Ctr, Div Nephrol, Box 172,750 Washington St, Boston, MA 02111 USA. NR 28 TC 305 Z9 338 U1 2 U2 21 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 18 PY 2000 VL 342 IS 20 BP 1493 EP 1499 DI 10.1056/NEJM200005183422006 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 314QT UT WOS:000087068200006 PM 10816188 ER PT J AU Siao, P Zukerberg, LR Cros, D Choi, NC AF Siao, P Zukerberg, LR Cros, D Choi, NC TI A 69-year-old man with myasthenia gravis and a mediastinal mass - Thymoma, predominantly cortical. Myasthenia gravis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACETYLCHOLINE-RECEPTOR ANTIBODY; THYMIC CARCINOMA; THYMECTOMY; SCLEROSIS; NEOPLASMS; DISORDERS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Siao, P (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 49 TC 4 Z9 4 U1 1 U2 1 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 MAY 18 PY 2000 VL 342 IS 20 BP 1508 EP 1514 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 314QT UT WOS:000087068200008 ER PT J AU Marin, MC Kaelin, WG AF Marin, MC Kaelin, WG TI p63 and p73: Old members of a new family SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID TUMOR-SUPPRESSOR P53; HUMAN BLADDER-CANCER; LUNG-CANCER; CELL-LINES; SV40-TRANSFORMED CELLS; P53-RELATED PROTEIN; MUTATIONAL ANALYSIS; EXPRESSION ANALYSIS; VIRAL ONCOPROTEINS; CHROMOSOME 1P36.3 C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Los Angeles, CA USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Marin Vieira, Maria del Carmen/B-8108-2015 OI Marin Vieira, Maria del Carmen/0000-0002-7149-287X NR 85 TC 50 Z9 50 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD MAY 17 PY 2000 VL 1470 IS 3 BP M93 EP M100 DI 10.1016/S0304-419X(00)00010-X PG 8 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 316VD UT WOS:000087188000002 PM 10799748 ER PT J AU Dong, ZM Brown, AA Wagner, DD AF Dong, ZM Brown, AA Wagner, DD TI Prominent role of P-selectin in the development of advanced atherosclerosis in apoE-deficient mice SO CIRCULATION LA English DT Article DE selectins; atherosclerosis; lipoproteins; leukocytes ID CELL-ADHESION MOLECULES; APOLIPOPROTEIN-E; KNOCKOUT MICE; LEUKOCYTE ADHESION; LESIONS; ENDOTHELIUM; HYPERCHOLESTEROLEMIA; MOUSE; LIPOPROTEINS; RECRUITMENT AB Background-Adhesive interactions between leukocytes and endothelial cells are characteristic or the development of atherosclerotic lesions, but the receptors involved remain to be defined. P-selectin is an adhesion receptor expressed on activated endothelial cells or platelets and was shown to be involved in fatty streak formation in LDL receptor-deficient mice on an atherogenic diet. The main purpose of this study is to examine the rule of P-selectin in the spontaneous development of advanced atherosclerosis in apoE-deficient mice. Methods and Results-We intercrossed P-selectin-deficient mice with mice lacking apoE and compared lesion development in apoE-deficient mice with P-selectin (apoE(-/-) P+/+) and without P-selectin (apoE(-/-) P-/-) that were fed normal mouse chow. At 4 months of age, apoE(-/-) P-/- mice had 3.5-fold smaller aortic sinus lesions than apoE(-/-) P+/+ mice. These were limited to fatty streaks in the apoE(-/-) P-/- mice, whereas 70% of apoE(-/-) P+/+ lesions contained smooth muscle cells. Significantly more of the aortic sinus circumference was covered by lesions in the apoE(-/-) P+/+ animals. The P-selectin genotype affected macrophage recruitment, because twice as many mononuclear cells were present in the P-selectin-positive lesions. At 15 months, the lesions progressed to the fibrous plaque stage in both genotypes and spread throughout the aorta, but this process was delayed in apoE(-/-) P-/- mice. In the aortic sinus, the lesions of the apoE(-/-) P-/- mice were 2.6-fold smaller and less calcified. Conclusions-P-selectin appears to be a key adhesion receptor mediating leukocyte recruitment into lesions and promoting advanced atherosclerosis in apoE-deficient mice. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-09869, HL-53756] NR 40 TC 182 Z9 190 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 16 PY 2000 VL 101 IS 19 BP 2290 EP 2295 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 314VK UT WOS:000087078100012 PM 10811597 ER PT J AU Chen, L Chen, MH Larson, MG Evans, J Benjamin, EJ Levy, D AF Chen, L Chen, MH Larson, MG Evans, J Benjamin, EJ Levy, D TI Risk factors for syncope in a community-based sample (The Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HYPERTROPHIC CARDIOMYOPATHY; DIAGNOSING SYNCOPE; SUDDEN-DEATH; MANAGEMENT; FAILURE AB The epidemiology of syncope has not been well described. Prior studies have examined risk factors for syncope in hospital-based or other acute or long-term core settings. To determine risk factors for syncope in a community-based sample, we performed a nested case-control study. We examined reports of syncope in Framingham Heart Study participants who underwent routine clinic visits from 1971 to 1990. For each syncope case (n = 543) 2 controls were matched for age, sex, and examination period. Mean age of subjects was 67 years (range 25 to 95); 59% were women. History of stroke or transient ischemic attack, history of myocardial infarction, high blood pressure, use of antihypertensive medication, use of other cardiac medication, smoking, alcohol intake, body moss index, systolic blood pressure, diastolic blood pressure, heart rate, atrial fibrillation, PR interval prolongation, interventricular block, and diabetes or elevated glucose level were examined as potential predictors. Using conditional logistic regression analysis, the predictors of syncope included a history of stroke or transient ischemic attack (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.62 to 4.04), use of cardiac medication (OR 1.67, 95% CI 1.21 to 2.30), and high blood pressure (OR 1.46, 95% CI 1.14 to 1.88). Lower body mass index was marginally associated with syncope (OR per 4 kg/m(2) decrement 1.10, 95% CI 0.99 to 1.22), as were increased alcohol intake (OR per 5 oz/week 1.11, 95% CI 0.99 to 1.26), and diabetes or on elevated glucose level (OR 1.29, 95% CI 0.96 to 1.75). To our knowledge, this study represents the first community-based study of risk factors for syncope. (C) 2000 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Boston Med Ctr, Div Cardiol & Prevent Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Clin Epidemiol, Boston, MA USA. VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Field Program, Seattle, WA USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [5-R01-NS-17950-16] NR 28 TC 17 Z9 21 U1 0 U2 1 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 MAY 15 PY 2000 VL 85 IS 10 BP 1189 EP 1193 DI 10.1016/S0002-9149(00)00726-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 312LV UT WOS:000086945500006 PM 10801999 ER PT J AU Dukas, L Willett, WC Colditz, GA Fuchs, CS Rosner, B Giovannucci, EL AF Dukas, L Willett, WC Colditz, GA Fuchs, CS Rosner, B Giovannucci, EL TI Prospective study of bowel movement, laxative use, and risk of colorectal cancer among women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cathartics; colorectal neoplasms; constipation; prospective studies ID MELANOSIS-COLI; CONSTIPATION; EPIDEMIOLOGY; POPULATION; SYMPTOMS; PEOPLE AB The authors prospectively examined the association between bower movement frequency, laxative use, and the risk of colorectal cancer in 84,577 women of the Nurses' Health Study living in the United States, 36-61 years of age and free of cancer in 1982, Between 1984 and 1996, 611 incident cases of colorectal cancer were documented. After controlling for age, body mass index, fiber intake, postmenopausal status and hormone use, physical activity and use of laxatives, the relative risks associated with having bowel movements every third day or less, compared with those with bowel movements once daily, were 0.94 (95% confidence interval (CI): 0.69, 1.28) for colorectal cancer, 0.88 (95% CI: 0.62, 1.26) for colon cancer, and 1.18 (95% CI: 0.63, 2.20) for rectal cancer. Compared with women who never used laxatives, the multivariate relative risks associated with weekly to daily laxative use were 1.00 (95% CI: 0.72, 1.40) for colorectal cancer, 1.09 (95% CI: 0.76, 1.57) for colon cancer, and 0.68 (95% CI: 0.29, 1.57) for rectal cancer. These findings do not support an association between infrequent bowel movement, laxative use, and risk of colorectal cancer and indicate that simple questions directed at bowel movement frequency are unlikely to enhance our ability to predict colorectal cancer risk. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Univ Basel, Kantonsspital, Geriatr Clin, CH-4031 Basel, Switzerland. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Giovannucci, EL (reprint author), 665 Huntington Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA40356] NR 45 TC 43 Z9 44 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 15 PY 2000 VL 151 IS 10 BP 958 EP 964 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 313JL UT WOS:000086996500005 PM 10853634 ER PT J AU Biaglow, JE Donahue, J Tuttle, S Held, K Chrestensen, C Mieyal, J AF Biaglow, JE Donahue, J Tuttle, S Held, K Chrestensen, C Mieyal, J TI A method for measuring disulfide reduction by cultured mammalian cells: Relative contributions of glutathione-dependent and glutathione-independent mechanisms SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE A549 lung carcinoma; MCF7 mammary carcinoma; DU145 prostate carcinoma; rodent cells; glucose; Chinese hamster ovary cells with and without the enzyme G6PD ID ALPHA-LIPOIC ACID; THIOLTRANSFERASE GLUTAREDOXIN; HYPERTHERMIC-SENSITIZATION; THIOREDOXIN REDUCTASE; OXIDATIVE STRESS; PROTEIN; THIOLS; RADIATION; SENSITIVITY; APOPTOSIS AB A method is described for measuring bioreduction of hydroxyethyl disulfide (HEDS) or alpha-lipoate by human A549 lung, MCF7 mammary, and DU145 prostate carcinomas as well as rodent tumor cells in vitro. Reduction of HEDS or alpha-lipoate was measured by removing aliquots of the glucose-containing media and measuring the reduced thiol wit DTNB (Ellman's reagent). Addition of DTNB to cells followed by disulfide addition directly measures the formation of newly reduced thiol. A549 cells exhibit the highest capacity to reduce alpha-lipoate, while Q(7) rat hepatoma cells show the highest rate of HEDS reduction. Millimolar quantities of reduced thiol are produced for both substrates. Oxidized dithiothreitol and cystamine were reduced to a lesser degree. DTNB, glutathione disulfide, and cystine were only marginally reduced by the cel cultures. Glucose-6-phosphate deficient CHO cells (E89) do not reduce alpha-lipoate and reduce HEDS at a much slower rate compared to wild-type CHO-K1 cells. Depletion of glutathione prevents the reduction of HEDS. The depletion of glutathione inhibited reduction of alpha-lipoate by 25% and HEDS by 50% in A549 cells, while GSH depletion did not inhibit alpha-lipoate reduction in Q(7) cells but completely blocked HEDS reduction. These data suggest that the relative participation of the thioltransferase (glutaredoxin) and thioredoxin systems in overall cellular disulfide reduction is cell line specific. The effects of various inhibitors of the thiol-disulfide oxidoreductase enzymes (1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), arsenite, and phenylarsine oxide) support this conclusion. (C) 2000 Academic Press. C1 Univ Penn, Sch Med, Dept Biochem, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. RP Biaglow, JE (reprint author), Univ Penn, Sch Med, Dept Biochem, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA63997, CA44982] NR 46 TC 39 Z9 39 U1 0 U2 8 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 MAY 15 PY 2000 VL 281 IS 1 BP 77 EP 86 DI 10.1006/abio.2000.4533 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 318KH UT WOS:000087282700011 PM 10847613 ER PT J AU Kimble, M Kaloupek, D Kaufman, M Deldin, P AF Kimble, M Kaloupek, D Kaufman, M Deldin, P TI Stimulus novelty differentially affects attentional allocation in PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Article DE PTSD; attention; P300; novelty; ERP; orienting ID POSTTRAUMATIC-STRESS-DISORDER; EVENT-RELATED POTENTIALS; TRAUMATIC STRESS; COGNITIVE FUNCTION; P300; MODULATION AB Background: This study investigated attentional allocation in 39 Vietnam combat veterans, 25 with and 14 without posttraumatic stress disorder, assessing P300 amplitudes and latencies during both three-tone and novelty "oddball" tasks. Methods: The three-tone oddball task consisted of three stimuli: frequent tones (85%), rare target tones (75%), and rare distracter tones (75%). The novelty oddball task was identical to the three-tone task except that the rare distracter tones were replaced with nonrepeating novel sounds (75%). Results: Combat veterans with posttraumatic stress disorder showed significant P300 amplitude enhancements at frontal sites in response to distracting stimuli during the novelty but not during the three-tone oddball tasks. There were no amplitude differences in target tones during either task. Conclusions: The data suggest that combat veterans with posttraumatic stress disorder demonstrate P300 responses consistent with a heightened orientation response to novel, distracting stimuli. This finding is consistent both with the clinical presentation of the disorder and with theoretical notions that individuals with posttraumatic stress disorder demonstrate information-processing biases towards vague or potentially threatening stimuli. (C) 2000 Society of Biological Psychiatry. C1 Boston Univ, Sch Med, VA Boston Healthcare Syst, Behav Sci Div,Natl Ctr PTSD, Boston, MA 02118 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Kimble, M (reprint author), Boston VA Med Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. OI Kaloupek, Danny/0000-0002-0795-593X FU NIMH NIH HHS [MH19836-01, MH19836-02] NR 38 TC 51 Z9 51 U1 4 U2 8 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 MAY 15 PY 2000 VL 47 IS 10 BP 880 EP 890 DI 10.1016/S0006-3223(99)00258-9 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 312XA UT WOS:000086968200005 PM 10807961 ER PT J AU Tamagnan, G Baldwin, RM Kula, NS Baldessarini, RJ Innis, RB AF Tamagnan, G Baldwin, RM Kula, NS Baldessarini, RJ Innis, RB TI Cyclopentadienyltricarbonylrheniumbenzazepines: Synthesis and binding affinity SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article; Proceedings Paper CT 5th International Symposium on Technetium in Chemistry and Nuclear Medicine CY SEP 06-09, 1998 CL BRESSANONE, ITALY ID DOPAMINE TRANSPORTER; NONHUMAN-PRIMATES; RECEPTOR; COMPLEXES; RHENIUM; LIGAND; PHARMACOKINETICS AB Analogues of the benzazepine dopamine D-1 receptor antagonist SCH-23390 incorporating the cyclo-pentadienyl-tricarbonyl-rhenium (CPTR) moiety were synthesized and evaluated pharmacologically. The CPTR derivatives retained affinity (0.3-2.9 nM) and D-1 selectivity of the parent compound, supporting their use as neuropharmacological surrogates for Tc-99m-labeled SPECT radiopharmaceuticals. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Yale Univ, Sch Med, VA Connecticut HCS, W Haven, CT 06516 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mailman Res Ctr,McLean Div,Dept Psychiat, Belmont, MA 02478 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mailman Res Ctr,McLean Div,Neurosci Program, Belmont, MA 02478 USA. RP Tamagnan, G (reprint author), Yale Univ, Sch Med, VA Connecticut HCS, 116A2,950 Campbell Ave, W Haven, CT 06516 USA. FU NIMH NIH HHS [MH-47370, MH-30929, MH-34006] NR 21 TC 10 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 15 PY 2000 VL 10 IS 10 BP 1113 EP 1115 DI 10.1016/S0960-894X(00)00185-2 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 317HD UT WOS:000087219200029 PM 10843230 ER PT J AU Wang, KS Frank, DA Ritz, J AF Wang, KS Frank, DA Ritz, J TI Interleukin-2 enhances the response of natural killer cells to interleukin-12 through up-regulation of the interleukin-12 receptor and STAT4 SO BLOOD LA English DT Article ID STIMULATORY FACTOR NKSF; IFN-GAMMA PRODUCTION; T-CELLS; TYROSINE PHOSPHORYLATION; HUMAN-LYMPHOCYTES; INTERFERON-GAMMA; TH2 CELLS; SELECTIVE EXPRESSION; RECOMBINANT IL-12; BETA-CHAIN AB Interleukin (IL)-12 plays a critical role in modulating the activities of natural killer (NK) cells and T lymphocytes, In animal models, IL-12 has potent antitumor effects that are likely mediated by its ability to enhance the cytotoxic activity of NK cells and cytotoxic T lymphocytes, and to induce the production of interferon (IFN)-gamma by NK and T cells. In addition to IL-12, NK cells are responsive to IL-2, and may mediate some of the antitumor effects of IL-2, In this study, we examine the interaction between IL-2 and the signaling events induced by IL-12 in NK cells. We find that IL-2 not only up-regulates the expression of IL-12R beta 1 and IL-12R beta 2, it also plays an important role in up-regulating and maintaining the expression of STAT4, a critical STAT protein involved in IL-12 signaling in NK cells, In contrast to the effects of IL-2 alone, expression of IL-12 receptors and STAT4 are unaffected or decreased by IL-12 or the combination of IL-2 and IL-12. Through expression of high levels of IL-12 receptors and STAT4, IL-2-primed NK cells show enhanced functional responses to IL-12 as measured by IFN-gamma production and the killing of target cells. NK cells from cancer patients who received low-dose IL-2 treatment also exhibited increased expression of IL-12 receptor chains, suggesting that IL-2 may enhance the response to IL-12 in vivo. These findings provide a molecular framework to understand the interaction between IL-2 and IL-12 in NK cells, and suggest strategies for improving the effectiveness of these cytokines in the immunotherapy of cancer, (C) 2000 by The American Society of Hematology. C1 Dana Farber Canc Inst, Ctr Hematol Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Ctr Hematol Oncol, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619] NR 51 TC 99 Z9 102 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2000 VL 95 IS 10 BP 3183 EP 3190 PG 8 WC Hematology SC Hematology GA 312PE UT WOS:000086951000026 PM 10807786 ER PT J AU Kishimoto, J Burgeson, RE Morgan, BA AF Kishimoto, J Burgeson, RE Morgan, BA TI Wnt signaling maintains the hair-inducing activity of the dermal papilla SO GENES & DEVELOPMENT LA English DT Article DE Wnt signaling; epithelial-mesenchymal interactions; dermal papilla; cell purification ID SONIC HEDGEHOG; FOLLICLE DEVELOPMENT; BETA-CATENIN; INDUCTION; MICE; LIMB; DIFFERENTIATION; CONSERVATION; PATHWAY; GROWTH AB The formation of the hair follicle and its cyclical growth, quiescence, and regeneration depend on reciprocal signaling between its epidermal and dermal components. The dermal organizing center, the dermal papilla (DP), regulates development of the epidermal follicle and is dependent on signals from the epidermis for its development and maintenance. GFP specifically expressed in DP cells of a transgenic mouse was used to purify this population and study the signals required to maintain it. We demonstrate that specific Wnts, but not Sonic hedgehog (Shh), maintain anagen-phase gene expression in vitro and hair inductive activity in a skin reconstitution assay. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Morgan, BA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. NR 19 TC 238 Z9 254 U1 0 U2 21 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 MAY 15 PY 2000 VL 14 IS 10 BP 1181 EP 1185 PG 5 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 316YT UT WOS:000087196400002 PM 10817753 ER PT J AU Bergeron, B AF Bergeron, B TI Touch points SO HOSPITAL PRACTICE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD MAY 15 PY 2000 VL 35 IS 5 BP 46A EP 46A PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 316YP UT WOS:000087196100019 ER PT J AU Klein, C Bueler, H Mulligan, RC AF Klein, C Bueler, H Mulligan, RC TI Comparative analysis of genetically modified dendritic cells and tumor cells as therapeutic cancer vaccines SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE tumor immunology; gene therapy; retrovirus; adenovirus; B16F10 ID COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; INDUCE ANTITUMOR IMMUNITY; CYTOTOXIC T-LYMPHOCYTES; IN-VIVO; CD40 LIGATION; GENE-TRANSFER; ANTIGEN; MURINE; POTENT AB We have directly compared the efficacy of two immunotherapeutic strategies for the treatment of cancer: "vaccination" of tumor-bearing mice with genetically modified dendritic cells (DCs), and vaccination with genetically modified tumor cells. Using several different preexisting tumor models that make use of B16F10 melanoma cells expressing a target tumor antigen (human melanoma-associated gene [MAGE]-1), we found that vaccination with bone marrow-derived DCs engineered to express MAGE-1 via adenoviral-mediated gene transfer led to a dramatic decrease in the number of metastases in a lung metastasis model, and led to prolonged survival and some long-term cures in a subcutaneous preexisting tumor model. In contrast, Vaccination with granulocyte/macrophage colony-stimulating factor (GM-CSF)-transduced tumor cells, previously shown to induce potent antitumor immunity in standard tumor challenge assays, led to a decreased therapeutic effect in the metastasis model and no effect in the subcutaneous tumor model. Further engineering of DCs to express either GM-CSF, tumor necrosis factor alpha, or CD40 ligand via retroviral-mediated gene transfer, led to a significantly increased therapeutic effect in the subcutaneous tumor model. The immunological mechanism, as shown for GM-CSF-transduced DCs, involves MAGE-1-specific CD4(+) and CD8(+) T cells. Expression of GM-CSF by DCs led to enhanced cytotoxic T lymphocyte activity, potentially mediated by increased numbers of DCs in draining lymph nodes. Our results suggest that clinical studies involving the vaccination with genetically modified DCs may be warranted. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Genet,Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. RP Mulligan, RC (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Genet,Howard Hughes Med Inst, Enders 861,320 Longwood Ave, Boston, MA 02115 USA. NR 50 TC 125 Z9 130 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 MAY 15 PY 2000 VL 191 IS 10 BP 1699 EP 1708 DI 10.1084/jem.191.10.1699 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 315VR UT WOS:000087134100008 PM 10811863 ER PT J AU Akashi, K Richie, LI Miyamoto, T Carr, WH Weissman, IL AF Akashi, K Richie, LI Miyamoto, T Carr, WH Weissman, IL TI B lymphopoiesis in the thymus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; RESCUES T-LYMPHOPOIESIS; RECEPTOR-DEFICIENT MICE; MOUSE BONE-MARROW; PROGENITORS; DIFFERENTIATION; MATURATION; LYMPHOCYTE; PHENOTYPE; BCL-2 AB The thymus has been regarded as the major site of T cell, differentiation. We find that in addition to alpha beta and ya T cells, a significant number (similar to 3 x 10(4) per day) of B220(+)IgM(+) mature B cells are exported from the thymus of C57BL/6 mice. Of these emigrating B cells, we estimate that at least similar to 2 x 10(4) per day are cells which developed intrathymically, whereas a maximum of similar to 0.8 x 10(4) per day are cells which circulated through the thymus from the periphery. The thymus possesses a significant number of pro-B and pre-B cells that express CD19, VpreB, lambda 5, and pax-5, These B cell progenitors were found in the thymic cortex, whereas increasingly mature B cells were found in the corticomedullar and medullary regions. Other lymphoid cells, including NK cells and lymphoid dendritic cells, are not exported from the thymus at detectable levels, Thus, the thymus contributes to the formation of peripheral pools of B cells as well as of alpha beta and gamma delta T cells. C1 Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. RP Akashi, K (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Sm 770B,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42551] NR 40 TC 80 Z9 81 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2000 VL 164 IS 10 BP 5221 EP 5226 PG 6 WC Immunology SC Immunology GA 312MW UT WOS:000086947900034 PM 10799882 ER PT J AU Sala, C Rudolph-Correia, S Sheng, M AF Sala, C Rudolph-Correia, S Sheng, M TI Developmentally regulated NMDA receptor-dependent dephosphorylation of cAMP response element-binding protein (CREB) in hippocampal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE MAP kinase; ERK1/2; synaptic plasticity; protein phosphatase-1; gene expression; critical period ID GENE-EXPRESSION; RAT-BRAIN; REGIONAL EXPRESSION; SUBUNIT COMPOSITION; CALCIUM REGULATION; VISUAL-CORTEX; IN-VIVO; TRANSCRIPTION; PHOSPHORYLATION; LOCALIZATION AB Developmental changes in the signaling properties of NMDA receptors have been proposed to underlie the loss of plasticity that accompanies brain maturation. Calcium influx through postsynaptic NMDA receptors can stimulate neuronal gene expression via signaling pathways such as the Ras-MAP kinase (MAPK) pathway and the transcription factor cAMP response element-binding protein (CREB). We analyzed MAPK (Erk1/2) and CREB activation in response to NMDA receptor stimulation during the development of hippocampal neurons in culture. At all stages of development NMDA stimulation induced a rapid phosphorylation of CREB on Ser-133 (phospho-CREB). However, the time course of decline in phospho-CREB changed dramatically with neuronal maturation. At 7 d in vitro (7 DIV) phospho-CREB remained elevated 2 hr after strong NMDA stimulation, whereas at 14 DIV phospho-CREB rose only transiently and fell back to below basal levels within 30 min. Moreover, at 14 DIV, but not at 7 DIV, NMDA receptor stimulation induced a dephosphorylation of CREB that previously had been phosphorylated by KCl depolarization or forskolin, suggesting an NMDA receptor-dependent activation of a CREB phosphatase. There was no developmental change in the time course of phospho-CREB induction that followed KCl depolarization or PKA activation, nor was there a developmental change in the time course of phospho-Erk1/2 induced by NMDA receptor activation. We suggest that, during neuronal maturation, NMDA receptor activation becomes linked specifically to protein phosphatases that act on Ser-133 of CREB. Such a developmentally regulated switch in the mode of NMDA receptor coupling to intracellular signaling pathways may contribute to the changes in neural plasticity observed during brain 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. RI Sala, Carlo/A-2493-2009 OI Sala, Carlo/0000-0003-0662-9523 NR 43 TC 143 Z9 148 U1 2 U2 5 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 MAY 15 PY 2000 VL 20 IS 10 BP 3529 EP 3536 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 312JK UT WOS:000086940000007 PM 10804193 ER PT J AU Shin, HW Hsueh, YP Yang, FC Kim, E Sheng, M AF Shin, HW Hsueh, YP Yang, FC Kim, E Sheng, M TI An intramolecular interaction between Src homology 3 domain and guanylate kinase-like domain required for channel clustering by postsynaptic density-95/SAP90 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE PDZ domain; ion channel clustering; postsynaptic density; Src tyrosine kinase; polyproline helix; disks large ID DENSITY PROTEIN PSD-95; NITRIC-OXIDE SYNTHASE; TUMOR-SUPPRESSOR GENE; K+ CHANNEL; EXCITATORY SYNAPSES; SHANK FAMILY; MEMBRANE; PDZ; BINDING; COMPLEX AB Members of the postsynaptic density-95 (PSD-95)/SAP90 family of membrane-associated guanylate kinase (MAGUK) proteins function as multimodular scaffolds that organize protein-signaling complexes at neuronal synapses. MAGUK proteins contain PDZ, Src homology 3 (SH3), and guanylate kinase (GK)-like domains, all of which can function as sites for specific protein-protein interactions. We report here a direct protein-protein interaction between the SH3 domain and the GK region in the PSD-95 family of MAGUKs. The SH3 domain of the PSD-95 family appears to have an atypical binding specificity, because the classical SH3 binding (-P-X-X-P-) motif is absent from the GK domain. Although SH3-GK binding can occur in either an intramolecular or intermolecular manner, the intramolecular mode is preferred, possibly because of additional tertiary interactions available when the SH3 and GK domains are adjacent in the same polypeptide. Mutations disrupting the intramolecular SH3-GK interaction do not interfere with PSD-95 association with the K+ channel Kv1.4 or with the GK domain-binding protein GKAP. The same mutations, however, inhibit the clustering of Kv1.4 by PSD-95, suggesting that the intramolecular SH3-GK interaction may modulate the clustering activity of PSD-95. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea. 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. RI Kim, Eunjoon/C-1566-2011; OI Hsueh, Yi-Ping/0000-0002-0866-6275 NR 44 TC 101 Z9 106 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 MAY 15 PY 2000 VL 20 IS 10 BP 3580 EP 3587 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 312JK UT WOS:000086940000013 PM 10804199 ER PT J AU Doughty, ML De Jager, PL Korsmeyer, SJ Heintz, N AF Doughty, ML De Jager, PL Korsmeyer, SJ Heintz, N TI Neurodegeneration in Lurcher mice occurs via multiple cell death pathways SO JOURNAL OF NEUROSCIENCE LA English DT Article DE lurcher; cerebellum; Bax; p53; caspase-3; apoptosis ID INFERIOR OLIVARY NEURONS; CEREBELLAR PURKINJE-CELLS; BAX-DEFICIENT MICE; CEREBRAL-ISCHEMIA; GRANULE CELLS; MUTANT WEAVER; APOPTOSIS; EXPRESSION; GENE; P53 AB Lurcher (Lc) is a gain-of-function mutation in the delta 2 glutamate receptor (GRID2) that results in the cell-autonomous death of cerebellar Purkinje cells in heterozygous lurcher (+/Lc) mice. This in turn triggers the massive loss of afferent granule cells during the first few postnatal weeks. Evidence suggests that the death of Purkinje cells as a direct consequence of GRID2 Lc activation and the secondary death of granule cells because of target deprivation occur by apoptosis. We have used mice carrying null mutations of both the Bax and p53 genes to examine the roles of these genes in cell loss in lurcher animals. The absence of Bax delayed Purkinje cell death in response to the GRID2 Lc mutation and permanently rescued the secondary death of granule cells. In contrast, the p53 deletion had no effect on either cell death pathway. Our results demonstrate that target deprivation induces a Bax-dependent, p53-independent cell death response in cerebellar granule cells in vivo. In contrast, Bax plays a minor role in GRID2(Lc)-mediated Purkinje cell death. C1 Rockefeller Univ, Mol Biol Lab, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Heintz, N (reprint author), Rockefeller Univ, Mol Biol Lab, 1230 York Ave, New York, NY 10021 USA. FU NIGMS NIH HHS [GM 07739]; NINDS NIH HHS [NS 30532] NR 38 TC 71 Z9 71 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 15 PY 2000 VL 20 IS 10 BP 3687 EP 3694 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 312JK UT WOS:000086940000024 PM 10804210 ER PT J AU Pawlik, TM Souba, WW Sweeney, TJ Bode, BP AF Pawlik, TM Souba, WW Sweeney, TJ Bode, BP TI Phorbol esters rapidly attenuate glutamine uptake and growth in human colon carcinoma cells SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 18-22, 1999 CL PHILADELPHIA, PENNSYLVANIA SP Assoc Acad Surg DE glutamine; phorbol esters; system ASC/B-o; nutrient transport; colon carcinoma ID PROTEIN-KINASE-C; AMINO-ACID TRANSPORTER; CULTURED HUMAN-FIBROBLASTS; CANCER-CELLS; SMALL-INTESTINE; HEPATOMA-CELLS; SYSTEM ASC; DIFFERENTIATION; PROLIFERATION; OVEREXPRESSION AB Background. The amino acid glutamine, while essential for gut epithelial growth, has also been shown to stimulate colon carcinoma proliferation and diminish differentiation. Human colon carcinomas are known to extract and metabolize glutamine at rates severalfold greater than those of normal tissues, but the regulation of this response is unclear. Previously we reported that phorbol esters regulate hepatoma System ASC/B-o-mediated glutamine uptake and cell growth. As human colon carcinoma cells use this same transporter for glutamine uptake, the present studies were undertaken to determine whether similar regulation functions in colon carcinoma, Materials and methods, Human colon carcinoma cell lines (WiDr and HT29) were treated with the protein kinase C (PKC) activator phorbol Ig-myristate 13-acetate (PMA) and initial-rate transport of glutamine and other nutrients was measured at specific times thereafter, Growth rates were monitored during culture +/- PMA or an excess of System ASC/B-o substrates relative to glutamine, Results, PMA treatment induced a rapid inhibition of glutamine uptake rates in WiDr and HT29 cells by 30 and 57%, respectively, after 1 h, Cycloheximide failed to block this response, indicating that the mechanism by which PMA exerts its effects is posttranslational, The inhibition of glutamine uptake by PMA was abrogated by the PKC inhibitor staurosporine, suggesting that this rapid System ASC/B-o regulation may be mediated by a PKC-dependent pathway. PMA also significantly decreased transport via System y(+) (arginine) and System A (small zwitterionic amino acids). Chronic phorbol ester treatment inhibited WiDr cell growth, as did attenuation of System Bo-mediated glutamine uptake with other transporter substrates, Conclusions. System ASC/B-o uptake governs glutamine-dependent growth in colon carcinoma cell lines, and is regulated by a phorbol ester-sensitive pathway that may involve PKC, The results further establish the link between glutamine uptake and colon carcinoma cell growth, a relationship worthy of further investigation with the goal of discovering novel cancer therapeutic targets, (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, Div Surg Oncol, Surg Oncol Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bode, BP (reprint author), St Louis Univ, Dept Biol, 3507 Laclede Ave, St Louis, MO 63103 USA. NR 43 TC 12 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY 15 PY 2000 VL 90 IS 2 BP 149 EP 155 DI 10.1006/jsre.2000.5872 PG 7 WC Surgery SC Surgery GA 317RD UT WOS:000087240000010 PM 10792956 ER PT J AU Weaver, DR AF Weaver, DR TI A clockwork green: timely reporting on circadian clock function SO NEUROREPORT LA English DT Article ID RAT SUPRACHIASMATIC NUCLEUS; GENE-EXPRESSION; RHYTHMS; LUCIFERASE; PERIOD; DROSOPHILA; CYANOBACTERIA; PROTEIN; NEURONS; MUTANTS C1 Massachusetts Gen Hosp, MassGen Hosp Children, Lab Dev Chronobiol GRJ 1226, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Weaver, DR (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Lab Dev Chronobiol GRJ 1226, Boston, MA 02114 USA. OI Weaver, David/0000-0001-7941-6719 NR 25 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 15 PY 2000 VL 11 IS 7 BP F9 EP F10 DI 10.1097/00001756-200005150-00004 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 316WN UT WOS:000087191200004 ER PT J AU Lin, TS Mahajan, S Frank, DA AF Lin, TS Mahajan, S Frank, DA TI STAT signaling in the pathogenesis and treatment of leukemias SO ONCOGENE LA English DT Article DE STAT; cytokines; cancer; leukemia; therapy ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW TRANSPLANTATION; PERIPHERAL-BLOOD CELLS; DNA-BINDING ACTIVITY; CONSTITUTIVE ACTIVATION; BCR-ABL; INTERFERON-GAMMA; MYELOID-LEUKEMIA; MONOCLONAL-ANTIBODY AB Leukemias continue to cause significant mortality in adults and children, and the use of standard cytotoxic chemotherapy has reached a therapeutic plateau, Thus, there is great interest in treatments directed against inappropriately activated cell signaling pathways which stimulate the uncontrolled growth of neoplastic cells. Increasing evidence suggests that the STAT signaling cascade may be one target of these therapies. Signal transducer and activator of transcription (STAT) proteins are critical in mediating the response of hematopoietic cells to a diverse spectrum of cytokines. Constitutive STAT activation is present in many malignancies and has been especially well characterized in acute and chronic leukemias. While STAT activation is a common characteristic of leukemias, the specific pattern of activated STATs and the manner by which STAT activation occurs vary with each disease. STAT tyrosine phosphorylation can occur through inappropriate Jak activation or by direct activation of an oncoprotein such as Bcr/Abl, and STAT serine phosphorylation may play an important role in leukemias as well. Thus, the STAT signaling pathway is an attractive target for therapeutic intervention, and strategies designed to inhibit STAT activation and STAT mediated gene transcription may play an important role in the next generation of anti-leukemia therapies. 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, Dept Med, Boston, MA 02115 USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA79547] NR 52 TC 173 Z9 183 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 15 PY 2000 VL 19 IS 21 BP 2496 EP 2504 DI 10.1038/sj.onc.1203486 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 321MN UT WOS:000087459400005 PM 10851048 ER PT J AU Bergeron, B AF Bergeron, B TI Touch points SO POSTGRADUATE MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD MAY 15 PY 2000 VL 107 IS 6 BP A46 EP A46 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 319ZJ UT WOS:000087376100021 ER PT J AU Kaihara, S Kim, SS Kim, BS Mooney, D Tanaka, K Vacanti, JP AF Kaihara, S Kim, SS Kim, BS Mooney, D Tanaka, K Vacanti, JP TI Long-term follow-up of tissue-engineered intestine after anastomosis to native small bowel SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Society-of-Transplant-Surgeons (ASTS) CY MAY 19-21, 1999 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Surg ID EPIDERMAL GROWTH-FACTOR; EPITHELIAL ORGANOID UNITS; PARENTERAL-NUTRITION; IN-VIVO; TRANSPLANTATION; SCAFFOLDS; LIVER; TUBES; RAT AB Background. Our laboratory has investigated the fabrication of a tissue-engineered intestine using biodegradable polymer scaffolds. Previously we reported that isolated intestinal epithelial organoid units on biodegradable polymer scaffolds formed cysts and the neointestine was successfully anastomosed to the native small bowel. The purpose of this study was to observe the development of tissue-engineered intestine after anastomosis and to demonstrate the effect of the anastomosis over a 9-month period. Methods. Microporous biodegradable polymer tubes were created from polyglycolic acid. Intestinal epithelial organoid units were harvested from neonatal Lewis rats and seeded onto the polymers, which were implanted into the abdominal cavity of adult male Lewis rats followed by 75% small bowel resection (n=24). Three weeks after implantation, the unit/polymer constructs were anastomosed to the native jejunum in a side-to-side fashion. The anastomosed tissue-engineered intestine was measured by laparotomy 10, 24, and 36 weeks after the implantation (n=14). During the laparotomy, all rats with an obstruction in their anastomosis were killed and excluded from the statistical analysis. Another five rats were also killed at 10 and 36 weeks for histological and morphometric studies. Results. All analyzed rats survived this study and significantly increased their body weight by 36 weeks. Obstruction of the anastomosis was observed in one rat at 24 weeks and in two rats at 36 weeks; however, the anastomosis was patent in the other 11 rats by 36 weeks. The tissue-engineered intestine of these 11 rats increased in length and diameter at 10, 24, and 36 weeks after anastomosis; there were statistically significant differences between each time point except between the length of 10 and 24 weeks (P<0.016 by Wilcoxon signed rank test). Histologically the inner surface of the tissue-engineered intestine was lined with well-developed neomucosa at 10 and 36 weeks; however, there were small bare areas lacking neomucosa in the tissue-engineered intestine at 36 weeks, Morphometric analysis demonstrated no significant differences in villus number, villus height, and surface length of the neomucosa at 10 and 36 weeks. Conclusions. Anastomosis between tissue-engineered intestine and native small bowel resulted in no complications after operation and maintained a high patency rate for up to 36 weeks. The tissue-engineered intestine increased in size and was lined with well-developed neomucosa for the duration of the study. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Kyoto Univ, Grad Sch Med, Dept Transplantat Immunol, Kyoto, Japan. Univ Chicago Hosp, Dept Surg, Chicago, IL 60637 USA. Childrens Hosp, Dept Urol, Boston, MA 02115 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Warren 11,55 Fruit St, Boston, MA 02114 USA. RI Kim, Byung-Soo/O-2352-2013 NR 29 TC 44 Z9 48 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 MAY 15 PY 2000 VL 69 IS 9 BP 1927 EP 1932 DI 10.1097/00007890-200005150-00031 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 316GP UT WOS:000087159500031 PM 10830233 ER PT J AU Tatsuta, T Shiraishi, A Mountz, JD AF Tatsuta, T Shiraishi, A Mountz, JD TI The prodomain of caspase-1 enhances Fas-mediated apoptosis through facilitation of caspase-8 activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1-BETA CONVERTING-ENZYME; DOMAIN-CONTAINING RECEPTOR; ICE FAMILY PROTEASES; CELL-DEATH; MONOCLONAL-ANTIBODY; CONTAINING PROTEIN; MAMMALIAN HOMOLOG; MOLECULAR-CLONING; ADAPTER MOLECULE AB Caspase-1 (interleukin-1 beta converting enzyme) is produced in the form of a latent precursor, which is cleaved to yield a prodomain in addition to the p20 and p10 subunits. It has been established that the (p20/p10)(2) heterotetramer processes the latent precursor of interleukin-1 beta into an active form during apoptosis, but the function of the residual prodomain of caspase-1 (Pro-C1) has not been established. To evaluate the involvement of Pro-C1 in apoptosis, a Pro-C1 expression vector was transfected into the HeLa cell line, which is susceptible to Fas-mediated apoptosis. Expression of recombinant Pro-C1 in HeLa cells enhanced apoptosis mediated by Fas, but not etoposide-induced apoptosis. This enhancement of Fas-mediated apoptosis was abolished by inhibitors of caspase-8 (Ile-Glu-Thr-Asp-fluoromethyl ketone) and caspase-3 (Asp-Glu-Val-Asp-aldehyde) but was only slightly diminished by an inhibitor of caspase-1 (acetyl- Tyr-Val-Ala-Asp-chloromethyl ketone). During apoptosis induced by an agonistic anti-Fas antibody, the activation of caspase-8 and caspase-3 was more pronounced and occurred more rapidly in HeLa/Pro-C1 cells than in the empty vector transfectant (HeLa/vec) cells; in contrast, caspase-1 was not activated in either HeLa/Pro-C1 or HeLa/vec cells. These results demonstrate an additional and novel function for caspase-1 in which Pro-C1 acts to enhance Fas-mediated apoptosis, most probably through facilitation of the activation of caspase-8. C1 Sankyo Co Ltd, Neurosci & Immunol Res Labs, Tokyo 1408710, Japan. Univ Alabama, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Tatsuta, T (reprint author), Sankyo Co Ltd, Neurosci & Immunol Res Labs, 1-2-58 Hiromachi, Tokyo 1408710, Japan. NR 45 TC 40 Z9 40 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 MAY 12 PY 2000 VL 275 IS 19 BP 14248 EP 14254 DI 10.1074/jbc.275.19.14248 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313NZ UT WOS:000087006900034 PM 10799503 ER PT J AU Pack-Chung, E Meyers, MB Pettingell, WP Moir, RD Brownawell, AM Cheng, I Tanzi, RE Kim, TW AF Pack-Chung, E Meyers, MB Pettingell, WP Moir, RD Brownawell, AM Cheng, I Tanzi, RE Kim, TW TI Presenilin 2 interacts with sorcin, a modulator of the ryanodine receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM-BINDING PROTEIN; AMYLOID PRECURSOR PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; BETA-CATENIN; CELLS; ASSOCIATION; MUTATIONS; COMPLEX; RELEASE; NOTCH AB Perturbed Ca2+ homeostasis is a common molecular consequence of familial Alzheimer's disease-linked presenilin mutations. We report here the molecular interaction of the large hydrophilic loop region of presenilin 2 (PS2) with sorcin, a penta-EF-hand Ca2+-binding protein that serves as a modulator of the ryanodine receptor intracellular Ca2+ channel. The association of endogenous sorcin and PS2 was demonstrated in cultured cells and human brain tissues. Membrane-associated sorcin and a subset of the functional PS2 complexes were co-localized to a novel subcellular fraction that is distinctively positive for calcineurin B. Sorcin was found to interact with PS2 endoproteolytic fragments but not full-length PS2, and the sorcin/PS2 interaction was greatly enhanced by treatment with the Ca2+ ionophore A23187. Our findings reveal a molecular link between PS2 and intracellular Ca2+ channels (i.e. ryanodine receptor) and substantiate normal and/or pathological roles of PS2 in intracellular Ca2+ homeostasis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. CUNY Mt Sinai Sch Med, Cardiovasc Inst, Dept Med, New York, NY 10029 USA. Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA. RP Kim, TW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. NR 60 TC 71 Z9 72 U1 1 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 MAY 12 PY 2000 VL 275 IS 19 BP 14440 EP 14445 DI 10.1074/jbc.M909882199 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313NZ UT WOS:000087006900060 PM 10748169 ER PT J AU Banks, AS Davis, SM Bates, SH Myers, MG AF Banks, AS Davis, SM Bates, SH Myers, MG TI Activation of downstream signals by the long form of the leptin receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE-PHOSPHATASE SHP-2; ERYTHROPOIETIN RECEPTOR; OB-R; EXTRACELLULAR DOMAIN; CYTOKINE RECEPTORS; GROWTH-FACTOR; DB/DB MICE; PROTEIN; KINASE; TRANSDUCTION AB The adipocyte-derived hormone leptin signals the status of body energy stores by activating the long form of the leptin receptor (LRb). Activation of LRb results in the activation of the associated Jak2 tyrosine kinase and the transmission of downstream phosphotyrosine-dependent signals. We have investigated the signaling function of mutant LRb intracellular domains under the control of the extracellular erythropoietin (Epo) receptor. By using this system, we confirm that two tyrosine residues in the intracellular domain of murine LRb become phosphorylated to mediate LRb signaling; Tyr(985) controls the tyrosine phosphorylation of SHP-8, and Tyr(1138) controls STAT3 activation. We furthermore investigated the mechanisms by which LRb controls downstream ERK activation and c-fos and SOCS3 message accumulation. Tyr(985)-mediated recruitment of SHP-8 does not alter tyrosine phosphorylation of Jak2 or STAT3 but results in GRB-2 binding to tyrosine-phosphorylated SHP-2 and is required for the majority of ERK activation during LRb signaling. Tyr(985) and ERK activation similarly mediate c-fos mRNA accumulation. In contrast, SOCS3 mRNA accumulation requires Tyr(1138)-mediated STAT3 activation. Thus, the two LRb tyrosine residues that are phosphorylated during receptor activation mediate distinct signaling pathways as follows: SHP-2 binding to Tyr(985) positively regulates the ERK --> c-fos pathway, and STAT3 binding to Tyr(1138) mediates the inhibitory SOCS3 pathway. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Myers, MG (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02130 USA. RI Banks, Alexander/B-4832-2012 OI Banks, Alexander/0000-0003-1787-6925 FU NIDDK NIH HHS [DK 56731] NR 67 TC 457 Z9 484 U1 1 U2 12 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 MAY 12 PY 2000 VL 275 IS 19 BP 14563 EP 14572 DI 10.1074/jbc.275.19.14563 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313NZ UT WOS:000087006900076 PM 10799542 ER PT J AU Bulik, DA van Ophem, P Manning, JM Shen, ZJ Newburg, DS Jarroll, EL AF Bulik, DA van Ophem, P Manning, JM Shen, ZJ Newburg, DS Jarroll, EL TI UDP-N-acetylglucosamine pyrophosphorylase, a key enzyme in encysting Giardia, is allosterically regulated SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; LAMBLIA; GENE; URIDYLTRANSFERASE; IDENTIFICATION; PURIFICATION; CARBOHYDRATE; ISOMERASE; CLONING; CYSTS AB Giardia synthesizes UDP-GalNAc during cyst wall formation (encystment) via a pathway of inducible enzymes similar to that used to synthesize chitin or peptidoglycan and that includes the UTP-requiring UDP-N-acetylglucosamine pyrophosphorylase. Although it has never been reported as a regulatory enzyme in any system studied to date, kinetic data including Hill plots demonstrate clearly that UDP-N-acetylglucosamine pyrophosphorylase activity, purified from encysting Giardia, is allosterically activated anabolically by physiological levels of glucosamine 6-phosphate (3 mu M). Capillary electrophoresis demonstrates that within 24 h after trophozoites are induced to encyst, the level of glucosamine g-phosphate increases 3-fold over that of non-encysting cells and that by 48 h into encystment the level of glucosamine 6-phosphate has decreased to non-encysting levels or below. UDP-N-acetylglucosamine pyrophosphorylase protein is present constitutively in encysting as well as non-encysting cells. UDP-N-acetylglucosamine pyrophosphorylase immunoaffinity purified from encysting and non-encysting cells exhibited the same molecular weight, amino acid composition, and circular dichroism spectra, Moreover, regardless of whether the enzyme came from encysting or nonencysting cells, the change in its circular dichroism spectra and up to a 6-fold increase in its specific activity anabolically were due to its activation with glucosamine 6-phosphate. Thus, the data support the idea that UDP-N-acetylglucosamine pyrophosphorylase is a major regulatory point in amino sugar synthesis in encysting Giardia and that its allosteric anabolic activation may shift the equilibrium of this pathway toward UDP-GalNAc synthesis. C1 Northeastern Univ, Dept Biol, Boston, MA 02115 USA. Shriver Ctr, Program Glycobiol, Waltham, MA 02460 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Jarroll, EL (reprint author), Northeastern Univ, Dept Biol, Boston, MA 02115 USA. NR 35 TC 34 Z9 35 U1 0 U2 6 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 MAY 12 PY 2000 VL 275 IS 19 BP 14722 EP 14728 DI 10.1074/jbc.275.19.14722 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313NZ UT WOS:000087006900095 PM 10799561 ER PT J AU Shearman, LP Sriram, S Weaver, DR Maywood, ES Chaves, I Zheng, BH Kume, K Lee, CC van der Horst, GTJ Hastings, MH Reppert, SM AF Shearman, LP Sriram, S Weaver, DR Maywood, ES Chaves, I Zheng, BH Kume, K Lee, CC van der Horst, GTJ Hastings, MH Reppert, SM TI Interacting molecular loops in the mammalian circadian clock SO SCIENCE LA English DT Article ID RAT SUPRACHIASMATIC NUCLEUS; PERIOD HOMOLOGS; GENE CLOCK; TIMELESS; EXPRESSION; PROTEIN; RHYTHMS; TRANSCRIPTION; OSCILLATION; NEURONS AB We show that, in the mouse, the core mechanism for the master circadian clock consists of interacting positive and negative transcription and translation feedback Loops. Analysis of Clock/Clock mutant mice, homozygous period2(Brdm1) mutants, and Cryptochrome-deficient mice reveals substantially altered Small rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the Bmal1 Loop. In vitro analysis of CRYPTOCHROME inhibition of CLOCK: BMAL1-mediated transcription shows that the inhibition is through direct protein:protein interactions, independent of the PERIOD and TIMELESS proteins. PERIOD2 is a positive regulator of the Bmal1 Loop, and CRYPTOCHROMES are the negative regulators of the Period and Cryptochrome cycles. C1 Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Cambridge, Dept Anat, Cambridge CB2 3DY, England. Erasmus Univ, Dept Cell Biol & Genet, Ctr Med Genet, NL-3000 DR Rotterdam, Netherlands. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Reppert, SM (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Lab Dev Chronobiol, Boston, MA 02114 USA. RI van der Horst, Gijsbertus/E-3661-2015 FU NHLBI NIH HHS [HL07901]; NICHD NIH HHS [R37 HD14427]; NINDS NIH HHS [R01 NS39303] NR 44 TC 770 Z9 801 U1 9 U2 61 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 12 PY 2000 VL 288 IS 5468 BP 1013 EP 1019 DI 10.1126/science.288.5468.1013 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 313EY UT WOS:000086988400028 PM 10807566 ER PT J AU Christmas, P Cheng, SM Weber, B Soberman, RJ AF Christmas, P Cheng, SM Weber, B Soberman, RJ TI Tissue specific expression and splicing of the CYP4F3 gene generates two functionally different isoforms. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1109 BP A1505 EP A1505 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401140 ER PT J AU Cogswell, LP Raines, DE Parekh, S Maggio, JE Strichartz, GR AF Cogswell, LP Raines, DE Parekh, S Maggio, JE Strichartz, GR TI Development of 2-hydroxy-3,5-diiodo-N-[2(diethylamino)ethyl]benzamide as a novel probe for measuring drug binding to human alpha 1-acid gylcoprotein SO FASEB JOURNAL LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Anesthesia Res Labs, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia Res Labs, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia Res Labs, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 914 BP A1471 EP A1471 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400945 ER PT J AU Fathallah, D Zerria, K Hammami, S Jerbi, E Boubaker, S Arnaout, MA Dellagi, K AF Fathallah, D Zerria, K Hammami, S Jerbi, E Boubaker, S Arnaout, MA Dellagi, K TI Recombinant integrin CD11b A-domain protects against skeletal muscle injury in a rat model SO FASEB JOURNAL LA English DT Meeting Abstract C1 Inst Pasteur, Tunis, Tunisia. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 269 BP A1357 EP A1357 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400301 ER PT J AU Goren, HJ Kulkarni, RN Kahn, CR AF Goren, HJ Kulkarni, RN Kahn, CR TI Genetic background influences glucose homeostasis in strains of mice used in transgenic studies SO FASEB JOURNAL LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 223 BP A1349 EP A1349 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400252 ER PT J AU Hellerstein, MS Yu, GS Gulick, T AF Hellerstein, MS Yu, GS Gulick, T TI OMC-3, an orphan mitochondrial metabolite carrier required for OXPHOS SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Diabet Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Weight Ctr, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 595 BP A1415 EP A1415 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400625 ER PT J AU Keutmann, HT Sidis, Y Sluss, PM Wang, QF Johnson, LH Schneyer, AL AF Keutmann, HT Sidis, Y Sluss, PM Wang, QF Johnson, LH Schneyer, AL TI Structure and activity of follistatin: essential role for the N-terminal domain in activin binding SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1036 BP A1492 EP A1492 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401069 ER PT J AU Kodama, T Hamblin, MR Doukas, AG AF Kodama, T Hamblin, MR Doukas, AG TI Cytoplasmic molecular delivery with shock waves SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 927 BP A1473 EP A1473 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400957 ER PT J AU Korsmeyer, SJ AF Korsmeyer, SJ TI Activation and inactivation of BCL-2 members SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 540 BP A1404 EP A1404 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400569 ER PT J AU Kumar, V Sabutini, D Pandey, P Gingras, A Majumder, P Kumar, M Yuan, ZM Carmichael, G Weichselbaum, R Sonenberg, N Kufe, D Kharbanda, S AF Kumar, V Sabutini, D Pandey, P Gingras, A Majumder, P Kumar, M Yuan, ZM Carmichael, G Weichselbaum, R Sonenberg, N Kufe, D Kharbanda, S TI Regulation of the rapamycin and fkbptarget 1/mTOR and cap-dependent initiation of translation by the e-Abl protein tyrosine kinase. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 830 BP A1456 EP A1456 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400863 ER PT J AU Kyriakis, JM Liu, H Nishitoh, H Ichijo, H AF Kyriakis, JM Liu, H Nishitoh, H Ichijo, H TI Activation of apoptosis signal-regulating kinase-1 (ASK1) by TNF receptor-associated factor-2 (TRAF2) requires prior redox-dependent dissociation of the ASK1 inhibitor thioredoxin SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Res Lab, Charlestown, MA USA. Tokyo Med & Dent Univ, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1117 BP A1506 EP A1506 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401149 ER PT J AU Partovian, C Horowitz, A Murakami, M Simons, M AF Partovian, C Horowitz, A Murakami, M Simons, M TI PKC alpha activates eNOS in an Akt-1 dependent manner SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Angiogenesis Res Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1294 BP A1537 EP A1537 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401326 ER PT J AU Partovian, C Horowitz, A Murakami, M Zhang, Y Li, J Simons, M AF Partovian, C Horowitz, A Murakami, M Zhang, Y Li, J Simons, M TI Basic FGF activates eNOS signaling via syndecan4-dependent pathway SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Angiogenesis Res Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1295 BP A1537 EP A1537 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401324 ER PT J AU Patel, TJ Farzan, M Sodroski, J AF Patel, TJ Farzan, M Sodroski, J TI Activation of CTL response in vivo to HIV envelope epitopes via CD40L/GP120 trimeric fusion protein SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 257 BP A1355 EP + PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400291 ER PT J AU Shao, ZH Raible, F Mollaaghababa, R Sif, S Narlikar, G Saurin, A Francis, N Weiss, A Wu, CT Bender, W Kingston, RE AF Shao, ZH Raible, F Mollaaghababa, R Sif, S Narlikar, G Saurin, A Francis, N Weiss, A Wu, CT Bender, W Kingston, RE TI Regulation of chromatin structure by polycomb and by SWI/SNF. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RI Raible, Florian/G-6019-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1546 BP A1582 EP A1582 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401575 ER PT J AU Shioda, T Yahata, T Isselbacher, KJ AF Shioda, T Yahata, T Isselbacher, KJ TI The MSG1 family proteins are non-DNA-binding, adaptor-type transcriptional activators that interact with coactivators p300/CBP (CREB binding protein) SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Tumor Biol, Ctr Canc, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 751 BP A1442 EP A1442 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400780 ER PT J AU Spiegelman, BM Wu, Z Puigserver, P AF Spiegelman, BM Wu, Z Puigserver, P TI Control of adipogenesis and energy balance through PPAR gamma and novel coactivators. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 545 BP A1406 EP A1406 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400576 ER PT J AU Takehara, T Takahashi, H AF Takehara, T Takahashi, H TI Bcl-xL is posttranslationally deamidated at asparagine residues. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1174 BP A1517 EP A1517 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401206 ER PT J AU White, K Kurada, P Bangs, P Franc, N Lisi, S Mazzon, I Peterson, C Marion, C AF White, K Kurada, P Bangs, P Franc, N Lisi, S Mazzon, I Peterson, C Marion, C TI The control and execution of apoptosis during drosophila development SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, CBRC, Charlestown, MA USA. RI Franc, Nathalie/C-2208-2009; White, Kristin/D-7936-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1564 BP A1586 EP A1586 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401594 ER PT J AU Willsky, G Kaszynski, P Godzalla, M Kostyniak, P Goldfine, A AF Willsky, G Kaszynski, P Godzalla, M Kostyniak, P Goldfine, A TI Pharmacokinetics of vanadyl sulfate in humans with NIDDM diabetes mellitus. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 960 BP A1479 EP A1479 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400993 ER PT J AU Yu, GS Hurier, AM Lu, YC Gulick, T AF Yu, GS Hurier, AM Lu, YC Gulick, T TI Regulation of carnitine palmitoyltransferase IB expression during the fetal-neonatal transition SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Diabet Res Lab, Boston, MA 02129 USA. Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 330 BP A1367 EP A1367 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400362 ER PT J AU Zhang, ZQ Apse, K Stanton, RC AF Zhang, ZQ Apse, K Stanton, RC TI Effect of high glucose on cell growth and cell death is dependent on cell type and is mediated, at least in part, by changes in the activity of glucose 6-phosphate dehydrogenase. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1183 BP A1519 EP A1519 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401214 ER PT J AU Etcoff, NL Ekman, P Magee, JJ Frank, MG AF Etcoff, NL Ekman, P Magee, JJ Frank, MG TI Lie detection and language comprehension SO NATURE LA English DT Article ID FACE C1 Massachusetts Gen Hosp East, Dept Psychiat, Charlestown, MA 02129 USA. Univ Calif San Francisco, Human Interact Lab, San Francisco, CA 94143 USA. Circle Com, Cambridge, MA 02138 USA. Rutgers State Univ, Sch Commun Informat & Lib Studies, New Brunswick, NJ 08901 USA. RP Etcoff, NL (reprint author), Massachusetts Gen Hosp East, Dept Psychiat, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 9 TC 41 Z9 42 U1 2 U2 19 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 11 PY 2000 VL 405 IS 6783 BP 139 EP 139 DI 10.1038/35012129 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314WG UT WOS:000087080100036 PM 10821259 ER PT J AU Helmlinger, G Endo, M Ferrara, N Hlatky, L Jain, RK AF Helmlinger, G Endo, M Ferrara, N Hlatky, L Jain, RK TI Growth factors - Formation of endothelial cell networks SO NATURE LA English DT Article ID TUMOR ANGIOGENESIS; HYPOXIA; PROLIFERATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Steele Lab,Dept Radiat Oncol, Boston, MA 02114 USA. Genentech Inc, S San Francisco, CA 94080 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02215 USA. RP Helmlinger, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Steele Lab,Dept Radiat Oncol, Boston, MA 02114 USA. NR 13 TC 104 Z9 109 U1 1 U2 8 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 11 PY 2000 VL 405 IS 6783 BP 139 EP 141 DI 10.1038/35012132 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314WG UT WOS:000087080100037 PM 10821260 ER PT J AU Hirsch, MS Brun-Vezinet, F D'Aquila, RT Hammer, SM Johnson, VA Kuritzkes, DR Loveday, C Mellors, JW Clotet, B Conway, B Demeter, LM Vella, S Jacobsen, DM Richman, DD AF Hirsch, MS Brun-Vezinet, F D'Aquila, RT Hammer, SM Johnson, VA Kuritzkes, DR Loveday, C Mellors, JW Clotet, B Conway, B Demeter, LM Vella, S Jacobsen, DM Richman, DD TI Antiretroviral drug resistance testing in adult HIV-1 infection - Recommendations of an International AIDS Society-USA panel SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE GENE; PROTEASE INHIBITORS; COMBINATION THERAPY; ZIDOVUDINE RESISTANCE; GENOTYPIC RESISTANCE; CONTROLLED TRIAL; DUAL RESISTANCE; VIRAL LOAD; IN-VIVO AB Objective Assays for drug resistance testing in human immunodeficiency virus type 1 (HIV-1) infection are now available and clinical studies suggest that viral drug resistance is correlated with poor virologic response to new therapy. The International AIDS Society-USA sought to update prior recommendations to provide guidance for clinicians regarding indications for HIV-1 resistance testing. Participants An International AIDS Society-USA 13-member physician panel with expertise in basic science, clinical research, and patient care involving HIV resistance to antiretroviral drugs was reconvened to provide recommendations for the clinical use of drug resistance testing. Evidence and Consensus Process The full panel met regularly between January and October 1999. Resistance and resistance testing data appearing in the last decade th rough April 2000 and presentations at national and international research conferences were reviewed. Recommendations and considerations were developed by 100% group consensus, acknowledging that definitive data to support final recommendations are not yet available. Conclusions Emerging data indicate that despite limitations, resistance testing should be incorporated into patient management in some settings. Resistance testing is recommended to help guide the choice of new regimens after treatment failure and for guiding therapy for pregnant women. It should be considered in treatment-naive patients with established infection, but cannot be firmly recommended in this setting. Testing also should be considered prior to initiating therapy in patients with acute HIV infection, although therapy should not be delayed pending the results. Expert interpretation is recommended given the complexity of results and assay limitations. C1 Harvard Univ, Sch Med, Boston, MA USA. Hop Bichat Claude Bernard, F-75877 Paris 18, France. Columbia Univ, Coll Phys & Surg, New York, NY USA. Univ Alabama, Sch Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Royal Free Hosp, Sch Med, London, England. Vet Affairs Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. Fdn IrsaCAIXA, Barcelona, Spain. Hosp Univ Germans Trias & Pujol, HIV Unit, Barcelona, Spain. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Rochester, Rochester, NY USA. Ist Super Sanita, I-00161 Rome, Italy. Univ Calif San Diego, San Diego, CA 92103 USA. San Diego Vet Affairs Med Ctr, San Diego, CA USA. Infect Dis Unit, Boston, MA 02114 USA. RP Hirsch, MS (reprint author), Int AIDS Soc USA, Presidio San Francisco,1001 B OReilly Ave,Box 29, San Francisco, CA 94129 USA. RI Vella, Stefano/D-4912-2015 OI Vella, Stefano/0000-0003-2347-5984 NR 94 TC 548 Z9 555 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 10 PY 2000 VL 283 IS 18 BP 2417 EP 2426 DI 10.1001/jama.283.18.2417 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 310CD UT WOS:000086808200037 PM 10815085 ER PT J AU Bressman, SB Sabatti, C Raymond, D de Leon, D Klein, C Kramer, PL Brin, MF Fahn, S Breakefield, X Ozelius, LJ Risch, NJ AF Bressman, SB Sabatti, C Raymond, D de Leon, D Klein, C Kramer, PL Brin, MF Fahn, S Breakefield, X Ozelius, LJ Risch, NJ TI The DYT1 phenotype and guidelines for diagnostic testing SO NEUROLOGY LA English DT Article DE dystonia; DYT1; Genetic testing ID IDIOPATHIC TORSION DYSTONIA; AUTOSOMAL DOMINANT INHERITANCE; ASHKENAZI JEWS; FAMILY; ONSET; 9Q34; GENE; MUTATION AB Objective: To develop diagnostic testing guidelines for the DYT1 GAG deletion in the Ashkenazi Jewish (AJ) and non-Jewish (NJ) primary torsion dystonia (PTD) populations and to determine the range of dystonic features in affected DYT1 deletion carriers. Methods: The authors screened 267 individuals with PTD; 170 were clinically ascertained for diagnosis and treatment, 87 were affected family members ascertained for genetic studies, and 10 were clinically and genetically ascertained and included in both groups, We used published primers and PCR amplification across the critical DYT1 region to determine GAG deletion status. Features of dystonia in clinically ascertained (affected) DYT1 GAG deletion carriers and noncarriers were compared to determine a classification scheme that optimized prediction of carriers. The authors assessed the range of clinical features in the genetically ascertained (affected) DYT1 deletion carriers and tested for differences between Al and NJ patients. Results: The optimal algorithm for classification of clinically ascertained carriers was disease onset before age 24 years in a limb (misclassification, 16.5%; sensitivity, 95%; specificity, 80%). Although application of this classification scheme provided good separation in the AJ group (sensitivity, 96%; specificity, 88%), as well as in the group overall, it was less specific in discriminating NJ carriers from noncarriers (sensitivity, 94%; specificity, 69%). Using age 26 years as the cut-off and any site at onset gave a sensitivity of 100%, but specificity decreased to 54% (63% in AJ and 43% in NJ). Among genetically ascertained carriers, onset up to age 44 years occurred, although the great majority displayed early limb onset. There were no significant differences between AJ and NJ genetically ascertained carriers, except that a higher proportion of NJ carriers had onset in a leg, rather than an arm, and widespread disease. Conclusions: Diagnostic DYT1 testing in conjunction with genetic counseling is recommended for patients with PTD with onset before age 26 years, as this single criterion detected 100% of clinically ascertained carriers, with specificities of 43% to 63%. Testing patients with onset after age 26 years also may be warranted in those having an affected relative with early onset, as the only carriers we observed with onset at age 26 or later were genetically ascertained relatives of individuals whose symptoms started before age 26 years. C1 Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Neurol Serv, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol & Genet, Boston, MA USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Mt Sinai Hosp, Dept Neurol, New York, NY 10029 USA. Columbia Presbyterian Med Ctr, Dept Neurol, New York, NY 10032 USA. RP Bressman, SB (reprint author), Beth Israel Med Ctr, Dept Neurol, 10 Union Sq E,Suite 2R, New York, NY 10003 USA. FU NINDS NIH HHS [NS28384, NS26656] NR 29 TC 185 Z9 190 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 9 PY 2000 VL 54 IS 9 BP 1746 EP 1752 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 311WC UT WOS:000086908000007 PM 10802779 ER PT J AU Buldyrev, SV Cruz, L Gomez-Isla, T Gomez-Tortosa, E Havlin, S Le, R Stanley, HE Urbanc, B Hyman, BT AF Buldyrev, SV Cruz, L Gomez-Isla, T Gomez-Tortosa, E Havlin, S Le, R Stanley, HE Urbanc, B Hyman, BT TI Description of microcolumnar ensembles in association cortex and their disruption in Alzheimer and Lewy body dementias SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SUPERIOR TEMPORAL SULCUS; RHESUS-MONKEY; NEURONAL LOSS; VISUAL AREAS; DISEASE; CONNECTIONS; ORGANIZATION; ARCHITECTURE; PROJECTIONS; DEPOSITION AB The cortex of the brain is organized into clear horizontal layers, laminae, which subserve much of the connectional anatomy of the brain. We hypothesize that there is also a vertical anatomical organization that might subserve local interactions of neuronal functional units, in accord with longstanding electrophysiological observations. We develop and apply a general quantitative method, inspired by analogous methods in condensed matter physics, to examine the anatomical organization of the cortex in human brain. We find, in addition to obvious laminae, anatomical evidence for tightly packed microcolumnar ensembles containing approximately 11 neurons, with a periodicity of about 80 mu m. We era mine the structural integrity of this new architectural feature in two common dementing illnesses, Alzheimer disease and dementia with Lewy bodies. In Alzheimer disease, there is a dramatic, nearly complete loss of microcolumnar ensemble organization. The relative degree of loss of microcolumnar ensembles is directly proportional to the number of neurofibrillary tangles, but not related to the amount of amyloid-beta deposition. In dementia with Lewy bodies, a similar disruption of microcolumnar ensemble architecture occurs despite minimal neuronal loss. These observations show that quantitative analysis of complex cortical architecture can be applied to analyze the anatomical basis of brain disorders. C1 Boston Univ, Dept Phys, Boston, MA 02215 USA. Boston Univ, Ctr Polymer Studies, Boston, MA 02215 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. Bar Ilan Univ, Gonda Goldschmied Ctr, IL-52900 Ramat Gan, Israel. Bar Ilan Univ, Dept Phys, IL-52900 Ramat Gan, Israel. RP Stanley, HE (reprint author), Boston Univ, Dept Phys, 590 Commonwealth Ave, Boston, MA 02215 USA. RI Urbanc, Brigita/G-5839-2011; Cruz Cruz, Luis/B-2685-2013; Buldyrev, Sergey/I-3933-2015 OI Urbanc, Brigita/0000-0001-9159-7698; FU NIA NIH HHS [AG08487, R01 AG008487] NR 36 TC 66 Z9 67 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 9 PY 2000 VL 97 IS 10 BP 5039 EP 5043 DI 10.1073/pnas.060009897 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 313KH UT WOS:000086998500009 PM 10805766 ER PT J AU Shioda, T Andriole, S Yahata, T Isselbacher, KJ AF Shioda, T Andriole, S Yahata, T Isselbacher, KJ TI A green fluorescent protein-reporter mammalian two-hybrid system with extrachromosomal maintenance of a prey expression plasmid: Application to interaction screening SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID 2-HYBRID SYSTEM; YEAST; CELLS; REPLICATION; GENE; MSG1 AB An improved mammalian two-hybrid system designed for interaction trap screening is described in this paper. CV-1/EBNA-1 monkey kidney epithelial cells expressing Epstein-Barr virus nuclear antigen 1 (EBNA-1) were stably transfected with a reporter plasmid for GAL4-dependent expression of the green fluorescent protein (GFP). A resulting clone, GB133, expressed GFP strongly when transfected transiently with transcriptional activators fused to GAL4 DNA-binding domain with minimal background GFP expression. CB133 cells maintained plasmids containing the OriP Epstein-Barr virus replication origin that directs replication of plasmids in mammalian cells in the presence of the EBNA-1 protein. CB133 cells transfected stably with a model bait expressed GFP when further transfected transiently with an expression plasmid for a known positive prey. When the bait-expressing GB133 cells were transfected transiently with an OriP-containing expression plasmid for the positive prey together with excess amounts of empty vector, cells that received the positive prey were readily identified by green fluorescence in cell culture and eventually formed green fluorescent microcolonies, because the prey plasmid was maintained by the EBNA-1/Ori-P system. The green fluorescent microcolonies were harvested directly from the culture dishes under a fluorescence microscope, and total DNA was then prepared. Prey-encoding cDNA was recovered by PCR using primers annealing to the vector sequences flanking the insert-cloning site. This system should be useful in mammalian cells for efficient screening of cDNA libraries by two-hybrid interaction. C1 Massachusetts Gen Hosp, Ctr Canc, Dept Tumor Biol, Charlestown, MA 02129 USA. RP Shioda, T (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Tumor Biol, Bldg 149 7th Floor,13th St, Charlestown, MA 02129 USA. NR 16 TC 26 Z9 26 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 MAY 9 PY 2000 VL 97 IS 10 BP 5220 EP 5224 DI 10.1073/pnas.97.10.5220 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 313KH UT WOS:000086998500041 PM 10805780 ER PT J AU Acosta, J Hettinga, J Fluckiger, R Krumrei, N Goldfine, A Angarita, L Halperin, J AF Acosta, J Hettinga, J Fluckiger, R Krumrei, N Goldfine, A Angarita, L Halperin, J TI Molecular basis for a link between complement and the vascular complications of diabetes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MEMBRANE-ATTACK-COMPLEX; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; REGULATORY PROTEIN CD59; FUNCTIONAL-CHARACTERIZATION; NONENZYMATIC GLYCOSYLATION; BIOLOGIC ACTIVITY; HUMAN-URINE; CELLS; MELLITUS; SITES AB Activated terminal complement proteins C5b to C9 form the membrane attack complex (MAC) pore. Insertion of the MAC into endothelial cell membranes causes the release of growth factors that stimulate tissue growth and proliferation. The complement regulatory membrane protein CD59 restricts MAC formation. Because increased cell proliferation characterizes the major chronic vascular complications of human diabetes and because increased glucose levels in diabetes cause protein glycation and impairment of protein function, we investigated whether glycation could inhibit CD59. Glycation-inactivation of CD59 would cause increased MAC deposition and MAC-stimulated cell proliferation. Here, we report that (i) human CD59 is glycated in vivo, (ii) glycated human CD59 loses its MAC-inhibitory function, and (iii) inactivation of CD59 increases MAC-induced growth factor release from endothelial cells. We demonstrate by site-directed mutagenesis that residues K41 and H44 form a preferential glycation motif in human CD59. The presence of this glycation motif in human CD59, but not in CD59 of other species, may help explain the distinct propensity of humans to develop vascular proliferative complications of diabetes. C1 Harvard Univ, Sch Med, Lab Membrane Transport, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02115 USA. RP Halperin, J (reprint author), Harvard Univ, Sch Med, Lab Membrane Transport, 240 Longwood Ave,C1-607, Boston, MA 02115 USA. OI Fluckiger, Rudolf/0000-0002-4655-2244 FU NIDDK NIH HHS [DK52855] NR 46 TC 109 Z9 120 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 MAY 9 PY 2000 VL 97 IS 10 BP 5450 EP 5455 DI 10.1073/pnas.97.10.5450 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 313KH UT WOS:000086998500081 PM 10805801 ER PT J AU Conigliaro, J Whittle, J Good, CB Hanusa, BH Passman, LJ Lofgren, RP Allman, R Ubel, PA O'Connor, M Macpherson, DS AF Conigliaro, J Whittle, J Good, CB Hanusa, BH Passman, LJ Lofgren, RP Allman, R Ubel, PA O'Connor, M Macpherson, DS TI Understanding racial variation in the use of coronary revascularization procedures - The role of clinical factors SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BYPASS GRAFT-SURGERY; OF-VETERANS-AFFAIRS; BLACK-AND-WHITE; ARTERY DISEASE; HEART-DISEASE; MYOCARDIAL-INFARCTION; MORTALITY; REGISTRY; SURVIVAL; ANGIOGRAPHY AB Background: Black patients undergo coronary artery bypass grafting and percutaneous transluminal coronary angioplasty less often than white patients. It is unclear how racial differences in clinical factors contribute to this variation. Methods: A retrospective cohort study was performed of 666 male patients (326 blacks and 340 whites), admitted to 1 of 6 Veterans Affairs hospitals from October 1, 1989, to September 30, 1995, with acute myocardial infarction or unstable angina who underwent cardiac catheterization. The primary comparison was whether racial differences in percutaneous transluminal coronary angioplasty and coronary artery bypass grafting rates persisted after stratifying by clinical appropriateness of the procedure, measured by the appropriateness scale developed by the RAND Corporation, Santa Monica, Calif. Results: Whites more often than blacks underwent a revascularization procedure (47% vs 28%). There was substantial variation in black-white odds ratios within differ ent appropriateness categories. Blacks were significantly less likely to undergo percutaneous transluminal coronary angioplasty (odds ratio, 0.30; 95% confidence interval, 0.14-0.63 [P<.01]) when the indication was rated "equivocal." Similarly, blacks were less likely to undergo coronary artery bypass grafting (odds ratio, 0.44; 95% confidence interval, 0.23-0.86 [P<.01]) when only coronary artery bypass grafting was indicated as "appropriate and necessary." Differences in comorbidity or use of cigarettes or alcohol did nor explain these variations. Using administrative data from the Veterans Health Administration, we found no differences in 1-year (5.2% vs 7.4%) and 5-year (23.3% vs 26.2%) mortality for blacks vs whites. Conclusion: Among patients with acute myocardial infarction or unstable angina, variation in clinical factors using RAND appropriateness criteria for procedures explained some, but not all, racial differences in coronary revascularization use. C1 VA Pittsburgh Hlth Care Syst, Gen Internal Med Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, VA Ctr Study Healthcare Provider Behav, Los Angeles, CA USA. Med Coll Wisconsin, Milwaukee Vet Affairs Med Ctr, Div Gen Internal Med, Milwaukee, WI 53226 USA. Univ Alabama, Birmingham Vet Affairs Med Ctr, Div Geriatr, Birmingham, AL USA. Univ Penn, Philadelphia Vet Affairs Med Ctr, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Conigliaro, J (reprint author), VA Pittsburgh Hlth Care Syst, Gen Internal Med Sect, Locat 11E-120,Univ Dr C, Pittsburgh, PA 15240 USA. RI Allman, Richard/D-5964-2011 NR 34 TC 73 Z9 74 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 8 PY 2000 VL 160 IS 9 BP 1329 EP 1335 DI 10.1001/archinte.160.9.1329 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 312DJ UT WOS:000086927700014 PM 10809037 ER PT J AU Jiang, QS Li, JQ Dubroff, R Ahn, YJ Foskett, JK Engelhardt, J Kleyman, TR AF Jiang, QS Li, JQ Dubroff, R Ahn, YJ Foskett, JK Engelhardt, J Kleyman, TR TI Epithelial sodium channels regulate cystic fibrosis transmembrane conductance regulator chloride channels in Xenopus oocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-SURFACE EXPRESSION; NA+ CHANNEL; ARGININE-VASOPRESSIN; ALPHA-SUBUNITS; GAMMA-SUBUNITS; BETA-SUBUNITS; CL CHANNELS; A6 CELLS; CFTR; INHIBITION AB The cystic fibrosis transmembrane conductance regulator (CFTR), in addition to its well defined Cl- channel properties, regulates other ion channels, CFTR inhibits epithelial Na+ channel (ENaC) currents in many epithelial and nonepithelial cells. Because modulation of net NaCl reabsorption has important implications in extracellular fluid volume homeostasis and airway fluid volume and composition, we investigated whether this regulation was reciprocal by examining whether ENaC regulates CFTR, Co-expression of human (h) CFTR and mouse (m) alpha beta gamma ENaC in Xenopus oocytes resulted in a significant, 3.7-fold increase in whole-cell hCFTR Cl- conductance compared with oocytes expressing hCFTR alone, The forskolin/3-isobutyl-1-methylxanthine-stimulated whole-cell conductance in hCFTR-mENaC co-injected oocytes was amiloride-insensitive, indicating an inhibition of mENaC following hCFTR activation, and it was blocked by DPC (diphenylamine-2-carboxylic acid) and was DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid)-insensitive. Enhanced hCFTR Cl- conductance was also observed when either the alpha- or beta-subunit of mENaC was co-expressed with hCFTR, but this was not seen when CFTR was co-expressed with the gamma-subunit of mENaC. Single Cl- channel analyses showed that both CFTR Cl- channel open probability and the number of CFTR Cl- channels detected per patch increased when hCFTR was co-expressed with alpha beta gamma mENaC. We conclude that in addition to acting as a regulator of ENaC, CFTR activity is regulated by ENaC. C1 Univ Penn, Div Renal, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Iowa, Dept Anat, Iowa City, IA 52242 USA. RP Kleyman, TR (reprint author), Univ Penn, Div Renal, Dept Med, 700 CRB,415 Curie Blvd, Philadelphia, PA 19104 USA. OI Foskett, J. Kevin/0000-0002-8854-0268 FU NIDDK NIH HHS [DK56305] NR 50 TC 49 Z9 50 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 2000 VL 275 IS 18 BP 13266 EP 13274 DI 10.1074/jbc.275.18.13266 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312CH UT WOS:000086925300018 PM 10788432 ER PT J AU De Windt, LJ Lim, HW Haq, S Force, T Molkentin, JD AF De Windt, LJ Lim, HW Haq, S Force, T Molkentin, JD TI Calcineurin promotes protein kinase C and c-Jun NH2-terminal kinase activation in the heart - Cross-talk between cardiac hypertrophic signaling pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT VENTRICULAR MYOCYTES; MUSCLE CELL HYPERTROPHY; GENE-EXPRESSION; CARDIOMYOCYTE HYPERTROPHY; T-LYMPHOCYTES; IN-VITRO; MICE; PHOSPHORYLATION; CYCLOSPORINE; ENDOTHELIN AB Multiple intracellular signaling pathways have been shown to regulate the hypertrophic growth of cardiomyocytes, Both necessary and sufficient roles have been described for the mitogen activated protein kinase (MAPR) signaling pathway, specific protein kinase C (PKC) isoforms, and calcineurin, Here we investigate the interdependence between calcineurin, MAPK, and PKC isoforms in regulating cardiomyocyte hypertrophy using three separate approaches. Hearts from hypertrophic calcineurin transgenic mice were characterized for PKC and MAPK activation. Transgenic hearts demonstrated activation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK1/2), but not p38 MAPK factors. Calcineurin transgenic hearts demonstrated increased activation of PKC alpha, beta(1), and theta, but not of epsilon, beta(2), or lambda. In a second approach, cultured cardiomyocytes were infected with a calcineurin adenovirus to induce hypertrophy and the effects of pharmacologic inhibitors or co-infection with a dominant negative adenovirus were examined. Calcineurin-mediated hypertrophy was prevented with PKC inhibitors, Ca2+ chelation, and attenuated with a dominant negative SEK-1 (MKK4) adenovirus, but inhibitors of ERK or p38 activation had no effect. In a third approach, we examined the activation of MAPK factors and PKC isoforms during the progression of load-induced hypertrophy in aortic banded rats with or without cyclosporine. We determined that inhibition of calcineurin activity with cyclosporine prevented PKC alpha, theta, and JNK activation, but did not affect PKC epsilon, beta, lambda, ERK1/2, or p38 activation. Collectively, these data indicate that calcineurin hypertrophic signaling is interconnected with PKC alpha, theta, and JNK in the heart, while PKC epsilon, beta, lambda, p38, and ERK1/2 are not involved in calcineurin-mediated hypertrophy. C1 Univ Cincinnati, Childrens Hosp, Med Ctr, Dept Pediat,Div Mol Cardiovasc Biol, Cincinnati, OH 45229 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. RP Molkentin, JD (reprint author), Univ Cincinnati, Childrens Hosp, Med Ctr, Dept Pediat,Div Mol Cardiovasc Biol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. OI Force, Thomas/0000-0002-0450-8659 FU NHLBI NIH HHS [HL69562, HL-62927]; NIDDK NIH HHS [DK50282] NR 57 TC 174 Z9 177 U1 0 U2 9 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 MAY 5 PY 2000 VL 275 IS 18 BP 13571 EP 13579 DI 10.1074/jbc.275.18.13571 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312CH UT WOS:000086925300060 PM 10788473 ER PT J AU Rudd, CE Schneider, H AF Rudd, CE Schneider, H TI Lymphocyte signaling: Cbl sets the threshold for autoimmunity SO CURRENT BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; C-CBL; T-CELL; NEGATIVE REGULATOR; DEFICIENT MICE; BINDING DOMAIN; PHOSPHORYLATION; UBIQUITINATION; PROTOONCOGENE; TRANSDUCTION AB CbI, a negative regulator of immune signaling, ha recently been shown to act as a ubiquitin-protein Further, two new papers describing Cbl-b-deficient mice suggest that CbI-b sets the threshold of signaling in T and B cells and prevents the development of autoimmunity. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. NR 21 TC 22 Z9 22 U1 2 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 4 PY 2000 VL 10 IS 9 BP R344 EP R347 DI 10.1016/S0960-9822(00)00463-2 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 348GZ UT WOS:000088978300010 PM 10801434 ER PT J AU Ludemann, HC Hillenkamp, F Redmond, RW AF Ludemann, HC Hillenkamp, F Redmond, RW TI Photoinduced hydrogen atom transfer in salicylic acid derivatives used as matrix-assisted laser desorption/ionization (MALDI) matrices SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID IONIZATION MASS-SPECTROMETRY; INTRAMOLECULAR PROTON-TRANSFER; DESORPTION IONIZATION; 2,5-DIHYDROXYBENZOIC ACID; METHYL SALICYLATE; FLASH-PHOTOLYSIS; QUANTUM YIELDS; TRIPLET-STATES; MOLECULES; FLUORESCENCE AB The triplet states of unsubstituted and 5-substituted derivatives of salicylic acid and methyl salicylate, some of which are used as matrices in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of macromolecules, were studied in acetonitrile and cyclohexane by transient absorption and time-resolved luminescence spectroscopy. The results suggest a tautomeric structure of the triplet states of salicylic acid as well as that of its methyl ester and its 5-hydroxy- and 5-methoxy-substituted derivatives. In this tautomeric structure, the ortho-hydroxy hydrogen has been transferred to the carbonyl oxygen. No differences were observed between the triplet-triplet absorption spectra of the acids and the corresponding methyl esters. For the 5-hydroxy- and 5-methoxy-compounds, evidence for long-lived phototautomers was found. The P-type delayed fluorescence of methyl salicylate is consistent with the known tautomer fluorescence at 440 nm, implying a tautomeric structure of the triplet state. Similarly, for the 5-methoxy-substituted compound a unique delayed fluorescence spectrum, red-shifted relative to the prompt fluorescence spectrum, was observed and attributed to excimer or tautomer fluorescence, The results presented here contrast with previous reports on the absence of intramolecular hydrogen atom transfer on the singlet surface of the MALDI matrices 5-methoxy-and 5-hydroxysalicylic acid and their respective methyl esters, The resulting tautomers and their reaction products may be relevant for analyte ionization in MALDI. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. Univ Munster, Inst Med Phys & Biophys, D-48149 Munster, Germany. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, WEL 224, Boston, MA 02114 USA. NR 55 TC 22 Z9 22 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD MAY 4 PY 2000 VL 104 IS 17 BP 3884 EP 3893 DI 10.1021/jp9939470 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 311EY UT WOS:000086872800004 ER PT J AU Fadok, VA Bratton, DL Rose, DM Pearson, A Ezekewitz, RAB Henson, PM AF Fadok, VA Bratton, DL Rose, DM Pearson, A Ezekewitz, RAB Henson, PM TI A receptor for phosphatidylserine-specific clearance of apoptotic cells SO NATURE LA English DT Article ID VITRONECTIN RECEPTOR; C-ELEGANS; MEMBRANE PHOSPHATIDYLSERINE; MACROPHAGE RECOGNITION; SPERMATOGENIC CELLS; MURINE MACROPHAGES; SERTOLI CELLS; PHAGOCYTOSIS; PROTEIN; EXPOSURE AB The culmination of apoptosis in vivo is phagocytosis of cellular corpses. During apoptosis, the asymmetry of plasma membrane phospholipids is lost, which exposes phosphatidylserine externally(1-4). The phagocytosis of apoptotic cells can be inhibited stereospecifically by phosphatidylserine and its structural analogues, but not by other anionic phospholipids, suggesting that phosphatidylserine is specifically recognized(1,5-10). Using phage display, we have cloned a gene that appears to recognize phosphatidylserine on apoptotic cells. Here we show that this gene, when transfected into B and T lymphocytes, enables them to recognize and engulf apoptotic cells in a phosphatidylserine-specific manner. Flow cytometric analysis using a monoclonal antibody suggested that the protein is expressed on the surface of macrophages, fibroblasts and epithelial cells; this antibody, like phosphatidylserine liposomes, inhibited the phagocytosis of apoptotic cells and, in macrophages, induced an anti-inflammatory state. This candidate phosphatidylserine receptor is highly homologous to genes of unknown function in Caenorhabditis elegans and Drosophila melanogaster, suggesting that phosphatidylserine recognition on apoptotic cells during their removal by phagocytes is highly conserved throughout phylogeny. C1 Natl Jewish Med & Res Ctr, Dept Pediat, Denver, CO 80206 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fadok, VA (reprint author), Natl Jewish Med & Res Ctr, Dept Pediat, 1400 Jackson St, Denver, CO 80206 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 30 TC 1030 Z9 1064 U1 5 U2 39 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 4 PY 2000 VL 405 IS 6782 BP 85 EP 90 DI 10.1038/35011084 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 311TK UT WOS:000086901600056 PM 10811223 ER PT J AU Brower, RG Matthay, MA Morris, A Schoenfeld, D Thompson, BT Wheeler, A Wiedemann, HP Arroliga, AC Fisher, CJ Komara, JJ Perez-Trepichio, P Parsons, PE Wolkin, R Welsh, C Fulkerson, WJ MacIntyre, N Mallatratt, L Sebastian, M McConnell, R Wilcox, C Govert, J Thompson, D Clemmer, T Davis, R Orme, J Weaver, L Grissom, C Eskelson, M Young, M Gooder, V McBride, K Lawton, C d'Hulst, J Peerless, JR Smith, C Brownlee, J Pluss, W Kallet, R Luce, JM Gottlieb, J Elmer, M Girod, A Park, P Daniel, B Gropper, M Abraham, E Piedalue, F Glodowski, J Lockrem, J McIntyre, R Reid, K Stevens, C Kalous, D Silverman, HJ Shanholtz, C Corral, W Toews, GB Arnoldi, D Bartlett, RH Dechert, R Watts, C Lanken, PN Anderson, H Finkel, B Hanson, CW Barton, R Mone, M Hudson, LD Lee, C Carter, G Maier, RV Steinberg, KP Bernard, G Stroud, M Swindell, B Stone, L Collins, L Mogan, S Ancukiewicz, M Hayden, D Molay, F Ringwood, N Wenzlow, G Kazeroonian, AS Gail, DB Bosken, CH Randall, P Waclawiw, M Spragg, RG Boyett, J Kelley, J Leeper, K Secundy, MG Slutsky, A Hyers, TM Emerson, SS Garcia, JGN Marini, JJ Pingleton, SK Shasby, MD Sibbald, WJ AF Brower, RG Matthay, MA Morris, A Schoenfeld, D Thompson, BT Wheeler, A Wiedemann, HP Arroliga, AC Fisher, CJ Komara, JJ Perez-Trepichio, P Parsons, PE Wolkin, R Welsh, C Fulkerson, WJ MacIntyre, N Mallatratt, L Sebastian, M McConnell, R Wilcox, C Govert, J Thompson, D Clemmer, T Davis, R Orme, J Weaver, L Grissom, C Eskelson, M Young, M Gooder, V McBride, K Lawton, C d'Hulst, J Peerless, JR Smith, C Brownlee, J Pluss, W Kallet, R Luce, JM Gottlieb, J Elmer, M Girod, A Park, P Daniel, B Gropper, M Abraham, E Piedalue, F Glodowski, J Lockrem, J McIntyre, R Reid, K Stevens, C Kalous, D Silverman, HJ Shanholtz, C Corral, W Toews, GB Arnoldi, D Bartlett, RH Dechert, R Watts, C Lanken, PN Anderson, H Finkel, B Hanson, CW Barton, R Mone, M Hudson, LD Lee, C Carter, G Maier, RV Steinberg, KP Bernard, G Stroud, M Swindell, B Stone, L Collins, L Mogan, S Ancukiewicz, M Hayden, D Molay, F Ringwood, N Wenzlow, G Kazeroonian, AS Gail, DB Bosken, CH Randall, P Waclawiw, M Spragg, RG Boyett, J Kelley, J Leeper, K Secundy, MG Slutsky, A Hyers, TM Emerson, SS Garcia, JGN Marini, JJ Pingleton, SK Shasby, MD Sibbald, WJ CA Acute Resp Distress Syndrome Netwo TI Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT International Conference of the American-Lung-Association/American-Thoracic-Society CY APR 26, 1999 CL SAN DIEGO, CALIFORNIA SP Amer Lung Assoc, Amer Thorac Soc ID PRESSURE-LIMITED VENTILATION; END-EXPIRATORY PRESSURE; MECHANICAL VENTILATION; PERMISSIVE HYPERCAPNIA; AIRWAY PRESSURES; CLINICAL-TRIALS; MORTALITY; SYSTEM; ADULTS; BAROTRAUMA AB Background: Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. Methods: Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The first primary outcome was death before a patient was discharged home and was breathing without assistance. The second primary outcome was the number of days without ventilator use from day 1 to day 28. Results: The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P<0.001), respectively, and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water (P<0.001), respectively. Conclusions: In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use. (N Engl J Med 2000;342:1301-8.) (C) 2000, Massachusetts Medical Society. C1 Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD 21287 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. LDS Hosp, Salt Lake City, UT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN USA. Denver Hlth Med Ctr, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Metrohlth Med Ctr, Cleveland, OH USA. Rose Med Ctr, Denver, CO USA. San Francisco Gen Hosp, Med Ctr, San Francisco, CA 94110 USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. Univ Maryland, College Pk, MD 20742 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Utah Hosp, Salt Lake City, UT USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Brower, RG (reprint author), Johns Hopkins Univ, Div Pulm & Crit Care Med, 600 N Wolfe St, Baltimore, MD 21287 USA. RI Garcia, Joe/E-8862-2010 NR 42 TC 4282 Z9 4413 U1 14 U2 113 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 MAY 4 PY 2000 VL 342 IS 18 BP 1301 EP 1308 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 309RE UT WOS:000086782400001 ER PT J AU Blobe, GC Schiemann, WP Lodish, HF AF Blobe, GC Schiemann, WP Lodish, HF TI Mechanisms of disease: Role of transforming growth factor beta in human disease. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; TGF-BETA; BREAST-CANCER; TUMOR-SUPPRESSOR; TRANSGENIC MICE; IN-VIVO; MICROSATELLITE INSTABILITY; GROWTH-FACTOR-BETA-1 GENE; COLORECTAL CANCERS; ENDOTHELIAL-CELLS C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lodish, HF (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [CA73161-01, CA63260] NR 93 TC 1587 Z9 1700 U1 7 U2 65 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 MAY 4 PY 2000 VL 342 IS 18 BP 1350 EP 1358 DI 10.1056/NEJM200005043421807 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 309RE UT WOS:000086782400007 PM 10793168 ER PT J AU Casarett, D Karlawish, JHT Sugarman, J AF Casarett, D Karlawish, JHT Sugarman, J TI Determining when quality improvement initiatives should be considered research - Proposed criteria and potential implications SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEALTH-SERVICES RESEARCH; NUCHAL-TRANSLUCENCY; SATISFACTION; DELIVERY; CONDUCT; PROJECT; CARE AB Quality improvement initiatives have become a major force in shaping health care, These initiatives are diverse but share a common goal of generating knowledge that will guide improvements in health care, Although quality improvement occupies an uncertain territory between clinical care and research, this difference is extremely important, If a quality improvement initiative is research, federal regulations require a variety of procedures that must be followed to protect the human subjects involved. Conversely, if the same initiative is not research, the regulations outlining these procedures are not applicable. This article proposes 2 criteria to determine whether a quality improvement initiative should be reviewed as research, Such an initiative should be reviewed and regulated as research if (1) the majority of patients involved are not expected to benefit directly from the knowledge to be gained or (2) if additional risks or burdens are imposed to make the results generalizable. Implementation of these criteria offers the possibility that the rights and interests of those who participate in quality improvement initiatives will be protected. C1 Univ Penn, Ctr Bioeth, Inst Aging, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Alzheimers Dis Ctr, Philadelphia, PA USA. Duke Univ, Dept Med, Durham, NC USA. Duke Univ, Dept Philosophy, Durham, NC USA. Duke Univ, Ctr Study Med Eth & Humanities, Durham, NC USA. RP Casarett, D (reprint author), Univ Penn, Ctr Bioeth, Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 18 TC 103 Z9 103 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 3 PY 2000 VL 283 IS 17 BP 2275 EP 2280 DI 10.1001/jama.283.17.2275 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 307UB UT WOS:000086671600036 PM 10807388 ER PT J AU Williams, JW Mulrow, CD Chiquette, E Noel, PH Aguilar, C Cornell, J AF Williams, JW Mulrow, CD Chiquette, E Noel, PH Aguilar, C Cornell, J TI A systematic review of newer pharmacotherapies for depression in adults: Evidence report summary SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID SEROTONIN REUPTAKE INHIBITORS; NATIONAL-COMORBIDITY-SURVEY; RANDOMIZED CLINICAL-TRIALS; LONG-TERM TREATMENT; ST-JOHNS WORT; PRIMARY-CARE; DOUBLE-BLIND; MAJOR DEPRESSION; TRICYCLIC ANTIDEPRESSANTS; DISCONTINUATION RATES AB Background: Depressive disorders are persistent, recurring illnesses that cause great suffering for patients and their families. Purpose: To evaluate the benefits and adverse effects of newer pharmacotherapies and herbal treatments for depressive disorders in adults and adolescents. Data Sources: English-language and non-English-language literature from 1980 to January 1998 was identified from a specialized registry of controlled trials, meta-analyses, and experts. Study Selection: Randomized trials evaluating newer antidepressants (such as serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and St. John's wort) that reported clinical outcomes were selected. Data Extraction: Two persons independently abstracted data that were then synthesized descriptively; some data were pooled by using a random-effects model. Data Synthesis: Of 315 eligible trials, most evaluated antidepressants in adults with major depression, were conducted among outpatients, and examined acute-phase treatment. Newer antidepressants were more effective than placebo for major depression (relative benefit, 1.6 [95% CI, 1.5 to 1.7]) and dysthymia (relative benefit, 1.7 [CI, 1.3 to 2.3]). They were effective among older adults and primary care patients. Efficacy did not differ among newer agents or between newer and older agents. Hypericum (St. John's wort) was more effective than placebo for mild to moderate depression (risk ratio, 1.9 [Cl, 1.2 to 2.8]), but publication bias may have inflated the estimate of benefit. Newer and older antidepressants did not differ for overall discontinuation rates, but side effect profiles varied significantly. Data were insufficient for determining the efficacy of newer antidepressants for subsyndromal depression, depression with coexisting medical or psychiatric illness, or depression in adolescents. Conclusions: Newer antidepressants are clearly effective in treating depressive disorders in diverse settings. Because of similar efficacy, both newer and older antidepressants should be considered when making treatment decisions. Better information is urgently needed on the efficacy of newer antidepressants in patients with nonmajor depression and in special populations, including adolescents. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio Evidence Based Practice Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, Kerrville, TX USA. RP Williams, JW (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio Evidence Based Practice Ctr, 7703 Floyd Curl Dr,Mail Code 7879, San Antonio, TX 78229 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 FU PHS HHS [290-97-0012] NR 114 TC 236 Z9 242 U1 4 U2 24 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 2 PY 2000 VL 132 IS 9 BP 743 EP 756 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 308VT UT WOS:000086734100010 PM 10787370 ER PT J AU Prabhu, SD Chandrasekar, B Murray, DR Freeman, GL AF Prabhu, SD Chandrasekar, B Murray, DR Freeman, GL TI beta-adrenergic blockade in developing heart failure - Effects on myocardial inflammatory cytokines, nitric oxide, and remodeling SO CIRCULATION LA English DT Article DE heart failure; adrenergic beta antagonists; cytokines; nitric oxide; myocardial infarction ID NECROSIS-FACTOR-ALPHA; RAT CARDIAC MYOCYTES; FAILING HUMAN HEART; EXPRESSION; STIMULATION; SYNTHASE; DYSFUNCTION; INFARCTION; INHIBITION; MECHANISM AB Background-Whether beta-adrenergic blockade modulates myocardial expression of inflammatory cytokines and nitric oxide (NO) in heart failure is unclear. Methods and Results-We administered oral metoprolol or no therapy to rats for 12 weeks after large myocardial infarction and subsequently examined left ventricular (LV) remodeling; myocardial tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 expression; and NO. In untreated rats, echocardiography revealed significant (P<0.001) LV dilatation and systolic dysfunction compared with sham. Papillary muscle studies revealed isoproterenol hyporesponsiveness to be unaltered by NO synthase (NOS) inhibition. Circulating NO metabolites were undetectable. In noninfarcted myocardium, although inducible NOS (iNOS) mRNA was absent, TNF-alpha, IL-1 beta, and IL-6 mRNA and protein were markedly elevated compared with sham (P<0.001), with 2-fold higher expression (P<0.025) of IL-6 compared with TNF-alpha or IL-1 beta. Metoprolol administration starting 48 hours after infarction (1) attenuated (P<0.02) LV dilatation and systolic dysfunction, (2) preserved isoproterenol responsiveness (P<0.025) via NO-independent mechanisms, and (3) reduced myocardial gene expression and protein production of TNF-alpha and IL-1 beta (P<0.025) but not IL-6, which remained high. Conclusions-During heart failure development, adrenergic activation contributes to increased myocardial expression of TNF-alpha and IL-1 beta but not TL-6, and one mechanism underlying the beneficial effects of beta-adrenergic blockade may involve attenuation of TNF-alpha and IL-1 beta expression independent of iNOS and NO. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. RP Prabhu, SD (reprint author), Univ Louisville, Dept Med Cardiol, ACB, 3rd Floor,550 S Jackson St, Louisville, KY 40292 USA. RI Prabhu, Sumanth/D-5223-2009 NR 28 TC 180 Z9 207 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 2 PY 2000 VL 101 IS 17 BP 2103 EP 2109 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 310EH UT WOS:000086813200016 PM 10790354 ER PT J AU Peters, AS Greenberger-Rosovsky, R Crowder, C Block, SD Moore, GT AF Peters, AS Greenberger-Rosovsky, R Crowder, C Block, SD Moore, GT TI Long-term outcomes of the new pathway program at Harvard medical school: A randomized controlled trial SO ACADEMIC MEDICINE LA English DT Article ID STUDENTS AB Purpose. To evaluate the long-term effects of an innovative curriculum, the New Pathway (NP) Program, on behaviors and attitudes related to humanistic medicine, lifelong learning, and social learning. Method. Long-term follow-up of Harvard Medical School students who participated in a randomized controlled trial. Descriptive study using 1998 telephone interviews of 100 1989 and 1990 graduates (50 who had studied the NP curriculum, 50 who had studied the traditional curriculum). The NP Program consisted of problem-based learning tutorials, with coordinated lectures, labs, experiences in humanistic medicine, and clinical experiences; the traditional program consisted of basic science lectures and labs. Results. Of 22 measures on the survey NP and traditional students differed significantly on only five (three humanism; two social learning): 40% of NP students and 18% of traditional students went on to practice primary care or psychiatry. NP students rated their preparation to practice humanistic medicine higher than did traditional students and expressed more confidence in their ability to manage patients with psychosocial problems. NP students were more likely than were traditional students to believe that faculty from the first two years continued to influence their thinking. NP students liked the pedagogic approaches of their program more than traditional students did. There was no difference between the groups on measures of lifelong learning. Conclusions. Differences between NP and traditional students in the humanism domain first appeared during medical school and residency and remained significant well into practice, suggesting that humanistic medicine can be taught and learned. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Brigham & Womens Hosp, Div Psychiat, Boston, MA 02115 USA. Dana Farber Canc Inst, Adult Psychosocial Oncol Program, Boston, MA USA. RP Peters, AS (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 126 Brookline Ave, Boston, MA 02215 USA. NR 13 TC 75 Z9 79 U1 0 U2 7 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 MAY PY 2000 VL 75 IS 5 BP 470 EP 479 DI 10.1097/00001888-200005000-00018 PG 10 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 313JQ UT WOS:000086996900016 PM 10824772 ER PT J AU de la Monte, SM Ganju, N Banerjee, K Brown, NV Luong, T Wands, JR AF de la Monte, SM Ganju, N Banerjee, K Brown, NV Luong, T Wands, JR TI Partial rescue of ethanol-induced neuronal apoptosis by growth factor activation of phosphoinositol-3-kinase SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ethanol; neuron; insulin; signal transduction; apoptosis ID CEREBELLAR GRANULE NEURONS; INSULIN-RECEPTOR SUBSTRATE-1; CENTRAL NERVOUS-SYSTEM; PROGRAMMED CELL-DEATH; C-JUN; PHOSPHATIDYLINOSITOL 3-KINASE; FACTOR-II; ALZHEIMERS-DISEASE; PROTEIN EXPRESSION; NEURITE FORMATION AB Background: Ethanol inhibition of insulin signaling pathways may contribute to impaired central nervous system (CNS) development in the fetal alcohol syndrome and brain atrophy associated with alcoholic neurodegeneration. Previous studies demonstrated ethanol inhibition of insulin-stimulated growth in PNET2 CNS-derived proliferative (immature) neuronal cells. We now provide evidence that the growth-inhibitory effect of ethanol in insulin-stimulated PNET2 cells is partly due to apoptosis. Methods: Control and ethanol-treated PNET2 cells were stimulated with insulin and analyzed for viability, apoptosis, activation of pro-apoptosis and survival gene expression and signaling pathways, and evidence of caspase activation. Results: Ethanol-treated PNET2 neuronal cells exhibited increased apoptosis mediated by increased levels of p53 and phospho-amino-terminal c-jun kinase (phospho-JNK), and reduced levels of Bcl-2, phosphoinositol 3-kinase (PI3 K), and intact (similar to 116 kD) poly (ADP ribose) polymerase (PARP), a deoxyribonucleic acid repair enzyme and important substrate for caspase 3. Partial rescue from ethanol-induced neuronal cell death was effected by culturing the cells in medium that contained 2% fetal calf serum instead of insulin, or insulin plus either insulin-like growth factor type I or nerve growth factor. The resulting enhanced viability was associated with reduced levels of p53 and phospho-JNK and increased levels of PI3 K and intact PARP. Conclusions: The findings suggest that ethanol-induced apoptosis of insulin-stimulated neuronal cells can be reduced by activating PI3 K and inhibiting pro-apoptosis gene expression and intracellular signaling through non-insulin-dependent pathways. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH E Canc Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP de la Monte, SM (reprint author), Rhode Isl Hosp, Pierre Galletti Res Bldg,55 Claverick St,Room 419, Providence, RI 02903 USA. FU NIAAA NIH HHS [AA-11431, AA-02666, AA-02169] NR 78 TC 72 Z9 73 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2000 VL 24 IS 5 BP 716 EP 726 DI 10.1097/00000374-200005000-00017 PG 11 WC Substance Abuse SC Substance Abuse GA 317FU UT WOS:000087216000017 PM 10832914 ER PT J AU Lloyd-Jones, DM Camargo, CA Giugliano, RP O'Donnell, CJ AF Lloyd-Jones, DM Camargo, CA Giugliano, RP O'Donnell, CJ TI Effect of leukocytosis at initial examination on prognosis in patients with primary unstable angina SO AMERICAN HEART JOURNAL LA English DT Article ID C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; BLOOD-CELL COUNT; CORONARY HEART-DISEASE; TROPONIN-T; MORTALITY; PECTORIS; PREDICTORS; FIBRINOGEN; INSIGHTS AB Background Leukocytosis with acute myocardial infarction at initial examination predicts adverse prognosis, but it is unknown whether it predicts outcome in patients with primary unstable angina. Methods and Results We studied 414 consecutive patients with unstable angina admitted through the emergency department to telemetry and intensive care units of an urban academic hospital. To study primary unstable angina, we excluded 134 patients with precipitants (eg, urosepsis, pneumonia) that may cause leukocytosis. Of 280 patients, 96 (34%) had leukocytosis (leukocyte count >10,000 per mu L) at initial examination. A total of 30 patients (11%) died and 47 (17%) died or had nonfatal myocardial infarction within 12 months of initial examination. In a univariate Cox model, patients with leukocytosis had a hazard ratio (HR) of 2.6 (95% confidence interval [CI] 1.3-5.4) for death by 1 year. In a multivariate Cox model the only significant predictors of 1-year death were congestive heart failure at initial examination (HR 7.8; 95% CI 2.8-22) and elevated creatinine (HR 2.7; 95% CI 1.3-5.7); in this model, the relation between leukocytosis and prognosis was markedly attenuated (HR 1.4, 95% CI 0.6-2.9). The adjusted HR for leukocytosis was 1.3 (95% CI 0.7-2.3) for death or nonfatal MI by 1 year. Conclusions Leukocytosis at initial examination is associated with adverse prognosis in patients with primary unstable angina. However, the association is confounded by other important predictors of prognosis. Leukocytosis may be a marker of stress associated with more severe cases of unstable angina or comorbid conditions. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Lloyd-Jones, DM (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [HL03533, HL07575] NR 32 TC 10 Z9 11 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2000 VL 139 IS 5 BP 867 EP 873 DI 10.1016/S0002-8703(00)90019-X PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 312XZ UT WOS:000086970400020 PM 10783221 ER PT J AU Sarosiek, J Jensen, RT Maton, PN Peura, DA Harlow, D Feng, TQ McCallum, RW Pisegna, JR AF Sarosiek, J Jensen, RT Maton, PN Peura, DA Harlow, D Feng, TQ McCallum, RW Pisegna, JR TI Salivary and gastric epidermal growth factor in patients with Zollinger-Ellison Syndrome: Its protective potential SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; HELICOBACTER-PYLORI; ESOPHAGEAL MUCOSA; ACID; SECRETION; RELEASE; HUMANS; ESOPHAGOPROTECTION; CYTOPROTECTION; PROSTAGLANDINS AB OBJECTIVE: Evidence is accumulating that epidermal growth factor (EGF) is a major molecule contributing to the maintenance of the integrity of the upper alimentary tract mucosa before and after injury by acid and pepsin. Patients with Zollinger-Ellison Syndrome (ZES) typically have hypersecretion of acid and pepsin; however, the concentration and rate of secretion of salivary and gastric EGF that could counteract these potentially aggressive factors are unknown. Accordingly, this study was conducted to determine whether EGF affords mucosal protection in ZES patients. METHODS: The concentration and output of salivary (sEGF) and gastric epidermal growth factor (gEGF) were measured in eight patients with ZES and the results compared to those in 17 patients with nonulcer dyspepsia (NUD), serving as a control group. All patients had normal esophageal and gastric mucosa as determined by endoscopy. Total saliva was collected during l-h parafilm- and l-h pentagastrin/parafilm-stimulated conditions, as well as basal and pentagastrin-stimulated gastric juice. The concentration and output of EGF were determined by radioimmunoassay. RESULTS: The concentration of EGF in saliva collected from ZES patients after parafilm chewing was significantly higher compared to that in NUD patients (4.61 +/- 0.59 vs 2.75 +/- 0.50 ng/ml, p < 0.05). The concentration of EGF in saliva collected after pentagastrin stimulation in ZES patients was also significantly higher than in NUD patients (4.37 +/- 0.73 vs 2.22 +/- 0.37 ng/ml, p < 0.05). Salivary EGF output during parafilm chewing in ZES and NUD were similar (68 +/- 6.4 vs 109 +/- 25.2 ng/h). Salivary EGF output after administration of pentagastrin in ZES and NUD was also similar (66 +/- 6.1 vs 132 +/- 45.4 ng/h). Basal EGF output in the gastric juice of patients with ZES was 3-fold higher than in patients with NUD (801 +/- 73 la 271 +/- 32 ng/h, p < 0.01). Pentagastrin-stimulated EGF output was similar in both groups (705 +/- 92 Is 675 +/- 168 ng/h). CONCLUSIONS: Patients with ZES have a significantly higher EGF concentration in saliva and EGF output in basal gastric juice. This elevated content of salivary and gastric EGF in ZES patients may ploy a protective role in preventing the development of reflux esophagitis and gastric ulcer under the impact of gastric acid and pepsin hypersecretion. (C) 2000 by Am. Cell. of Gastroenterology. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Training Program Gastroenterol, Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. NIH, Digest Dis Branch, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22903 USA. RP Pisegna, JR (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Training Program Gastroenterol, Vet Affairs Greater Los Angeles Hlth Care Syst, Bldg 115,Room 316, Los Angeles, CA 90073 USA. NR 42 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2000 VL 95 IS 5 BP 1158 EP 1165 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 310WW UT WOS:000086853300010 PM 10811321 ER PT J AU Chey, WD Metz, DC Shaw, S Kearney, D Montague, J Murthy, U AF Chey, WD Metz, DC Shaw, S Kearney, D Montague, J Murthy, U TI Appropriate timing of the C-14-urea breath test to establish eradication of Helicobacter pylori infection SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID SUPPRESSION; DYSPEPSIA; ACCURACY AB OBJECTIVE: The aim of this study was to determine the performance characteristics of the C-14-urea breath test (UBT) performed 2 wk after the completion of therapy for Helicobacter pylori using a 4 to 6 wk study as the gold standard. METHODS: Patients with active Helicobacter pylori infection at four medical centers received proton pump inhibitor-based triple or quadruple therapy for 10-14 days. Patients underwent the C-14-UBT 2 and 4-6 wk after the completion of therapy. A positive test was defined as (CO2)-C-14 excretion of >200 dpm, a negative test as <50 dpm, and an equivocal test as >50 but <200 dpm. Performance characteristics of the 2-wk UBT were calculated using the 4 to 6-wk result as a gold standard. RESULTS: Eighty-five patients were enrolled and 82 patients (mean +/- SD age, 62 +/- 15 yr; 15 women) completed the protocol. Four patients had equivocal UBT results and were excluded from the analysis. Of the 78 patients, 68 (87%) had a negative 4 to 6-wk UBT. The 2-week UBT yielded a sensitivity of 90% (95% confidence interval 72-100%), specificity of 99% (97-100%), and accuracy of 97% (93-100%). In patients with a persistently positive UBT, (CO2)-C-14 excretion at 2 wk was significantly lower than at 4-6 wk after therapy (p = 0.03). CONCLUSIONS: A UBT performed 2 wk after therapy yielded results comparable to 4 to 6 wk testing. Further studies to evaluate the optimal time of confirmatory testing in the age of more effective proton pump inhibitor-based triple therapies are warranted. (C) 2000 by Am. Cell. of Gastroenterology. C1 Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Univ Penn Hlth Syst, Philadelphia, PA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. VA Med Ctr, Syracuse, NY USA. RP Chey, WD (reprint author), 3912 Taubman Ctr, Box 0362, Ann Arbor, MI 48109 USA. NR 15 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2000 VL 95 IS 5 BP 1171 EP 1174 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 310WW UT WOS:000086853300012 PM 10811323 ER PT J AU Santhosh-Kumar, CR Bisping, JS Kick, SD Deutsch, JC Kolhouse, JF AF Santhosh-Kumar, CR Bisping, JS Kick, SD Deutsch, JC Kolhouse, JF TI Folate sufficient subjects do not accumulate additional folates during supplementation SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE folate assays; insufficiency; deficiency ID HOMOCYSTEINE; WOMEN; SERUM; ACID AB In a double-blinded placebo-controlled trial of folic acid supplementation in 82 alcoholic subjects, it was found that whole blood folate levels, determined by a mass spectrometric method, do not increase in subjects whose baseline folate levels are above the third quartile (folate sufficiency). Since a state of folate sufficiency can now be identified, a recommended daily allowance (RDA) for folate can be determined using objective means, Am. J. Hematol, 64:71-72, 2000. (C) 2000 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Div Hematol, Denver, CO 80262 USA. Denver VAH, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Gastroenterol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Denver, CO 80262 USA. Royal Hosp, Dept Med, Muscat, Oman. RP Kolhouse, JF (reprint author), Univ Colorado, Hlth Sci Ctr, Div Hematol, 4200 E 9th Ave,B-170, Denver, CO 80262 USA. FU NIDDK NIH HHS [R44 DK50519] NR 10 TC 4 Z9 4 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2000 VL 64 IS 1 BP 71 EP 72 DI 10.1002/(SICI)1096-8652(200005)64:1<71::AID-AJH13>3.0.CO;2-Z PG 2 WC Hematology SC Hematology GA 306HB UT WOS:000086590300013 PM 10815792 ER PT J AU Grimm, C AF Grimm, C TI Teaching managed care principles: We need to do better SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Editorial Material ID RESIDENTS; MEDICINE; ENVIRONMENT; SYSTEMS C1 VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Los Angeles, CA USA. RP Grimm, C (reprint author), St Vincents Med Ctr, 2800 Main St,Level 8, Bridgeport, CT 06606 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD MAY PY 2000 VL 6 IS 5 BP 625 EP 627 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 313XG UT WOS:000087024500008 PM 10977470 ER PT J AU Rudski, LG Picard, MH AF Rudski, LG Picard, MH TI Artifacts, truths, and consequences SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID TRANSESOPHAGEAL ECHOCARDIOGRAPHY; REGURGITATION; FLOW; DIAGNOSIS; ORIFICE C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, VBK508,55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 14 TC 2 Z9 2 U1 0 U2 0 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 MAY PY 2000 VL 108 IS 7 BP 589 EP 591 DI 10.1016/S0002-9343(00)00326-0 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 312LQ UT WOS:000086945100011 PM 10806292 ER PT J AU Lev, MH AF Lev, MH TI Diffusion-weighted MR imaging of multiple sclerosis: added clinical value or "just another pretty face?" SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material ID MAGNETIC-RESONANCE; LESIONS; ANISOTROPY; BRAIN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 13 TC 1 Z9 2 U1 0 U2 0 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 MAY PY 2000 VL 21 IS 5 BP 805 EP 808 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 313CU UT WOS:000086983400002 PM 10815651 ER PT J AU Staecker, H Nadol, JB Ojeman, R Ronner, S McKenna, MJ AF Staecker, H Nadol, JB Ojeman, R Ronner, S McKenna, MJ TI Wearing preservation in acoustic neuroma surgery: Middle fossa versus retrosigmoid approach SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article DE hearing preservation surgery; retrosigmoid approach; middle fossa approach; intracanalicular tumor ID HEARING PRESERVATION; CEREBELLOPONTINE ANGLE; TUMOR SURGERY; COCHLEAR NERVE; REMOVAL; RESECTION; MONKEYS AB Objective: To compare the results of the middle fossa approach with those of the retrosigmoid approach in acoustic neuroma hearing preservation surgery, Study Design: Retrospective review. Setting: Tertiary care facility. Patients: patients of the otology service with acoustic neuromas and useful hearing. Fifteen intracanalicular tumors were removed via a middle fossa approach and matched with 15 intracanalicular tumors removed via the retrosigmoid approach. Four additional patients with larger tumors were operated on via the middle fossa approach and matched with patients having similar turners removed via the retrosigmoid approach. Main Outcome Measures: The 1994 Committee on Hearing and Equilibrium guidelines for the evaluation of hearing preservation in acoustic neuroma were applied. Facial nerve results were graded according to the House-Brackmann grading scale 3 months postoperatively. Results: In the group operated on by the middle fossa approach, the average preoperative pure-tone threshold average (PTA) was 23 dB with a word recognition score (WRS) of 79%, and the postoperative PTA averaged 49 dB with a mean WRS of 56%. In the group operated on by the retrosigmoid approach, the mean preoperative PTA was 16 dB with a WRS of 95% and a postoperative PTA value of 62 dB and WRS of 51% (hearing preservation rate of 47%). The middle fossa patients had an average change in PTA of 19 dB and an average change in WRS of 20% (hearing preservation rare of 57%). Overall, the retrosigmoid patients had an average change in PTA of 42 dB and an average change in WRS of 40%. The average change in PTA for larger tumors removed via the middle fossa approach was 32 dB, whereas all matched retrosigmoid patients lost all hearing. The rate of cerebrospinal fluid leak and facial nerve outcomes were similar between the two groups. The retrosigmoid group had a higher rate of post operative headache. Conclusions: Compared with the retrosigmoid approach, the middle fossa approach for hearing preservation surgery yields better hearing results for intracanalicular tumors and also has a lower incidence of postoperative headache. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. RP McKenna, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. OI Staecker, Hinrich/0000-0002-0348-3015 NR 28 TC 60 Z9 64 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD MAY PY 2000 VL 21 IS 3 BP 399 EP 404 DI 10.1016/S0196-0709(00)80051-4 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 311UL UT WOS:000086904000020 PM 10821555 ER PT J AU Gimm, O Perren, A Weng, LP Marsh, DJ Yeh, JJ Ziebold, U Gil, E Hinze, R Delbridge, L Lees, JA Mutter, GL Robinson, BG Komminoth, P Dralle, H Eng, C AF Gimm, O Perren, A Weng, LP Marsh, DJ Yeh, JJ Ziebold, U Gil, E Hinze, R Delbridge, L Lees, JA Mutter, GL Robinson, BG Komminoth, P Dralle, H Eng, C TI Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SUPPRESSOR PTEN; PHOSPHATASE-ACTIVITY; CELL-SURVIVAL; GLIOBLASTOMA CELLS; GERMLINE MUTATIONS; PROSTATE-CANCER; COWDENS DISEASE; PTEN/MMAC1; GENE; GROWTH AB Germline mutations In PTEN (MMAC1/TEP1) are found in patients with Cowden syndrome, a familial cancer syndrome which is characterized by a high risk of breast and thyroid neoplasia, Although somatic Intragenic PTEN mutations have rarely been found in benign and malignant sporadic thyroid tumors, loss of heterozygosity (LOH) has been reported in up to one fourth of follicular thyroid adenomas (FAs) and carcinomas, In this study, we examined PTEN expression In 139 sporadic nonmedullary thyroid tumors (55 FA, 27 follicular thyroid carcinomas, 35 papillary thyroid carcinomas, and 22 undifferentiated thyroid carcinomas) using immunohistochemistry and correlated this to the results of LOH studies. Normal follicular thyroid cells showed a strong to moderate nuclear or nuclear membrane signal although the cytoplasmic staining was less strong. In FAs the neoplastic nuclei had less intense PTEN staining, although the cytoplasmic PTEN-staining intensity did not differ significantly from that observed in normal follicular cells. In thyroid carcinomas as a group, nuclear PTEN immunostaining was mostly weak in comparison with normal thyroid follicular cells and FAs. The cytoplasmic staining was more intense than the nuclear staining in 35 to 49% of carcinomas, depending on the histological type. Among 81 informative tumors assessed for LOH, there seemed to be an associative trend between decreased nuclear and cytoplasmic staining and 10q23 LOH (P = 0.003, P = 0.008, respectively). These data support a role for PTEN in the pathogenesis of follicular thyroid tumors. 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. Univ Zurich, Dept Pathol, CH-8006 Zurich, Switzerland. Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. MIT, Boston, MA USA. Univ Halle Wittenberg, Dept Pathol, Halle, Germany. Univ Halle Wittenberg, Dept Surg, Halle, Germany. Univ Sydney, Royal N Shore Hosp, Dept Surg, St Leonards, NSW 2065, Australia. Univ Sydney, Royal N Shore Hosp, Kolling Inst Med Res, St Leonards, NSW 2065, Australia. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Cambridge, Canc Res Campaign Human Canc Genet Res Grp, Cambridge, England. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, 420 W 12th Ave,Room 690C Med Rec Facil, Columbus, OH 43210 USA. RI Mutter, George/C-5819-2009; Ziebold, Ulrike/N-4487-2013; Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145; Perren, Aurel/0000-0002-6819-6092 FU NCI NIH HHS [P30 CA016058, P30CA16058] NR 45 TC 215 Z9 231 U1 0 U2 7 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2000 VL 156 IS 5 BP 1693 EP 1700 DI 10.1016/S0002-9440(10)65040-7 PG 8 WC Pathology SC Pathology GA 312XY UT WOS:000086970300023 PM 10793080 ER PT J AU Miyamoto, K Khosrof, S Bursell, SE Moromizato, Y Aiello, LP Ogura, Y Adamis, AP AF Miyamoto, K Khosrof, S Bursell, SE Moromizato, Y Aiello, LP Ogura, Y Adamis, AP TI Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability is mediated by intercellular adhesion molecule-1 (ICAM-1) SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; IN-VIVO; LEUKOCYTE ADHESION; TRANSGENIC MICE; EXPRESSION; ANGIOGENESIS; CELLS; RATS; NEOVASCULARIZATION; MICROCIRCULATION AB Two prominent vascular endothelial growth factor (VEGF)-induced retinal effects are vascular permeability and capillary nonperfusion. The mechanisms by which these effects occur are not completely known. Using a rat model, we show that intravitreous injections of VEGF precipitate an extensive retinal leukocyte stasis (leukostasis) that coincides with enhanced vascular permeability and capillary nonperfusion. The leukostasis is accompanied by the up-regulation of intercellular adhesion molecule-1 expression in the retina. The inhibition of intercellular adhesion molecule-1 bioactivity with a neutralizing antibody prevents the permeability and leukostasis increases by 79% and 54%, respectively. These data are the first to demonstrate that a nonendothelial cell type contributes to VEGF-induced vascular permeability. Additionally, they identify a potential mechanism for VEGF-induced retinal capillary nonperfusion. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Surg Res Lab, Boston, MA 02115 USA. Harvard Univ, Joslin Diabet Ctr, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Nagoya City Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 467, Japan. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [R01 EY12611, EY11627] NR 35 TC 191 Z9 204 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 MAY PY 2000 VL 156 IS 5 BP 1733 EP 1739 DI 10.1016/S0002-9440(10)65044-4 PG 7 WC Pathology SC Pathology GA 312XY UT WOS:000086970300027 PM 10793084 ER PT J AU Breton, S Nsumu, NN Galli, T Sabolic I Smith, PJS Brown, D AF Breton, S Nsumu, NN Galli, T Sabolic, I Smith, PJS Brown, D TI Tetanus toxin-mediated cleavage of cellubrevin inhibits proton secretion in the male reproductive tract SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE vas deferens; epididymis; hydrogen-adenosine 3 ' 5 '-triphosphatase; vesicle endocytosis; soluble N-ethyl malemide-sensitive factor attachment protein receptors ID SYNAPTIC VESICLE FUSION; APICAL PLASMA-MEMBRANE; EPITHELIAL-CELLS; ADENOSINE-TRIPHOSPHATASE; CLOSTRIDIAL NEUROTOXINS; CARBONIC-ANHYDRASE; RAT EPIDIDYMIS; INTERCALATED CELLS; ALKALI LOADS; CHRONIC ACID AB Our laboratory has previously shown that the vacuolar H(+)-ATPase, located in a subpopulation of specialized cells establishes a luminal acidic environment in the epididymis and proximal part of the vas deferens (Breton S, Smith PJS, Lui B, and Brown D. Nat Med 2: 470-472, 1996). Low luminal pH is critical for sperm maturation and maintenance of sperm in a quiescent state during storage in these organs. In the present study we examined the regulation of proton secretion in the epididymis and vas deferens. In vivo microtubule disruption by colchicine induced an almost complete loss of H(+)-ATPase apical polarity. Endocytotic vesicles, visualized by Texas red-dextran internalization, contain H(+)-ATPase, indicating active endocytosis of the pump. Cellubrevin, an analog of the vesicle soluble N-ethyl malemide-sensitive factor attachment protein (SNAP) receptor (V-SNARE) synaptobrevin, is highly enriched in H(+)-ATPase-rich cells of the epididymis and vas deferens, and tetanus toxin treatment markedly inhibited bafilomycin-sensitive proton secretion by 64.3 +/- 9.0% in the proximal vas deferens. Western blotting showed effective cleavage of cellubrevin by tetanus toxin in intact vas deferens, demonstrating that the toxin gained access to cellubrevin. These results suggest that H(+)-ATPase is actively endocytosed and exocytosed in proton-secreting cells of the epididymis and vas deferens and that net proton secretion requires the participation of the V-SNARE cellubrevin. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Program, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Inst Curie, F-5248 Paris, France. Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Zagreb 1000, Croatia. Marine Biol Lab, Biocurrents Res Ctr, Woods Hole, MA 02543 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St,8th Floor, Charlestown, MA 02129 USA. EM sbreton@receptor.harvard.mgh.edu FU NCRR NIH HHS [P41-RR-O1395]; NIDDK NIH HHS [DK-38452] NR 58 TC 48 Z9 48 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2000 VL 278 IS 5 BP F717 EP F725 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 315JN UT WOS:000087110700004 PM 10807583 ER PT J AU Murthy, V Haddad, LA Smith, N Pinney, D Tyszkowski, R Brown, D Ramesh, V AF Murthy, V Haddad, LA Smith, N Pinney, D Tyszkowski, R Brown, D Ramesh, V TI Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE tuberous sclerosis; hamartomas; intercalated cells; apical membrane ID SCLEROSIS GENE-2 PRODUCT; RAT-KIDNEY; H+-ATPASE; INTERCALATED CELLS; RENAL INVOLVEMENT; GROWTH SUPPRESSOR; CHROMOSOME 9Q34; TARGET RAP1; TSC1 GENE; EKER RAT AB Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in multiple organs, notably the brain and kidneys. The disease is caused by mutations in TSC1 or TSC2 genes, coding hamartin and tuberin, respectively. Immunofluorescence analysis of tuberin and hamartin performed here demonstrates that both proteins are specifically expressed in the distal urinary tubule, comprising the distal tubules, connecting segment, and collecting ducts. Hamartin, distinct from tuberin, is expressed in the thick ascending limbs of Henle and in juxtaglomerular cells, where it colocalizes with renin. In positive epithelial cells, tuberin localizes to the cytoplasm as well as the apical membrane. Hamartin, however, preferentially localizes to the apical membrane. The two proteins colocalize at the apical membrane of type A intercalated cells and connecting tubule cells, whereas in type B intercalated cells they reveal a variable pattern of expression. The cell-specific expression of tuberin and hamartin described here will provide critical insight into the cell types that give rise to kidney lesions, and the tumor suppressor role of these proteins in TSC. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. RP Ramesh, V (reprint author), MGH E, Mol Neurogenet Unit, Bldg 149,6th Floor,13th St, Charlestown, MA 02129 USA. EM ramesh@helix.mgh.harvard.edu RI Haddad, Luciana/D-8002-2012 FU NIDDK NIH HHS [DK-42596]; NINDS NIH HHS [NS-24279] NR 44 TC 29 Z9 29 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2000 VL 278 IS 5 BP F737 EP F746 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 315JN UT WOS:000087110700006 PM 10807585 ER PT J AU Biederman, J Mick, E Faraone, SV AF Biederman, J Mick, E Faraone, SV TI Age-dependent decline of symptoms of attention deficit hyperactivity disorder: Impact of remission definition and symptom type SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PSYCHIATRIC STATUS; FOLLOW-UP; CHILDREN; BOYS AB Objective: Symptom decline in attention deficit hyperactivity disorder (ADHD) was examined with different definitions of remission. Method: Symptoms in 128 boys were measured five times over 4 years. The prevalences of syndromatic (less than full syndrome), symptomatic (less than subthreshold diagnosis), and functional (full recovery) remission were estimated as a function of age with multivariate logistic regression. Results: Age was significantly associated with decline in total ADHD symptoms and symptoms of hyperactivity, impulsivity, and inattention. Symptoms of inattention remitted for fewer subjects than did symptoms of hyperactivity or impulsivity. The proportion of subjects experiencing remission varied considerably with the definition used (highest for syndromatic remission, lowest for functional remission). Conclusions: These results indicate that differences in reported remission rates reflect the definition used rather than the disorder's course. They provide systematic support for the clinical observation that hyperactivity and impulsivity symptoms tend to decline at a higher rate than inattention symptoms. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Commonwealth Res Ctr, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, ACC 725,15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH41314] NR 8 TC 661 Z9 686 U1 7 U2 56 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 MAY PY 2000 VL 157 IS 5 BP 816 EP 818 DI 10.1176/appi.ajp.157.5.816 PG 3 WC Psychiatry SC Psychiatry GA 309QY UT WOS:000086781800023 PM 10784477 ER PT J AU Evins, AE Fitzgerald, SM Wine, L Rosselli, R Goff, DC AF Evins, AE Fitzgerald, SM Wine, L Rosselli, R Goff, DC TI Placebo-controlled trial of glycine added to clozapine in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting of the NIMH New Clinical Drug Evaluation Unit CY JUN 10-13, 1998 CL BOCA RATON, FLORIDA SP NIMH ID HIGH-DOSE GLYCINE; D-CYCLOSERINE; CONVENTIONAL NEUROLEPTICS; NEGATIVE SYMPTOMS; D-SERINE AB Objective: The purpose of this study was to evaluate the effects of high-dose oral glycine on positive and negative symptoms and cognitive function when added to clozapine in adults with schizophrenia. Method: The authors conducted a double-blind, placebo-controlled, parallel-group trial of 60 g/day of glycine added to clozapine for 8 weeks in 30 adults with schizophrenia. Clinical ratings were performed every 2 weeks. Results: Twenty-seven patients completed the trial. Glycine augmentation of clozapine produced no statistically significant change in positive or negative symptoms or cognitive functioning. No subjects showed clinically significant worsening of clinical ratings. Conclusions: These data, combined with data from previous trials with D-cycloserine and glycine, suggest that agonists at the glycine site may be less effective when combined with clozapine than they are when combined with conventional antipsychotics. C1 Massachusetts Gen Hosp, Psychot Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Tufts Univ, Sch Med, New England Med Ctr, Boston, MA 02111 USA. RP Evins, AE (reprint author), Freedom Trail Clin, 25 Stanford St, Boston, MA 02114 USA. NR 11 TC 101 Z9 104 U1 0 U2 5 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2000 VL 157 IS 5 BP 826 EP 828 DI 10.1176/appi.ajp.157.5.826 PG 3 WC Psychiatry SC Psychiatry GA 309QY UT WOS:000086781800027 PM 10784481 ER PT J AU Esteban, A Anzueto, A Alia, I Gordo, F Apezteguia, C Palizas, F Cide, D Goldwaser, R Soto, L Bugedo, G Rodrigo, C Pimentel, J Raimondi, G Tobin, MJ AF Esteban, A Anzueto, A Alia, I Gordo, F Apezteguia, C Palizas, F Cide, D Goldwaser, R Soto, L Bugedo, G Rodrigo, C Pimentel, J Raimondi, G Tobin, MJ CA Mech Ventilation Int Study Grp TI How is mechanical ventilation employed in the intensive care unit? An international utilization review SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; OBSTRUCTIVE PULMONARY-DISEASE; ACUTE EXACERBATION; NATIONAL SURVEY; TIDAL VOLUME; LUNG-DISEASE; MORTALITY; FAILURE; DEFINITIONS AB A 1-d point-prevalence study was performed with the aim of describing the characteristics of conventional mechanical ventilation in intensive care units ICUs from North America, South America Spain, and Portugal. The study involved 412 medical-surgical ICUs and 1,638 patients receiving mechanical ventilation at the moment of the study. The main outcome measures were characterization of the indications for initiation of mechanical ventilation, the artificial airways used to deliver mechanical ventilation, the ventilator modes and settings, and the methods of weaning. The median age of the study patients was 67 yr, and the median duration of mechanical ventilation at the time of the study was 7 d. Common indications for the initiation of mechanical ventilation included acute respiratory failure (66%), acute exacerbation of chronic obstructive pulmonary disease (13%), coma (10%), and neuromuscular disorders (10%). Mechanical ventilation was delivered via an endotracheal tube in 75% of patients, a tracheostomy in 24%, and a facial mask in 1%. Ventilator modes consisted of assist/control ventilation in 47% of patients and 46% were ventilated with synchronized intermittent mandatory ventilation, pressure support, or the combination of both. The median tidal volume setting was 9 ml/kg in patients receiving assist/control and the median setting of pressure support was 18 cm H2O. Positive end-expiratory pressure was not employed in 31% of patients. Method of weaning varied considerably from country to country, and even within a country several methods were in use. We conclude that the primary indications for mechanical ventilation and the ventilator settings were remarkably similar across countries, but the selection of modes of mechanical ventilation and methods of weaning varied considerably from country to country. C1 Univ Madrid, Hosp Getafe, Unidad Cuidados Intensivos, Madrid 28905, Spain. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Hosp Profesor Posadas, Buenos Aires, DF, Argentina. Clin Bazterr, Buenos Aires, DF, Argentina. Univ Fed Rio de Janeiro, Hosp Clementino Fraga Filho, Rio De Janeiro, Brazil. Inst Nacl Enfermedades Resp & Cirugia Torac, Santiago, Chile. Pontificia Univ Catolica Chile, Santiago, Chile. Asociac Espanola Primera Socorros Mutuos, Montevideo, Uruguay. Hosp Univ Coimbra, Coimbra, Portugal. FLENI, Buenos Aires, DF, Argentina. Loyola Univ, Chicago, IL 60611 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Esteban, A (reprint author), Univ Madrid, Hosp Getafe, Unidad Cuidados Intensivos, Carretera Toledo Km 12-500, Madrid 28905, Spain. NR 35 TC 337 Z9 368 U1 0 U2 7 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY PY 2000 VL 161 IS 5 BP 1450 EP 1458 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 312LU UT WOS:000086945400012 PM 10806138 ER PT J AU Cooper, JAD AF Cooper, JAD TI Pulmonary fibrosis - Pathways are slowly coming into light SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; P53 EXPRESSION; FAS LIGAND; BLEOMYCIN; MICE; APOPTOSIS; COLLAGEN; STIMULATION; INDUCTION; DISEASE C1 Univ Alabama, Div Pulm Allergy & Crit Care Med, Univ Stn, Pulm Sect, Birmingham, AL 35294 USA. Birmingham VAMC, Pulm Sect, Birmingham, AL USA. RP Cooper, JAD (reprint author), Univ Alabama, Div Pulm Allergy & Crit Care Med, Univ Stn, Pulm Sect, Birmingham, AL 35294 USA. NR 32 TC 53 Z9 59 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 MAY PY 2000 VL 22 IS 5 BP 520 EP 523 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 313EC UT WOS:000086986500003 PM 10783121 ER PT J AU Dubinett, SM Batra, RK Miller, PW Sharma, S AF Dubinett, SM Batra, RK Miller, PW Sharma, S TI Tumor antigens in thoracic malignancy SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; PULSED DENDRITIC CELLS; HUMAN LUNG-CANCER; IN-VIVO; GENE-THERAPY; B-CELLS; PROSTAGLANDIN E(2); IMMUNE RECOGNITION; PRESENTING CELLS; AUTOLOGOUS TUMOR C1 Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med,Wadsworth Pulm Lab, Jonsson Comprehens Canc Ctr,Dept Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med,Wadsworth Pulm Lab, Jonsson Comprehens Canc Ctr,Dept Med, 37-131 Ctr Hlth Sci,10833 LeConte Ave, Los Angeles, CA 90095 USA. NR 75 TC 5 Z9 5 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 MAY PY 2000 VL 22 IS 5 BP 524 EP 527 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 313EC UT WOS:000086986500004 PM 10783122 ER PT J AU Batra, RK Dubinett, SM Henkle, BW Sharma, S Gardner, BK AF Batra, RK Dubinett, SM Henkle, BW Sharma, S Gardner, BK TI Adenoviral gene transfer is inhibited by soluble factors in malignant pleural effusions SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID FIBROSIS AIRWAY EPITHELIA; PENTON BASE PROTEIN; I CLINICAL-TRIAL; IMMUNE-RESPONSES; LUNG-CANCER; ADENOASSOCIATED VIRUS; MOLECULAR MEDICINE; HELPER VIRUS; MOUSE-LIVER; DELIVERY AB Direct in vivo gene delivery is a prerequisite for many gene therapy strategies; however, efficacy has been limited by a lack of therapeutic gene transfer. in studying intrapleural malignancy as a model for the gene therapy of non-small cell lung cancer, we previously identified soluble chondroitin sulfate-proteoglycans/glycosaminoglycans (CS-PG/GAGs) in malignant pleural effusions (MPE) as factors that inhibit retroviral vector (RV) transduction. Similarly, we have observed inhibition to gene transfer in the fluid component of MPE using adenoviral (Ad) vectors. Analyses indicate that the factors responsible for the block are filterable, soluble, titrable, and heat stable (56 degrees C). Passage through microporous membranes fractionates the inhibitory factors into large (> 100 kD) components of the effusions. In contrast to RV transduction, hyaluronic acid or CS-PG/GAGs are not the inhibitors because the block is not reversed by pretreatment of the effusions with mammalian hyaluronidase, and exogenous addition of GAGs into the transduction media does not diminish Ad transduction. In considering the mechanism of action of the inhibitory factors, we observe that Ad entry, and specifically the binding of radiolabeled Ad to its target cell, is inhibited in the presence of MPE. Ad internalization may also be impaired; however, these studies exclude soluble fibronectin in MPE as a competitive inhibitor of Ad transduction. Lastly, sepharose A-mediated immunoglobulin depletion of MPE only partially reverses the block, and significant inhibition to Ad gene transfer persists at lower adenovirus:target cell ratios. Identifying the structural and functional basis for inhibition to Ad gene transfer may yield specific strategies to enable better in vivo translation of gene therapy approaches. C1 Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Wadsworth Pulm Immunol Lab, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Batra, RK (reprint author), Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Vet Adm Greater Los Angeles Hlth Care Syst, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [R01CA78654, R01 CA078654-01A1] NR 45 TC 13 Z9 14 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 MAY PY 2000 VL 22 IS 5 BP 613 EP 619 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 313EC UT WOS:000086986500016 PM 10783134 ER PT J AU Rabkin, JM Oroloff, SL Corless, CL Benner, KG Flora, KD Rosen, HR Olyaei, AJ AF Rabkin, JM Oroloff, SL Corless, CL Benner, KG Flora, KD Rosen, HR Olyaei, AJ TI Association of fungal infection and increased mortality in liver transplant recipients SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the North-Pacific-Surgical-Association CY NOV 12-13, 1999 CL VANCOUVER, CANADA SP N Pacific Surg Assoc ID AMPHOTERICIN-B AMBISOME; RISK-FACTORS; INVASIVE FUNGAL; CYTOMEGALOVIRUS DISEASE; PROPHYLAXIS; CANDIDA; FLUCONAZOLE; BACTERIAL; TRIAL AB BACKGROUND: Invasive fungal infection is associated with increased morbidity and mortality following orthotopic liver transplantation (OLTx). Understanding the risk factors associated with fungal infection may facilitate identification of high-risk patients and guide appropriate initiation of antifungal therapy. OBJECTIVES: The aim of this study was to determine the incidence of fungal infections, identify the most common fungal pathogens, and determine the risk factors associated with fungal infections and mortality in OLTx recipients. METHODS: Medical records from 96 consecutive OLTx in 90 American veterans (88 males, 2 females; mean age 48 years, range 32 to 67) performed from January 1994 to December 1997 were retrospectively reviewed for fungal infection in the first 120 days after transplantation. Infection was defined by positive cultures from either blood, urine (<105 CFU/mL), cerebrospinal or peritoneal fluid, and/or deep tissue specimens. Superficial fungal infection and asymptomatic colonization were excluded from study. All patients received cyclosporine, azathioprine, and prednisone as maintenance immunosuppressive therapy. Fungal prophylaxis consisted of oral clotrimazole (10 mg) troches, five times per day during the study period. RESULTS: Thirty-five patients (38%) had documented infection with one or more fungal pathogens, including Candida albicans (25 of 35; 71%), C torulopsis (7 of 35; 20%), C tropicalis (2 of 35; 6%), non-C albicans (2 of 35; 6%), Aspergillus fumigatus (4 of 35; 11%), and Cryptococcus neoformans (1 of 35; 3%). The crude survival for cases with or without fungal infection was 68% and 87%, respectively (P < 0.0001), The median intensive cave unit stay and overall duration of hospitalization were significantly longer for patients with fungal infection (P < 0.01). The mean time interval from transplantation to the development of fungal infection was 15 days (range 4 to 77) with a mean survival time from fungal infection to death of 21 days (range 3 to 64). Fungal infections occurred significantly more often in patients with renal insufficiency (serum creatinine > 2.5 mg/dL), biliary/vascular complications, and retransplantation, CONCLUSIONS: Fungal infections weve associated with increased morbidity and mortality following OLTx, with Candida albicans being the most common pathogen. Treatment strategies involving antifungal prophylaxis for high-risk patients and earlier initiation of antifungal therapy in cases of presumed infection ave warranted. (C) 2000 by Excerpta Medica, Inc. C1 Oregon Hlth Sci Univ, Dept Surg, Sect Liver Transplantat, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Dept Pathol, Portland, OR USA. Portland Vet Affairs Med Ctr, Dept Med, Div Gastroenterol, Portland, OR USA. Portland Vet Affairs Med Ctr, Dept Pharm, Portland, OR USA. RP Rabkin, JM (reprint author), Sect Liver Pancreas Transplantat Hepatobiliary Su, 3181 SW Sam Jackson Pk Rd,L590, Portland, OR 97201 USA. NR 32 TC 57 Z9 82 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 2000 VL 179 IS 5 BP 426 EP 430 DI 10.1016/S0002-9610(00)00366-4 PG 5 WC Surgery SC Surgery GA 341ZL UT WOS:000088620800020 PM 10930495 ER PT J AU Gong, WS Merfeld, DM AF Gong, WS Merfeld, DM TI Prototype neural semicircular canal prosthesis using patterned electrical stimulation SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE vestibular; prosthesis; guinea pig ID SQUIRREL-MONKEY; NEURONS; ACCELERATION; RESPONSES; EYE AB The design of a prototype semicircular canal prosthesis is presented along with preliminary results. This device measures angular velocity of the head (+/-500 degrees/s) using a piezoelectric vibrating gyroscope. With a digital filter this velocity is filtered to match the dynamic characteristics of the semicircular canals, which are the physiological rotation sensors of the vestibular system. This digitally filtered signal is used to modulate the pulse rate of electrical stimulation. The pulse rate is varied between 50 and 250 Hz via a sigmoidal lookup table relating pulse rate to angular velocity; the steady-state rate is 150 Hz. A current source utilizes these timing pulses to deliver charge balanced, cathodic-first, biphasic, current pulses to the nerves innervating the semicircular canal via platinum electrodes.. Power is supplied via lithium batteries. dc/dc converters are used to generate regulated +/-5 V supplies from the batteries. All of the components are contained in a small, lightweight, Nylon box measuring roughly 43 mm x 31 mm x 25 mm, which can be mounted on the top of an animal's head. This device has been tested in guinea pigs having surgically implanted platinum electrodes, and the results show that the prosthesis can provide a rotational cue to the nervous system. (C) 2000 Biomedical Engineering Society. [S0090-6964(00)00405-7]. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, WM Keck Fdn, Neural Prosthesis Res Ctr, Cambridge, MA 02139 USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC03066] NR 20 TC 75 Z9 78 U1 0 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD MAY PY 2000 VL 28 IS 5 BP 572 EP 581 DI 10.1114/1.293 PG 10 WC Engineering, Biomedical SC Engineering GA 336VB UT WOS:000088322700010 PM 10925955 ER PT J AU Colevas, AD Adak, S Amrein, PC Barton, JJ Costello, R Posner, MR AF Colevas, AD Adak, S Amrein, PC Barton, JJ Costello, R Posner, MR TI A phase II trial of palliative docetaxel plus 5-fluorouracil for squamous-cell cancer of the head and neck SO ANNALS OF ONCOLOGY LA English DT Article DE 5-FU; docetaxel; head and neck cancer; phase II; squamous-cell carcinoma ID METASTATIC BREAST-CANCER; HIGH-DOSE CISPLATIN; RANDOMIZED TRIAL; ONCOLOGY-GROUP; 5-FU INFUSION; SINGLE-AGENT; ACTIVE-DRUG; CARCINOMA; RECURRENT; CHEMOTHERAPY AB Purpose: A phase II study to determine the response rate and toxicity of docetaxel and 5-fluorouracil (5-FU) every four weeks ('TF'), in patients with incurable SCCHN. Patients and methods: Patients with metastatic or recurrent SCCHN with an ECOG PS < 3 were enrolled in an institutional review board approved trial. Prior induction or adjuvant chemotherapy was permitted provided six months had elapsed. The regimen was docetaxel 70 mg/m(2) i.v., day 1 and 5-FU 800 mg/m(2)/d x 5 days, days 1-5, as a continuous intravenous infusion, repeated every 28 days. Planned intra-patient dose modifications were based on hematological, cutaneous, and gastrointestinal toxicities. Patients were removed from the study for progression of disease or unacceptable toxicity. Results: Seventeen patients were enrolled. Fourty-six cycles of TF were administered. Reasons for discontinuance of TF included: progressive disease, 12 patients; toxicity, 3 patients; concomitant illness, 1 patient; death, 1 patient. The most common toxicities were neutropenia, mucositis, anemia, fatigue, alopecia, pain, diarrhea and nausea. Evaluation of responses to TF showed that there were four patients of seventeen (24%, 95% exact CI: 6.8-49.9) who achieved a PR or CR. Accrual was terminated after interim analysis of the response rate of the first 17 patients failed to exceed 4 of 17. Conclusions: The response rate to TF in patients with SCCHN was lower than expected. Trials of other regimens should take precedence over further exploration of the TF regimen. C1 Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Colevas, AD (reprint author), Dana Farber Canc Inst, Head & Neck Oncol Program, 44 Binney St, Boston, MA 02115 USA. NR 29 TC 22 Z9 22 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2000 VL 11 IS 5 BP 535 EP 539 DI 10.1023/A:1008355413788 PG 5 WC Oncology SC Oncology GA 323TR UT WOS:000087581500012 PM 10907945 ER PT J AU Merchant, SN Tsuji, K Wall, C Velazquez-Villasenor, L Glynn, RJ Rauch, SD AF Merchant, SN Tsuji, K Wall, C Velazquez-Villasenor, L Glynn, RJ Rauch, SD TI Temporal bone studies of the human peripheral vestibular system 1. Normative vestibular hair cell data SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE temporal bone; vestibular hair cell ID EPITHELIA AB Quantitative studies of the vestibular system with serially sectioned human temporal bones have been limited because of difficulty in distinguishing hair cells from supporting cells and type I from type II hair cells. In addition, there is only a limited amount of normative data available regarding vestibular hair cell counts in humans. In this study, archival temporal bone sections were examined by Nomarski (differential interference contrast) microscopy, which permitted visualization of the cuticular plate and stereociliary bundle so as to allow unambiguous identification of hair cells. The density of type I, type II, and total numbers of vestibular hair cells in each of the 5 sense organs was determined in a set of 67 normal temporal bones that ranged from birth through 100 years of age. The mean total densities at birth were 76 to 79 cells per 0.01 mm(2) in the cristae, 68 cells per 0.01 mm(2) in the utricle, and 61 cells per 0.01 mm(2) in the saccule. The ratio of type I to type II hair cells at birth was 2.4:1 in the cristae and 1.3:1 in the maculae. There was a highly significant age-related decline in all sense organs for total, type I, and type II hair cell densities that was best fit by a linear regression model. The cristae lost type I cells with advancing age at a significantly greater rate than the maculae, whereas age-related losses for type Il cells occurred at the same rate for all 5 sense organs. Hair cell densities in the cristae were significantly higher at the periphery than at the center. There were no significant sex or interaural differences for any of the counts. Mathematical models were developed to calculate the mean and 95% prediction intervals for the total, type I, and type II hair cell densities in each sense organ on the basis of age. There was overall good agreement between the hair cell densities determined in this study and those reported by others using surface preparation techniques. Our data and related models will serve as a normative database that will be useful for comparison to counts made from subjects with known vestibular disorders. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Otopathol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 21 TC 22 Z9 23 U1 1 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 MAY PY 2000 VL 109 IS 5 SU 181 BP 3 EP 13 PN 2 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 314YM UT WOS:000087085200002 ER PT J AU Velazquez-Villasenor, L Tsuji, K Wall, C Merchant, SN Glynn, RJ Rauch, SD AF Velazquez-Villasenor, L Tsuji, K Wall, C Merchant, SN Glynn, RJ Rauch, SD TI Temporal bone studies of the human peripheral vestibular system 2. Normative Scarpa's ganglion cell data SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE Scarpa's ganglion; temporal bone; vestibular ganglion ID NERVE AB Scarpa's ganglion cell counts were performed in 106 serially sectioned, normal human temporal bones from 75 individuals. Of these 106 bones, 15 were from neonates less than 30 days old, 14 were from infants between the ages of 1 and 12 months, and the remainder were distributed throughout each decade of life, with sample sizes ranging from 4 to 10 per decade. All temporal bones had to meet 2 criteria: no symptoms or signs of inner ear disease except for presbycusis in the medical case history and no abnormality in the inner ear on light microscopy. The total ganglion cell counts declined significantly with age at an average rate of 57 cells per year. The age-related decline was significantly greater in the superior division than in the inferior division. There was also a significant sex effect, independent of age: for any age, the count in men averaged 1,526 cells higher than in women. There was no significant interaural difference. Mathematical models were developed to compute the mean and 95% prediction intervals for Scarpa's ganglion cell counts in terms of age and sex parameters. The counts and models will serve as a normative database against which to compare counts made in temporal bones from subjects with known vestibular disorders. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Otopathol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 31 Z9 33 U1 1 U2 3 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 MAY PY 2000 VL 109 IS 5 SU 181 BP 14 EP 19 PN 2 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 314YM UT WOS:000087085200003 PM 10821230 ER PT J AU Tsuji, K Rauch, SD Wall, C Velazquez-Villasenor, L Glynn, RJ Merchant, SN AF Tsuji, K Rauch, SD Wall, C Velazquez-Villasenor, L Glynn, RJ Merchant, SN TI Temporal bone studies of the human peripheral vestibular system 3. Aminoglycoside ototoxicity SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE aminoglycosides; ototoxicity; Scarpa's ganglion; temporal bone; vestibular hair cells AB Quantitative assessments of vestibular hair cells and Scarpa's ganglion cells were performed on 17 temporal bones from 10 individuals who had well-documented clinical evidence of aminoglycoside ototoxicity (streptomycin, kanamycin, and neomycin). Assessment of vestibular hair cells was performed by Nomarski (differential interference contrast) microscopy. Hair cell counts were expressed as densities (number of cells per 0.01 mm(2) surface area of the sensory epithelium). The results were compared with age-matched normal data. Streptomycin caused a significant loss of both type I and type II hair cells in all 5 vestibular sense organs. In comparing the ototoxic effect on type I versus type II hair cells, there was greater type I hair cell loss for all 3 cristae, but not for the maculae. The vestibular ototoxic effects of kanamycin appeared to be similar to those of streptomycin, but the small sample size precluded definitive conclusions from being made. Neomycin did not cause loss of vestibular hair cells. Within the limits of this study (maximum postototoxicity survival time of 12 months), there was no significant loss of Scarpa's ganglion cells for any of the 3 drugs. The findings have implications in several clinical areas, including the correlation of vestibular test results to pathological findings, the rehabilitation of patients with vestibular ototoxicity, the use of aminoglycosides to treat Meniere's disease, and the development of a vestibular prosthesis. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Otopathol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 17 Z9 18 U1 2 U2 5 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 MAY PY 2000 VL 109 IS 5 SU 181 BP 20 EP 25 PN 2 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 314YM UT WOS:000087085200004 PM 10821231 ER PT J AU Tsuji, K Rauch, SD Wall, C Velazquez-Villasenor, L Glynn, RJ Merchant, SN AF Tsuji, K Rauch, SD Wall, C Velazquez-Villasenor, L Glynn, RJ Merchant, SN TI Temporal bone studies of the human peripheral vestibular system 4. Meniere's disease SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE Meniere's disease; Scarpa's ganglion cells; temporal bone; vestibular hair cells AB Quantitative assessments of vestibular hair cells and Scarpa's ganglion cells were performed on temporal bones from 24 patients with well-documented Meniere's disease. Of these, 18 had unilateral disease and 6 had bilateral disease. Vestibular hair cell counts were made in each of the 5 sense organs by Nomarski (differential interference contrast) microscopy. Hair cell counts were expressed as densities: number of cells per 0.01 mm(2) surface area of the sensory epithelium. The results were compared with age- and sex-matched normal data. The type I hair cell densities for all vestibular sense organs were within the range for normative data. On the other hand, there was a significant loss (p < .01) of type II hair cells for all 3 cristae and both maculae. There was also a significant loss of Scarpa's ganglion cells (p < .001) when compared with normative data. The findings indicate a selective loss of type II hair cells and Scarpa's ganglion cells in Meniere's disease. These new observations have implications regarding the pathophysiological mechanism and clinical manifestations of Meniere's disease. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Otopathol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 25 Z9 27 U1 1 U2 1 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 MAY PY 2000 VL 109 IS 5 SU 181 BP 26 EP 31 PN 2 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 314YM UT WOS:000087085200005 PM 10821232 ER PT J AU Deschler, DG Doherty, ET Reed, CG Hayden, RE Singer, MI AF Deschler, DG Doherty, ET Reed, CG Hayden, RE Singer, MI TI Prevention of pharyngoesophageal spasm after laryngectomy with a half-muscle closure technique SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE half-muscle closure; laryngectomy; pharyngoesophageal spasm; tracheoesophageal puncture ID PRIMARY VOICE RESTORATION; TRACHEOESOPHAGEAL VOICE; EXPERIENCE; RECONSTRUCTION; REHABILITATION; NEOPHARYNX AB Because pharyngoesophageal spasm can limit successful voice restoration after total laryngectomy, 24 patients underwent a modified pharyngeal closure in an effort to avoid this problem. All patients underwent total laryngectomy with appropriate neck dissections and pharyngeal closure with a half-muscle closure technique in which only one side of the remnant constrictor muscles was used to reinforce the primary closure. Twenty-three patients underwent voice restoration. Twenty-two (96%) had a functional voice, and 1 patient (4%) had pharyngoesophageal spasm that required a secondary myotomy. One fistula (4%) occurred and resolved with conservative measures. Quantitative voice analysis demonstrated no significant differences between half-closure patients and control patients for fundamental frequency (96 Hz versus 101 Hz) or intensity (57 dB versus 64 dB). Extensive qualitative analysis by trained and naive listeners revealed no differences. This preliminary report indicates the half-muscle closure modification of the pharyngeal closure at primary laryngectomy may provide a simple and effective means of avoiding pharyngoesophageal spasm and maintaining an effective voice without increased complications. C1 MCP Hahnemann Univ, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA USA. San Francisco Vet Hosp, Dept Speech & Audiol, San Francisco, CA USA. Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 8 Z9 8 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAY PY 2000 VL 109 IS 5 BP 514 EP 518 PN 1 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 313JU UT WOS:000086997200013 PM 10823483 ER PT J AU Reiter, ER Varvares, MA August, M Curtin, HD AF Reiter, ER Varvares, MA August, M Curtin, HD TI Mucocele of the infratemporal fossa as an unusual complication of midfacial fracture SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID FACIAL TRANSLOCATION; MAXILLARY SINUS; CLASSIFICATION; BASE C1 Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Div Head & Neck Surg, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA USA. RP Varvares, MA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Div Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. NR 18 TC 3 Z9 3 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAY PY 2000 VL 109 IS 5 BP 522 EP 525 PN 1 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 313JU UT WOS:000086997200015 PM 10823485 ER PT J AU Miron, A Schildkraut, JM Rimer, BK Winer, EP Skinner, CS Futreal, PA Culler, D Calingaert, B Clark, S Marcom, PK Iglehart, JD AF Miron, A Schildkraut, JM Rimer, BK Winer, EP Skinner, CS Futreal, PA Culler, D Calingaert, B Clark, S Marcom, PK Iglehart, JD TI Testing for hereditary breast and ovarian cancer in the southeastern United States SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 111th Annual Meeting of the Southern-Surgical-Association CY DEC 05-08, 1999 CL HOT SPRINGS, VIRGINIA SP SO Surg Assoc ID DECISION-MAKING; SUSCEPTIBILITY GENES; BRCA2 MUTATIONS; FAMILY HISTORY; RISK; CARRIERS; WOMEN; ATTITUDES AB Objectives To detail characterization of mutations and uncharacterized variants in the breast cancer susceptibility genes BRCA1 and BRCA2, as observed in a population of breast cancer patients from the southeastern United States, and to examine baseline characteristics of women referred for counseling and testing and provide a preliminary look at how counseling and testing affected intentions toward prophylactic surgery, Background Mutations in the BRCA1 and BRCA2 genes give rise to a dramatically increased risk of developing breast or ovarian cancer or both. There are many reports about special populations in which deleterious mutations are present ata high frequency. it is useful to study these genes in more heterogeneous populations, reflecting different geographic regions. Interest in preventive surgery for gene carriers is high in women and their surgeons. Methods Women were recruited through a prospective clinical trial of counseling and free genetic testing. BRCA1 and BRCA2 were screened for mutations using standard techniques, and results were given to participants. Baseline questionnaires determined interest in preventive surgery at the beginning of the study. Follow-up questionnaires for those who completed testing surveyed interest in prophylactic surgery after counseling and receiving test results, Results OC 213 women who completed counseling and testing, 44 (20.6%) had 29 separate mutations; there were II Jewish women carrying three founder mutations. Twenty-eight women (13.1%) had uncharacterized variants in BRCA1 or BRCA2; nine were not previously reported. Women overestimated their chances of possessing a deleterious gene mutation compared to a statistical estimate of carrier risk, A number of women changed their intentions toward preventive surgery after genetic counseling and testing, Conclusions Hereditary breast cancer due to mutations in BRCA1 and BRCA2 was a heterogeneous syndrome in the southeastern United States. Most mutations were seen just once, and uncharacterized variants were common and of uncertain clinical significance. in general, positive test results tended to reinforce intentions toward prophylactic surgery. in contrast, women not interested in surgery at the time of entry tended to remain reluctant after testing and counseling. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Family & Community Med, Durham, NC 27710 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Iglehart, JD (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. NR 32 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2000 VL 231 IS 5 BP 624 EP 632 DI 10.1097/00000658-200005000-00002 PG 9 WC Surgery SC Surgery GA 311CM UT WOS:000086867300002 PM 10767783 ER PT J AU Jimenez, RE Hartwig, W Antoniu, BA Compton, CC Warshaw, AL Fernandez-del Castillo, C AF Jimenez, RE Hartwig, W Antoniu, BA Compton, CC Warshaw, AL Fernandez-del Castillo, C TI Effect of matrix metalloproteinase inhibition on pancreatic cancer invasion and metastasis - An additive strategy for cancer control SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 111th Annual Meeting of the Southern-Surgical-Association CY DEC 05-08, 1999 CL HOT SPRINGS, VIRGINIA SP SO Surg Assoc ID BREAST CARCINOMAS; BASEMENT-MEMBRANE; TISSUE INHIBITOR; BATIMASTAT BB-94; TUMOR-CELLS; IN-VITRO; EXPRESSION; SURVIVAL; GROWTH; MODEL AB Objective To investigate the effect of a matrix metalloproteinase (MMP) inhibitor, BB-94, on the viability, invasion, and metastases of pancreatic cancer. Summary Background Data Inhibitors of MMPs, enzymes that degrade extracellular matrix, have been tested as single chemotherapeutic agents for pancreatic cancer. Methods Capan1 and AsPC1 cell lines were studied, BE-94 cytotoxicity was evaluated by cell proliferation assays. Production of MMP2 and MMP9 in conditioned media was demonstrated by gelatin zymography. The in vitro effect of BE-94 on cell invasion was assayed using invasion chambers. Hepatic metastases from pancreatic cancer were induced by intrasplenic injections of Capan1 or AsPC1 cells in nude mice. The in vivo effect of BE-94 on liver metastases was evaluated by comparing animals receiving BE-94 treatment with controls receiving vehicle alone. Variables measured included death rate and tumor burden (liver-to-body weight ratio). Results BE-94 was not cytotoxic between 3 and 3,000 ng/ml, Zymography demonstrated production of MMP2 and MMPS by both cell lines, with complete inhibition of these enzymes by 88-94 at 48 ng/ml. Invasion chamber assays showed that 88-94 (48-400 ng/mi) impeded cell invasion in vitro compared with untreated controls. In vivo, BE-94 prevented death or reduced the death rate from hepatic metastases in animals injected with Capan1 or AsPC1 cells, BE-94 treatment resulted in significant reductions in hepatic tumor burden com pared with untreated controls. Conclusions Inhibition of MMP reduces both growth of pancreatic cancer metastases and the death rate. These actions do not reflect cytotoxicity but rather result from impaired cancer cell attachment, migration, and organ invasion. MMP inhibitors may provide an additive effect to cytotoxic agents in multidimensional treatment regimens for pancreatic cancer. C1 Massachusetts Gen Hosp, Dept Surg, WACC 336, 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, Boston, MA 02114 USA. NR 37 TC 53 Z9 57 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2000 VL 231 IS 5 BP 644 EP 652 DI 10.1097/00000658-200005000-00004 PG 9 WC Surgery SC Surgery GA 311CM UT WOS:000086867300006 PM 10767785 ER PT J AU Grillo, HC AF Grillo, HC TI Education or training in cardiothoracic surgery? SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Thorac Surg, Thorac Surg Unit, Boston, MA 02114 USA. RP Grillo, HC (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, Thorac Surg Unit, Warren 1101,55 Fruit St, Boston, MA 02114 USA. NR 2 TC 4 Z9 4 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 MAY PY 2000 VL 69 IS 5 BP 1319 EP 1320 DI 10.1016/S0003-4975(00)01332-1 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 324DD UT WOS:000087605800005 PM 10881797 ER PT J AU Urbani, M Mathisen, DJ AF Urbani, M Mathisen, DJ TI Repair of esophageal perforation after treatment for achalasia SO ANNALS OF THORACIC SURGERY LA English DT Article ID PNEUMATIC DILATATION AB Esophageal perforation after treatment for achalasia is a devastating complication. Successful closure of the perforation and relief of the obstruction from achalasia are paramount. This can be accomplished by careful closure of the mucosa. The mucosal closure is buttressed by a pedicled intercostal muscle carefully sewn to the edges of the muscular defect. This approach deals effectively with the perforation and maintains the myotomy for relief of esophageal obstruction from achalasia. (C) 2000 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Gen Thorac Surg Unit, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Gen Thorac Surg Unit, 32 Fruit St,Blake 1570, Boston, MA 02114 USA. NR 5 TC 3 Z9 4 U1 0 U2 1 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 MAY PY 2000 VL 69 IS 5 BP 1609 EP 1611 DI 10.1016/S0003-4975(00)01149-8 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 324DD UT WOS:000087605800085 PM 10881864 ER PT J AU Tsukurov, OI Kwolek, CJ L'Italien, GJ Benbrahim, A Milinazzo, BB Conroy, NE Gertler, JP Orkin, RW Abbott, WM AF Tsukurov, OI Kwolek, CJ L'Italien, GJ Benbrahim, A Milinazzo, BB Conroy, NE Gertler, JP Orkin, RW Abbott, WM TI The response of adult human saphenous vein endothelial cells to combined pressurized pulsatile flow and cyclic strain, in vitro SO ANNALS OF VASCULAR SURGERY LA English DT Article ID NITRIC-OXIDE SYNTHASE; FLUID SHEAR-STRESS; MESSENGER-RNA LEVELS; GENE-EXPRESSION; VASCULAR WALL; HEMODYNAMICS; STRETCH; RELEASE; DEVICE; FORCES AB Adult human saphenous vein endothelial cells (HVEC) were cultured in a compliant tubular device and evaluated by Northern hybridization for the effects of combined pressurized pulsatile flow and cyclic strain on the expression of mRNAs for endothelin-1 (ET-1), endothelial cell nitric oxide synthase (ecNOS), tissue plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1). The hemodynamic environment was designed to mimic shear stress conditions at the distal anastomosis of a saphenous vein graft, a common site of intimal proliferation. Steady-state mRNA levels in experimental tubes were expressed relative to that in controls. No changes were observed in ET-1 mRNA after 1 and 24 hr, but a 50% decrease in experimental cultures was observed after 48 hr in the vascular simulating device. Similar results were obtained for ecNOS mRNA, although a subgroup (4 of 11) showed a significant decrease (>50%) by 24 hr. For tPA mRNA, no change was observed after 1 hr, but a significant decrease (>60%) was measured after 24 hr and no message was detectable after 48 hr. Steady-state levels for PAI-1 mRNA remained unchanged through 48 hr of treatment. These results show that pressure, pulsatile flow, and cyclic strain, when applied in concert, differentially alter vasoactive and fibrinolytic functions in HVEC. Moreover, the dramatic decrease in steady-state levels of tPA mRNA is consistent with a shift toward an increased thrombotic state. DOI: 10.1007/s100169910044. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg,Surg Serv, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Abbott, WM (reprint author), Massachusetts Gen Hosp, Chief Div Vasc Surg, WAC 458,15 Parkman St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL52183] NR 32 TC 22 Z9 22 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD MAY PY 2000 VL 14 IS 3 BP 260 EP 267 DI 10.1007/s100169910044 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 308VW UT WOS:000086734400010 PM 10796958 ER PT J AU Al-Abdely, HM Najvar, L Bocanegra, R Fothergill, A Loebenberg, D Rinaldi, MG Graybill, JR AF Al-Abdely, HM Najvar, L Bocanegra, R Fothergill, A Loebenberg, D Rinaldi, MG Graybill, JR TI SCH 56592, amphotericin B, or itraconazole therapy of experimental murine cerebral phaeohyphomycosis due to Ramichloridium obovoideum ("Ramichloridium mackenziei") SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PHEOHYPHOMYCOSIS; INFECTIONS AB Ramichloridium obovoideum ("Ramichloridium makenziei") is a rare cause of lethal cerebral phaeohyphomycosis. It has been, so far, geographically restricted to the Middle East. BALB/c mice were inoculated with two strains of R. obovoideum intracranially. Therapy with amphotericin B, itraconazole, or the investigational triazole SCH 56592 was conducted for 10 days. Half the mice were monitored for survival and half were killed for determination of the fungal load in brain tissue. Recipients of SCH 56592 had significantly prolonged survival and lower brain fungal burden, and this result was found for mice infected with both of the fungal strains tested. Itraconazole reduced the brain fungal load in mice infected with one strain but not the other, while amphotericin B had no effect on brain fungal concentrations. This study indicates a possible role of SCH 56592 in the treatment of the serious cerebral phaeohyphomycosis due to R. obovoideum. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. Audie L Murphy Vet Adm Hosp, San Antonio, TX 78284 USA. Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA. RP Al-Abdely, HM (reprint author), King Faisal Specialist Hosp & Res Ctr, Dept Med MBC 46, POB 3354, Riyadh 2211, Saudi Arabia. NR 11 TC 46 Z9 48 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2000 VL 44 IS 5 BP 1159 EP 1162 DI 10.1128/AAC.44.5.1159-1162.2000 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 306YC UT WOS:000086625400007 PM 10770745 ER PT J AU Perea, S Pennick, GJ Modak, A Fothergill, AW Sutton, DA Sheehan, DJ Rinaldi, MG AF Perea, S Pennick, GJ Modak, A Fothergill, AW Sutton, DA Sheehan, DJ Rinaldi, MG TI Comparison of high-performance liquid chromatographic and microbiological methods for determination of voriconazole levels in plasma SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE PULMONARY ASPERGILLOSIS; TRIAZOLE ANTIFUNGAL AGENTS; IN-VITRO ACTIVITIES; EXPERIMENTAL-MODEL; FLUCONAZOLE; UK-109,496; ITRACONAZOLE; CANDIDA; EFFICACY; PATHOGENS AB A new selective high-performance liquid chromatography (HPLC) method with UV detection for the determination of the investigational triazole voriconazole in human plasma by using acetonitrile precipitation followed by reverse-phase HPLC on a C-18 column was compared with a simple agar well diffusion bioassay method with Candida kefyr ATCC 46764 as the assay organism. Pooled plasma was used to prepare standard and control samples for both methods. The results of analyses with spiked serum samples (run as unknowns) were concordant by the bioassay and HPLC methods, with expected values being obtained. HPLC demonstrated an improved precision (3.47 versus 12.12%) and accuracy (0.81 versus 1.28%) compared to those of the bioassay method. The range of linearity obtained by both methods (from 0.2 to 10 mu g/ml for HPLC and from 0.25 to 20 mu g/ml for the bioassay) includes the range of concentrations of voriconazole (from 1.2 to 4.7 mu g/ml) which are considered clinically relevant. Although either methodology could be used for the monitoring of patient therapy, the smaller variability observed with HPLC compared to that observed with the bioassay favors the use of HPLC for pharmacokinetic studies. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audir Murphy Div, San Antonio, TX USA. Pfizer Inc, Pfizer Pharmaceut Grp, New York, NY USA. RP Perea, S (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr,Mail Code 7881, San Antonio, TX 78229 USA. NR 21 TC 76 Z9 79 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2000 VL 44 IS 5 BP 1209 EP 1213 DI 10.1128/AAC.44.5.1209-1213.2000 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 306YC UT WOS:000086625400015 PM 10770753 ER PT J AU Park, GH McNeil, MR Tompkins, CA AF Park, GH McNeil, MR Tompkins, CA TI Reliability of the five-item revised token test for individuals with aphasia SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 29th Clinical Aphasiology Conference (CAC) CY JUN, 1999 CL KEY WEST, FLORIDA AB Two trained raters and 11 aphasic subjects were used to evaluate test-retest, interrater and intra-rater reliabilities of the Five-Item (55 total) Revised Token Test (Arvedson et al. 1985). Results revealed high reliability for overall mean scores, and moderate to high reliability for individual subtests and linguistic elements scores. Standard error of measurement (SEM) values were also determined based on the aphasic subjects' data. A discrepancy between large SEM values and the mean absolute difference value suggests that further evaluation of SEM is required with a larger sample size. Results suggest that the Five-Item Revised Token Test is a reliable instrument to assess auditory processing impairments in adults with aphasia. Given the time constraints experienced in clinical and research settings, this assessment tool is useful due to its validity, reliability, and brevity. C1 Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Aphasia Rehabil Res Lab & Clin, Pittsburgh, PA USA. RP Park, GH (reprint author), Vet Adm Med Ctr, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 15 TC 13 Z9 13 U1 0 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD MAY-JUN PY 2000 VL 14 IS 5-6 BP 527 EP 535 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 316ME UT WOS:000087170400008 ER PT J AU Doyle, PJ McNeil, MR Park, G Goda, A Rubenstein, E Spencer, K Carroll, B Lustig, A Szwarc, L AF Doyle, PJ McNeil, MR Park, G Goda, A Rubenstein, E Spencer, K Carroll, B Lustig, A Szwarc, L TI Linguistic validation of four parallel forms of a story retelling procedure SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 29th Clinical Aphasiology Conference (CAC) CY JUN, 1999 CL KEY WEST, FLORIDA ID CONNECTED SPEECH; APHASIA; ADULTS AB This study reports the development and validation of four parallel forms of a story retelling procedure. The equivalency of forms was based on the performance of 15 adults with aphasia on 12 operationally defined productive language variables including measures of (a) verbal productivity, (b) information content, (c) grammatical well-formedness, (d) phoneme production, and (e) verbal disruptions. The results revealed no significant differences among the four forms of the test for any of the dependent measures, and strong, positive and significant correlations among forms for 11 of the 12 dependent measures. These results suggest that a wide variety of productive language variables can be reliably measured using parallel forms of the story-retelling procedure described herein. C1 VA Pittsburgh Healthcare Syst, Aphasia Rehabil Res Lab & Clin, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Off Measurement & Evaluat Teaching, Pittsburgh, PA 15260 USA. RP Doyle, PJ (reprint author), Vet Adm Med Ctr, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 23 TC 23 Z9 23 U1 0 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD MAY-JUN PY 2000 VL 14 IS 5-6 BP 537 EP 549 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 316ME UT WOS:000087170400009 ER PT J AU Spencer, KA Doyle, PJ McNeil, MR Wambaugh, JL Park, G Carroll, B AF Spencer, KA Doyle, PJ McNeil, MR Wambaugh, JL Park, G Carroll, B TI Examining the facilitative effects of rhyme in a patient with output lexicon damage SO APHASIOLOGY LA English DT Article; Proceedings Paper CT 29th Clinical Aphasiology Conference (CAC) CY JUN, 1999 CL KEY WEST, FLORIDA ID APHASIA; ACTIVATION; BUFFER; SPEECH; ACCESS AB A theory-driven treatment was designed to facilitate access to the impaired output lexicons of a 47-year-old woman with aphasia resulting from a left parietal haemorrhage. In the context of a multiple-baseline design, lists of rhymed word pairs from four semantic categories were trained using a systematic cueing hierarchy. Performance measures were based on the subject's generation of targeted words, verbally and in writing, when presented with a rhyme of the target. Results demonstrated positive acquisition, generalization and maintenance effects for treated and untreated items across semantic categories. Delayed generalization patterns may be explained by retrieval inhibition (Blaxton and Bookheimer 1993) or lateral inhibition (McClelland and Rumelhart 1981). C1 VA Pittsburgh Healthcare Syst, Aphasia Rehabil Res Lab & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Univ Utah, Salt Lake City, UT USA. Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA. RP Spencer, KA (reprint author), Univ Washington, Dept Speech & Hearing Sci, 1417 NE 42nd St, Seattle, WA 98105 USA. NR 43 TC 17 Z9 17 U1 6 U2 8 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD MAY-JUN PY 2000 VL 14 IS 5-6 BP 567 EP 584 PG 18 WC Clinical Neurology SC Neurosciences & Neurology GA 316ME UT WOS:000087170400011 ER PT J AU Asawanonda, P Anderson, RR Chang, YC Taylor, CR AF Asawanonda, P Anderson, RR Chang, YC Taylor, CR TI 308-nm excimer laser for the treatment of psoriasis - A dose-response study SO ARCHIVES OF DERMATOLOGY LA English DT Article ID UVB PHOTOTHERAPY; SUN EXPOSURE; MELANOMA AB Objective: To determine the dose-response relationship of excimer laser-generated 308-nm UV-B radiation for treating psoriasis. Design: Pilot study with a before-after design. Setting: A university dermatology service. Patients: Thirteen consecutive patients with at least 4 large, stable psoriasis plagues. Interventions: Excimer laser-generated 308-nm UV-B radiation was given to each of 4 plaques, which received 1, 2, 4, and 20 treatments, respectively. Untreated areas within each plaque served as controls. Within each plaque, 8 doses based on multiples,of a predetermined minimal erythema dose (MED) were tested in distinct sites. The multiples were 0.5 and 1 (low dose); 2, 3, 4, and 6 (medium dose); and 8 and 16 (high dose). At every treatment, the dose for each site remained fixed at the same MED multiple. A psoriasis severity index score was determined for each area before, every 2 weeks during, and 2 and 4 months after treatment. Results: The mean+/-SD MED was 203.03 +/- 57.84 mJ/cm(2). Treatment with high fluences produced significantly better results than that with medium and low fluences at weeks 4, 6, 8, and 10 (P<.05). At 4 months' follow-up, all sites that received low or medium fluences had recurrences, whereas those that underwent a single treatment at 8 and 16 MED multiples remained in remission. Conclusions: With 308-nm UV-B radiation generated by an excimer laser, it is possible to clear psoriasis with as little as 1 treatment with moderately long remission. In contrast to traditional phototherapy techniques, this handheld excimer laser UV-B therapy is selectively directed toward lesional skin, thus sparing the surrounding normal skin from unnecessary radiation exposure. Treatment of other inflammatory diseases and limited psoriasis seems reasonable to pursue with this modality. C1 Harvard Univ, Dept Dermatol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Taylor, CR (reprint author), Harvard Univ, Dept Dermatol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Bartlett 410, Boston, MA 02114 USA. NR 13 TC 118 Z9 120 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 2000 VL 136 IS 5 BP 619 EP 624 DI 10.1001/archderm.136.5.619 PG 6 WC Dermatology SC Dermatology GA 313FJ UT WOS:000086989400005 PM 10815855 ER PT J AU Baldessarini, RJ Tohen, M Tondo, L AF Baldessarini, RJ Tohen, M Tondo, L TI Maintenance treatment in bipolar disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID CLINICAL-TRIALS; LITHIUM; MANIA; ILLNESS; THERAPY C1 Harvard Univ, Dept Psychiat, Sch Med, Boston, MA 02115 USA. Harvard Univ, Program Neurosci, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Belmont, MA 02478 USA. Eli Lilly Corp, Lilly Res Ctr, Indianapolis, IN USA. Univ Cagliari, Dept Psychol, Cagliari, Italy. RP Baldessarini, RJ (reprint author), Harvard Univ, Dept Psychiat, Sch Med, Boston, MA 02115 USA. FU NIMH NIH HHS [MH-47370] NR 20 TC 40 Z9 40 U1 0 U2 0 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 MAY PY 2000 VL 57 IS 5 BP 490 EP 492 DI 10.1001/archpsyc.57.5.490 PG 3 WC Psychiatry SC Psychiatry GA 312DG UT WOS:000086927500008 PM 10807489 ER PT J AU Hyman, BT Strickland, D Rebeck, GW AF Hyman, BT Strickland, D Rebeck, GW TI Role of the low-density lipoprotein receptor-related protein in beta-amyloid metabolism and Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Review ID PHOSPHOTYROSINE-BINDING DOMAIN; APOLIPOPROTEIN-E EPSILON-4; PRECURSOR PROTEIN; ALPHA(2)-MACROGLOBULIN RECEPTOR; ALPHA-2-MACROGLOBULIN RECEPTOR; GENETIC ASSOCIATION; FIBRIL FORMATION; SENILE PLAQUES; IN-VITRO; NEUROFIBRILLARY TANGLES AB Deposition of beta-amyloid (A beta), a metabolite of approximately 4 kd of the amyloid precursor protein, is a critical pathological feature in Alzheimer disease. We postulate that deposition reflects an imbalance of A beta synthesis and clearance. Several pathways that impact A beta converge on a single receptor molecule, the low-density lipoprotein receptor-related protein (LRP). This multifunctional receptor is the major neuronal receptor both for apolipoprotein E (apoE, protein; APOE, gene) and for alpha(2)-macroglobulin (alpha(2)M, protein, A2M, gene), and it mediates clearance of apoE/A beta and alpha(2)M/A beta complexes. The LRP also interacts with the amyloid precursor protein itself. In this review, we highlight data that support a role for LRP in A beta metabolism and hypothesize that LRP therefore plays a critical role in Alzheimer disease. C1 Massachusetts Gen Hosp, Alzheimer Dis Res Lab, Boston, MA 02129 USA. Amer Red Cross, Holland Lab, Rockville, MD USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimer Dis Res Lab, 149 13th St,Room 6405, Boston, MA 02129 USA. FU NIA NIH HHS [AG12406] NR 84 TC 84 Z9 85 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2000 VL 57 IS 5 BP 646 EP 650 DI 10.1001/archneur.57.5.646 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 311WG UT WOS:000086908400004 PM 10815129 ER PT J AU Daly, E Zaitchik, D Copeland, M Schmahmann, J Gunther, J Albert, M AF Daly, E Zaitchik, D Copeland, M Schmahmann, J Gunther, J Albert, M TI Predicting conversion to Alzheimer disease using standardized clinical information SO ARCHIVES OF NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; DEMENTIA; SCALE AB Objective: To identify aspects of a standardized clinical assessment that call predict which individuals within the category of "questionable" Alzheimer disease (AD) have a high likelihood of converting to AD over time. Design: Detailed semistructured interviews were performed at baseline and annually for 3 years. Setting: University-based gerontology research program. Patients: The patient population consisted of 165 individuals 65 years and older: 42 of the participants had a Clinical Dementia Rating (CDR) of normal cognition (CDR rating, 0.0) and 123 had a rating of questionable AD (CDR rating, 0.5). After 3 years of follow-up, 23 of the 123 subjects with questionable AD were diagnosed with probable AD Main Outcome Measures: The interview was used to generate a summary measure based on the sum of 6 CDR categories, known as the Total Box Score. The responses to 32 selected questions from the interview also were examined. Results: Likelihood of progression to AD during the follow-up period was strongly related to the Total Box Score. For example, more than 50% of individuals with a Total Box Score of 2.0 or higher at baseline developed AD during the follow-up interval, whereas about 10% of individuals with a Total Box Score of 1.0 or lower developed AD during this same period. Selected questions from the standardized clinical interview also were highly predictive of subsequent conversion to AD among the study population. Eight selected questions from the clinical interview at baseline, combined with the CDR Total Box Score, identified 88.6% of such individuals accurately (questionable group, 82/91; converter group, 19/23). Conclusions: A standardized clinical assessment can be used to identify the subgroup of individuals within the category of questionable AD who have a high likelihood of converting to AD over time. Subjects who met the criteria for questionable AD had a variety of trajectories during a 3-year follow-up, suggesting that diverse factors may influence the functional changes observed in this population. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Albert, M (reprint author), Massachusetts Gen Hosp E, 149-9124,149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [P01-AG04953] NR 18 TC 220 Z9 230 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2000 VL 57 IS 5 BP 675 EP 680 DI 10.1001/archneur.57.5.675 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 311WG UT WOS:000086908400008 PM 10815133 ER PT J AU Cho, EY Hankinson, SE Willett, WC Stampfer, MJ Spiegelman, D Speizer, FE Rimm, EB Seddon, JM AF Cho, EY Hankinson, SE Willett, WC Stampfer, MJ Spiegelman, D Speizer, FE Rimm, EB Seddon, JM TI Prospective study of alcohol consumption and the risk of age-related macular degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; FOOD FREQUENCY QUESTIONNAIRE; CIGARETTE-SMOKING; CORONARY-DISEASE; MACULOPATHY; WOMEN; REPRODUCIBILITY; VALIDITY; DIETARY; HEALTH AB Objective: To describe the relationship between alcohol consumption and the incidence of age-related macular degeneration (AMD). Methods: We conducted a prospective study among female nurses between 1980 and 1994 and among male health professionals between 1986 and 1994. We included 32 764 women and 29 488 men who were 50 years or older, without a diagnosis of AMD or cancer at baseline, and added additional subjects to the analysis as they reached 50 years of age. Their alcohol intake was assessed at baseline and updated during follow-up evaluations using a validated semiquantitative food-frequency questionnaire. After separate analyses for women and men, pooled estimates of the relationship of alcohol to the risk of AMD were calculated. Results: Age-related macular degeneration associated with a visual acuity loss of 20/30 or worse, including the early and dry and wet types was diagnosed in 298 women (from 697 498 person-years of follow-up) and 153 men (229 180 person-years) by 1994, the end of follow-up. After controlling for age, smoking, and other risk factors, the pooled relative risks (RRs) and 95% confidence intervals (CIs) for AMD compared with nondrinkers were 1.0 (0.7-2.2) for drinkers who consumed 0.1 to 4.9 dd of alcohol; 0.9 (0.6-1.4) for 5 to 14.9 gid; 1.1 (0.7-1.7) for 15 to 29.9 g/d; and 1.3 (0.9-1.8) for 30 g/d or more. Among women, there was a suggestion of a modest increased risk of the disease in drinkers who consumed 30 g/d or more (RR, 1.5; 95% CI, 1.0-2.4); this was limited to an increased risk of the early and dry form (RR, 2.0; 95% CI, 1.2-3.4). No specific type of alcohol provided protection against AMD. Conclusion: This prospective study does not support an inverse relationship between moderate alcohol consumption and risk of AMD. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Epidemiol Unit, Boston, MA USA. RP Cho, EY (reprint author), Channing Lab, Nurses Hlth Study, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 40356, CA 55075]; NEI NIH HHS [EY 09611] NR 37 TC 39 Z9 45 U1 0 U2 3 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 MAY PY 2000 VL 118 IS 5 BP 681 EP 688 PG 8 WC Ophthalmology SC Ophthalmology GA 313HJ UT WOS:000086994000010 PM 10815161 ER PT J AU Boninger, ML Baldwin, M Cooper, RA Koontz, A Chan, L AF Boninger, ML Baldwin, M Cooper, RA Koontz, A Chan, L TI Manual wheelchair pushrim biomechanics and axle position SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE wheelchair user; biomechanics; rehabilitation ID SEAT POSITION; PROPULSION; FORCES; KINETICS AB Objective: The biomechanics of wheelchair propulsion have been linked to upper extremity injury. Specifically, prior studies have correlated increased median nerve dysfunction with increasing propulsion frequency and a higher rate of rise of the resultant, or total, pushrim force. Despite this link, there is little research on the effect of wheelchair setup on propulsion biomechanics. The objective of this study was to determine the effect of rear axle position relative to the shoulder on pushrim biomechanics, Design: Case series. Setting: Biomechanics laboratory. Participants: Forty individuals with paraplegia who use manual wheelchairs for mobility. Intervention: Subjects propelled their own wheelchairs on a dynamometer at two different steady-state speeds and going from a dead stop to maximum speed, Bilateral biomechanical data were obtained using a force- and moment-sensing pushrim and a motion analysis system. Main Outcome Measures: Position of the axle relative to the shoulder at rest both horizontal (XPOS) and vertical (YPOS), and pushrim biomechanical variables including frequency of propulsion, peak and rate of rise of the resultant force, planar moment, and push angle. Partial correlation coefficients between relative axle position and propulsion biomechanics variables were calculated. Results: After controlling for subject characteristics, XPOS was significantly correlated with the frequency of propulsion (p <.01) and the rate of rise of the resultant force (p <.05). In addition, both XPOS and YPOS were significantly correlated with the push angle at multiple speeds (p <.05). Conclusion: Specific biomechanical parameters known to correlate with median nerve injuries were found to be related to axle position relative to the shoulder. Providing wheelchair users with adjustable axle position and then Fitting the user to the wheelchair can improve propulsion biomechanics and likely reduce the risk of injury. C1 Univ Pittsburgh, Div Phys Med & Rehabil, Dept Orthopaed Surg, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. US Hlth Care Financing Adm, Div Clin Stand & Qual, Seattle, WA USA. RP Boninger, ML (reprint author), Univ Pittsburgh, Div Phys Med & Rehabil, Dept Orthopaed Surg, Suite 901 Kaufmann Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA. RI Moro, Juan Carlos/A-4315-2015; OI Moro, Juan Carlos/0000-0002-4886-2967; Boninger, Michael/0000-0001-6966-919X FU NICHD NIH HHS [5 P01 HD33989 03, K08 HD01122-01] NR 17 TC 103 Z9 104 U1 2 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2000 VL 81 IS 5 BP 608 EP 613 DI 10.1053/mr.2000.1455 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 311CT UT WOS:000086867800012 PM 10807100 ER PT J AU Yang, CC Stiens, SA AF Yang, CC Stiens, SA TI Antegrade continence enema for the treatment of neurogenic constipation and fecal incontinence after spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE constipation; colon; neurogenic bowel; spinal cord injury; antegrade continence enema; rehabilitation ID COLONIC ENEMA; CHILDREN AB Objective: To describe the effects of an antegrade continence enema stoma formed in a paraplegic man with intractable constipation and fecal incontinence. Design: Case report. Setting: Spinal cord injury unit, Veterans Affairs hospital. Participants: Spinal cord injury (SCI) patient with T12 paraplegia. Intervention: Surgical formation of antegrade continence enema stoma. Main Outcome Measures: Time of bowel program care, ease of fecal elimination, safety of procedure. Results: Bowel care time was decreased from 2 hours to 50 minutes daily; 6 bowel medications were discontinued; fecal incontinence was eliminated; and no surgical or medical side effects noted after the procedure. Conclusion: The antegrade continence enema procedure is a safe and effective means of treating intractable constipation and fecal incontinence in the adult SCI patient. This option should be considered for those persons in whom medical management of bowel care has been unsuccessful. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Urol Sect 112U, Seattle, WA 98108 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Yang, CC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Urol Sect 112U, Seattle, WA 98108 USA. NR 13 TC 9 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2000 VL 81 IS 5 BP 683 EP 685 DI 10.1053/mr.2000.3869 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 311CT UT WOS:000086867800023 PM 10807111 ER PT J AU Clark, WR Shinaberger, JH AF Clark, WR Shinaberger, JH TI Clinical evaluation of a new high efficiency hemodialyzer: Polysynthane (TM) SO ASAIO JOURNAL LA English DT Article ID NATIONAL COOPERATIVE DIALYSIS; MASS-TRANSFER; HEMATOCRIT; MORBIDITY; SURVIVAL; KT/V AB Two increasingly common characteristics of the American chronic hemodialysis (HD) population, high hematocrit and large body size, may vender the currently recommended adequacy targets difficult to achieve, even with very efficient dialyzers. In a group of patients with these characteristics, we assessed the ability of a new high efficiency dialyzer (PSN(TM)210; Baxter Healthcare Corporation) to achieve the currently recommended adequacy targets. Six patients (mean pre-HD weight and hematocrit, 90.3 +/- 18.0 kg and 0.40 +/- 0.03 kg, respectively) were evaluated. At prescribed blood and dialysate flow rates of 400 and 800 ml/min, respectively, and a mean treatment duration of 4 hrs, mean delivered urea Kt/V and reduction ratio (URR) were 1.38 +/- 0.25 and 0.73 +/- 0.07, respectively. For the same flow rates, whole blood clearances for urea, creatinine, and phosphate were 315 +/- 13, 246 +/- 28, and 260 +/- 27 ml/min, respectively. These data indicate this dialyzer has an efficient mass transfer design allowing adequate dialysis to be delivered even to very large patients under high efficiency conditions. C1 Baxter Healthcare Corp, Div Renal, Mcgaw Pk, IL USA. Indiana Univ, Sch Med, Div Nephrol, Indianapolis, IN USA. W Los Angeles Dept Vet Affairs Med Ctr, Dialysis Unit, Los Angeles, CA USA. RP Clark, WR (reprint author), Wishard Mem Hosp, Baxter Healthcare Corp, Hemodialysis Res Lab, Myers Bldg,Room D711, Indianapolis, IN 46202 USA. NR 30 TC 17 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD MAY-JUN PY 2000 VL 46 IS 3 BP 288 EP 292 DI 10.1097/00002480-200005000-00009 PG 5 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 346RF UT WOS:000088884300009 PM 10826738 ER PT J AU Bhorade, R Weissleder, R Nakakoshi, T Moore, A Tung, CH AF Bhorade, R Weissleder, R Nakakoshi, T Moore, A Tung, CH TI Macrocyclic chelators with paramagnetic cations are internalized into mammalian cells via a HIV-tat derived membrane translocation peptide SO BIOCONJUGATE CHEMISTRY LA English DT Article ID NUCLEAR-LOCALIZATION SEQUENCE; IN-VIVO; INTERCELLULAR TRAFFICKING; FUSION PROTEINS; PLASMA-MEMBRANE; DELIVERY; TRANSDUCTION; INHIBITION; AGENT AB A major obstacle to using paramagnetic MR contrast agents for in vivo cell tracking or molecular sensing is their generally low cellular uptake. In this study, we show that a paramagnetically labeled DOTA chelator derivatized with a 13-mer HIV-tat peptide is efficiently internalized into mammalian cells. Intracellular concentrations were attained that were readily detectable by MR imaging using both gadolinium and dysprosium chelates. Using this paradigm, it should be feasible to internalize a variety of chemically different agents into mammalian cells. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Sch Med, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Sch Med, 149 13th St,5406, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NIAID NIH HHS [R01AI-CA46973]; NIDDK NIH HHS [R21DK55713] NR 37 TC 146 Z9 149 U1 1 U2 5 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 MAY-JUN PY 2000 VL 11 IS 3 BP 301 EP 305 DI 10.1021/bc990168d PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 318YX UT WOS:000087313200001 PM 10821645 ER PT J AU Rauch, SL Whalen, PJ Shin, LM McInerney, SC Macklin, ML Lasko, NB Orr, SP Pitman, RK AF Rauch, SL Whalen, PJ Shin, LM McInerney, SC Macklin, ML Lasko, NB Orr, SP Pitman, RK TI Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: A functional MRI study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE amygdala; posttraumatic stress disorder; functional magnetic resonance imaging; anterior cingulate cortex; anxiety; emotion ID POSITRON-EMISSION-TOMOGRAPHY; SCRIPT-DRIVEN IMAGERY; CONDITIONED FEAR; PTSD; EXPRESSIONS; CORTEX; PERCEPTION; TRAUMA; BRAIN; FACE AB Background: Converging lines of evidence have implicated the amygdala in the pathophysiology of posttraumatic stress disorder (PTSD). We previously developed a method for measuring automatic amygdala responses to general threat-related stimuli; in conjunction with functional magnetic resonance imaging, we used a passive viewing task involving masked presentations of human facial stimuli. Methods: We applied this method to study veterans with PTSD and a comparison cohort of combat-exposed veterans without PTSD. Results: The findings indicate that patients with PTSD exhibit exaggerated amygdala responses to masked-fearful versus masked-happy faces. Conclusions: Although some previous neuroimaging studies of PTSD have demonstrated amygdala recruitment in response to reminders of traumatic events, this represents the first evidence for exaggerated amygdala responses to general negative stimuli in PTSD. Furthermore, by using a probe that emphasizes automaticity, we provide initial evidence of amygdala hyperresponsivity dissociated from the "top-down " influences of medial frontal cortex. Biol Psychiatry 2000;47:769-776 (C) 2000 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. VA Res Serv, Manchester, NH USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp East, Dept Psychiat, 13th St,Bldg 149,Room 9130, Boston, MA 02129 USA. FU NIMH NIH HHS [K20MH01215] NR 44 TC 615 Z9 628 U1 5 U2 54 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 MAY 1 PY 2000 VL 47 IS 9 BP 769 EP 776 DI 10.1016/S0006-3223(00)00828-3 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 312DW UT WOS:000086928800001 PM 10812035 ER PT J AU Levisohn, L Cronin-Golomb, A Schmahmann, JD AF Levisohn, L Cronin-Golomb, A Schmahmann, JD TI Neuropsychological consequences of cerebellar tumour resection in children - Cerebellar cognitive affective syndrome in a paediatric population SO BRAIN LA English DT Article DE cerebellum; cognition; affect; behaviour; cerebellar cognitive affective syndrome; posterior fossa syndrome ID POSITRON EMISSION TOMOGRAPHY; WHOLE-BRAIN RADIOTHERAPY; POSTERIOR-FOSSA TUMORS; LONG-TERM SURVIVORS; MENTAL SKILLS; MEMORY; MEDULLOBLASTOMA; THOUGHT; INTELLIGENCE; IMPAIRMENT AB Acquired cerebellar lesions in adults have been shown to produce impairments in higher function as exemplified by the cerebellar cognitive affective syndrome, It is not yet known whether similar findings occur in children with acquired cerebellar lesions, and whether developmental factors influence their presentation. In studies to date, survivors of childhood cerebellar tumours who demonstrate long-term deficits in cognitive functions have undergone surgery as well as cranial irradiation or methotrexate treatment. Investigation of the effects of the cerebellar lesion independent of the known deleterious effects of these agents is important for understanding the role of the cerebellum in cognitive and affective development and for informing treatment and rehabilitation strategies, If the cerebellar contribution to cognition and affect is significant, then damage in childhood may influence a wide range of psychological processes, both as an immediate consequence and as these processes fail to develop normally later on, In this study we evaluated neuropsychological data in 19 children who underwent resection of cerebellar tumours but who received neither cranial irradiation nor methotrexate chemotherapy. Impairments were noted in executive function; including planning and sequencing, and in visual-spatial function, expressive language, verbal memory and modulation of affect, These deficits were common and in some cases could be dissociated from motor deficits. Lesions of the vermis in particular were associated with dysregulation of affect. Behavioural deficits were more apparent in older than younger children. These results reveal that clinically relevant neuropsychological changes may occur following cerebellar tumour resection in children. Age at the time of surgery and the site of the cerebellar lesion influence the neurobehavioural outcome. The results of the present study indicate that the cerebellar cognitive affective syndrome is evident in children as well as in adults, and they provide further clinical evidence that the cerebellum is an essential node in the distributed neural circuitry subserving higher order behaviours. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 915,Fruit St, Boston, MA 02114 USA. NR 46 TC 381 Z9 388 U1 3 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2000 VL 123 BP 1041 EP 1050 DI 10.1093/brain/123.5.1041 PN 5 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 323TK UT WOS:000087580900017 PM 10775548 ER PT J AU Guadagnoli, E Soumerai, SB Gurwitz, JH Borbas, C Shapiro, CL Weeks, JC Morris, N AF Guadagnoli, E Soumerai, SB Gurwitz, JH Borbas, C Shapiro, CL Weeks, JC Morris, N TI Improving discussion of surgical treatment options for patients with breast cancer: local medical opinion leaders versus audit and performance feedback SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; breast conserving surgery; hospital practices; mastectomy; physician behavior ID CONSERVING SURGERY; STAGE-I; CARE; REQUIREMENTS; GUIDELINES; QUALITY AB We studied whether a hospital intervention utilizing medical opinion leaders and performance feedback reduced the proportion of women who reported that surgeons did not discuss options prior to surgery for early stage breast cancer. Opinion leaders provided clinical education to their peers using a variety of strategies and were selected for their ability to influence their peers. Performance feedback involved distributing performance reports that contained data on the outcomes of interest as well as on other treatment patterns. Twenty-eight hospitals in Minnesota were randomized to the intervention or to a control group that received performance feedback only. The proportion of patients at intervention hospitals who said that their surgeon did not discuss options decreased significantly (p < 0.001) from 33% to 17%, but a similar decrease was observed among control hospitals. Using medical opinion leaders to intervene in hospitals appeared as effective as performance feedback. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Fallon Healthcare Syst, Meyers Primary Care Inst, Worcester, MA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Healthcare Educ & Res Fdn Inc, St Paul, MN USA. Arthur James Canc Hosp, Columbus, OH USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Guadagnoli, E (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA59408, CA57755] NR 14 TC 25 Z9 25 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 2000 VL 61 IS 2 BP 171 EP 175 DI 10.1023/A:1006475012861 PG 5 WC Oncology SC Oncology GA 329LJ UT WOS:000087908200009 PM 10942103 ER PT J AU Dellian, M Yuan, F Trubetskoy, VS Torchilin, VP Jain, RK AF Dellian, M Yuan, F Trubetskoy, VS Torchilin, VP Jain, RK TI Vascular permeability in a human tumour xenograft: molecular charge dependence SO BRITISH JOURNAL OF CANCER LA English DT Article DE tumour; vascular permeability; macromolecules; charge; drug delivery ID HUMAN ADENOCARCINOMA LS174T; ENDOTHELIAL GROWTH-FACTOR; BRAIN-BARRIER TRANSPORT; SINGLE FROG CAPILLARIES; BOVINE SERUM-ALBUMIN; MICROVASCULAR PERMEABILITY; GLOMERULAR-FILTRATION; MONOCLONAL-ANTIBODY; CATIONIZED FERRITIN; SOLID TUMORS AB Molecular charge is one of the main determinants of transvascular transport. There are, however, no data available on the effect of molecular charge on microvascular permeability of macromolecules in solid tumours. To this end, we measured tumour microvascular permeability to different proteins having similar size but different charge. Measurements were performed in the human colon adenocarcinoma LS174T transplanted in transparent dorsal skinfold chambers in severe combined immunodeficient (SCID) mice. Bovine serum albumin (BSA) and IgG were fluorescently labelled and were either cationized by conjugation with hexamethylenediamine or anionized by succinylation. The molecules were injected i.v, and the fluorescence in tumour tissue was quantified by intravital fluorescence microscopy. The fluorescence intensity and pharmacokinetic data were used to calculate the microvascular permeability. We found that tumour vascular permeability of cationized BSA (pl-range: 8.6-9.1) and IgG (pl: 8.6-9.3) was more than two-fold higher (4.25 and 4.65 x 10(-7) cm s(-1)) than that of the anionized BSA (pl approximate to 2.0) and IgG (pl: 3.0-3.9; 1.11 and 1.93 x 10(-7) cm s(-1), respectively). Our results indicate that positively charged molecules extravasate faster in solid tumours compared to the similar-sized compounds with neutral or negative charges. However, the plasma clearance of cationic molecules was similar to 2 x faster than that of anionic ones, indicating that the modification of proteins enhances drug delivery to normal organs as well. Therefore, caution should be exercised when such a strategy is used to improve drug and gene delivery to solid tumours. (C) 2000 Cancer Research Campaign. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Munich, Dept Otorhinolaryngol, D-81366 Munich, Germany. Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. Mirus Corp, Madison, WI USA. Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RI Yuan, Fan/A-1287-2011 FU NCI NIH HHS [R35-CA-56591] NR 50 TC 127 Z9 130 U1 1 U2 25 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 MAY PY 2000 VL 82 IS 9 BP 1513 EP 1518 PG 6 WC Oncology SC Oncology GA 304JT UT WOS:000086480600003 PM 10789717 ER PT J AU Liu, G Ghadirian, P Vesprini, D Hamel, N Paradis, AJ Lai, G Gallinger, S Narod, SA Foulkes, WD AF Liu, G Ghadirian, P Vesprini, D Hamel, N Paradis, AJ Lai, G Gallinger, S Narod, SA Foulkes, WD TI Polymorphisms in GSTM1, GSTT1 and CYP1A1 and risk of pancreatic adenocarcinoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE pancreatic cancer; genetic susceptibility; cytochrome P450; glutathione S-transferase ID CANCER SUSCEPTIBILITY; GENETIC-POLYMORPHISM; EPIDEMIOLOGY; BREAST AB A prospective study of 149 unselected incident cases of pancreatic adenocarcinoma and 146 ethnically-matched controls found no associations between GSTM1 (adjusted odds ratio (AOR) 1.14), GSTT1 (AOR: 1.19) and CYP1A1 (AOR: 1.08) polymorphisms and pancreatic cancer susceptibility. Smoking and drinking status did not affect results. These polymorphisms do not appear to be important gene modifiers in pancreatic cancer. (C) 2000 Cancer Research Campaign. C1 Univ Toronto, Womens Coll Hosp, Ctr Res Womens Hlth, Toronto, ON M5G 1N8, Canada. CHUM, Ctr Rech, Montreal, PQ H2W 1T8, Canada. McGill Univ, Dept Med, Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada. Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. RP Liu, G (reprint author), Dana Farber Canc Inst, Dana 1056,44 Binney St, Boston, MA 02115 USA. RI Gallinger, Steven/E-4575-2013; Liu, Geoffrey/N-4421-2016 NR 13 TC 31 Z9 35 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 2000 VL 82 IS 10 BP 1646 EP 1649 PG 4 WC Oncology SC Oncology GA 311VK UT WOS:000086906400006 PM 10817498 ER PT J AU Glue, P Schenker, S Gupta, S Clement, RP Zambas, D Salfi, M AF Glue, P Schenker, S Gupta, S Clement, RP Zambas, D Salfi, M TI The single dose pharmacokinetics of ribavirin in subjects with chronic liver disease SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE liver disease; pharmacokinetics; ribavirin ID CHRONIC HEPATITIS-C; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; INTERFERON-ALPHA-2B; COMBINATION; VOLUNTEERS; VIRUS AB Aims The primary objective of this study was to describe the single dose pharmacokinetics of ribavirin in subjects with normal liver function and those with various degrees of stable chronic liver disease. Additionally this study assessed the safety and tolerability of ribavirin in this population. Methods Single oral 600 mg doses of ribavirin were administered to healthy male and female volunteers (n=6) and patients with stable chronic Liver disease (n=17), in a parallel group study. Pharmacokinetic sampling and tolerability assessments were performed up to 168 h post dose. Results Single oral doses of 600 mg ribavirin were well tolerated by healthy volunteers and patients with varying degrees of hepatic dysfunction. Although mean C-max increased with the severity of hepatic dysfunction, there was no change in extent of absorption or renal clearance of ribavirin. Conclusions There are no pharmacokinetic reasons for initial dose adjustment of ribavirin in patients with hepatic dysfunction. C1 Schering Plough Res Inst, Kenilworth, NJ 07033 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Glue, P (reprint author), Schering Plough Res Inst, 2015 Galloping Hill Rd, Kenilworth, NJ 07033 USA. OI Glue, Paul/0000-0002-7305-2800 NR 20 TC 28 Z9 29 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD MAY PY 2000 VL 49 IS 5 BP 417 EP 421 DI 10.1046/j.1365-2125.2000.00186.x PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 312EM UT WOS:000086930300003 PM 10792198 ER PT J AU Leivo, T Kiistala, U Vesterinen, M Owaribe, K Burgeson, RE Virtanen, I Oikarinen, A AF Leivo, T Kiistala, U Vesterinen, M Owaribe, K Burgeson, RE Virtanen, I Oikarinen, A TI Re-epithelialization rate and protein expression in the suction-induced wound model: comparison between intact blisters, open wounds and calcipotriol-pretreated open wounds SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE calcipotriol; hemidesmosome; integrin; laminin; suction blister; wound healing ID EPIDERMAL BASEMENT-MEMBRANE; CELL-ADHESION; DERMATITIS-HERPETIFORMIS; MONOCLONAL-ANTIBODIES; KERATINOCYTE MOTILITY; EXTRACELLULAR DOMAIN; INTEGRIN EXPRESSION; ANCHORING FILAMENTS; ALPHA(9) INTEGRIN; HUMAN TENASCIN AB We have investigated re-epithelialization following induction of suction blisters in humans in intact blisters, open wounds, i,e, blister roofs removed immediately after blister induction, and calcipotriol-pretreated open wounds. intact blisters simulate blister healing in bullous disease, while open wounds simulate re-epithelialization during wound healing, Re-epithelialization was clearly faster in open wounds than in intact blisters, and was not affected by calcipotriol pretreatment, Bullous pemphigoid antigen 2 (BP180), bullous pemphigoid antigen 1 (BP230), plectin/hemidesmosomal 1 protein (HD1), laminin 5, laminin alpha 5, laminin beta 1, type VII collagen, tenascin-C, beta 4, alpha v beta 5, alpha 5 and alpha 9 integrins were studied in intact blisters and open wounds by immunohistochemistry. Hemidesmosomal plaque proteins BP230 and plectin/HD1, which connect the keratin cytoskeleton to the hemidesmosome, appeared earlier at the leading edge in intact blisters than in open wounds. Band-like immunostaining in the basement membrane for laminin 5, alpha 5 and beta 1 chains was continuous in blister bases, but partially discontinuous in open wound bases. The other antigens studied showed similar expression in intact blisters and open wounds. BP180, BP230, plectin/HD1, beta 4 integrin, laminin 5 and tenascin-C expression were further studied in calcipotriol-pretreated open wounds. Calcipotriol did not affect the expression of these antigens, The immunohistochemical results suggest that the keratin cytoskeleton is linked to the basal plasma membrane of migrating basal cells via BP230 and plectin/HD1 earlier in the more slowly re-epithelializing blisters than in open wounds, An intact laminin sheath may inhibit keratinocyte migration in intact blisters. C1 Univ Helsinki, Dept Anat, Inst Biomed, FIN-00014 Helsinki, Finland. Oulu Univ Hosp, Dept Dermatol, Oulu, Finland. Oulu Univ, Oulu, Finland. Cent Mil Hosp, Dept Dermatol, Helsinki, Finland. Univ Helsinki, Dept Dent, FIN-00014 Helsinki, Finland. Nagoya Univ, Sch Informat & Sci, Grad Sch Human Informat Biol Syst, Chikusa Ku, Nagoya, Aichi 46401, Japan. Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Leivo, T (reprint author), Melikonkatu 1 B 51, FIN-00210 Helsinki, Finland. NR 50 TC 15 Z9 15 U1 1 U2 4 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 MAY PY 2000 VL 142 IS 5 BP 991 EP 1002 DI 10.1046/j.1365-2133.2000.03484.x PG 12 WC Dermatology SC Dermatology GA 317PH UT WOS:000087235100024 PM 10809861 ER PT J AU Sternberg, DW Aird, W Neuberg, D Thompson, L MacNeill, K Amrein, P Shulman, LN AF Sternberg, DW Aird, W Neuberg, D Thompson, L MacNeill, K Amrein, P Shulman, LN TI Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine - A pharmacologically based regimen SO CANCER LA English DT Article DE acute myelogenous leukemia; Ara-C; mitoxantrone; disease remission ID ACUTE MYELOID-LEUKEMIA; COLONY-STIMULATING FACTOR; CYTOSINE-ARABINOSIDE; FLAG FLUDARABINE; ELDERLY PATIENTS; SINGLE-CENTER; G-CSF; CHEMOTHERAPY; SURVIVAL; TRIAL AB BACKGROUND. Although chemotherapy can achieve a high rate of disease remission induction in patients with newly diagnosed acute myelogenous leukemia (AML), patients with recurrent or refractory AML generally have a poorer rate of response. This study assessed the utility of mitoxantrone and intermediate-dose cytarabine (Ara-C) in the treatment of patients with recurrent or refractory AML. METHODS. Forty-seven patients with recurrent or refractory AML were treated with Ara-C, 0.5 gm/m(2), intravenously (i.v.) every 12 hours x 12 doses on Days 1-6 and mitoxantrone, 5 mg/m(2), i.v. on Days 1-5. RESULTS. Twenty-nine of the 47 patients (62%) achieved a complete response. The median duration of disease remission was 112 days (range, 29 days-8 years). Of the 25 patients age greater than or equal to 60 years, 19 (76%) had a complete disease remission and the median duration of disease remission in this group was 114 days (range, 33-370 days), although all patients subsequently developed a disease recurrence. The chemotherapy generally was well tolerated, with a mean duration of neutropenia of 31 days and a mean duration of thrombocytopenia of 33 days. Three patients died of infectious complications between 23-26 days after the initiation of chemotherapy, 1 patient died of sudden cardiac arrest 13 days after the initiation of chemotherapy, and 1 patient developed cutaneous desquamation. Three patients developed acute cerebellar dysfunction. CONCLUSIONS. The use of mitoxantrone and Ara-C is effective in the treatment of patients with recurrent and refractory AML. The subgroup of patients age greater than or equal to 60 years also had a high rate of disease remission induction with this regimen, and the regimen generally was well tolerated. (C) 2000 American Cancer Society. C1 Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Shulman, LN (reprint author), Dana Farber Canc Inst, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. NR 17 TC 14 Z9 14 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 2000 VL 88 IS 9 BP 2037 EP 2041 DI 10.1002/(SICI)1097-0142(20000501)88:9<2037::AID-CNCR8>3.0.CO;2-K PG 5 WC Oncology SC Oncology GA 306HX UT WOS:000086592200008 PM 10813714 ER PT J AU D'Amico, AV Whittington, R Malkowicz, SB Schultz, D Tomaszewski, JE Wein, A AF D'Amico, AV Whittington, R Malkowicz, SB Schultz, D Tomaszewski, JE Wein, A TI Prostate specific antigen outcome based on the extent of extracapsular extension and margin status in patients with seminal vesicle negative prostate carcinoma of Gleason score <= 7 SO CANCER LA English DT Article DE prostate carcinoma; extracapsular extension; margin status; Gleason score; outcome; prostate specific antigen ID RADICAL RETROPUBIC PROSTATECTOMY; CLINICAL FAILURES; CANCER; RADIOTHERAPY; RADIATION AB BAGKGROUND, Early (less than or equal to 2 years) prostate specific antigen (PSA) failure after radical prostatectomy (RP) has been shown to predict for distant failure. After excluding patients with the pathologic predictors of early PSA failure, an analysis of PSA failure free (bNED) survival was performed to identify patients who may benefit from the use of postprostatectomy radiation therapy (RT). METHODS, Of 1028 patients treated with Re for clinically localized prostate carcinoma between 1989 and 1999, 862 (84%) had either organ confined (OC), specimen confined (SC), or margin positive disease with negative seminal vesicles (SV) and a prostatectomy Gleason score less than or equal to 7. A Cox regression multivariate analysis was performed in these patients evaluating the ability of the extent of extracapsular extension (ECE) (into but not through the capsule, SC focal ECE, SC established ECE, margin positive) and prostatectomy Gleason score (2-6 vs. 7) to predict time to postoperative PSA failure. RESULTS. SC focal ECE (P = 0.0017), SC established ECE (P < 0.0001), and margin positive disease (P < 0.0001) were significant predictors of lime to postoperative PSA failure, whereas prostatectomy Gleason score and disease extending into but not through the capsule were not. Five-year bNED rates were 90%, 88%, 69%, 45%, and 33% for patients with OC, into but not through capsule, SC focal ECE, SC established ECE, and margin positive prostate carcinoma, respectively. CONCLUSIONS. Patients with SC ECE or margin positive prostate carcinoma and a prostatectomy Gleason score less than or equal to 7 with no evidence of SV invasion may benefit from adjuvant postoperative RT. (C) 2000 American Cancer Society. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Radiat Urol, Philadelphia, PA 19104 USA. Millersville Univ, Dept Math, Millersville, PA 17551 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02215 USA. NR 17 TC 20 Z9 20 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 MAY 1 PY 2000 VL 88 IS 9 BP 2110 EP 2115 DI 10.1002/(SICI)1097-0142(20000501)88:9<2110::AID-CNCR17>3.0.CO;2-E PG 6 WC Oncology SC Oncology GA 306HX UT WOS:000086592200017 PM 10813723 ER PT J AU Jonasch, E Kumar, UN Linette, GP Hodi, FS Soiffer, RJ Ryan, BF Sober, AJ Mihm, MC Tsao, H Langley, RG Cosimi, BA Gadd, MA Tanabe, KK Souba, W Haynes, HA Barnhill, R Osteen, R Haluska, FG AF Jonasch, E Kumar, UN Linette, GP Hodi, FS Soiffer, RJ Ryan, BF Sober, AJ Mihm, MC Tsao, H Langley, RG Cosimi, BA Gadd, MA Tanabe, KK Souba, W Haynes, HA Barnhill, R Osteen, R Haluska, FG TI Adjuvant high-dose interferon alfa-2b in patients with high-risk melanoma SO CANCER JOURNAL LA English DT Article DE melanoma; interferon alfa; side effects; disease-free survival; overall survival; adjuvant therapy ID RESECTED CUTANEOUS MELANOMA; COOPERATIVE-ONCOLOGY-GROUP; METASTATIC MELANOMA; TRIAL; THERAPY; INTERLEUKIN-2; COMBINATION; ALPHA-2A AB We performed an analysis of toxicity and survival in stage III melanoma patients receiving adjuvant interferon alfa-2b (IFN). This was a retrospective single-arm analysis of 40 patients with stage III melanoma who received (IFN) administered at maximum tolerated doses of 20 mU/m(2)/day intravenously (IV) for 1 month and 10 mU/m(2) three times per week subcutaneously (SC) for 48 weeks. Toxicity in our series is comparable to that experienced in the Eastern Cooperative Oncology Group (ECOG) 1684 trial, except for higher rates of dose-limiting myelosuppression and hepatotoxicity. AU 40 patients experienced constitutional symptoms, but only 14/40 (35%) experienced grade 3 to 4 symptoms. Of the 40 patients, 36 (90%) experienced neurologic symptoms, but only seven (17.5%) experienced grade 3 to 4 neurotoxicity. Two patients stopped treatment because of severe psychiatric symptoms; one patient attempted suicide, and a psychosis developed in another. Thirty-nine (97.5%) patients experienced myelosuppression; 31 (77.5%) developing grade 3 to 4 myelosuppression. Hepatotoxicity was evident in 39 (97.5%) patients, and 26 (65%) experienced grade 3 to 4 hepatotoxicity. Three patients (7.5%) experienced mild renal toxicity. At a median follow-up of 27 months from initiation of therapy, there have been 19 relapses (47.5% disease-free survival [DFS]) and 10 deaths (75% OS) resulting from progression of disease. The DFS compares with the treatment arm in ECOG 1684 at 27 months, but overall survival is higher in our series of patients at the same time point. In a single program setting, IFN can be administered with similar side effects and outcome profiles seen in multi-institutional studies. Modifications in the induction regimen resulted in notably higher hematologic and hepatic toxicities but did not preclude administering further therapy and did not result in increased attrition rate among patients: only nine patients (22.5%) had their treatment stopped as a result of IFN-related toxicity. In comparison, 26% of patients had to have their treatment discontinued because of toxicity in ECOG 1684. C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Melanoma Program, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jonasch, E (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Melanoma Program, Fruit St, Boston, MA 02114 USA. NR 17 TC 14 Z9 15 U1 0 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAY-JUN PY 2000 VL 6 IS 3 BP 139 EP 145 PG 7 WC Oncology SC Oncology GA 343GV UT WOS:000088694100004 PM 10882328 ER PT J AU Longo, DL Duffey, PL Gribben, JG Jaffe, ES Curti, BD Gause, BL Janik, JE Braman, VM Esseltine, D Wilson, WH Kaufman, D Wittes, RE Nadler, LM Urba, WJ AF Longo, DL Duffey, PL Gribben, JG Jaffe, ES Curti, BD Gause, BL Janik, JE Braman, VM Esseltine, D Wilson, WH Kaufman, D Wittes, RE Nadler, LM Urba, WJ TI Combination chemotherapy followed by an immunotoxin (anti-B4-blocked ricin) in patients with indolent lymphoma: Results of a phase II study SO CANCER JOURNAL LA English DT Article ID NON-HODGKINS-LYMPHOMAS; TRIAL AB The purpose of this article was to evaluate the antitumor effects of a combination chemotherapy program based on ProMACE (prednisone, methotrexate, doxorubicin [Adriamycin], cyclophosphamide, etoposide) followed by a B cell-specific immunotoxin in the treatment of patients with advanced-stage indolent histology non-Hodgkin's lymphomas. We performed a prospective phase II clinical trial in a referral-based patient population. After confirmation of diagnosis and staging evaluation, 44 patients (10 small lymphocytic lymphoma, 27 follicular lymphoma, 7 mantle cell lymphoma; 30 without prior therapy, 14 previously treated) received six cycles of ProMACE-CytaBOM (cytarabine, bleomycin, vincristine [Oncovin], mechlorethamine) combination chemotherapy (with etoposide given orally daily for five days) followed by a 7-day continuous infusion of anti-B4-blocked ricin immunotoxin at 30 mu g/kg/day given every 14 days for up to six cycles. A complete response was achieved in 25 of 44 patients (57%), 21 from the chemotherapy alone, 3 converted from partial to complete response with the immunotoxin, and 1 patient became a complete responder after a surgical procedure to remove an enlarged spleen that was histologically negative for lymphoma. With a median follow-up of 5 years, 14 of 25 complete responders have relapsed (56%); median remission duration was 2 years, and overall survival was 61%. Forty-two percent of the complete responders have been in continuous remission for more than 4 years. The median number of courses of immunotoxin delivered was two usually because of the development of human anti-ricin antibodies. ProMACE- CytaBOM plus anti-B4-blocked ricin does not produce durable complete remissions in the majority of patients with indolent lymphoma. However, the remissions appear quite durable (> 4 years) in about 40% of the complete responders. C1 NCI, Frederick Canc Res & Dev Ctr, Biol Response Modifiers Program, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Div Clin Sci, Pathol Lab, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. ImmunoGen Inc, Cambridge, MA USA. RP Longo, DL (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 10 TC 27 Z9 28 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAY-JUN PY 2000 VL 6 IS 3 BP 146 EP 150 PG 5 WC Oncology SC Oncology GA 343GV UT WOS:000088694100005 PM 10882329 ER PT J AU Netti, PA Berk, DA Swartz, MA Grodzinsky, AJ Jain, RK AF Netti, PA Berk, DA Swartz, MA Grodzinsky, AJ Jain, RK TI Role of extracellular matrix assembly in interstitial transport in solid tumors SO CANCER RESEARCH LA English DT Article ID ARTICULAR-CARTILAGE; NEOPLASTIC TISSUES; MOLECULAR MEDICINE; HYALURONIC-ACID; FLUID TRANSPORT; DIFFUSION; DELIVERY; CELLS; PERMEABILITY; COMPRESSION AB The extracellular matrix (ECM) may contribute to the drug resistance of a solid tumor by preventing the penetration of therapeutic agents. We measured differences in interstitial resistance to macromolecule. (IGG) motion in four tumor types and found an unexpected correspondence between transport resistance and the mechanical stiffness. The interstitial diffusion coefficient of IGG was measured in situ by fluorescence redistribution after photobleaching. Tissue elastic modulus and hydraulic conductivity were measured by confined compression of excised tissue. In apparent contradiction to an existing paradigm, these functional properties are correlated with total tissue content of collagen, not glycosaminoglycan. An extended collagen network was observed in the more penetration-resistant tumors. Collagenese treatment of the more penetration-resistant tumors significantly increased the IGG interstitial diffusion rate. We conclude that collagen influences the tissue resistance to macromolecule transport, possibly by binding and stabilizing the glycosaminoglycan component of the ECM. These findings suggest a new method to screen tumors for potential resistance to macromolecule-based therapy. Moreover, collagen and collagen-proteoglycans bonds are identified as potential targets of treatment to improve macromolecule delivery. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Dept Elect Engn, Cambridge, MA 02139 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Swartz, Melody/B-7633-2009; Berk, David/A-4863-2012; Swartz, Melody/F-9563-2011; OI Berk, David/0000-0002-3855-6886; NETTI, PAOLO/0000-0002-2435-7181 FU NCI NIH HHS [R35-CA56591] NR 48 TC 528 Z9 539 U1 10 U2 80 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2000 VL 60 IS 9 BP 2497 EP 2503 PG 7 WC Oncology SC Oncology GA 311AM UT WOS:000086862100032 PM 10811131 ER PT J AU Colorado, PC Torre, A Kamphaus, G Maeshima, Y Hopfer, H Takahashi, K Volk, R Zamborsky, ED Herman, S Sarkar, PK Ericksen, MB Dhanabal, M Simons, M Post, M Kufe, DW Weichselbaum, RR Sukhatme, VP Kalluri, R AF Colorado, PC Torre, A Kamphaus, G Maeshima, Y Hopfer, H Takahashi, K Volk, R Zamborsky, ED Herman, S Sarkar, PK Ericksen, MB Dhanabal, M Simons, M Post, M Kufe, DW Weichselbaum, RR Sukhatme, VP Kalluri, R TI Anti-angiogenic cues from vascular basement membrane collagen SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-GROWTH; IV COLLAGEN; INHIBITS ANGIOGENESIS; IN-VITRO; ENDOSTATIN; BINDING; EXPRESSION; CARCINOMA; INTEGRIN AB Vascular basement membrane is an important structural component of blood vessels and has been shown to interact with and modulate vascular endothelial behavior during angiogenesis, During the inductive phase of tumor angiogenesis, this membrane undergoes many degradative and structural changes and reorganizes to a native state around newly formed capillaries in the resolution phase. Such matrix changes are potentially associated with molecular modifications that include expression of matrix gene products coupled with conformational changes, which expose cryptic protein modules for interaction with the vascular endotheliun, We speculate that these interactions provide important endogenous angiogenic and anti-angiogenic cues. In this report, we identify an important antiangiogenic vascular basement membrane-associated protein, the 2.6-kDa NC1 domain of the alpha(1) chain of type IV collagen, termed arresten, Arresten was isolated from human placenta and produced as a recombinant molecule in Escherichia coli and 293 embryonic kidney cells. We demonstrate that arresten functions as an anti-angiogenic molecule by inhibiting endothelial cell proliferation, migration, tube formation, and Matrigel neovascularization, Arresten inhibits the growth of two human xenograft tumors in nude mice and the development of tumor metastases, Additionally, we show that the anti-angiogenic activity of arresten is potentially mediated via mechanisms involving cell surface proteoglycans and the alpha(1)beta(1) integrin on endothelial cells. Collectively, our results suggest that arresten is a potent inhibitor of angiogenesis with a potential for therapeutic use. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Ctr Canc, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Kalluri, R (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, RW 563A,330 Brookline Ave, Boston, MA 02215 USA. RI Simons, Michael/G-8553-2014; Kalluri, Raghu/E-2677-2015 OI Simons, Michael/0000-0003-0348-7734; Kalluri, Raghu/0000-0002-2190-547X FU NCI NIH HHS [R01-CA-42596-12]; NIDDK NIH HHS [DK-51711, DK-55001] NR 30 TC 265 Z9 307 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2000 VL 60 IS 9 BP 2520 EP 2526 PG 7 WC Oncology SC Oncology GA 311AM UT WOS:000086862100035 PM 10811134 ER PT J AU Duell, EJ Wiencke, JK Cheng, TJ Varkonyi, A Zuo, ZF Ashok, TDS Mark, EJ Wain, JC Christiani, DC Kelsey, KT AF Duell, EJ Wiencke, JK Cheng, TJ Varkonyi, A Zuo, ZF Ashok, TDS Mark, EJ Wain, JC Christiani, DC Kelsey, KT TI Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells SO CARCINOGENESIS LA English DT Article ID SISTER-CHROMATID EXCHANGE; NUCLEOTIDE EXCISION-REPAIR; STRAND BREAK REPAIR; POLY(ADP-RIBOSE) POLYMERASE; CHROMOSOME; FREQUENCY; ADDUCTS; TRANSCRIPTION; SENSITIVITY; OXIDATION AB Polymorphisms in several DNA repair genes have recently been identified, but little is known about their phenotypic significance, To determine whether variation in DNA repair genes is related to host DNA damage, we studied the association between polymorphisms in XRCC1 (codon 399) and ERCC2 (codon 751) and two markers of DNA damage, sister chromatid exchange (SCE) frequencies (n = 76) and polyphenol DNA adducts (n = 61). SCE frequencies were determined using a modified fluorescence-Giemsa method and polyphenol DNA adducts were determined using a P1-enhanced P-32-post-labeling procedure. XRCC1 and ERCC2 genotypes were identified using PCR-RFLP, Mean SCE frequencies among current smokers who were homozygous carriers of the 399Gln allele in XRCC1 mere greater than those in 399Arg/Arg current smokers. We also observed a possible gene-dosage effect for XRCC1 399Gln and detectable DNA adducts, and significantly more adducts among older subjects who mere carriers of the 399Gln allele than in younger subjects with the 399Arg/Arg genotype, The polymorphism in ERCC2 was unrelated to SCE frequency or DNA adduct level. Our results suggest that carriers of the polymorphic YRCC1 399Gln allele may be at greater risk for tobacco- and age-related DNA damage. C1 Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Lab Mol Epidemiol, San Francisco, CA 94143 USA. Natl Taiwan Univ, Coll Publ Hlth, Inst Occupat Med & Ind Hyg, Taipei 10764, Taiwan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Kelsey, KT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, 665 Huntington Ave, Boston, MA 02115 USA. RI Cheng, Tsun-Jen /D-3495-2012; Kelsey, Karl/I-1252-2014; OI CHENG, TSUN-JEN/0000-0002-2613-8230 FU NCI NIH HHS [T32CA09078]; NIEHS NIH HHS [ES04705, ES06717] NR 26 TC 356 Z9 374 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2000 VL 21 IS 5 BP 965 EP 971 DI 10.1093/carcin/21.5.965 PG 7 WC Oncology SC Oncology GA 315WZ UT WOS:000087137100016 PM 10783319 ER PT J AU Jones, RC Jacobson, M AF Jones, RC Jacobson, M TI Angiogenesis in the hypertensive lung: response to ambient oxygen tension SO CELL AND TISSUE RESEARCH LA English DT Article DE lung; microvessels; capillaries; fibroblasts; perivascular cells; elastic lamina; rat (Sprague Dawley) ID HYPEROXIC PULMONARY-HYPERTENSION; SMOOTH-MUSCLE CELLS; ENDOTHELIAL GROWTH-FACTOR; RAT-LUNG; FIBROBLASTS; ARTERIES; HYPOXIA; MICROVESSELS; ELASTASE; VASCULATURE AB The present study further analyzes the growth and reorganization of the vessels adjacent to capillaries in the hyperoxia-adapted lung in response to a lower ambient oxygen tension. The aim of the study was to determine the source of the new smooth muscle cells known to develop in these segments on return to breathing air. To accomplish this we determined the reorganization of vessel walls by quantitative light-microscopy techniques, and vascular cell phenotype(s) by high-resolution microscopy, in the lungs of rats that breathed a high oxygen tension (87% O-2 for 4 weeks), followed by weaning to a lower oxygen tension (87-20% O-2 over 1 week) and return to breathing air (for 1, 2 or 4 weeks). Return to breathing air initially triggered wall growth in a subset of vessels and wall thinning in others before wall thinning predominated throughout the vessel population. Interstitial fibroblasts were identified as the source of new perivascular cells. The recruitment of these cells was accompanied by loss of elastic laminae from vessel walls. Subsequently, most perivascular cells expressed a smooth muscle phenotype and elastic laminae were restored. Arteriography demonstrated an increase in the number of patent vessels on return to air, and light- and high-resolution microscopy restitution of the capillary network. We propose that in the hyperoxia-adapted lung return to breathing air represents a relative hypoxia that triggers differential patterns of vessel and capillary growth to meet new functional demands set by the lower ambient oxygen tension. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol & Cell Biol Lab,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp E, Charlestown, MA 02129 USA. RP Jones, RC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol & Cell Biol Lab,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. FU PHS HHS [R01 45737] NR 52 TC 20 Z9 21 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD MAY PY 2000 VL 300 IS 2 BP 263 EP 284 DI 10.1007/s004419900100 PG 22 WC Cell Biology SC Cell Biology GA 321KZ UT WOS:000087455800006 PM 10867822 ER PT J AU Ito, Y Pandey, P Place, A Sporn, MB Gribble, GW Honda, T Kharbanda, S Kufe, D AF Ito, Y Pandey, P Place, A Sporn, MB Gribble, GW Honda, T Kharbanda, S Kufe, D TI The novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid induces apoptosis of human myeloid leukemia cells by a caspase-8-dependent mechanism SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID INTERNUCLEOSOMAL DNA FRAGMENTATION; CYTOCHROME-C; IONIZING-RADIATION; 1-BETA-D-ARABINOFURANOSYLCYTOSINE INCORPORATION; INCREASED EXPRESSION; INDUCTION; ACTIVATION; PROTEASE; MITOCHONDRIA; INHIBITION AB The oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a multifunctional molecule that induces growth inhibition and differentiation of human myeloid leukemia cells. The present studies demonstrate that CDDO treatment results in apoptosis of U-937 and HL-60 myeloid leukemia cells. Similar to 1-beta-D-arabinofuranosylcytosine (ara-C), another agent that inhibits growth and induces apoptosis of these cells, CDDO induced the release of mitochondrial cytochrome c and activation of caspase-3. Overexpression of Bcl-x(L) blocked cytochrome c release, caspase-3 activation, and apoptosis in ara-C-treated cells. By contrast, CDDO-induced release of cytochrome c, and activation of caspase-3 were diminished only in part by Bcl-x(L). In concert with these findings, we demonstrate that CDDO, but not ara-C, activates caspase-8 and thereby caspase-3 by a cytochrome c-independent mechanism. The results also show that CDDO-induced cytochrome c release is mediated by caspase-8-dependent cleavage of Bid, These findings demonstrate that CDDO induces apoptosis of myeloid leukemia cells and that this novel agent activates an apoptotic signaling cascade distinct from that induced by the cytotoxic agent ara-C. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA. Dartmouth Coll, Sch Med, Dept Pharmacol, Hanover, NH 03755 USA. Dartmouth Coll, Sch Med, Norris Cotton Canc Ctr, Hanover, NH 03755 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-42802, CA-29431] NR 39 TC 103 Z9 110 U1 0 U2 4 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 MAY PY 2000 VL 11 IS 5 BP 261 EP 267 PG 7 WC Cell Biology SC Cell Biology GA 321YJ UT WOS:000087482700005 PM 10845427 ER PT J AU Silverman, EK Speizer, FE Weiss, ST Chapman, HA Schuette, A Campbell, EJ Reilly, JJ Ginns, LC Drazen, JM AF Silverman, EK Speizer, FE Weiss, ST Chapman, HA Schuette, A Campbell, EJ Reilly, JJ Ginns, LC Drazen, JM TI Familial aggregation of severe, early-onset COPD - Candidate gene approaches SO CHEST LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Utah, Salt Lake City, UT USA. NR 0 TC 17 Z9 17 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 MAY PY 2000 VL 117 IS 5 SU 1 BP 273S EP 274S DI 10.1378/chest.117.5_suppl_1.273S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 316PY UT WOS:000087178200031 ER PT J AU Earle, CC Venditti, LN Neumann, PJ Gelber, RD Weinstein, MC Potosky, AL Weeks, JC AF Earle, CC Venditti, LN Neumann, PJ Gelber, RD Weinstein, MC Potosky, AL Weeks, JC TI Who gets chemotherapy for metastatic lung cancer? SO CHEST LA English DT Article DE chemotherapy; non-small cell lung cancer; practice patterns ID MULTICENTER RANDOMIZED TRIAL; NEGATIVE BREAST-CANCER; 2 RURAL STATES; PROSTATE-CANCER; SOCIOECONOMIC-STATUS; TREATMENT PATTERNS; OLDER WOMEN; CARE; RACE; MANAGEMENT AB Study objectives: To determine the prevalence and factors associated with chemotherapy use in elderly patients presenting with advanced lung cancer. Design: A retrospective cohort study using administrative data. Setting and patients: We analyzed the medical bills for the 6,308 Medicare patients > 65 years old with diagnosed stage IV non-small cell lung cancer (NSCLC) in the 11 SEER (survival, epidemiology, and end results) regions between 1991 and 1993, The main outcome measure, chemotherapy administration, was identified by the relevant medical billing codes, Patient sociodemographic and disease characteristics were obtained from the SEER database and census data. Results: Almost 22% of patients received chemotherapy at some time for their metastatic NSCLC. As expected, younger patients and those with fewer comorbid conditions were more likely to receive chemotherapy. However, several nonmedical factors, such as nonblack race, higher socioeconomic status, treatment in a teaching hospital, and living in the Seattle/Puget Sound or Los Angeles SEER regions, also significantly increased a patient's likelihood of receiving chemotherapy, Conclusion: Compared to previous reports, the prevalence of chemotherapy use for advanced NSCLC appears to be increasing, However, despite uniform health insurance coverage, there is wide variation in the utilization of palliative chemotherapy among Medicare patients, and nonmedical factors are strong predictors of whether a patient receives chemotherapy. While it is impossible to know the appropriate rate of usage, nonmedical factors should only influence a patient's likelihood of receiving treatment if they reflect patient treatment preference. Research to further clarify the costs, benefits, and patient preferences for chemotherapy in this patient population is warranted in order to minimize the effect of nonmedical biases on management decisions. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Program Econ Evaluat Med Technol, Boston, MA 02115 USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. RP Earle, CC (reprint author), Dana Farber Canc Ctr, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 72663] NR 60 TC 175 Z9 177 U1 2 U2 6 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2000 VL 117 IS 5 BP 1239 EP 1246 DI 10.1378/chest.117.5.1239 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 315DL UT WOS:000087097300008 PM 10807806 ER PT J AU Adams, SG Melo, J Luther, M Anzueto, A AF Adams, SG Melo, J Luther, M Anzueto, A TI Antibiotics are associated with lower relapse rates in outpatients with acute exacerbations of COPD SO CHEST LA English DT Article DE acute exacerbation of chronic bronchitis; antibiotics; bronchitis; COPD; pulmonary function; recurrence; relapse ID OBSTRUCTIVE PULMONARY-DISEASE; 30-CENTER NATIONAL SURVEILLANCE; RESPIRATORY-TRACT INFECTIONS; PROTECTED SPECIMEN BRUSH; CHRONIC-BRONCHITIS; ANTIMICROBIAL RESISTANCE; HAEMOPHILUS-INFLUENZAE; UNITED-STATES; STREPTOCOCCUS-PNEUMONIAE; BACTERIAL-COLONIZATION AB Background: COPD is a complex disease with exacerbations characterized by worsening of symptoms resulting in deteriorating lung function. Study objective: To assess predictive factors of relapse for patients with acute exacerbations of COPD (AECB). Design: Retrospective cohort analysis of visits for AECB, Setting: Veterans Affairs Medical Center. Patients: Three hundred sixty-two visits (173 patients) with documented COPD treated as outpatients for AECB. Measurements: Severity of underlying COPD, severity of AECB, comorbid conditions, therapy, and relapse rates (return visit within 14 days with persistent or worsening symptoms). Results: Each. visit was analyzed individually (referred to as a patient-visit). One group received antibiotics (270 patient-visits), and the second group (92 patient-visits) did not. Both groups had similar demographics and severity of underlying COPD, The overall relapse rate was 22%. The majority of patient-visits (95%) with severe symptoms at presentation were prescribed antibiotics vs only 40% of those with mild symptoms, Twenty-nine of 92 patient-visits (32%) were followed by relapse in the group that was not given antibiotics, whereas only 50 of 270 (19%) treated with antibiotics relapsed (p < 0.001), Those treated with amoxicillin had an even higher relapse rate (20 of 37 patient-visits, or 54%) than those who did not receive antibiotics (p = 0.006). Conclusions: Relapse from AECB was not related to the severity of underlying disease or to the severity of the acute exacerbation. Patients treated with antibiotics had significantly lower relapse rates than those who did not receive antibiotics. However, the specific choice of antibiotic is important because those treated with amoxicillin had the highest relapse rates of all groups. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Pulm Dis Crit Care Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Clin Medellin, Medellin, Colombia. RP Anzueto, A (reprint author), Audie L Murphy Mem Vet Hosp, Pulm Dis Sect 111E, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 49 TC 120 Z9 124 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 MAY PY 2000 VL 117 IS 5 BP 1345 EP 1352 DI 10.1378/chest.117.5.1345 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 315DL UT WOS:000087097300023 PM 10807821 ER PT J AU Steele, BG Holt, L Belza, B Ferris, S Lakshminaryan, S Buchner, DM AF Steele, BG Holt, L Belza, B Ferris, S Lakshminaryan, S Buchner, DM TI Quantitating physical activity in COPD using a triaxial accelerometer SO CHEST LA English DT Article DE ambulatory monitoring; chronic limitation of activity; COPD; exercise ID OBSTRUCTIVE PULMONARY-DISEASE; ENERGY-EXPENDITURE; OBESE CHILDREN; SELF-REPORT; REHABILITATION; RELIABILITY; STABILITY; ACCURACY; EXERCISE; VALIDITY AB Study Objective: To determine the reliability, validity, and stability of a triaxial accelerometer for walking and daily activity measurement in a COPD sample. Design: Cross-sectional, correlational, descriptive design, Setting: Outpatient pulmonary rehabilitation program in a university-affiliated Veterans Affairs medical center. Participants: Forty-seven outpatients (44 men and 3 women) with stable COPD (FEV1, 37% predicted; SD, 16%) prior to entry into a pulmonary rehabilitation program, Measurements and results: Test-retest reliability of a triaxial movement sensor (Tritrac R3D Research Ergometer; Professional Products; Madison, WI) was evaluated in 35 of the 47 subjects during three standardized 6-min walks (intraclass correlation coefficient [rICC] = 0.84). Pearson correlations evaluated accelerometer concurrent validity as a measure of walking (in vector magnitude units), compared to walking distance in all 47 subjects during three sequential 6-min walks (0.84, 0.85, and 0.95, respectively; p < 0.001). The validity of the accelerometer as a measure of daily activity over 3 full days at home was evaluated in all subjects using Pearson correlations with other indicators of functional capacity. The accelerometer correlated with exercise capacity (maximal G-min walk, r = 0.74; p < 0.001); level of obstructive disease (FEV1 percent predicted, r = 0.62; p < 0.001); dyspnea (Functional Status and Dyspnea Questionnaire, dyspnea over the past 30 days, r = - 0.29; p < 0.05); and activity self-efficacy (Activity Self-Efficacy Questionnaire, r = 0.43; p < 0.01); but not with self-report of daily activity (Modified Activity Recall Questionnaire, r = 0.14; not significant). Stability of the accelerometer to measure 3 full days of activity at home was determined by an rICC of 0.69, Conclusions: This study provides preliminary data suggesting that a triaxial movement sensor is a reliable, valid, and stable measure of walking and daily physical activity in COPD patients, It has the potential to provide more precise measurement of everyday physical functioning in this population than self-report measures currently in use, and measures an important dimension of functional status not previously well-described. C1 Vet Affairs Puget Sound Hlth Care Syst, Med Specialties & Primary Care Serv 111B, Seattle, WA 98108 USA. Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Good Samaritan Med Ctr, Puyallup, WA USA. Ctr Dis Control & Prevent, Phys Act & Hlth Branch, Div Nutr & Phys Act, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Steele, BG (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Med Specialties & Primary Care Serv 111B, 1660 Columbian Way S, Seattle, WA 98108 USA. RI Schmoelz, Camilie/D-1707-2012 OI Schmoelz, Camilie/0000-0003-2221-9954 NR 29 TC 130 Z9 133 U1 2 U2 9 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2000 VL 117 IS 5 BP 1359 EP 1367 DI 10.1378/chest.117.5.1359 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 315DL UT WOS:000087097300025 PM 10807823 ER PT J AU Bishop, SJ Murphy, JM Hicks, R Quinn, D Lewis, PJ Grace, M Jellinek, MS AF Bishop, SJ Murphy, JM Hicks, R Quinn, D Lewis, PJ Grace, M Jellinek, MS TI What progress has been made in meeting the needs of seriously maltreated children? The course of 200 cases through the Boston Juvenile Court SO CHILD ABUSE & NEGLECT LA English DT Article DE child abuse; child neglect; juvenile court; policy ID SAMPLE; MISTREATMENT; PREVALENCE AB Objectives: The study examined child, parent, and case characteristics in a sample of 200 cases of serious child maltreatment brought before the Boston Juvenile Court (BJC) on Care and Protection petitions in 1994. Whether recent changes in Massachusetts law have been effective in reducing delays in adjudication and helping children achieve permanent placements more quickly was also examined. Method: Data were abstracted from court records by the research team. The 200 cases were followed prospectively for 4 years. Retrospective data on the families' previous involvement with the protective service system were also abstracted from the records. Data from the 1994 cases were compared to that obtained from a sample of cases brought before the BJC in 1985-1986. Results: Children permanently removed from parental custody in the 1994 sample required less time post-disposition to achieve permanent placements. However, overall, rime frames for the 1993 cases remained remarkably similar to those in 1985-1986: children were in the protective service system an average of 5 years; cases required an average of 1.6 years in court; and half of the children permanently removed from parental custody were still in "temporary" foster care at 4-year follow-up. Conclusions: Although some improvements have occurred since 1985-1986, the system still fails to meet the needs of seriously maltreated children to achieve permanent placements promptly. The implications of the findings for system reform are discussed. (C) 2000 Elsevier Science Ltd. C1 Yale Univ, Bush Ctr Child Dev & Social Policy, New Haven, CT 06511 USA. Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Lumen Vitae, Boston, MA USA. Commonwealth Massachusetts Juvenile Court, Boston, MA USA. RP Bishop, SJ (reprint author), Yale Univ, Bush Ctr Child Dev & Social Policy, 310 Prospect St, New Haven, CT 06511 USA. FU NIMH NIH HHS [MH 50629] NR 18 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD MAY PY 2000 VL 24 IS 5 BP 599 EP 610 DI 10.1016/S0145-2134(00)00125-3 PG 12 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA 300XM UT WOS:000086279100002 PM 10819093 ER PT J AU Cataltepe, S Schick, C Luke, CJ Pak, SCO Goldfarb, D Chen, P Tanasiyevic, MJ Posner, MR Silverman, GA AF Cataltepe, S Schick, C Luke, CJ Pak, SCO Goldfarb, D Chen, P Tanasiyevic, MJ Posner, MR Silverman, GA TI Development of specific monoclonal antibodies and a sensitive discriminatory immunoassay for the circulating tumor markers SCCA1 and SCCA2 SO CLINICA CHIMICA ACTA LA English DT Article DE squamous cell carcinoma antigen; SCCA1; SCCA2; serpin; squamous cell carcinoma; monoclonal antibody; ELISA ID SQUAMOUS-CELL CARCINOMA; UTERINE CERVIX; NECK-CANCER; ANTIGEN; RADIOIMMUNOASSAY; SERPIN; HEAD AB The squamous cell carcinoma antigen (SCCA) serves as a serologic marker for advanced squamous cell carcinomas (SCC) of the uterine cervix, lung, esophagus, head and neck and vulva. Elevations in serum levels of SCCA following treatment for SCC correlate with tumor relapse or metastasis. Recent molecular studies show that SCCA is transcribed by two nearly identical genes (SCCA1 and SCCA2) that encode for members of the high molecular weight serine proteinase inhibitor (serpin) family. Despite a high degree of similarity in their amino acid sequences, SCCA1 and SCCA2 have distinct biochemical properties: SCCA1 is an inhibitor of papain like cysteine proteinases, such as cathepsins (cat) L, S and K, whereas SCCA2 inhibits chymotrypsin-like serine proteinases, catG and mast cell chymase. In this paper, we report the generation and characterization of anti-SCCA1 and anti-SCCA2 specific monoclonal antibodies (MAbs). Using these MAbs, we developed an enzyme-linked immunoassay (ELISA) that discriminated between SCCA1 and SCCA2 without any cross-reaction. This assay measured both the native and complexed forms of SCCA1 and SCCA2. The sensitivity of detection of SCCA1 and SCCA2 assays were 0.17 ng ml(-1) and 0.19 ng ml(-1), respectively. Mean inter- and intra-assay coefficients of variation were 12.1% and 9.9% for SCCA1 assay and 12% and 8.8% for SCCA2 assay, respectively. Recovery and parallellism studies indicated that SCCA1 and SCCA2 were detected in the plasma and amniotic fluids without any major interference by the biologic fluid components. This assay provides a simple and accurate procedure for the quantitation of total SCCA1 and SCCA2. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Childrens Hosp, Sch Med, Div Newborn Med,Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Head & Neck Oncol Program, Boston, MA 02115 USA. RP Silverman, GA (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Div Newborn Med,Dept Pediat, 300 Longwood Ave,Enders 970, Boston, MA 02115 USA. FU NCI NIH HHS [CA69331, CA73031]; NICHD NIH HHS [HD28475] NR 25 TC 27 Z9 27 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAY PY 2000 VL 295 IS 1-2 BP 107 EP 127 DI 10.1016/S0009-8981(00)00197-2 PG 21 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 311AZ UT WOS:000086863300009 PM 10767398 ER PT J AU Keith, RL Miller, YE Germmill, RM Drabkin, HA Dempsey, EC Kennedy, TC Prindiville, S Franklin, WA AF Keith, RL Miller, YE Germmill, RM Drabkin, HA Dempsey, EC Kennedy, TC Prindiville, S Franklin, WA TI Angiogenic squamous dysplasia in bronchi of individuals at high risk for lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID X-C CHEMOKINES; CELL-PROLIFERATION; FORMER SMOKERS; LESIONS; P53; CARCINOMA; TUMORS; KI-67; FLUORESCENCE; EPITHELIUM AB Lung carcinogenesis is assumed to be a multistep process, but detailed understanding of the sequential morphological and molecular changes preceding invasive lung cancer remains elusive. To better understand early lung carcinogenesis, we initiated a program of fluorescence bronchoscopy in smokers at high risk for lung cancer. in the bronchial biopsies from these subjects, we observed a unique lesion consisting of capillary blood vessels closely juxtaposed to and projecting into metaplastic or dysplastic squamous bronchial epithelium, angiogenic squamous dysplasia (ASD). Serial sections of the capillary projections confirmed that they represent intramucosal capillary loops. Microvessel density in ASD was elevated in comparison to normal mucosa (P = 0.0003) but not in comparison to other forms of hyperplasia or dysplasia, ASD thus represents a qualitatively distinct form of angiogenesis in which there is architectural rearrangement of the capillary microvasculature. Genetic analysis of surface epithelium in a random subset of lesions revealed toss of heterozygosity at chromosome 3p in 53% of ASD lesions. No confirmed p53 mutations were identified, Compared with normal epithelium, proliferative activity was markedly elevated in ASD lesions. ASD occurred in 54 of 158 (34%) high-risk smokers without carcinoma and in 6 of 10 patients with squamous carcinoma who underwent fluorescence bronchoscopy, One early-stage invasive carcinoma was noteworthy fur the occurrence of ASD juxtaposed to invasive tumor. Seventy-seven (59%) of the ASD lesions mere detected by abnormal fluorescence alone. Twenty: bronchial sites (11 patients) were rebiopsied I year after the initial diagnosis. At nine (45%) of these sites, the lesion was found to persist. The Lesion was not present in biopsies from 16 normal nonsmoker control subjects. The presence of this lesion in high-risk smokers suggests that aberrant patterns of microvascularization mag occur at an early stage of bronchial carcinogenesis. C1 Univ Colorado, Hlth Sci Ctr, SPORE Lung Canc, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Dept Pulm Sci & Crit Care Med, Denver, CO 80220 USA. RP Franklin, WA (reprint author), Univ Colorado, Hlth Sci Ctr, SPORE Lung Canc, Box B-216,4200 E 9th Ave, Denver, CO 80262 USA. FU NCI NIH HHS [CA 58187, U01-CA85070] NR 47 TC 114 Z9 128 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 MAY PY 2000 VL 6 IS 5 BP 1616 EP 1625 PG 10 WC Oncology SC Oncology GA 312LY UT WOS:000086945800004 PM 10815878 ER PT J AU Eder, JP Kantoff, PW Roper, K Xu, GX Bubley, GJ Boyden, J Gritz, L Mazzara, G Oh, WK Arlen, P Tsang, KY Panicali, D Schlom, J Kufe, DW AF Eder, JP Kantoff, PW Roper, K Xu, GX Bubley, GJ Boyden, J Gritz, L Mazzara, G Oh, WK Arlen, P Tsang, KY Panicali, D Schlom, J Kufe, DW TI A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; CARCINOEMBRYONIC ANTIGEN; CELL-LINE; MELANOMA; PEPTIDE; PSA; RESTRICTION; GENERATION; PROTEINS; GENES AB A recombinant vaccinia virus encoding human prostate-specific antigen (rV-PSA) was administered as three consecutive monthly doses to 33 men with rising PSA levels after radical prostatectomy, radiation therapy, both, or metastatic. disease at presentation. Dose levels were 2.65 x 10(6), 2.65 x 10(7), and 2.65 x 10(8) plaque forming units. Ten patients who received the highest dose also received 250 mu g/m(2) granulocyte-macrophage colony-stimulating factor (GM-CSF) as an immunostimulatory adjunct. No patient experienced any virus-related effects beyond grade I cutaneous toxicity. Pustule formation and/or erythema occurred after the first dose in all 27 men who received greater than or equal to 2.65 x 10(7) plaque forming units. GM-CSF administration was associated with fevers and myalgias of grade 2 or lower in 9 of 10 patients. PSA levels in 14 of 33 men treated with rV-PSA with or without GM-CSF were stable for at least 6 months after primary immunization. Nine patients remained stable for 11-25 months; six of these remain progression free with stable PSA levels. Immunological studies demonstrated a specific T-cell response to PSA-3, a 9-mer peptide derived from PSA. rV-PSA is safe and can elicit clinical and immune responses, and certain patients remain without evidence of clinical progression for up to 21 months or longer. C1 Brigham & Womens Hosp, Dept Med, Div Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Dept Med,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. NCI, NIH, Bethesda, MD 20892 USA. Ther Biol Corp, Cambridge, MA 02142 USA. RP Eder, JP (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 1B34, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU NCI NIH HHS [UO-CA62490] NR 30 TC 211 Z9 216 U1 2 U2 8 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 MAY PY 2000 VL 6 IS 5 BP 1632 EP 1638 PG 7 WC Oncology SC Oncology GA 312LY UT WOS:000086945800006 PM 10815880 ER PT J AU Virella, G Koskinen, S Krings, G Onorato, JM Thorpe, SR Lopes-Virella, M AF Virella, G Koskinen, S Krings, G Onorato, JM Thorpe, SR Lopes-Virella, M TI Immunochemical characterization of purified human oxidized low-density lipoprotein antibodies SO CLINICAL IMMUNOLOGY LA English DT Article DE arteriosclerosis; autoimmunity; autoantibodies; cardiolipin; crossreactivity; diabetes; oxidized LDL; oxLDL antibodies ID CONTAINING IMMUNE-COMPLEXES; CORONARY-ARTERY DISEASE; OXIDATIVE MODIFICATION; ANTICARDIOLIPIN ANTIBODIES; MONOCLONAL-ANTIBODIES; ANTIPHOSPHOLIPID ANTIBODIES; CAROTID ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; LIPID-PEROXIDATION; HUMAN MACROPHAGES AB The goal of this study was to characterize the isotypes and reactivity of human autoantibodies to copper oxidized LDL (oxLDL). Forty-six purified oxLDL antibodies contained immunoglobulins of the three major isotypes, with a predominance of IgG;, subclasses 1 and 3. These IgG isotypes are known to interact with FcR gamma I and to activate the complement system and thus are potentially able to activate macrophages and cause foam cell formation. The same purified antibodies were tested for cross-reactivity with malondialdehyde (MDA)-, glycated (Glyc)-, and native (n)LDL and cardiolipin. Absorption with oxLDL resulted in a decrease of reactivity of 77.2 +/- 4.7%. Absorption with MDA-LDL resulted in a wider range of reduction of reactivity values, ranging from 50 to 87%, possibly reflecting differences in the degree of MDA modification. Absorption with Glyc- and nLDL caused a minor decrease in the reactivity of antibodies to oxLDL (5.9 +/- 7.1 and 6.8 +/- 6.4%, respectively), comparable to the reduction of reactivity (2.1 +/- 4.0%) measured after absorption with transferrin, an irrelevant protein used as a negative control. These results suggest that oxLDL antibodies recognize primarily MDA epitopes. To determine whether purified oxLDL antibodies also recognize other epitopes known to be generated during copper oxidation of LDL, such as 4-hydroxynonenal (HNE- and N''(carboxymethyl)-lysine (CML), two additional sets of experiments were carried out. First, we monitored the formation of CML-, MDA-lysine, and HNE-lysine at different times during copper oxidation of two LDL pools. Both pools showed simultaneous increases in protein modification, as indicated by increasing fluorescence emission at 430 nm, and in immunoreactivity with oxLDL antibodies, coinciding closely with MDA modification of lysine groups. Second, we assessed whether the reactivity of oxLDL antibodies could be blocked by absorption with CML- or HNE-LDL. HNE-LDL did not react with isolated oxLDL antibodies. Highly modified CML-LDL (>90% of lysine residues modified) reduced the reactivity of oxLDL antibodies, but only by 25.5%. Finally, we investigated the possible cross-reactivity of oxLDL antibodies with cardiolipin. Seventeen purified oxLDL antibodies were used in this study, which showed that absorption with oxLDL or nLDL did not affect their reactivity with immobilized cardiolipin, (C) 2000 Academic Press. C1 Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Univ S Carolina, Dept Chem & Biochem, Columbia, SC USA. RP Virella, G (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL-55782]; NIDDK NIH HHS [DK19971] NR 52 TC 43 Z9 47 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAY PY 2000 VL 95 IS 2 BP 135 EP 144 DI 10.1006/clim.2000.4857 PG 10 WC Immunology SC Immunology GA 311HA UT WOS:000086877600008 PM 10779407 ER PT J AU Jorgensen, JH Ferraro, MJ AF Jorgensen, JH Ferraro, MJ TI Antimicrobial susceptibility testing: Special needs for fastidious organisms and difficult-to-detect resistance mechanisms SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; STREPTOCOCCUS-PNEUMONIAE; VANCOMYCIN RESISTANCE; UNITED-STATES; KLEBSIELLA-PNEUMONIAE; BROTH MICRODILUTION; DISK DIFFUSION; EMERGENCE; AUREUS; SURVEILLANCE AB Clinical microbiology laboratories are faced with the challenge of accurately detecting emerging antibiotic resistance among a number of bacterial pathogens. In recent years, vancomycin resistance among enterococci has become prevalent, as has penicillin resistance and multidrug resistance in pneumococci. More recently, strains of methicillin-resistant Staphylococcus nul eus with reduced susceptibility to vancomycin have been encountered. In addition, molecular techniques have demonstrated that there are still problems detecting methicillin resistance in staphylococci, especially in coagulase-negative species. Among members of the family Enterobacteriaceae, mutated P-lactamase enzymes mar confer difficult-to-detect resistance to later-generation penicillins and cephalosporins, Anaerobic bacteria are no longer entirely predictable in their susceptibility to agents that might be selected for empiric therapy. Therefore, clinical microbiology laboratories may not be able to rely on a single susceptibility testing method or system to detect all those emerging resistant or fastidious organisms, For reliable detection, laboratories may need to employ conventional, quantitative susceptibility testing methods or use specially developed, single concentration agar screening tests for some resistant species. Certain of these screening tests are highly specific, while others may require additional confirmatory testing for definitive results. Therefore, laboratories must retain the versatility to apply several different approaches to detect resistance in both common and infrequently encountered bacterial pathogens. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Massachusetts Gen Hosp, Microbiol Lab, Boston, MA 02114 USA. RP Jorgensen, JH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 49 TC 30 Z9 33 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 2000 VL 30 IS 5 BP 799 EP 808 DI 10.1086/313788 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 323GN UT WOS:000087557900014 PM 10816150 ER PT J AU North, PE Mizeracki, A Mihm, MC Mrak, RE AF North, PE Mizeracki, A Mihm, MC Mrak, RE TI GLUT1 immunoreaction patterns reliably distinguish hemangioblastoma from metastatic renal cell carcinoma SO CLINICAL NEUROPATHOLOGY LA English DT Article DE brain; GLUT1; hemangioblastoma; immunohistochemistry; renal cell carcinoma ID TUMOR-SUPPRESSOR GENE; BLOOD-BRAIN-BARRIER; CENTRAL-NERVOUS-SYSTEM; HIPPEL-LINDAU-DISEASE; TRANSPORTER MESSENGER-RNA; ENDOTHELIAL GROWTH-FACTOR; GLUCOSE-TRANSPORTER; CEREBELLAR HEMANGIOBLASTOMAS; CAPILLARY HEMANGIOBLASTOMAS; 3'-UNTRANSLATED REGION AB Background: Hemangioblastoma and metastatic renal cell carcinoma (RCC) may show striking histologic similarities, and the distinction between these two tumors can be difficult. Both occur in middle age, and both occur with increased incidence in von Hippel-Lindau disease (vHL). GLUT1 is an erythrocyte-type glucose transporter protein that is highly expressed by endothelia in brain - but not most peripheral - microvasculature, and by tumor cells in many epithelial malignancies. GLUT1 is expressed by endothelial cells in juvenile hemangiomas, and endothelial GLUT1 expression has been reported for 2 hemangioblastomas arising in a single patient with vHL. Methods: We performed immunoreactions for GLUT1 on archival hemangioblastomas from 12 patients tone with vHL), and on RCCs metastatic to brain of 9 patients. Results: Hemangioblastomas showed intense endothelial GLUT1 reactivity in 11/12 tumors resections; the only GLUT1-negative tumor was one for which only previously frozen material was available for immunoreaction, and this tissue showed poor GLUT1 immunoreactivity of internal erythrocyte controls. Hemangioblastoma stromal cell reactivity was found in only 1 case, and was weak and focal. RCCs, in contrast, showed no intralesional endothelial GLUT1 reactivity, but did show intense tumor cell membrane reactivity in 9/9 cases. Conclusion: that GLUT1 immunoreactivity patterns reliably distinguish hemangioblastoma from RCC. C1 Arkansas Childrens Hosp, Dept Pediat Pathol, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Cent Arkansas Vet Hlth Syst, Pathol & Lab Med Serv, Little Rock, AR USA. Massachusetts Gen Hosp, Div Dermatopathol, Boston, MA 02114 USA. RP North, PE (reprint author), Arkansas Childrens Hosp, Dept Pediat Pathol, 800 Marshall St, Little Rock, AR 72202 USA. NR 33 TC 17 Z9 17 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0722-5091 J9 CLIN NEUROPATHOL JI Clin. Neuropathol. PD MAY-JUN PY 2000 VL 19 IS 3 BP 131 EP 137 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 316QN UT WOS:000087179700004 PM 14606586 ER PT J AU Mankin, HJ AF Mankin, HJ TI Boston's contributions to the development of orthopaedics in the United States - A brief history SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB Since the early part of the nineteenth century, physicians from Boston have had a major impact on orthopaedics in America. Initially, the general surgeons such as John Ball Brown and his son, Buckminster had an impact on orthopaedics, but contributors such as Henry Bigelow and Charles Scudder added greatly to the knowledge and capacity for care. The first orthopaedic ward, Ward I, was located at the Massachusetts General Hospital and began the new era. Surgical treatment by orthopaedists began in the twentieth century with such contributors as Philip Wilson, EA Codman, Robert B. Osgood, Joel Goldthwait, Elliot Brackett, Robert Lovett, and Edward Bradford. These physicians not only treated patients at the Children's, Tufts University, Boston City, the Beth Israel, and the Massachusetts General Hospitals, but assumed the academic responsibilities of a major educational center. More recently the contributors to orthopaedics have included Marius Smith-Petersen, Otto Aufranc, Henry Banks, Edward Cave, Carter Rowe, Joseph Barr, and others who have created a spectacular program for education, research, and clinical care. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Serv Gray 604, Boston, MA 02114 USA. NR 21 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 2000 IS 374 BP 47 EP 54 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 311BM UT WOS:000086864600007 PM 10818968 ER PT J AU Rosenfeld, K Wenger, NS AF Rosenfeld, K Wenger, NS TI Measuring quality in end-of-life care SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID CANCER PAIN MANAGEMENT; ADVANCE DIRECTIVES; TERMINALLY ILL; TREATMENT CHOICES; LUNG-CANCER; HEALTH; OLDER; QUESTIONNAIRE; RESUSCITATION; DECISIONS AB Scrutiny of the quality of medical care near the end of Life is increasing. Experts have begun to define and conceptualize quality of care for dying patients and are developing measurement tools to assess quality of care in this population. Definitions and conceptual models of quality of care at the end of life are reviewed. Approaches for measuring the processes and outcomes of end-of-life care are discussed. Approaches for initiating quality assessment of end-of-life care among geriatric patients are suggested. C1 VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA 90012 USA. RP Rosenfeld, K (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Gen Med 111G, 11301 Wilshire Blvd, Los Angeles, CA 90012 USA. NR 61 TC 18 Z9 18 U1 3 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2000 VL 16 IS 2 BP 387 EP + DI 10.1016/S0749-0690(05)70063-X PG 16 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 312VJ UT WOS:000086964400012 PM 10783435 ER PT J AU Ghaemi, SN Boiman, E Goodwin, FK AF Ghaemi, SN Boiman, E Goodwin, FK TI Insight and outcome in bipolar, unipolar, and anxiety disorders SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID SCHIZOPHRENIC-PATIENTS; CLINICAL-PSYCHIATRY; PSYCHOSIS; ILLNESS; AWARENESS; SCALE AB We performed a study to assess the relationship between impairment of insight and the long-term outcome in affective and anxiety disorders. Standardized insight assessments were made using the Scale to Assess Unawareness of Mental Disorder (SUMD) in 101 outpatients with psychiatric disorders, mostly affective and anxiety disorders, treated over 1 year in a university-based clinic. Outcome was prospectively assessed with the Clinical Global Impression (CGI) and Global Assessment of Functioning (GAF) rating scales. The mean follow-up period was 3.9 months. Initial Impairment of insight did not correlate with poor outcome. However, improvement in insight correlated with good outcome, particularly in bipolar disorder type I (r = .56 to .67, P = .0005), Insight was similarly impaired in bipolar and unipolar major depressive disorders, and more so than in anxiety disorders (P = .002), An association between a lack of improvement in insight and a poor outcome, most significantly in bipolar disorder type I, was observed in this sample. We found a greater relative impairment of insight in mood versus anxiety disorders. Copyright (C) 2000 by W.B. Saunders Company. C1 Harvard Univ, Massachusetts Gen Hosp, Bipolar Res Program, Consolidated Dept Psychiat, Boston, MA 02114 USA. George Washington Univ, Dept Psychiat, Washington, DC USA. RP Ghaemi, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Bipolar Res Program, Consolidated Dept Psychiat, 15 Parkman St,WAC-812, Boston, MA 02114 USA. NR 21 TC 42 Z9 45 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAY-JUN PY 2000 VL 41 IS 3 BP 167 EP 171 DI 10.1016/S0010-440X(00)90043-9 PG 5 WC Psychiatry SC Psychiatry GA 316GY UT WOS:000087160300003 PM 10834624 ER PT J AU Barsky, AJ Bailey, ED Fama, JM Ahern, DK AF Barsky, AJ Bailey, ED Fama, JM Ahern, DK TI Predictors of remission in DSM hypochondriasis SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL TREATMENT; RANDOMIZED CONTROLLED TRIAL; III-R HYPOCHONDRIASIS; SOMATOSENSORY AMPLIFICATION; DIAGNOSTIC INTERVIEW; MEDICAL OUTPATIENTS; PRIMARY-CARE; SOMATIZATION; DISORDERS; TRANSIENT AB Although hypochondriasis is generally believed to be a chronic and refractory disorder, relatively little is known about its natural history and course. Based on a cognitive/perceptual model of hypochondriasis, we hypothesized that the disorder would be more chronic in patients who both amplify benign bodily symptoms and tend to attribute them to disease. Thirty-eight patients with DSM hypochondriasis were assessed with a structured, diagnostic interview and self-report questionnaire. A logistic regression model containing sociodemographic characteristics and a B-way interaction term composed of the tendency to amplify bodily sensations, the tendency to attribute common symptoms to disease, and somatization (all measured at inception) correctly classified the remission status of 81.6% of the patients at follow-up 4 years later. These results suggest that patients who somatize, who are amplifiers of bodily sensation, and those who tend to attribute ambiguous symptoms to disease have more chronic and more refractory hypochondriasis. It is the co-occurrence of these cognitive and perceptual characteristics, rather than their occurrence individually, which predicts the persistence of this disorder. Copyright (C) 2000 by W.B. Saunders Company. C1 Brigham & Womens Hosp, Div Psychiat, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. RP Barsky, AJ (reprint author), Brigham & Womens Hosp, Div Psychiat, Dept Med, 75 Francis St, Boston, MA 02115 USA. FU NIMH NIH HHS [MH-40487] NR 35 TC 5 Z9 5 U1 2 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAY-JUN PY 2000 VL 41 IS 3 BP 179 EP 183 DI 10.1016/S0010-440X(00)90045-2 PG 5 WC Psychiatry SC Psychiatry GA 316GY UT WOS:000087160300005 PM 10834626 ER PT J AU Rordorf, G Koroshetz, W Efird, JT Cramer, SC AF Rordorf, G Koroshetz, W Efird, JT Cramer, SC TI Predictors of mortality in stroke patients admitted to an intensive care unit SO CRITICAL CARE MEDICINE LA English DT Article DE stroke; Acute Physiology and Chronic Health Evaluation; II score; Glasgow Coma Scale score; intensive care unit; mortality ID BLOOD-CELL COUNT; APACHE-II SCORE; SERUM CREATININE; MYOCARDIAL-INFARCTION; INDEPENDENT PREDICTOR; CARDIAC-ARREST; PROGNOSIS; DISEASE; COMA; SEVERITY AB Objective: Improved pathophysiologic insight and prognostic information regarding in-hospital risk of mortality among stroke patients admitted to an intensive care unit. Design: Retrospective analysis. Setting: Neurology/neurosurgery intensive care unit in a tertiary care university medical center. Patients: A total of 63 consecutive ischemic stroke patients. Interventions: Patients were classified according to in-hospital mortality. Charts were reviewed to retrospectively generate an admitting Acute Physiology and Chronic Health Evaluation (APACHE) II score. The APACHE II score and its individual components were assessed for predicting subsequent death. Measurements and Main Results: Of 63 patients, 13 died and 50 survived to either discharge or surgical intervention. The mean admitting APACHE II score of survivors (6.9) was lower than that of patients who died (17.2; p < .0001). None of the 33 patients with a score <9 died, compared with 43% of those with a score greater than or equal to 9. A score greater than or equal to 18 was uniformly associated with fatal outcome (n = 8). Univariate analysis identified APACHE II total score, Glasgow Coma Scale score, temperature, pH, and white blood cell count as significant predictors of death. Among multivariate logistic regression models examining the components of the APACHE II score, the model containing white blood cells, temperature, and creatinine best predicted death. Conclusions: Several features of the APACHE II score are associated with risk of death in this patient population. The findings suggest particular physiologic derangements that are associated with, and may contribute to, increased mortality in critically ill patients with acute ischemic stroke. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Palo Alto, CA 94304 USA. Roche Global Dev, Dept Biometr, Palo Alto, CA USA. Harvard Mit Div Hlth Sci & Technol, Clin Invest Training Program, Boston, MA USA. Pfizer Inc, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Rordorf, G (reprint author), Massachusetts Gen Hosp, Dept Neurol, BLK1291,55 Fruit St, Boston, MA 02114 USA. NR 41 TC 44 Z9 48 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 MAY PY 2000 VL 28 IS 5 BP 1301 EP 1305 DI 10.1097/00003246-200005000-00007 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 316LE UT WOS:000087167800007 PM 10834669 ER PT J AU Hess, D AF Hess, D TI Prolonged use of heat and moisture exchangers: Why do we keep changing things? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE humidity; heat and moisture exchanger; mechanical ventilation; ventilator-associated pneumonia ID VENTILATOR-ASSOCIATED PNEUMONIA; EVERY 48 HOURS; HYGROSCOPIC CONDENSER HUMIDIFIER; INTENSIVE-CARE UNIT; MECHANICAL VENTILATION; CIRCUIT CHANGES; NOSOCOMIAL PNEUMONIA; MINUTE VENTILATION; HOURS RATHER; COLONIZATION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hess, D (reprint author), Massachusetts Gen Hosp, Ellison 401,55 Fruit St, Boston, MA 02114 USA. NR 33 TC 8 Z9 8 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 MAY PY 2000 VL 28 IS 5 BP 1667 EP 1668 DI 10.1097/00003246-200005000-00079 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 316LE UT WOS:000087167800079 PM 10834741 ER PT J AU Schulz, JT Ryan, CM AF Schulz, JT Ryan, CM TI The frustrating problem of smoke inhalation injury SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE burn; smoke; inhalation injury; respiratory failure; acute respiratory distress syndrome; ovine model; sheep ID PATHO-PHYSIOLOGY; BURN; COMBUSTION; PRODUCTS C1 Shriners Burn Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Sumner Redstone Burn Ctr, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ryan, CM (reprint author), Shriners Burn Hosp, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM T32-07035, GM P50-21700] NR 10 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 MAY PY 2000 VL 28 IS 5 BP 1677 EP 1678 DI 10.1097/00003246-200005000-00085 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 316LE UT WOS:000087167800085 PM 10834747 ER PT J AU Chen, TN Fowler, A Toner, M AF Chen, TN Fowler, A Toner, M TI Literature review: Supplemented phase diagram of the trehalose-water binary mixture SO CRYOBIOLOGY LA English DT Article DE trehalose; water; binary mixture; supplemented phase diagram; glass transition; melting point; maximal freeze concentration; anhydrobiosis; freeze-drying; cryoprotectant ID GLASS-TRANSITION; VITRIFICATION; CRYSTALLIZATION; ANHYDROBIOSIS; SOLUBILITY; BEHAVIOR; STATE AB Trehalose is of great interest in many fields, including freeze-drying, cryoprotection, and anhydrobiosis. Although data for the trehalose-water supplemented phase diagram have previously appeared in the literature, the data have been widely scattered and reported in several units. In this study, literature data for the binary trehalose-water system were collected and analyzed. The literature data were found to be reasonably consistent, with substantial agreement on the melting points for water, trehalose, and trehalose dihydrate and the glass transition temperature of water. There was also good agreement for the solubility, freezing, and glass transition curves. However, there was no general agreement on the glass transition temperature of pure trehalose. Additionally, the trehalose-water glass transition curve was modeled using the Gordon-Taylor equation, with a value for k of 5.2. The collected data in this report will be of much use in further studies of the protective abilities of trehalose. (C) 2000 Academic Press. C1 Shriners Hosp Crippled Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Ctr Engn, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv,Ctr Engn, Boston, MA 02114 USA. Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. RP Toner, M (reprint author), Shriners Hosp Crippled Children, 51 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK46270] NR 41 TC 112 Z9 116 U1 2 U2 32 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD MAY PY 2000 VL 40 IS 3 BP 277 EP 282 DI 10.1006/cryo.2000.2244 PG 6 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 322QN UT WOS:000087520400009 PM 10860627 ER PT J AU Mattix, H Singh, AK AF Mattix, H Singh, AK TI Estrogen replacement therapy: implications for postmenopausal women with end-stage renal disease SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Editorial Material ID BONE-MINERAL DENSITY; SYSTEMIC LUPUS-ERYTHEMATOSUS; CARDIOVASCULAR RISK-FACTORS; CHRONIC DIALYSIS PATIENTS; CORONARY HEART-DISEASE; HEPATITIS-C VIRUS; PULSE CYCLOPHOSPHAMIDE; VENOUS THROMBOEMBOLISM; CHRONIC-HEMODIALYSIS; COGNITIVE FUNCTION AB Little information is available about either the potential beneficial or harmful effects of estrogen replacement therapy in postmenopausal women with end-stage renal disease, Although evidence supports a role for estrogen replacement therapy in postmenopausal women in the prevention of cardiovascular disease and bone loss, possible improvement in cognitive function, and the relief of menopausal symptoms, these conclusions may not be applicable to patients with end-stage renal disease, since these studies have generally excluded such women, This issue is of considerable importance since cardiovascular causes account far more than 50% of the all-cause mortality in patients with end-stage renal disease. However, estrogen replacement therapy may also have untoward effects in patients with the disease, including an increased risk of dialysis access thrombosis and potentially worsening coronary artery disease in postmenopausal patients. Furthermore, dosing of estrogens needs to be done carefully since renal excretion is important for the elimination of estrogen metabolites. Low dose or alternate day dosing in addition to monitoring estrogen levels may be warranted when prescribing estrogen replacement therapy to women with end-stage renal disease. In this review, it is our objective to analyze the evidence published in the literature so far and to weigh the risks and benefits of estrogen therapy in postmenopausal women with end-stage renal disease, Curr Opin Nephrol Hypertens 9:207-214, (C) 2000 Lippincott Willlams & Wilkins. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, Boston, MA 02111 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02111 USA. RP Singh, AK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, 75 Francis St, Boston, MA 02111 USA. NR 97 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 2000 VL 9 IS 3 BP 207 EP 214 DI 10.1097/00041552-200005000-00001 PG 8 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 312PL UT WOS:000086951600001 PM 10847319 ER PT J AU Lee, PL Gonzalez, RG AF Lee, PL Gonzalez, RG TI Magnetic resonance spectroscopy of brain tumors SO CURRENT OPINION IN ONCOLOGY LA English DT Review ID PROTON MR SPECTROSCOPY; IN-VIVO; RADIATION-THERAPY; RESOLUTION; GLIOMAS; CLASSIFICATION; METABOLITES; DIAGNOSIS; DISORDERS; ACCURACY AB Magnetic resonance spectroscopy provides metabolic information about brain tumors beyond what can be obtained from anatomic images, in contrast to other metabolism-based imaging techniques such as single photon emission computed tomography and positron-emission tomography, magnetic resonance spectroscopy yields multiparametric data, does not require radio-labeled tracers or ionizing radiation, and can be performed in conjunction with other magnetic resonance imaging studies. Magnetic resonance spectral patterns have been shown to be distinct for different tumor types and grades. Response to radiation therapy is also reflected by magnetic resonance spectral patterns. Although there are quantitative issues still to be addressed, correlation of in vivo spectral patterns with ex vivo spectral patterns obtained from actual biopsy samples indicates that magnetic resonance spectroscopy is a fundamentally valid tool for monitoring disease progression and therapeutic response in patients with brain tumors. Curr Opin Oncol 2000, 12:199-204 (C) 2000 Lippincott Williams & Wilkins, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Bldg 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA83159-01, R21 CA80113-01] NR 27 TC 24 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAY PY 2000 VL 12 IS 3 BP 199 EP 204 DI 10.1097/00001622-200005000-00003 PG 6 WC Oncology SC Oncology GA 357BT UT WOS:000089479200003 PM 10841191 ER PT J AU Schumacher, HR AF Schumacher, HR TI Gout and other crystal-associated arthritis SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Editorial Material C1 Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), Vet Affairs Med Ctr, 151K,Univ & Woodland Ave, Philadelphia, PA 19104 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 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAY PY 2000 VL 12 IS 3 BP 211 EP 212 DI 10.1097/00002281-200005000-00009 PG 2 WC Rheumatology SC Rheumatology GA 307BN UT WOS:000086633700009 ER PT J AU Majumdar, A Lun, K Brand, M Drummond, IA AF Majumdar, A Lun, K Brand, M Drummond, IA TI Zebrafish no isthmus reveals a role for pax2.1 in tubule differentiation and patterning events in the pronephric primordia SO DEVELOPMENT LA English DT Article DE zebrafish; no isthmus; noi; pronephros; pax2.1; wt1; tubulogenesis ID TUMOR-SUPPRESSOR GENE; DENYS-DRASH-SYNDROME; EMBRYONIC KIDNEY DEVELOPMENT; MIDBRAIN-HINDBRAIN BOUNDARY; UROGENITAL DEVELOPMENT; XENOPUS-LAEVIS; DANIO-RERIO; EXPRESSION; PAX-2; MUTATIONS AB Pax genes are important developmental regulators and function at multiple stages of vertebrate kidney organogenesis. In this report, we have used the zebrafish pax2.1 mutant no isthmus to investigate the role for pax2.1 in development of the pronephros. We demonstrate a requirement for pax2.1 in multiple aspects of pronephric development including tubule and duct epithelial differentiation and cloaca morphogenesis. Morphological analysis demonstrates that noi(-) larvae specifically lack pronephric tubules while glomerular cell differentiation is unaffected. In addition, pax2.1 expression in the lateral cells of the pronephric primordium is required to restrict the domains of Wilms' tumor suppressor (wt1) and vascular endothelial growth factor (VEGF) gene expression to medial podocyte progenitors. Ectopic podocyte-specific marker expression in pronephric duct cells correlates with loss of expression of the pronephric tubule and duct-specific markers mAb 3G8 and a Na+/K+ ATPase alpha 1 subunit. The results suggest that the failure in pronephric tubule differentiation in noi arises from a patterning defect during differentiation of the pronephric primordium and that mutually inhibitory regulatory interactions play an important role in defining the boundary between glomerular and tubule progenitors in the forming nephron. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Univ Heidelberg, Dept Neurobiol, D-69120 Heidelberg, Germany. MPI Cell Biol & Genet, D-69120 Heidelberg, Germany. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. RI Brand, Michael/A-5509-2010 OI Brand, Michael/0000-0001-5711-6512 FU NIDDK NIH HHS [P01 DK 54711, R01 DK53093, DK09763] NR 46 TC 87 Z9 88 U1 1 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 MAY PY 2000 VL 127 IS 10 BP 2089 EP 2098 PG 10 WC Developmental Biology SC Developmental Biology GA 324TB UT WOS:000087636500009 PM 10769233 ER PT J AU Link, BA Fadool, JM Malicki, J Dowling, JE AF Link, BA Fadool, JM Malicki, J Dowling, JE TI The zebrafish young mutation acts non-cell-autonomously to uncouple differentiation from specification for all retinal cells SO DEVELOPMENT LA English DT Article DE retina; zebrafish; lamination; neuron; cell differentiation ID DANIO-RERIO; BRACHYDANIO-RERIO; VERTEBRATE RETINA; HOMEOBOX GENE; IN-VITRO; MONOCLONAL-ANTIBODIES; EXPRESSION; PHOTORECEPTORS; GANGLION; NEURONS AB Embryos from mutagenized zebrafish were screened for disruptions in retinal lamination to identify factors involved in vertebrate retinal cell specification and differentiation. Two alleles of a recessive mutation, young, were isolated in which final differentiation and normal lamination of retinal cells were blocked. Early aspects of retinogenesis including the specification of cells along the inner optic cup as retinal tissue, polarity of the retinal neuroepithelium, and confinement of cell divisions to the apical pigmented epithelial boarder were normal in young mutants. BrdU incorporation experiments showed that the initiation and pattern of cell cycle withdrawal across the retina was comparable to wild-type siblings; however, this process took longer in the mutant. Analysis of early markers for cell type differentiation revealed that each of the major classes of retinal neurons, as well as nonneural Muller glial cells, are specified in young embryos. However, the retinal cells fail to elaborate morphological specializations, and analysis of late cell-type-specific markers suggests that the retinal cells were inhibited from fully differentiating. Other regions of the nervous system showed no obvious defects in young mutants,Mosaic analysis demonstrated that the young mutation auts non-cell-autonomously within the retina, as final morphological and molecular differentiation was rescued when genetically mutant cells were transplanted into wild-type hosts. Conversely, differentiation was prevented in wild-type cells when placed in young mutant retinas. Mosaic experiments also suggest that young functions at or near the cell surface and is not freely diffusible. We conclude that the young mutation disrupts the post-specification development of all retinal neurons and glia cells. C1 Harvard Univ, Dept Cell & Mol Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Link, BA (reprint author), Harvard Univ, Dept Cell & Mol Biol, Cambridge, MA 02138 USA. RI malicki, jarema/G-8611-2014 FU NEI NIH HHS [EY06898-01, EY00811, EY00824] NR 67 TC 85 Z9 85 U1 0 U2 2 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 MAY PY 2000 VL 127 IS 10 BP 2177 EP 2188 PG 12 WC Developmental Biology SC Developmental Biology GA 324TB UT WOS:000087636500017 PM 10769241 ER PT J AU Bangs, P White, K AF Bangs, P White, K TI Regulation and execution of apoptosis during Drosophila development SO DEVELOPMENTAL DYNAMICS LA English DT Review DE apoptosis; Drosophila; development ID PROGRAMMED CELL-DEATH; ECDYSONE RECEPTOR ISOFORMS; EMBRYONIC PATTERN REPAIR; REAPER-INDUCED APOPTOSIS; EGF RECEPTOR; MAMMALIAN-CELLS; INHIBITOR; CASPASE; GENE; GRIM AB The development of the Drosophila embryo into an adult fly is a process that integrates cell proliferation and differentiation with programmed cell death, or apoptosis, Apoptosis is an evolutionarily conserved process that is controlled in the developing fly by the products of the genes reaper, grim, and hid. We discuss the role of programmed cell death in the establishment and maintenance of correct patterning in the embryo, and examine the coordination of apoptosis with the hormonally controlled degeneration of larval tissues during metamorphosis. Finally, we address the architecture of the adult eye as an example of how programmed cell death plays a key role in the development of many adult structures. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP White, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI White, Kristin/D-7936-2013 NR 81 TC 54 Z9 54 U1 0 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAY PY 2000 VL 218 IS 1 BP 68 EP 79 DI 10.1002/(SICI)1097-0177(200005)218:1<68::AID-DVDY6>3.0.CO;2-9 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 309WJ UT WOS:000086792000006 PM 10822260 ER PT J AU Stoffers, DA Kieffer, TJ Hussain, MA Drucker, DJ Bonner-Weir, S Habener, JF Egan, JM AF Stoffers, DA Kieffer, TJ Hussain, MA Drucker, DJ Bonner-Weir, S Habener, JF Egan, JM TI Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas SO DIABETES LA English DT Article ID TYPE-2 DIABETES-MELLITUS; FACTOR-I IPF-1; TRANSCRIPTION FACTOR; BETA-CELLS; GENE-TRANSCRIPTION; GLUCOSE-TOLERANCE; MICE; REGENERATION; RECEPTOR; PDX-1 AB Diabetes is caused by a failure of the pancreas to produce insulin in amounts sufficient to meet the body's needs. A hallmark of diabetes is an absolute (type 1) or relative (type 2) reduction in the mass of pancreatic beta-cells that produce insulin, Mature beta-cells have a lifespan of similar to 48-56 days (rat) and are replaced by the replication of preexisting beta-cells and by the differentiation and proliferation of new beta-cells (neogenesis) derived from the pancreatic ducts. Here, we show that the insulinotropic hormone glucagon-like peptide (GLP)-1, which is produced by the intestine, enhances the pancreatic expression of the homeodomain transcription factor IDX-1 that is critical for pancreas development and the transcriptional regulation of the insulin gene. Concomitantly, GLP-1 administered to diabetic mice stimulates insulin secretion and effectively lowers their blood sugar levels. GLP-1 also enhances beta-cell neogenesis and islet size. Thus, in addition to stimulating insulin secretion, GLP-1 stimulates the expression of the transcription factor IDX-1 while stimulating beta-cell neogenesis and may thereby be an effective treatment for diabetes. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Howard Hughes Med Inst, Boston, MA 02114 USA. Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Natl Inst Aging, Clin Invest Lab, Diabet Sect, Baltimore, MD USA. Toronto Gen Hosp, Dept Med, Toronto, ON M5G 1L7, Canada. Univ Alberta, Dept Med, Heritage Med Res Ctr, Edmonton, AB, Canada. Univ Alberta, Dept Physiol, Heritage Med Res Ctr, Edmonton, AB, Canada. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Howard Hughes Med Inst, 55 Fruit St,WEL320, Boston, MA 02114 USA. RI Stoffers, Doris/H-6157-2012; Drucker, Daniel/A-4092-2010 FU NIDDK NIH HHS [DK30457, DK30834, DK44523] NR 45 TC 417 Z9 451 U1 3 U2 17 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2000 VL 49 IS 5 BP 741 EP 748 DI 10.2337/diabetes.49.5.741 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 313EP UT WOS:000086987600011 PM 10905482 ER PT J AU Pham, H Harkless, LB Armstrong, DG Giurini, JM Harvey, C Veves, A AF Pham, H Harkless, LB Armstrong, DG Giurini, JM Harvey, C Veves, A TI Screening techniques to identify people at high risk for diabetic foot ulceration - A prospective multicenter trial SO DIABETES CARE LA English DT Article ID LIMITED JOINT MOBILITY; AMPUTATION; THRESHOLDS; NEUROPATHY; PRESSURES AB OBJECTIVE - Diabetic foot ulceration is a preventable long-term complication of diabetes. A multicenter prospective follow-up study was conducted to determine which risk factors in foot screening have a high association with the development of foot ulceration. RESEARCH DESIGN AND METHODS - A total of 248 patients from 3 large diabetic foot centers were enrolled in a prospective study. Neuropathy symptom score, neuropathy disability score (NDS), vibration perception threshold (VPT), Semmes-Weinstein monofilaments (SWFs),joint mobility, peak plantar foot pressures, and vascular status were evaluated in all patients at the beginning of the study Patients were followed-up every 6 months for a mean period of 30 months (range 6-40), and all new foot ulcers were recorded. The sensitivity, specificity, and positive predictive value of each risk factor were evaluated. RESULTS - Foot ulcers developed in 95 feet (19%) or 73 patients (29%) during the study. Patients who developed foot ulcers were more frequently men, had diabetes for a longer duration, had nonpalpable pedal pulses, had reduced joint mobility, had a high NDS, had a high VPT and had an inability to feel a 5.07 SWE NDS alone had the best sensitivity, whereas the combination of the NDS and the inability to feel a 5.07 SWF reached a sensitivity of 99%. On the other hand, the best specificity for a single factor was offered by foot pressures, and the best combination was that of NDS and foot pressures. Univariate logistical regression analysis yielded a statistically significant odds ratio (OR) for sex, race, duration of diabetes, palpable pulses, history of foot ulceration, high NDSs, high VPTs, high SWFs, and high foot pressures. In addition, 94 (99%) of the 95 ulcerated feet had a high NDS and/or SWF; which resulted in the highest OR of 26.2 (95% CI 3.6-190). Furthermore, in multivariate logistical regression analysis, the only significant factors were high NDSs, VPTs, SWFs, and foot pressures. CONCLUSIONS - Clinical examination and a 5.07 SWF test are the two most sensitive tests in identifying patients at risk for foot ulceration, especially when the tests are used in conjunction with each other. VPT measurements are also helpful and can be used as an alternative. Finally, foot pressure measurements offer a substantially higher specificity and can be used as a postscreening test in conjunction with providing appropriate footwear. C1 Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. Joslin Beth Israel Deaconess Foot Ctr, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Texas, Hlth Sci Ctr, Dept Orthopaed, Div Podiatry, San Antonio, TX 78284 USA. Calif Coll Podiat Med, San Francisco, CA USA. RP Veves, A (reprint author), Beth Israel Deaconess Med Ctr, Microcirculat Lab, Palmer 317,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. OI Pham, Hau/0000-0003-4583-9873 NR 27 TC 264 Z9 290 U1 4 U2 24 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2000 VL 23 IS 5 BP 606 EP 611 DI 10.2337/diacare.23.5.606 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 313WN UT WOS:000087022800010 PM 10834417 ER PT J AU Meigs, JB Ordovas, JM Cupples, LA Singer, DE Nathan, DM Schaefer, EJ Wilson, PWF AF Meigs, JB Ordovas, JM Cupples, LA Singer, DE Nathan, DM Schaefer, EJ Wilson, PWF TI Apolipoprotein E isoform polymorphisms are not associated with insulin resistance - The Framingham Offspring Study SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; DEPENDENT DIABETES-MELLITUS; ARTERY DISEASE; RISK FACTOR; E PHENOTYPE; TRIGLYCERIDE LEVELS; PLASMA; HYPERINSULINEMIA; POPULATION AB OBJECTIVE - Insulin resistance and the apolipoprotein (apo) allele e4 have both been associated with coronary heart disease (CHD). We examined the relationship between insulin resistance and apo(e) polymorphisms among participants in the Framingham Offspring Study. RESEARCH DESIGN END METHODS- During 1991-1995, subjects underwent a clinical examination and an oral glucose tolerance test with measurement of fasting and 2-h glucose, insulin levels, and fasting lipid levels. We measured insulin resistance using the homeostasis model, in which insulin resistance (HOMA-IR) = Easting insulin x glucose/22.5. Apo(e) isoforms and phenotypes were determined in 1983-1987 using isoelectric focusing of plasma VLDL. Of the 2,120 subjects with complete HOMA-IR and apo(e) data, 204 with type 2 diabetes were excluded. The remainder were classified with features of the insulin resistance syndrome including impaired glucose tolerance (1997 American Diabetes Association criteria), hypertension (criteria from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [6th report]), obesity (BMI >85th percentile), high waist-to-hip ratio (>85th percentile), and high triglyceride and low HDL levels (NCEP-2 criteria). We analyzed data with contingency tables and age- and sex-adjusted logistic regression models. RESULTS - Among the 1,916 subjects, the mean age was 55 (range 28-83 years) and 51% were women. Median HOMA-IR was 6.4 (interquartile range 5.2-8.2), and allele frequencies were 7.8, 79.9, and 12.4% for apo(e) alleles e2, e3, and e4, respectively There were no differences in proportions of apo(e) isoforms or alleles across increasing quintiles of HOMA-IR. A less dramatic increase in proportions occurred with elevated triglycerides associated with increasing HOMA-IR among those with apo(e) isoforms 2/2 and u3 compared with the others (P less than or equal to 0.01 for interaction). Otherwise, apo(e) did not substantially modify associations between insulin resistance and features of the insulin resistance syndrome. CONCLUSIONS - There is no association between apo(e) polymorphisms and insulin resistance. These appear to represent 2 completely independent risk factors for CHD. C1 Massachusetts Gen Hosp, Gen Internal Med Unit S50 9, Dept Med, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Dept Med, Boston, MA 02114 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Boston Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Boston, MA 02111 USA. Boston Univ, Sch Med, Boston, MA 02111 USA. Boston Univ, Sch Med, Framingham Heart Study, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit S50 9, Dept Med, Div Gen Med, Boston, MA 02114 USA. OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [N01-HC-38083, R01 HL 54776] NR 43 TC 19 Z9 20 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2000 VL 23 IS 5 BP 669 EP 674 DI 10.2337/diacare.23.5.669 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 313WN UT WOS:000087022800021 PM 10834428 ER PT J AU Faquin, WC Pilch, BZ Keel, SB Cooper, TL AF Faquin, WC Pilch, BZ Keel, SB Cooper, TL TI Fine-needle aspiration of dedifferentiated chondrosarcoma of the larynx SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE chondrosarcoma; cytology; larynx; dedifferentiated; FNA ID MALIGNANT FIBROUS HISTIOCYTOMA; CYTOLOGY; COMPONENT; TUMORS; HEAD; NECK AB We present a case of dedifferentiated chondrosarcoma of the larynx in which the dedifferentiated component was initially diagnosed by fine-needle aspiration (FNA). The patient was a 74-yr-old man who presented with difficulty breathing and an anterior neck mass. A CT scan demonstrated a 4.5-cm cartilaginous lesion involving the left thyroid cartilage, with an anterior soft-tissue component. Nine years prior, the patient had an incomplete resection of a low-grade chondrosarcoma at the same site. FNA was performed on the current lesion, demonstrating a high-grade spindle-cell sarcoma with a storiform pattern. The cytomorphology together with immunocytochemistry and electron microscopy were diagnostic of malignant fibrous histiocytoma (MFH), and synthesis of the clinical, radiographic, and cytomorphologic features resulted in a diagnosis of dedifferentiated chondrosarcoma. The cytologic diagnosis was histologically confirmed by laryngectomy. Although rare. dedifferentiated chondrosarcoma should be included in the differential diagnosis of high-grade sarcomas of bone and cartilage assessed by FNA. Diagn. Cytopathol. 2000, 22:288-292. (C) 2000 Wiley-Liss. Inc. C1 Massachusetts Gen Hosp, Dept Pathol, WRN 2, Boston, MA 02114 USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 2, 55 Fruit St, Boston, MA 02114 USA. NR 34 TC 9 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD MAY PY 2000 VL 22 IS 5 BP 288 EP 292 DI 10.1002/(SICI)1097-0339(200005)22:5<288::AID-DC6>3.0.CO;2-F PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 307NJ UT WOS:000086659100006 PM 10790235 ER PT J AU Sasada, T Ghendler, Y Wang, JH Reinherz, EL AF Sasada, T Ghendler, Y Wang, JH Reinherz, EL TI Thymic selection is influenced by subtle structural variation involving the p4 residue of an MHC class I-bound peptide SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE thymic selection; TCR; MHC; cell death; altered peptide ligand ID T-CELL-RECEPTOR; THYMOCYTE POSITIVE SELECTION; INDUCED NEGATIVE SELECTION; SINGLE MHC/PEPTIDE LIGAND; CD8 BETA-CHAIN; SELF-PEPTIDES; LYMPHOCYTES-T; MICE LACKING; ANTIGEN; COMPLEX AB The T lineage repertoire is shaped by opposing processes of positive and negative selection. To probe the specificity of selection, N15 TCR-transgenic (tg) recombinase-activating gene (RAG)-2(-/-) H-2(b) mice recognizing the VSV8 octapeptide RGYVYQGL bound to K-b were utilized in conjunction with VSV8 variants differing only at the central p4 position. The V41 mutant octamer, like VSV8, induces negative selection of immature double-positive thymocytes on the beta(2)-microglobulin (B2M)(+/+) background and is a strong agonist for mature N15 T cells. In contrast, V4L or V4norvaline octamers promote positive selection in N15tg RAG-2(-/-) beta(2)M(-/-) H-2(b) fetal thymic organ culture and are weak agonists for N15 T cells. Hence, the absence of a p4 side chain C beta-methyl group results in positive selection of the N15 TCR. Hydrophobicity of the p4 residues also modulates thymocyte fate: the positively selecting norvaline and leucine variants have one and two C gamma-methyl groups, respectively white the weakly selecting gamma-methylleucine p4 contains three C gamma-methyl groups. Moreover, the most hydrophobic octamer containing p4 cyclohexylglycine substitution fails to select. Thus, for N15 and presumably other MHC class I-restricted TCR, there is a high degree of structural specificity to peptide-dependent thymic selection processes. C1 Dana Farber Canc Inst, Immunol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunol Lab, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI45022] NR 62 TC 13 Z9 13 U1 0 U2 2 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 MAY PY 2000 VL 30 IS 5 BP 1281 EP 1289 DI 10.1002/(SICI)1521-4141(200005)30:5<1281::AID-IMMU1281>3.0.CO;2-D PG 9 WC Immunology SC Immunology GA 317VM UT WOS:000087247700004 PM 10820373 ER PT J AU Hudson, CC Krebs, DE AF Hudson, CC Krebs, DE TI Frontal plane dynamic stability and coordination in subjects with cerebellar degeneration SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE cerebellar disease; postural stability; coordination; ataxia; human ID POSTURAL RESPONSES; ATAXIA; DYSFUNCTION; MOVEMENT; BALANCE; STANCE; SET AB Objective attempts to characterize postural control in subjects with cerebellar (Cb) pathology have focused primarily on sagittal plane responses to static standing, semi-dynamic standing, and platform perturbation. Repeated, dynamic, functional movement may provide a better opportunity to study the effects of ataxia on frontal plane postural stability. The purpose of this investigation was to quantify lateral stability using center of gravity (CG) and center of pressure (CP) movement analysis, and to examine motor responses necessary to complete a repetitive stepping task. Whole body kinematic and kinetic data were collected as patients with Cb degeneration and Iron-disabled volunteers repeatedly ascended forward and descended backward From a 7.6-cm step to the beat of a metronome. Cb subjects demonstrated significantly greater lateral CG instability, consistent with increased CC velocity and displacement variability in the frontal plane compared to non-disabled subjects. Significantly greater lateral CP displacement was found in subjects with Cb degeneration. Phase plot patterns from patients with Cb degeneration showed poor movement quality, indicated by abruptly changing CG phase plot patterns and abnormal CG acceleration and deceleration phases. Ataxic postural reactions were observed consistently during lateral weight shifting phases toward the stance limb. We hypothesized that lateral postural instability in Cb subjects stems from altered lower extremity intersegmental coordination and inadequate lateral CG velocity control. Frontal plane CG instability may necessitate a wide-based gait. Despite the varied neuroanatomic sites of degenerative Cb pathology, subjects with Cb pathology demonstrated similar CG movement patterns and altered motor strategies to avoid destabilization, Dynamic assessment provides important information regarding frontal plane instability not revealed by static assessment methods. These findings suggest that a dynamic, constrained stepping task effectively differentiates Cb and non-disabled volunteers, contributing to our knowledge of the effect of ataxic movement disturbances on frontal plane postural stability and lower limb coordination. C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. RP Krebs, DE (reprint author), MGH Inst Hlth Profess, 101 Merrimac St, Boston, MA 02114 USA. FU NIA NIH HHS [R01AG11255] NR 28 TC 14 Z9 15 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 2000 VL 132 IS 1 BP 103 EP 113 DI 10.1007/s002219900291 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 313AZ UT WOS:000086977300010 PM 10836640 ER PT J AU Siwicki, JK Hedberg, Y Nowak, R Loden, M Zhao, JY Landberg, G Roos, G AF Siwicki, JK Hedberg, Y Nowak, R Loden, M Zhao, JY Landberg, G Roos, G TI Long-term cultured IL-2-dependent T cell lines demonstrate p16(INK4a) overexpression, normal pRb/p53, and upregulation of cyclins E or D2 SO EXPERIMENTAL GERONTOLOGY LA English DT Article ID SENESCENT HUMAN FIBROBLASTS; BREAST-CANCER; REPLICATIVE SENESCENCE; RETINOBLASTOMA PROTEIN; TELOMERASE ACTIVITY; DEPENDENT KINASE-4; LIFE-SPAN; IN-VITRO; EXPRESSION; P16 AB Acquisition of an immortal phenotype by circumvention of the normal senescence program can be an important step in tumor development and progression. The regulation of life-span checkpoints is complex and abrogation of these processes can occur at different levels. To better understand these mechanisms in long-term cultured lymphocytes we have characterized two human long-term cultured IL-2-dependent T cell lines regarding telomere length, telomerase activity, and the expression of selected cell cycle regulators (pRb, p53, cyclin E, cyclin D1, cyclin D2, cyclin D3, cdk4, p16(INK4a), p21(WAF1), p27(KIP1), c-myc, bcl-2, and NPAT). We compared these cell lines with a primary T lymphoblast population with a limited life span from the same donor. Both T cell lines with extraordinary growth capacity showed telomere length stabilization, high telomerase activity and demonstrated wild-type pattern of pRb and p53 but strong p16(INK4a) protein expression. The growth inhibitory activity of p16(INK4a) Seemed to be abrogated by enhanced expression of cyclin D2, cdk4, and c-myc in one T cell line and overexpression of cyclin E in the second T cell line. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Umea Univ, Dept Med Biosci, S-90185 Umea, Sweden. Marie Sklodowska Curie Mem Canc Ctr, Dept Immunol, Warsaw, Poland. Inst Oncol, Warsaw, Poland. Marie Sklodowska Curie Mem Canc Ctr, Dept Mol Biol, Warsaw, Poland. Massachusetts Gen Hosp, Ctr Canc, Oncol Mol Lab, Charlestown, MA 02129 USA. RP Roos, G (reprint author), Umea Univ, Dept Med Biosci, S-90185 Umea, Sweden. NR 51 TC 15 Z9 17 U1 0 U2 0 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 MAY PY 2000 VL 35 IS 3 BP 375 EP 388 DI 10.1016/S0531-5565(00)00088-7 PG 14 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 322XV UT WOS:000087535400010 PM 10832057 ER PT J AU Wilbanks, AM Mahajan, S Frank, DA Druker, BJ Gilliland, DG Carroll, M AF Wilbanks, AM Mahajan, S Frank, DA Druker, BJ Gilliland, DG Carroll, M TI TEL/PDGF beta R fusion protein activates STAT1 and STAT5: A common mechanism for transformation by tyrosine kinase fusion proteins SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE TEL/PDGF beta R; tyrosine kinases; STAT5; CMML ID CHRONIC MYELOMONOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HEMATOPOIETIC-CELL LINES; PERIPHERAL-BLOOD CELLS; DNA-BINDING ACTIVITY; SIGNAL-TRANSDUCTION; CONSTITUTIVE ACTIVATION; TRANSCRIPTION FACTORS; TARGETED DISRUPTION; RECEPTOR-BETA AB Objective. TEL/PDGF beta R is a tyrosine kinase fusion protein associated with the pathogenesis of chronic myelomonocytic leukemia, The following experiments were undertaken to understand the mechanisms whereby TEL/PDGF beta R transforms cells. Materials and Methods. Activation of JAK: and STAT proteins was studied in an interleukin 3 (IL3)-dependent cell line, Ba/F3, transformed to IL-3 independence by TEL/PDGF beta R. Results. TEL/PDGF beta R activates STAT1 and STAT5 in transformed Ba/F3 cells through a JAK-independent pathway. Activation of STAT proteins requires the kinase activity of TEL/PDGF beta R, JAK1, JAK2, JAK3, and TYK2 are not phosphorylated by TEL/PDGR beta R. However, TEL/PDGF beta R can phosphorylate STAT5 in transiently transfected COS tells, suggesting that TEL/PDGF beta R may itself be the kinase involved in tyrosine phosphorylation of STAT proteins. In contrast, native PDGF beta R stimulated by PDGF ligand does not activate STAT proteins to a significant degree in this hematopoietic context. STAT1 and STAT5 also are activated by TEL/ABL and TEL/JAK2. fusion proteins associated with human leukemia, Conclusions. STAT activation may be a common mechanism of transformation by leukemogenic tyrosine kinase fusion proteins. (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Hematol & Oncol, Boston, MA USA. Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Div Hematol & Med Oncol, Portland, OR 97201 USA. RP Carroll, M (reprint author), Univ Penn, Div Hematol & Oncol, BRB 2,Room 708,421 Curie Blvd, Philadelphia, PA 19104 USA. FU NCI NIH HHS [K08CA73749-01]; NIDDK NIH HHS [P01DK50654-01] NR 53 TC 43 Z9 43 U1 0 U2 1 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 MAY PY 2000 VL 28 IS 5 BP 584 EP 593 DI 10.1016/S0301-472X(00)00138-7 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 314RR UT WOS:000087071800013 PM 10812249 ER PT J AU Albanese, C Reutens, AT Bouzahzah, B Fu, MF D'Amico, M Link, T Nicholson, R Depinho, RA Pestell, RG AF Albanese, C Reutens, AT Bouzahzah, B Fu, MF D'Amico, M Link, T Nicholson, R Depinho, RA Pestell, RG TI Sustained mammary gland-directed, ponasterone A-inducible expression in transgenic mice SO FASEB JOURNAL LA English DT Article DE ecdysteroids; gland-specific transgenics; DNA binding site ID SITE-SPECIFIC RECOMBINATION; GENE-EXPRESSION; MAMMALIAN-CELLS; TRANSCRIPTIONAL ACTIVATION; ECDYSONE RECEPTOR; MOUSE; INDUCTION; ONCOGENE; LIGANDS; PRODUCT AB The ability to regulate temporal- and spatial-specific expression of target genes in transgenic mice will facilitate analysis of gene function and enable the generation of murine models of human diseases. The genetic analysis of mammary gland tumorigenesis requires the development of mammary gland-specific transgenics, which are tightly regulated throughout the adult mammary epithelium. Analysis of genes implicated in mammary gland tumorigenesis has been hampered by mosaic transgene expression and the findings that homozygous deletion of several candidate genes (cyclin D1, Stat5A, prolactin receptor) abrogates normal mammary gland development. We describe the development of transgenic mouse lines in which sustained transgene expression was inducibly regulated, both specifically and homogeneously, in the adult mammary gland epithelium. Transgenes encoding RXR alpha and a chimeric ecdysone receptor under control of a modified MMTV-LTR, which targets mammary gland expression, were used. These transgenic 'receptor' lines were crossed with transgenic 'enhancer' lines in which the ecdysone/RXR binding site induced ligand-dependent expression of transgenic beta-galactoxidase. Pharmacokinetic analysis of a highly bioactive ligand (ponasterone A), identified through screening ecdysteroids from local plants, demonstrated sustained release and transgene expression in vivo. This transgenic model with both tightly regulated and homogeneous transgene expression, which was sustained in vivo using ligands readily extracted from local flora, has broad practical applicability for genetic analysis of mammary gland disease. C1 Yeshiva Univ Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. Smith Coll Lyman Conservatory, Northampton, MA 01636 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pestell, RG (reprint author), Yeshiva Univ Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Med, 1300 Morris Pk Ave,Chanin 302, Bronx, NY 10461 USA. FU NCI NIH HHS [5-P30-CA13330-26, R01CA75503, R29CA70896-01] NR 34 TC 45 Z9 48 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2000 VL 14 IS 7 BP 877 EP 884 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 309CG UT WOS:000086749500005 PM 10783141 ER PT J AU Peteet, JR AF Peteet, JR TI Cancer and the meaning of work SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID QUALITY-OF-LIFE; BREAST-CANCER; ISSUES; SURVIVORSHIP; EMPLOYMENT; OUTCOMES; PATIENT AB The importance of work in patients with cancer has received relatively little attention. This article reviews the existing literature and uses case examples to illustrate the themes that characterize work-related distress. Whereas loss of occupational identity can be a source of significant anxiety and depression, continuing or returning to the workplace allows many patients to maintain a sense of normalcy or control. The experience of discrimination can become a focus for strong feelings about fairness. Clinicians need to both address work-related distress directly and appreciate the larger significance these themes may have in their patients' coping. A closer look at the importance of work in oncology suggests several areas for future research. (C) 2000 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Dana Farber Partners Canc Care, Adult Psychosocial Oncol Program, Boston, MA 02115 USA. RP Peteet, JR (reprint author), Harvard Univ, Sch Med, Dana Farber Partners Canc Care, Adult Psychosocial Oncol Program, 44 Binney St, Boston, MA 02115 USA. NR 34 TC 85 Z9 85 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAY-JUN PY 2000 VL 22 IS 3 BP 200 EP 205 DI 10.1016/S0163-8343(00)00076-1 PG 6 WC Psychiatry SC Psychiatry GA 332ER UT WOS:000088061700010 PM 10880715 ER PT J AU Lin, AE Ticho, BS Houde, K Westgate, MN Holmes, LB AF Lin, AE Ticho, BS Houde, K Westgate, MN Holmes, LB TI Heterotaxy: Associated conditions and hospital-based prevalence in newborns SO GENETICS IN MEDICINE LA English DT Article DE Asplenia; cardiovascular malformations; congenital heart defects; defects of right; left determination; generic epidemiology; heterotaxy; isomerism; laterality defects; maternal diabetes; polysplenia; prevalence; situs ambiguous; situs inversus ID HUMAN SITUS DETERMINATION; BALANCED TRANSLOCATION; EXTRACARDIAC ANOMALIES; CARDIAC-MALFORMATIONS; ASPLENIA SYNDROME; ATRIAL ISOMERISM; BILIARY ATRESIA; POLYSPLENIA; DIAGNOSIS; DEFECTS AB Purpose: To provide insight into the possible etiology and prevalence of heterotaxy, we studied conditions associated with heterotaxy in a consecutive hospital population of newborns. Methods: From 1972 to March, 1999 (except February 16, 1972 to December 31, 1978), 58 cases of heterotaxy were ascertained from a cohort of 201,084 births in the ongoing Active Malformation Surveillance Program at the Brigham and Women's Hospital. This registry includes livebirths, stillbirths, and elective abortions. Prevalence among nontransfers (i.e., patients whose mothers had planned delivery at this hospital) was calculated as approximately 1 per 10,000 total births (20 of 201,084). Results: We analyzed a total of 58 patients consisting of 20 (34%) nontransfers and 38 (66%) transfers. Patients were categorized by spleen status as having asplenia (7 nontransfers, 25 total), polysplenia (8, 20), right spleen (4, 11), normal left (0, 1), and unknown (1, 0). Among the 20 nontransfer and 59 total heterotaxy patients, the following associated medical conditions were present: chromosome abnormality (1 nontransfer, 2 total), suspected Mendelian or chromosome microdeletion disorder (1 nontransfer, 6 total), and maternal insulin-dependent diabetes mellitus (1 nontransfer, 2 total). There were 6 twins (1 member each from 6 twin pairs including 1 dizygous, 4 monozygous, 1 conjoined; 2 were nontransfers). An associated condition occurred in 5 (25%) nontransfer and 16 (28%) total patients, or among 10 of 53 singleton births (19%). Conclusions: Although most cases of heterotaxy in this series were sporadic events, an associated condition was present in about one-fourth of the cases. Not all of these conditions would be considered causative etiologies. Based on this small series alone, maternal insulin-dependent diabetes cannot be viewed as a risk factor for heterotaxy. However, the specific association of diabetes with polysplenia with/without left atrial isomerism is noteworthy, and adds weight to animal and epidemiologic case-control data. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Teratol Unit,Pediat Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Cardiol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Newborn Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lin, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Teratol Unit,Pediat Serv, Warren 801, Boston, MA 02114 USA. NR 51 TC 73 Z9 80 U1 1 U2 7 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 MAY-JUN PY 2000 VL 2 IS 3 BP 157 EP 172 DI 10.1097/00125817-200005000-00002 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 409PV UT WOS:000167392800002 PM 11256661 ER PT J AU Spiro, MJ Spiro, RG AF Spiro, MJ Spiro, RG TI Use of recombinant endomannosidase for evaluation of the processing of N-linked oligosaccharides of glycoproteins and their oligosaccharide-lipid precursors SO GLYCOBIOLOGY LA English DT Article DE endomannosidase; glycoprotein processing; quality control of proteins; glucosylated N-linked oligosaccharides; oligosaccharide-lipids ID ALPHA-D-MANNOSIDASE; LYSOSOMAL MEMBRANE-GLYCOPROTEINS; THYROID MICROSOMAL-ENZYMES; VESICULAR STOMATITIS-VIRUS; RAT-LIVER GOLGI; ENDOPLASMIC-RETICULUM; POLYMANNOSE OLIGOSACCHARIDES; MOLECULAR CHAPERONE; SECRETORY PATHWAY; QUALITY-CONTROL AB Although glucose residues in a triglucosyl sequence are essential for the N-glycosylation of proteins and in their monoglucosyl form have been implicated in lectin-like interactions with chaperones, their removal is required for the formation of mature carbohydrate units and represents the initial steps in the glycoprotein processing sequence. In order to provide a probe for the glucosylation state of newly synthesized glycoproteins obtained from normal or altered cells, we have evaluated the usefulness of recombinant endo-alpha-mannosidase employing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) to monitor the change in molecular mass brought about by the release of glucosylated mannose (Glc(1-3)Man), With this approach the presence of two triglucosylated-N-linked oligosaccharides in vesicular stomatis virus (VSV) G protein formed by castanospermine-treated CHO cells or the glucosidase I deficient Lec23 mutant could be clearly demonstrated and an even more pronounced change in migration was observed upon endomannosidase treatment of their more heavily N-glycosylated lysosomal membrane glycoproteins, Furthermore, the G protein of the temperature sensitive VSV ts045 mutant was found to be sensitive to endomannosidase, resulting in a change in electrophoretic mobility consistent with the presence of monoglucosylated-N-linked oligosaccharides, The finding that endomannosidase also acts effectively on oligosaccharide lipids, as assessed by SDS-PAGE or thin layer chromatography, indicated that it would be a valuable tool in assessing the glucosylation state of these biosynthetic intermediates in normal cells as well as in mutants or altered metabolic states, even if the polymannose portion is truncated. Endomannosidase can also be used to determine the glucosylation state of the polymannose oligosaccharides released during glycoprotein quality control and when used together with endo-beta-N-acetylglucosaminidase H can distinguish between those terminating in a single N-acetylglucosamine or in a di-N-acetylchitobiose sequence. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02215 USA. RP Spiro, RG (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK17477] NR 43 TC 11 Z9 11 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD MAY PY 2000 VL 10 IS 5 BP 521 EP 529 DI 10.1093/glycob/10.5.521 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304NY UT WOS:000086491400010 PM 10764841 ER PT J AU Melki, SA Safar, A Yaghouti, F Scharper, P Scharper, M Zeligs, B MacDowell, AL Goldberg, MA Lustbader, J AF Melki, SA Safar, A Yaghouti, F Scharper, P Scharper, M Zeligs, B MacDowell, AL Goldberg, MA Lustbader, J TI Effect of topical povidone-iodine versus topical ofloxacin on experimental Staphylococcus keratitis SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article AB Purpose: To compare the antibacterial effect of povidone-iodine (PI) with that of ofloxacin in an experimental model of bacterial keratitis. Methods: Staphyloccocal keratitis was induced in 21 eyes of Dutch Belted rabbits by intrastromal inoculation of approximately 280 organisms of Staphylococcus aureus. Six hours later, the animals were divided in four groups treated topically with saline 0.9%, Betadine 10%, Betadine 0.5% or Ofloxacin 0.3% (2 gtt every 30 min for 8 h). The central 8-mm cornea was excised, washed and homogenized. Colony counts were performed on serial 10-fold dilutions plated on blood and brain infusion agar and incubated overnight. Results: Colony-forming units per cornea were 7.4x10(7) for the saline group compared to 8.2x10(7) for PI 10% (P>0.5), 4.3x10(7) for PI 0.5% (P<0.01) and no organisms for ofloxacin 0.3%. Conclusions: Betadine 0.5% demonstrates a statistically significant bactericidal effect compared with untreated staphyloccocal keratitis in our experimental model. Ofloxacin has superior antibacterial effect under the conditions studied. Further improvements in the povidone-iodine formulation are warranted prior to consideration for human keratitis. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, Boston, MA 02114 USA. Georgetown Univ, Med Ctr, Dept Microbiol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Ophthalmol, Washington, DC 20007 USA. RP Melki, SA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 18 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD MAY PY 2000 VL 238 IS 5 BP 459 EP 462 DI 10.1007/s004170050379 PG 4 WC Ophthalmology SC Ophthalmology GA 329BP UT WOS:000087886500012 PM 10901479 ER PT J AU Tung, N Berkowitz, R Matulonis, U Quartulli, M Seiden, M Kim, Y Niloff, J Cannistra, SA AF Tung, N Berkowitz, R Matulonis, U Quartulli, M Seiden, M Kim, Y Niloff, J Cannistra, SA TI Phase I trial of carboplatin, paclitaxel, etoposide, and cyclophosphamide with granulocyte colony stimulating factor as first-line therapy for patients with advanced epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; ORAL ETOPOSIDE; PLATINUM-RESISTANT; RANDOMIZED TRIAL; CARCINOMA; CISPLATIN; DOXORUBICIN; I/II AB Objectives. The goal of this study was to determine the maximally tolerated doses (MTDs) of carboplatin, paclitaxel (Taxol), etoposide, and cyclophosphamide (CTEC) with granulocyte-colony stimulating factor (G-CSF, Filgrastim) support as first-line chemotherapy in women with advanced epithelial ovarian cancer (EOC). Methods. Newly diagnosed patients with either stage IV EOC, or stage III EOC and any amount of gross residual tumor after surgical debulking were eligible to receive six cycles of CTEC over five different dose levels in this phase I trial (planned 21-day cycle length). Paclitaxel, carboplatin, and cyclophosphamide were administered intravenously on Day 1, and oral etoposide was administered on Days 1, 2, and 3. G-CSF was administered beginning Day 4. Results. Twenty patients received a total of 98 cycles of CTEC over the five dose levels evaluated. Bone marrow suppression was the major toxic effect, with grade 4 neutropenia and thrombocytopenia being observed in 25 and 23% of cycles, respectively. The overall incidence of febrile neutropenia was 10%, and no toxic deaths occurred. No grade IV thrombocytopenia or febrile neutropenia was observed once the carboplatin dose was reduced from AUC of 7 to 5. Nonhematologic toxicity was generally mild (grade 2 or less). Dose-limiting toxicity was not observed at the highest dose level evaluated in this study, preventing assignment of the MTD. The clinical complete response rate was 92%, although 15 of 16 evaluable patients have progressed with a median progression-free interval of 4 months (range, 2-11 months). One patient remains disease-free 9 months from the completion of CTEC. Conclusions. The CTEC regimen is well tolerated and highly active. Although the MTD was not reached in this study, the short median progression-free interval suggests that this regimen is unlikely to be superior to standard treatment with paclitaxel and carboplatin, Strategies to optimize the development of future combination chemotherapy regimens in the treatment of newly diagnosed ovarian cancer are discussed. (C) 2000 Academic Press. C1 Beth Israel Deaconess Med Ctr, Program Gynecol Med Oncol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Gynecol Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Partners Canc Care, Boston, MA 02115 USA. RP Cannistra, SA (reprint author), Beth Israel Deaconess Med Ctr, Program Gynecol Med Oncol, 330 Brookline Ave, Boston, MA 02215 USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2000 VL 77 IS 2 BP 271 EP 277 DI 10.1006/gyno.2000.5778 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 313YX UT WOS:000087028300010 PM 10785477 ER PT J AU Ghaemi, SN Gaughan, S AF Ghaemi, SN Gaughan, S TI Novel anticonvulsants: A new generation of mood stabilizers? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID REFRACTORY BIPOLAR DISORDER; MANIC-DEPRESSIVE ILLNESS; LAMOTRIGINE TREATMENT; GABAPENTIN; LITHIUM; TOPIRAMATE; DRUG AB Accumulating evidence suggests that at least some novel anticonvulsants may have mood-stabilizing properties. This paper reviews the literature for empirical studies of this topic. Lamotrigine has the most evidence in favor of its efficacy, with two double-blind studies in which it was more efficacious than placebo in the treatment of bipolar depression. However, it is associated with a 1/1000 risk of potentially fatal Stevens-Johnson syndrome. Gabapentin, although safe and well-tolerated, has been found in two double-blind studies not to be efficacious in treatment-refractory mania or refractory bipolar depression. Topiramate is currently supported only by naturalistic evidence of mild to moderate mood-stabilizing efficacy, but it has the advantage of often producing weight loss. Based on these data, lamotrigine may be effective, in monotherapy or as an adjunct, for treating depression in type 1 bipolar disorder, but suggestions regarding gabapentin and topiramate await further efficacy data. Most of the current findings derive from small, non-double-blind studies, and further research is required before clinicians can consider any of these agents to be mood stabilizers. C1 Harvard Univ, Massachusetts Gen Hosp, Bipolar Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. RP Ghaemi, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Bipolar Res Program, 50 Staniford St,5th Floor, Boston, MA 02114 USA. NR 47 TC 23 Z9 26 U1 0 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 MAY-JUN PY 2000 VL 8 IS 1 BP 1 EP 7 DI 10.1093/hrp/8.1.1 PG 7 WC Psychiatry SC Psychiatry GA 306JR UT WOS:000086594000001 PM 10824292 ER PT J AU Youngren, VR Alonso, A Nahum, JP AF Youngren, VR Alonso, A Nahum, JP TI When goodbye precedes hello: A "premature" termination SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID GROUP-THERAPY C1 Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. McLean Hosp, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. Boston Psychoanalyt Soc & Inst, Boston, MA USA. Massachusetts Inst Psychoanal, Boston, MA USA. RP Youngren, VR (reprint author), Suite 1-C,1105 Massachusetts Ave, Cambridge, MA 02138 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2000 VL 8 IS 1 BP 25 EP 35 PG 11 WC Psychiatry SC Psychiatry GA 306JR UT WOS:000086594000004 PM 10824295 ER PT J AU Schouten, R AF Schouten, R TI Impaired physicians: Is there a duty to report to state licensing boards? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article C1 Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. RP Schouten, R (reprint author), Massachusetts Gen Hosp, Law & Psychiat Serv, Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2000 VL 8 IS 1 BP 36 EP 39 DI 10.1093/hrp/8.1.36 PG 4 WC Psychiatry SC Psychiatry GA 306JR UT WOS:000086594000005 PM 10824296 ER PT J AU Furst, M Aharonson, V Levine, RA Fullerton, BC Tadmor, R Pratt, H Polyakov, A Korczyn, AD AF Furst, M Aharonson, V Levine, RA Fullerton, BC Tadmor, R Pratt, H Polyakov, A Korczyn, AD TI Sound lateralization and interaural discrimination. Effects of brainstem infarcts and multiple sclerosis lesions SO HEARING RESEARCH LA English DT Article DE auditory pathway; brainstem magnetic resonance imaging; lateralization; multiple sclerosis; infarct ID AUDITORY-EVOKED-POTENTIALS; CLICK LATERALIZATION; PONTINE LESIONS; STEM LESIONS; HUMANS AB Subjects with brainstem lesions due to either an infarct or multiple sclerosis (MS) underwent two types of binaural testing (lateralization testing and interaural discrimination) for three types of sounds (clicks and high and low frequency narrow-band noise) with two kinds of interaural differences (level and time). Two major types of abnormalities were revealed in the lateralization performances: perception of all stimuli, regardless of interaural differences (time and/or level) in the center of the head (center-oriented), or lateralization of all stimuli to one side or the other of the head (side-oriented). Similar patterns of abnormal lateralization (center-oriented and side-oriented) occurred for MS and stroke patients. A subject's pattern of abnormal lateralization testing was the same regardless of the type of stimulus or type of interaural disparity. Lateralization testing was a more sensitive test than interaural discrimination testing for both types of subjects. Magnetic resonance image (MRI) scanning in three orthogonal planes of the brainstem was used to detect lesions. A semi-automated algorithm superimposed the auditory pathway onto each MRI section. Whenever a lesion overlapped the auditory pathway, some binaural performance was abnormal and vice versa. Given a lateralization test abnormality, whether the pattern was center-oriented or side-oriented was mainly determined by lesion site. Center-oriented performance was principally associated with caudal pontine lesions and side-oriented performance with lesions rostral to the superior olivary complex. For lesions restricted to the lateral lemniscus and/or inferior colliculus, whether unilateral or bilateral, just noticeable differences (JNDs) were nearly always abnormal, but for caudal pontine lesions JNDs could be normal or abnormal. MS subjects were more sensitive to interaural time delays than interaural level differences particularly for caudal pontine lesions, while stroke patients showed no differential sensitivity to the two kinds of interaural differences. These results suggest that neural processing of binaural stimuli is multilevel and begins with independent interaural time and level analyzers in the caudal pens. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Tel Aviv Univ, Fac Engn, Dept Elect Engn Syst, IL-69978 Tel Aviv, Israel. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tel Aviv Univ, Sackler Fac Med, Dept Radiol, IL-69978 Tel Aviv, Israel. Technion Israel Inst Technol, Evoked Potentials Lab, IL-32000 Haifa, Israel. Tel Aviv Univ, Sackler Sch Med, Sieratzki Chair Neurol, IL-69978 Tel Aviv, Israel. RP Furst, M (reprint author), Tel Aviv Univ, Fac Engn, Dept Elect Engn Syst, IL-69978 Tel Aviv, Israel. EM mira@eng.tau.ac.il RI Korczyn, Amos/C-3461-2017; OI Korczyn, Amos/0000-0003-0125-2579; Aharonson, Vered/0000-0002-4406-6525 NR 18 TC 28 Z9 28 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 2000 VL 143 IS 1-2 BP 29 EP 42 DI 10.1016/S0378-5955(00)00019-8 PG 14 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 309AK UT WOS:000086744900004 PM 10771182 ER PT J AU Rabinowitz, D Zanchi, A Schaumberg, D Krolewski, A AF Rabinowitz, D Zanchi, A Schaumberg, D Krolewski, A TI Testing mode of inheritance of a candidate mutation at a quantitative trait locus SO HUMAN HEREDITY LA English DT Article DE additivity; ascertainment; association; diabetic nephropathy; disequilibrium; dominant; linkage analysis; population admixture; recessive; transmission ID DEPENDENT DIABETES-MELLITUS; DISEQUILIBRIUM; RISK AB Here is presented an approach to testing whether the effect of a candidate gene on a quantitative trait is dominant and for testing whether the effect is recessive, The approach uses parental genotype information in nuclear families to adjust for bias due to population admixture, The approach is applicable regardless of the nature of the sampling, The results of an application of the methods to a candidate mutation for diabetic nephropathy are used for illustration. Copyright (C) 2000 S. Karger AG, Basel. C1 Columbia Univ, Dept Stat, New York, NY 10027 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Rabinowitz, D (reprint author), Columbia Univ, Dept Stat, Math Bldg,Mail Code 4403,Broadway & 120th St, New York, NY 10027 USA. FU NIDDK NIH HHS [DK-41256]; NIGMS NIH HHS [GM5597] NR 9 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PD MAY-JUN PY 2000 VL 50 IS 3 BP 184 EP 188 DI 10.1159/000022912 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 289CB UT WOS:000085600800008 PM 10686498 ER PT J AU Sepulveda, AR Wu, L Ota, H Gutierrrez, O Kim, JG Genta, RM Graham, DY AF Sepulveda, AR Wu, L Ota, H Gutierrrez, O Kim, JG Genta, RM Graham, DY TI Molecular identification of main cellular lineages as a tool for the classification of gastric cancer SO HUMAN PATHOLOGY LA English DT Article DE gastric; carcinoma; molecular; classification; microsatellite; instability; phenotype ID INSTABILITY-ASSOCIATED MUTATIONS; HIGH-RISK POPULATION; MICROSATELLITE INSTABILITY; HELICOBACTER-PYLORI; INTESTINAL-TYPE; ORGANOID DIFFERENTIATION; MUCOUS CELLS; SIALOSYL-TN; CARCINOMA; EXPRESSION AB Gastric carcinomas (GC) are heterogeneous tumors comprising variable amounts of cells of different lineage phenotype, including gastric mucous cells (surface-SMC or gland-GMC) and intestinal cells (IC). The evaluation of tumor behavior has classically depended on strictly morphological classifications of tumors. Microsatellite instability (MSI) is frequently detected in GC, but whether MSI affects all gastric cellular lineages or exclusively occurs in unique cellular lineages in GC is not known. The aims of this study were to test a combination of anti-mucin antibodies to classify gastric cancer into predominant cell lineage phenotype and to determine whether MSI in GC is associated with particular cellular tumor phenotypes. Fifty-five GC were immunophenotyped with antibodies specific for SMC, GMC, or IC. DNA was extracted from tumor and non-neoplastic gastric tissues and amplified with 5 microsatellite markers. A mixed cellular pattern was the most frequent phenotype of GC (61%) and was seen in both glandular (63%) and diffuse (58%)-type tumors. No significant difference in the rate of MSI was found in tumors with predominant gastric, intestinal or mixed phenotype. However, tumors with null or low-level expression of cellular lineage differentiation markers displayed MSI more frequently than tumors with high-level expression (40% v 20%). In conclusion, different gastric carcinoma cell lineage patterns can be easily identified with the 3 immunohistochemical markers used in this study. The 3 main cellular lineage components of gastric cancer can be similarly affected by microsatellite instability, consistent with the notion that MSI is an early event in gastric carcinogenesis. Copyright (C) 2000 by W.B. Saunders Company. C1 Vet Affairs Med Ctr 111D, Dept Med, Houston, TX 77030 USA. Vet Affairs Med Ctr 111D, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Korea Univ, Guro Hosp, Coll Med, Seoul 136701, South Korea. Univ Nacl Colombia, Bogota, Colombia. RP Sepulveda, AR (reprint author), Vet Affairs Med Ctr 111D, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 45 TC 15 Z9 15 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2000 VL 31 IS 5 BP 566 EP 574 DI 10.1053/hp.2000.6684 PG 9 WC Pathology SC Pathology GA 313TE UT WOS:000087014700006 PM 10836295 ER PT J AU Khan, IA MacLean, JA Lee, FS Casciotti, L DeHaan, E Schwartzman, JD Luster, AD AF Khan, IA MacLean, JA Lee, FS Casciotti, L DeHaan, E Schwartzman, JD Luster, AD TI IP-10 is critical for effector T cell trafficking and host survival in Toxoplasma gondii infection SO IMMUNITY LA English DT Article ID SECONDARY LYMPHOID ORGANS; IFN-GAMMA; CHEMOKINE RECEPTOR; DIFFERENTIAL EXPRESSION; MULTIPLE-SCLEROSIS; INTERFERON-GAMMA; GENE-EXPRESSION; MICE; LYMPHOCYTES; IMMUNITY AB The generation of an adaptive immune response against intracellular pathogens requires the recruitment of effector T cells to sites of infection. Here we show that the chemokine IP-10, a specific chemoattractant for activated T cells, controls this process in mice naturally infected with Toxoplasma gondii. Neutralization of IP-10 in infected mice inhibited the massive influx of T cells into tissues and impaired antigen-specific T cell effector functions. This resulted in >1000-fold increase in tissue parasite burden and a marked increase in mortality compared to control antibody-treated mice. These observations suggest that IP-10 may play a broader role in the localization and function of effector T cells at sites of Th1 inflammation. C1 Harvard Univ, Massachusetts Gen Hosp, AIDS Res Ctr, Sch Med,Allergy & Immunol Unit,Infect Dis Unit, Boston, MA 02114 USA. Dartmouth Med Ctr, Dept Med, Hanover, NH 03755 USA. Dartmouth Med Ctr, Dept Pathol, Hanover, NH 03755 USA. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, AIDS Res Ctr, Sch Med,Allergy & Immunol Unit,Infect Dis Unit, Boston, MA 02114 USA. FU NCI NIH HHS [CA69212]; NIAID NIH HHS [AI33325, AI46999] NR 48 TC 185 Z9 196 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2000 VL 12 IS 5 BP 483 EP 494 DI 10.1016/S1074-7613(00)80200-9 PG 12 WC Immunology SC Immunology GA 319RT UT WOS:000087356400004 PM 10843381 ER PT J AU Exley, M Garcia, J Wilson, SB Spada, F Gerdes, D Tahir, SMA Patton, KT Blumberg, RS Porcelli, S Chott, A Balk, SP AF Exley, M Garcia, J Wilson, SB Spada, F Gerdes, D Tahir, SMA Patton, KT Blumberg, RS Porcelli, S Chott, A Balk, SP TI CD1d structure and regulation on human thymocytes, peripheral blood T cells, B cells and monocytes SO IMMUNOLOGY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; I-LIKE MOLECULE; POSITIVE SELECTION; ANTIGEN RECEPTOR; ALPHA-CHAIN; MOUSE CD1; EXPRESSION; RECOGNITION; LYMPHOCYTES; SUBSETS AB Human T cells expressing CD161 and an invariant T-cell receptor (TCR) alpha-chain (V alpha 24(invt) T cells) specifically recognize CD1d and appear to have immunoregulatory functions. However, the physiological target cells for this T-cell population, and whether alterations in CD1d expression contribute to the regulation of V alpha 24(invt) T-cell responses, remain to be determined. A series of antibodies were generated to assess CD1d expression, structure and regulation on human lymphoid and myeloid cells. CD1d was expressed at high levels by human cortical thymocytes and immunoprecipitation analyses showed it to be a 48 000-MW glycosylated protein. However, after solubilization, the majority of the thymocyte CD1d protein, but not CD1d expressed by transfected cells, lost reactivity with monoclonal antibodies (mAbs) against native CD1d, indicating that it was alternatively processed. Moreover, thymocytes were not recognized by CD1d-reactive V alpha 24(invt) T-cell clones. Medullary thymocytes and resting peripheral blood T cells were CD1d(-), but low-level CD1d expression was induced on activated T cells. CD1d was expressed by B cells in peripheral blood and lymph node mantle zones, but germinal centres were CD1d(-). Resting monocytes were CD1d(+) but, in contrast to CD1a, b and c, their surface expression of CD1d was not up-regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) activation. These results demonstrate constitutive CD1d expression by human professional antigen-presenting cells and that post-translational processing of CD1d may contribute to regulation of the activity of CD1d-specific T cells. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Lymphocyte Biol Sect, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Univ Vienna, Dept Clin Pathol, A-1010 Vienna, Austria. RP Balk, SP (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, HIM Bldg Room 1047,330 Brookline Ave, Boston, MA 02215 USA. FU NIAID NIH HHS [R01 AI045051, R01AI3319, R01AI42955]; NIDDK NIH HHS [R37 DK044319, R01 DK044319, DK44319, R01 DK051362] NR 43 TC 116 Z9 118 U1 0 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAY PY 2000 VL 100 IS 1 BP 37 EP 47 DI 10.1046/j.1365-2567.2000.00001.x PG 11 WC Immunology SC Immunology GA 317DK UT WOS:000087210900006 PM 10809957 ER PT J AU Patel, NJ Bush, RK AF Patel, NJ Bush, RK TI Role of environmental allergens in rhinitis SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID HOUSE DUST MITES; FEL-D-I; LABORATORY-ANIMAL ALLERGY; CAT-ALLERGEN; ASPERGILLUS-FUMIGATUS; ALTERNARIA-ALTERNATA; MOLECULAR-CLONING; POLLEN ALLERGENS; INDOOR ALLERGENS; MAJOR ALLERGEN AB This article reviews the various important aspects of commonly implicated environmental allergens in allergic rhinitis. As evident by the high prevalence of allergic rhinitis in the general population, environmental allergens are among the most common causes of rhinitis. Environmental allergens may be categorized into those that are found in the outdoor environment and those that are found in the indoor environment. Pollens and fungi are the two primary allergen sources in the outdoor environment and most often provoke seasonal symptoms (especially in temperate climates). important indoor allergens include animals, dust mites, and fungi, which are usually present perennially, and commonly produce chronic symptoms. Environmental control measures should be considered in the treatment of allergic rhinitis; however, given the enormous distribution of many allergens, they are often difficult to carry out. C1 William S Middleton Mem Vet Hosp, Dept Allergy & Immunol, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Allergy & Immunol Sect, Madison, WI USA. RP Bush, RK (reprint author), William S Middleton Mem Vet Hosp, Dept Allergy & Immunol, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 81 TC 6 Z9 6 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 2000 VL 20 IS 2 BP 323 EP + DI 10.1016/S0889-8561(05)70151-X PG 32 WC Allergy; Immunology SC Allergy; Immunology GA 319WD UT WOS:000087365600006 ER PT J AU Bonanno, E Iurlaro, M Madri, JA Nicosia, RF AF Bonanno, E Iurlaro, M Madri, JA Nicosia, RF TI Type IV collagen modulates angiogenesis and neovessel survival in the rat aorta model SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE endothelium; basement membrane; elongation; proliferation; stabilization ID ENDOTHELIAL GROWTH-FACTOR; BASEMENT-MEMBRANE; EXTRACELLULAR-MATRIX; CELL PROLIFERATION; IN-VITRO; INVITRO; LAMININ; METALLOPROTEINASES; DIFFERENTIATION; MICROVESSELS AB Type IV collagen is a major basement membrane component that has been implicated in the regulation of angiogenesis. The purpose of this study was to evaluate the effect of type IV collagen an the angiogenic response of native endothelial cells in three-dimensional vascular organ culture. Rings of rat aorta were cultured under serum-free conditions in gels of type I collagen with or without type IV collagen. In the absence of type IV collagen, aortic rings generated neovessels, which proliferated until day 9 and gradually regressed during the second and third weeks of culture. Type IV collagen promoted neovessel elongation and survival in a dose-dependent manner. Microvascular length increased by 43, 57, and 119% over control values in cultures treated with 3, 30, and 300 mu g/ml type IV collagen, respectively. When used at high concentrations (300 mu g/ml) type TV collagen stabilized the neovascular outgrowths and prevented vascular regression. Type IV collagen also promoted the formation of neovessels, but significant stimulatory effects were observed only at an intermediate concentration (30 mu g/ml) and were no longer significant at the high concentration (300 mu g/ml). The observation that type IV collagen has dose-dependent effects on vascular elongation, proliferation, and stabilization, supports the concept that the developing basement membrane of neovessels acts as a solid-phase regulator of angiogenesis, whose function varies depending on the concentration of its molecular components. C1 VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Lab S 113, Diagnost Serv, Seattle, WA 98108 USA. Univ Roma Tor Vergata, Dept Surg, Rome, Italy. Univ Bari, Dept Biomed Sci & Human Oncol, Bari, Italy. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Nicosia, RF (reprint author), VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Lab S 113, Diagnost Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. OI bonanno, elena/0000-0002-0222-0141 FU NHLBI NIH HHS [HL52585] NR 35 TC 42 Z9 43 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD MAY PY 2000 VL 36 IS 5 BP 336 EP 340 PG 5 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 341NP UT WOS:000088596700011 PM 10937837 ER PT J AU Hellman, J Loiselle, PM Tehan, MM Allaire, JE Boyle, LA Kurnick, JT Andrews, DM Kim, KS Warren, HS AF Hellman, J Loiselle, PM Tehan, MM Allaire, JE Boyle, LA Kurnick, JT Andrews, DM Kim, KS Warren, HS TI Outer membrane protein A, peptidoglycan-associated lipoprotein, and murein lipoprotein are released by Escherichia coli bacteria into serum SO INFECTION AND IMMUNITY LA English DT Article ID GRAM-NEGATIVE BACTERIA; ENDOTOXIN-ASSOCIATED PROTEIN; CELL-ENVELOPE; SALMONELLA-TYPHIMURIUM; OMPA PROTEIN; CYTOKINE PRODUCTION; SEPTIC SHOCK; LIPOPOLYSACCHARIDE; ANTIBODIES; MUTANT AB Complexes containing lipopolysaccharide (LPS) and three outer membrane proteins (OMPs) are released by gram-negative bacteria incubated in human serum and into the circulation in an experimental model of sepsis. The same OMPs are bound by immunoglobulin G (IgG) in the cross-protective antiserum raised to Escherichia coli J5 (anti-J5 IgG). This study was performed to identify the three OMPs. The 35-kDa OMP was identified as outer membrane protein A (OmpA) by immunoblotting studies using OmpA-deficient bacteria and recombinant OmpA protein. The 18-kDa OMP was identified as peptidoglycan-associated lipoprotein (PAL) based on peptide sequences from the purified protein and immunoblotting studies using PAL-deficient bacteria. The 5- to 9-kDa OMP was identified as murein lipoprotein (MLP) based on immunoblotting studies using MLP-deficient bacteria. The studies identify the OMPs released into human serum and into the circulation in an experimental model of sepsis as OmpA, PAL, and MLP. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. RP Hellman, J (reprint author), Infect Dis Unit, 5th Floor,149 13th St, Charlestown, MA 02129 USA. EM hellman@etherdome.mgh.harvard.edu FU NIAID NIH HHS [AI39617-02] NR 69 TC 49 Z9 51 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 MAY PY 2000 VL 68 IS 5 BP 2566 EP 2572 DI 10.1128/IAI.68.5.2566-2572.2000 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 305ZX UT WOS:000086572600024 PM 10768945 ER PT J AU Taubman, MA Smith, DJ Holmberg, CJ Eastcott, JW AF Taubman, MA Smith, DJ Holmberg, CJ Eastcott, JW TI Coimmunization with complementary glucosyltransferase peptides results in enhanced immunogenicity and protection against dental caries SO INFECTION AND IMMUNITY LA English DT Article ID MUTANS STREPTOCOCCAL GLUCOSYLTRANSFERASE; GLUCAN-BINDING DOMAIN; B-CELL EPITOPES; IMMUNOLOGICAL CHARACTERISTICS; SITE PEPTIDE; ACTIVE-SITE; SOBRINUS; SEQUENCES; SUCROSE; IMMUNIZATION AB Peptide constructs from the catalytic (CAT) and glucan-binding (GLU) regions of the mutans streptococcal glucosyltransferase enzymes (GTF) can provide immunity to dental caries infection. A strategy of coimmunization was tested to determine whether protection could be enhanced. Rats were immunized with one of the previously described peptide constructs from the CAT or GLU region of the GTF of mutans streptococci or coimmunized with a combination of these constructs (CAT-GLU). Coimmunized animals demonstrated significantly higher serum immunoglobulin G (IgG) and salivary IgA antibody levels to CAT or GTF than rats immunized with either construct alone, To assess the functional significance of coimmunization with these constructs, animals were immunized as above or with Streptococcus sobrinus GTF and then infected with S. sobrinus to explore the effects of immunization on immunological, microbiological, and disease (dental caries) parameters. Serum antibody from the communized group inhibited S. sobrinus GTF-mediated insoluble glucan synthesis in vitro above that of the individual-construct-immunized groups. Immunization with CAT or GLU constructs resulted in significantly reduced dental caries after infection with S. sobrinus compared with sham-immunized animals. Coimmunization produced greater reductions in caries than after immunization with either CAT or GLU. Also, significant elevations in lymphocyte proliferative responses to CAT, GLU, and GTF were observed after coimmunization with CAT-GLU compared with the responses after immunization with the individual constructs. The results suggested that increased numbers of memory T cells, which could proliferate to CAT were generated by coimmunization. The experiments support the functional significance of these GTF domains in dental caries pathogenesis and present coimmunization as a simple alternative to intact GTF to enhance protective immunity against cariogenic microorganisms. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Taubman, MA (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [R56 DE004733, R01 DE004733, DE04733] NR 35 TC 20 Z9 25 U1 2 U2 2 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 MAY PY 2000 VL 68 IS 5 BP 2698 EP 2703 DI 10.1128/IAI.68.5.2698-2703.2000 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 305ZX UT WOS:000086572600041 PM 10768962 ER PT J AU Murley, YM Behari, J Griffin, R Calderwood, SB AF Murley, YM Behari, J Griffin, R Calderwood, SB TI Classical and El Tor biotypes of Vibrio cholerae differ in timing of transcription of tcpPH during growth in inducing conditions SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI; REGULATORY GENE; TOXR REGULON; ARAC FAMILY; VIRULENCE; PROTEIN; EXPRESSION; ACTIVATION; STRAINS; PROMOTER AB Two protein pairs in Vibrio cholerae, ToxRS and TcpPH, are necessary for transcription from the toxT promoter and subsequent expression of cholera virulence genes. We have previously shown that transcription of tcpPH in classical strains of V. cholerae is activated at mid-log-phase growth in ToxR-inducing conditions, while transcription of tcpPH in El Tor strains is not. In this study, we showed that while transcription of tcpPH differs at mid-log-phase growth in ToxR-inducing conditions between the biotypes, transcription is equivalently high during growth in AKI conditions. We used tcpPH::gusA transcriptional fusions to quantitate expression of tcpPH in each biotype throughout growth in ToxR-inducing conditions and shelved that although transcription of tcpPH. is reduced at mid-log-phase growth in an El Tor strain, transcription is turned on later in growth to levels in excess of those in the classical strain (although cholera toxin is not produced). This suggests that the difference in expression of cholera virulence factors in response to ToxR-inducing conditions between the El Tor and classical biotypes of V. cholerae mag. be related to the timing of transcription of tcpPH rather than the absolute Levels of transcription. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI44487, T32 AI007061, T32 AI07061] NR 30 TC 17 Z9 18 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 MAY PY 2000 VL 68 IS 5 BP 3010 EP 3014 DI 10.1128/IAI.68.5.3010-3014.2000 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 305ZX UT WOS:000086572600084 PM 10769005 ER PT J AU Mizoguchi, E Mizoguchi, A Preffer, FI Bhan, AK AF Mizoguchi, E Mizoguchi, A Preffer, FI Bhan, AK TI Regulatory role of mature B cells in a murine model of inflammatory bowel disease SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE adoptive transfer; B cells; colitis; knockout mice; TCR ID ALPHA-MUTANT MICE; T-CELLS; AUTOIMMUNE ENCEPHALOMYELITIS; INTERFERON-GAMMA; TRANSGENIC MICE; CHRONIC COLITIS; RECEPTOR; RESPONSES; DEFICIENT; ANTIGEN AB The spontaneous chronic colitis in TCR a mutant (TCR alpha(-/-)) mice mediated by CD4(+) TCR alpha(-)beta(+) T cells is more severe in the absence of mature B cells, suggesting a suppressive role of B cells and Ig in the development of chronic colitis. To investigate the direct role of B cells in the suppression of this colitis, cell transfer studies were performed in TCR alpha(-/-) x 1g mu(-/-)(alpha mu(-/-)) double-mice after the adoptive knockout mice. The chronic colitis was markedly attenuated in alpha mu(-/-) transfer of peripheral B cells from TCR alpha(-/-) mice into 3- to 4-week-old alpha mu(-/-) mice prior to the development of colitis. Furthermore, transfer of mature B cells from TCR alpha(-/-) mice markedly alpha mu(-/-) mice with established decreased the number of pathogenic colonic CD4(+) TCR alpha(-)beta(+) T cells in alpha mu(-/-) colitis. This B cell effect required the presence of functional co-stimulatory molecules CD40 and B7-2 (CD86) but not B7-1 (CD80). These results indicate that mature B cells play an important role in the development of chronic colitis in TCR alpha(-/-) mice by directly regulating the pathogenic T cells (CD4(+) TCR alpha(-)beta(+) T cells). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Bhan, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 100 Blossom St,Cox 5, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351, DK47677] NR 34 TC 108 Z9 115 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 2000 VL 12 IS 5 BP 597 EP 605 DI 10.1093/intimm/12.5.597 PG 9 WC Immunology SC Immunology GA 315TM UT WOS:000087129100002 PM 10784605 ER PT J AU Solvason, N Wu, WW Parry, D Mahony, D Lam, EWF Glassford, J Klaus, GGB Sicinski, P Weinberg, R Liu, YJ Howard, M Lees, E AF Solvason, N Wu, WW Parry, D Mahony, D Lam, EWF Glassford, J Klaus, GGB Sicinski, P Weinberg, R Liu, YJ Howard, M Lees, E TI Cyclin D2 is essential for BCR-mediated proliferation and CD5 B cell development SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE anti-Ig; B1B cells; B-CLL; cell cycle; chronic lymphocytic leukemia ID ANTI-IMMUNOGLOBULIN; T-CELL; EXPRESSION; LYMPHOCYTES; DIFFERENTIATION; ANTIBODIES; ACTIVATION; PROTEINS; LACKING; OVEREXPRESSION AB Progression into G(1) in a lymphocytes is regulated by cyclins D2 and D3, components of the cell cycle machinery currently believed to have overlapping and potentially redundant roles in cell cycle control. To study the specific role of cyclin D2 in a lymphocyte proliferation, we examined a cells from cyclin D2(-/-) mice and demonstrate a specific requirement for cyclin D2 in BCR- but not CD40- or lipopolysaccharide-induced proliferation. Furthermore, conventional a cell development proceeds normally in the mutant mice; however, the CD5 B cell compartment is dramatically reduced, suggesting that cyclin D2 is important in CD5 a cell development as well as antigen-dependent B cell clonal expansion. C1 DNAX Res Inst Mol & Cellular Biol Inc, Dept Cell Signaling, Palo Alto, CA 94304 USA. DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunol, Palo Alto, CA 94304 USA. Univ London Imperial Coll Sci Technol & Med, Ludwig Inst Canc Res, London W2, England. Univ London Imperial Coll Sci Technol & Med, Virol & Cell Biol Sect, London W2, England. Natl Inst Med Res, London NW7, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Lees, E (reprint author), DNAX Res Inst Mol & Cellular Biol Inc, Dept Cell Signaling, 901 Calif Ave, Palo Alto, CA 94304 USA. NR 41 TC 92 Z9 97 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 2000 VL 12 IS 5 BP 631 EP 638 DI 10.1093/intimm/12.5.631 PG 8 WC Immunology SC Immunology GA 315TM UT WOS:000087129100006 PM 10784609 ER PT J AU Egan, CL Liu, V Harris, RM White, SM Lessin, SR Weinberg, JM AF Egan, CL Liu, V Harris, RM White, SM Lessin, SR Weinberg, JM TI Linear IgA disease associated with membranous glomerulonephropathy SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID TARGET ANTIGENS; BULLOUS DERMATOSIS AB A 33-year-old Caucasian man developed an acute nephrotic syndrome with a proteinuria of 15 g/day. His past medical history was significant for a cholecystectomy secondary to complications of hypercholesterolemia, and his medications included niacinamide, simvastatin, and multivitamins. A renal biopsy revealed a membranous glomerulonephropathy, with thickening of the capillary loops by light microscopy and 4+ granular immunoglobulin G (IgG) staining of the capillary loops by immunofluorescence. Multiple discrete subepithelial deposits were also noted by electron microscopy. He was treated with cyclophosphamide, chlorambucil, and high dose steroids. Laboratory data at that time were notable for an elevated erythrocyte sedimentation rate (ESR), decreased albumin, a negative antinuclear antibody, and normal complement levels. His symptoms improved, and the proteinuria stabilized to 7 g/day. His systemic therapy was discontinued without a flare in his renal disease. Approximately 9 months later, he developed a pruritic, blistering eruption which began on his face and neck. An initial skin biopsy showed a subepidermal blister with many eosinophils and eosinophilic spongiosis. A direct immunofluorescence (DIF) study revealed linear deposits of IgG and IgA, and focally linear C3 at the basement membrane zone. This pattern was interpreted to be most consistent with bullous pemphigoid. He was referred to the Philadelphia VA Medical Center for further evaluation and treatment. Cutaneous examination revealed multiple urticarial plaques with tense bullae studding the peripheral margin, in a rosette pattern, distributed on his face, trunk, groin, extremities, and feet, with one healing erosion on the hard palate. Laboratory data revealed abnormal, but stable, renal disease, with an elevated blood urea nitrogen (21.1) and creatinine (1.5). Serum IgA was elevated (400), and serum albumin (3.3) and a total protein (5.5) were decreased. A second skin biopsy from a blister edge demonstrated a subepidermal bulla with numerous eosinophils and collections of neutrophils at the dermal papillae tips (Fig. 1). DIF revealed 3+ linear IgA deposition at the basement membrane zone (Fig. 2), and an indirect immunofluorescence study on monkey esophagus showed linear IgA deposition in the basement membrane zone. A diagnosis of linear IgA disease was made. Dapsone 50 mg p.o. daily was started, with a dramatic improvement on his blistering within 2 weeks. His renal disease remained stable. C1 New York Med Coll, Metropolitan Hosp Ctr, Dept Dermatol, New York, NY 10029 USA. Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Weinberg, JM (reprint author), New York Med Coll, Metropolitan Hosp Ctr, Dept Dermatol, 1901 1st Ave, New York, NY 10029 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD MAY PY 2000 VL 39 IS 5 BP 379 EP 382 DI 10.1046/j.1365-4362.2000.00841-6.x PG 4 WC Dermatology SC Dermatology GA 319JY UT WOS:000087338800015 PM 10849404 ER PT J AU Sharkansky, EJ King, DW King, LA Wolfe, J Erickson, DJ Stokes, LR AF Sharkansky, EJ King, DW King, LA Wolfe, J Erickson, DJ Stokes, LR TI Coping with Gulf War combat stress: Mediating and moderating effects SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID MALE VIETNAM VETERANS; TRAUMA-RELATED GUILT; POSTTRAUMATIC-STRESS; SOCIAL SUPPORT; LIFE EVENTS; PERITRAUMATIC DISSOCIATION; MENTAL-HEALTH; PREDICTORS; DISORDER; FEMALE AB The authors examined relationships between method of coping with combat-related stress and psychological symptoms among Gulf War Army personnel (N = 1,058). Participants were surveyed on return From the Gulf region (Time 1) with the Coping Responses Inventory (R. Moos, 1990) and a measure of combat exposure. Outcomes were symptom measures of postraumatic stress disorder (PTSD) and depression. At Time 2 (18-24 months) participants completed the same symptom measures and an index of postwar stress. Higher proportions of approach-based coping in the war zone were related to lower levels of psychological symptoms. Combat exposure moderated the effects of coping on Time 1 PTSD. Coping predicted changes in symptoms of depression but not PTSD. Combat exposure affected changes in depression through postwar stress but had a direct negative effect on PTSD. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div 116B 3, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. RP Sharkansky, EJ (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div 116B 3, 150 S Huntington Ave, Boston, MA 02130 USA. NR 53 TC 80 Z9 80 U1 6 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2000 VL 109 IS 2 BP 188 EP 197 DI 10.1037//0021-843X.109.2.188 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 328ZA UT WOS:000087880600002 PM 10895556 ER PT J AU Seidman, LJ Biederman, J Monuteaux, MC Weber, W Faraone, SV AF Seidman, LJ Biederman, J Monuteaux, MC Weber, W Faraone, SV TI Neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; OSTERRIETH COMPLEX FIGURE; QUANTITATIVE MORPHOLOGY; SUSTAINED ATTENTION; EXECUTIVE FUNCTIONS; CAUDATE-NUCLEUS; CORPUS-CALLOSUM; ADHD; PERFORMANCE; COMORBIDITY AB The goal of this study was to assess neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder (ADHD). Participants were 156 siblings of ADHD probands with (N = 40) and without (N = 116) ADHD (according to criteria of the Diagnostic and Statistical Manual of Mental Disorders (3rd edition, revised; American Psychiatric Association, 1987) and 118 siblings of non-ADHD normal controls of similar age, IQ, and grade level. Information on attention, executive, and memory functions was obtained in a standardized manner without knowledge of clinical status. Compared with siblings of controls, siblings with ADHD were significantly impaired on the Stroop test and on verbal learning and memory. In contrast, siblings without ADHD were similar to controls on virtually all measures. These data suggest that some executive. attention, and verbal learning deficits are found in nonreferred individuals with ADHD but that neuropsychological deficits are unlikely to constitute an endophenotype to ADHD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit ACC725,Dept Psychiat, Boston, MA 02114 USA. Massachusetts Mental Hlth Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Publ Hlth, Dept Psychiat, Cambridge, MA 02138 USA. McLean Hosp, Belmont, MA 02178 USA. RP Biederman, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit ACC725,Dept Psychiat, Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01MH-41314] NR 70 TC 69 Z9 71 U1 4 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2000 VL 109 IS 2 BP 252 EP 265 DI 10.1037//0021-843X.109.2.252 PG 14 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 328ZA UT WOS:000087880600009 PM 10895563 ER PT J AU Fones, CSL Pollack, MH Susswein, L Otto, M AF Fones, CSL Pollack, MH Susswein, L Otto, M TI History of childhood attention deficit hyperactivity disorder (ADHD) features among adults with panic disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE attention deficit hyperactivity disorder (ADHD); childhood anxiety; comorbidity; panic disorder ID ANXIETY DISORDERS; RISK-FACTORS; PSYCHIATRIC STATUS; MAJOR DEPRESSION; DOUBLE-BLIND; CHILDREN; COMORBIDITY; FAMILY; SYMPTOMS; SAMPLE AB Background: The prevalence of ADHD features during childhood and its relationship to the course and presentation of panic in adults with panic disorder was examined. Methods: The presence of DSM-III-R ADHD was retrospectively ascertained in a cohort of 85 adults with panic disorder by structured interview. Results: Childhood ADHD features occurred in 23.5% of panic subjects; 9.4% satisfied full DSM-III-R criteria for ADHD, 14.1% had 'subthreshold' diagnoses. Two-thirds of panic patients with ADHD indicated persistence of symptoms into adulthood. Fewer had married or completed college than those with panic alone. There was no significant difference in clinical pattern and severity of panic, or comorbidity of adult Axis I and childhood anxiety disorders in both groups. Conclusion: Given its frequency and persistence, ADHD comorbidity is an important clinical consideration in all panic patients. Its co-occurrence does not influence the clinical pattern of panic, but may contribute to adverse social outcome. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Natl Univ Singapore, Dept Psychol Med, Singapore 117548, Singapore. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, 15 Parkman St,ACC 815, Boston, MA 02114 USA. NR 60 TC 25 Z9 25 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 MAY PY 2000 VL 58 IS 2 BP 99 EP 106 DI 10.1016/S0165-0327(99)00065-8 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 316FK UT WOS:000087156800002 PM 10781699 ER PT J AU Wong, JT Nagy, CS Krinzman, SJ MacLean, JA Bloch, KJ AF Wong, JT Nagy, CS Krinzman, SJ MacLean, JA Bloch, KJ TI Rapid oral challenge-desensitization for patients with aspirin-related urticaria-angioedema SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE aspirin; acetylsalicylic acid; nonsteroidal anti-inflammatory drug; urticaria; angioedema; desensitization; coronary artery disease ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BRONCHIAL BIOPSIES; SENSITIVE PATIENTS; INDUCED ASTHMA; HYPERSENSITIVITY; PATHOGENESIS; TICLOPIDINE; SYNTHASE; IGE AB Background: Acetylsalicylic acid (ASA), commonly known as aspirin, is indicated in the treatment of coronary artery disease (CAD). Many patients are denied treatment with ASA because of a history of ASA or nonsteroidal anti-inflammatory drug (NSAID)-induced urticaria or angioedema. Objective: We sought to develop a safe and practical protocol to allow the administration of ASA to patients with a history of ASA- or NSAID-induced urticaria-angioedema. Methods: Eleven subjects with a history of ASA- or NSAID-induced urticaria-angioedema were challenged-desensitized by oral protocols based on rapidly escalating doses of ASA. Most had CAD, one had a history of pulmonary embolism, and one had refractory chronic sinusitis and asthma. Starting doses ranged from 0.1 to 10 mg and were administered at intervals of 10 to 30 minutes. Dosing was individualized for each patient but followed this general sequence (in milligrams): 0.1, 0.3, 1, 3, 10, 20,40, 81, 162, 325. Results: Nine patients tolerated the procedure without adverse effects and continued taking ASA for periods ranging from 1 to 24 months, without development of urticaria or angioedema. A patient who had a history of chronic idiopathic urticaria in addition to aspirin-induced urticaria had chest tightness during the protocol. Another patient who had continuing urticaria and angioedema associated with antithyroid antibodies developed angioedema several hours after completing the protocol. Conclusion: In patients with historical ASA- or NSAID-induced urticaria-angioedema reactions but who did not have urticaria and angioedema independent of ASA/NSAID, rapid oral challenge-desensitization to ASA was performed safely and permitted patients with CAD and other diseases to receive treatment with ASA. C1 Massachusetts Gen Hosp, Clin Immunol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Allergy Unit, Boston, MA 02114 USA. RP Wong, JT (reprint author), Massachusetts Gen Hosp, Clin Immunol Unit, Bulfinch 422, Boston, MA 02114 USA. NR 24 TC 72 Z9 73 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 MAY PY 2000 VL 105 IS 5 BP 997 EP 1001 DI 10.1067/mai.2000.104571 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 316TW UT WOS:000087185000020 PM 10808182 ER PT J AU Perell, KL Gregor, RJ Scremin, AME AF Perell, KL Gregor, RJ Scremin, AME TI Bicycle pedal kinetics following force symmetry feedback training in subjects with unilateral cerebrovascular accident SO JOURNAL OF APPLIED BIOMECHANICS LA English DT Article DE cycling; hemiplegia; biomechanics; cerebral vascular disorders; asymmetry; feedback ID ELECTROMYOGRAPHIC FEEDBACK; BIOFEEDBACK; ERGOMETER; MECHANICS AB The purpose of this study was to compare individual pedal reaction force components following bicycle training with and without effective force feedback in subjects with unilateral cerebrovascular accident (CVA). Eight ambulatory subjects with CVA were studied on a recumbent bicycle equipped with custom-built pedals, which measure normal and tangential components of the load applied to the pedal surface. Comparisons of normal and tangential pedal reaction forces were made following 1 month of bicycle training (3 times/week for 3 weeks) during retention tests performed without feedback. The ratios of involved to contralateral (I/C ratios) force parameters were used to assess symmetry. Subjects were randomly assigned to 2 groups: (a) a feedback group that received visual/verbal. feedback regarding Effective force patterns, bilaterally, after each trial; and (b) a no-feedback group that received no feedback. Two critical results were found: (a) tangential pedal forces were significantly more posteriorly directed bilaterally following training across all subjects, but the change war; greater for the no-feedback group relative to the feedback group, and (b) effective force feedback training did net demonstrate improvements in the I/C ratios above that of the control group. A more posteriorly applied tangential pedal force may represent increased dorsiflexion and may suggest that bicycle training facilitated ankle control. The cyclical nature of cycling, however, may allow for natural patterns to develop without feedback or may require less frequent use of feedback based on retention test performance. C1 W LA Healthcare Ctr, VA Greater LA Healthcare Syst, Phys Med & Rehabil Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, PM&R Div, Los Angeles, CA 90024 USA. Mt St Marys Coll, Dept Phys Therapy, Los Angeles, CA 90049 USA. Georgia Inst Technol, Dept Hlth & Performance Sci, Atlanta, GA 30332 USA. RP Perell, KL (reprint author), W LA Healthcare Ctr, VA Greater LA Healthcare Syst, Phys Med & Rehabil Serv, Los Angeles, CA 90073 USA. NR 22 TC 2 Z9 2 U1 1 U2 2 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1065-8483 J9 J APPL BIOMECH JI J. Appl. Biomech. PD MAY PY 2000 VL 16 IS 2 BP 124 EP 141 PG 18 WC Engineering, Biomedical; Sport Sciences SC Engineering; Sport Sciences GA 316UM UT WOS:000087186500002 ER PT J AU Deem, S Berg, JT Kerr, ME Swenson, ER AF Deem, S Berg, JT Kerr, ME Swenson, ER TI Effects of the RBC membrane and increased perfusate viscosity on hypoxic pulmonary vasoconstriction SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE anemia; nitric oxide; hypoxia; red blood cells ID NITRIC-OXIDE GENERATION; ISOLATED RAT LUNGS; VASCULAR-RESISTANCE; METHYLENE-BLUE; RABBIT LUNGS; BLOOD; ENDOTHELIUM; HEMOGLOBIN; CELLS; SCAVENGE AB Red blood cells (RBCs) augment hypoxic pulmonary vasoconstriction (HPV) in part by scavenging of nitric oxide (NO) by Hb (Deem 8, Swenson ER, Alberts MK, Hedges RG, and Bishop MJ, Am J Respir Grit Care Med 157: 1181-1186, 1998). We studied the contribution of the RBC compartmentalization of Hb to augmentation of HPV and scavenging of NO in isolated perfused rabbit lungs. Lungs were initially perfused with buffer; HPV was provoked by a 5-min challenge with hypoxic gas (inspired O-2 fraction 0.05). Expired NO was measured continuously. Addition of free Hb to the perfusate (0.25 mg/ml) resulted in augmentation of HPV and a fall in expired NO that were similar in magnitude to those associated with a hematocrit of 30% (intracellular Hb of 100 mg/ml). Addition of dextran resulted in a blunting of HPV after free Hb but no change in expired NO. Blunting of HPV by dextran was not prevented by NO synthase inhibition with N-omega-nitro-L-arginine and/or cyclooxygenase inhibition. RBC ghosts had a mild inhibitory effect on HPV but caused a small reduction in expired NO. In conclusion, the RBC membrane provides a barrier to NO scavenging and augmentation of KPV by Hb. Increased perfusate viscosity inhibits HPV by an undetermined mechanism. C1 Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Deem, S (reprint author), Harborview Med Ctr, Dept Anesthesiol, Box 359724,325 9th Ave, Seattle, WA 98104 USA. FU NHLBI NIH HHS [HL03796, HL45571] NR 37 TC 14 Z9 14 U1 0 U2 2 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 MAY PY 2000 VL 88 IS 5 BP 1520 EP 1528 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 313DL UT WOS:000086985000003 PM 10797107 ER PT J AU Watnick, P Kolter, R AF Watnick, P Kolter, R TI Biofilm, city of microbes SO JOURNAL OF BACTERIOLOGY LA English DT Review ID PSEUDOMONAS-AERUGINOSA BIOFILM; SIGNAL-TRANSDUCTION PROTEIN; CHITIN-BINDING PROTEINS; IN-SITU HYBRIDIZATION; CHOLERAE EL-TOR; GENE-EXPRESSION; BACTERIAL BIOFILMS; ESCHERICHIA-COLI; EXOPOLYSACCHARIDE PRODUCTION; CAULOBACTER-CRESCENTUS C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Kolter, R (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, 200 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [K08 AI001588] NR 50 TC 634 Z9 682 U1 23 U2 161 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2000 VL 182 IS 10 BP 2675 EP 2679 DI 10.1128/JB.182.10.2675-2679.2000 PG 5 WC Microbiology SC Microbiology GA 309JE UT WOS:000086764100001 PM 10781532 ER PT J AU Holgado, R Haire, H Ross, D Sprague, S Pahl, M Jara, A Martin-Malo, A Rodriguez, M Almaden, Y Felsenfeld, AJ AF Holgado, R Haire, H Ross, D Sprague, S Pahl, M Jara, A Martin-Malo, A Rodriguez, M Almaden, Y Felsenfeld, AJ TI Effect of a low calcium dialysate on parathyroid hormone secretion in diabetic patients on maintenance hemodialysis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE calcium; diabetes; hemodialysis; parathyroid hormone; renal osteodystrophy ID ADYNAMIC BONE-DISEASE; SET-POINT; SECONDARY HYPERPARATHYROIDISM; APLASTIC OSTEODYSTROPHY; PROXIMAL CALCIPHYLAXIS; RENAL OSTEODYSTROPHY; CAPD PATIENTS; PREDIALYSIS; ALUMINUM; PTH AB Diabetic patients on maintenance dialysis often are characterized by a relative parathyroid hormone (PTH) deficiency and a form of renal osteodystrophy with low bone turnover known as adynamic bone. The goal of the present study was to determine whether a reduction in the dialysate calcium concentration would increase the predialysis (basal) PTH and maximal PTH level. Thirty-three diabetic maintenance hemodialysis patients with basal PTH values less than 300 pg/ml were randomized to be dialyzed with either a regular (3.0 mEq/liter or 3.5 mEq/liter, group I) or low (2.25 mEq/liter or 2.5 mEq/liter, group II) calcium dialysate for 1 year. At baseline and after 6 months and 12 months of study, low (1 mEq/liter) and high (4 mEq/liter) calcium dialysis studies were performed to determine parathyroid function. At baseline, basal (I, 126 +/- 20 vs. II, 108 +/- 19 pg/ml) and maximal (I, 269 pg/ml +/- 40 pg/ml vs. II, 342 pg/ml +/- 65 pg/ml) PTH levels were not different. By 6 months, basal (I, 98 +/- 18 vs. II, 200 +/- 34 pg/ml, p = 0.02) and maximal (I, 276 pg/ml +/- 37 pg/ml vs. II, 529 pg/ml +/- 115 pg/ml; p = 0.05) PTH levels were greater in group II. Repeated measures analysis of variance (ANOVA) of the 20 patients who completed the entire 12-month study showed that only in group II patients were basal PTH (p = 0.01), maximal PTH (p = 0.01), and the basal/maximal PTH ratio (p = 0.03) different; by post hoc test, each was greater (p < 0.05) at 6 months and 12 months than at baseline. When study values at 0, 6, and 12 months in all patients were combined, an inverse correlation was present between basal calcium and both the basal/maximal PTH ratio (r = -0.59; p < 0.001) and the basal PTH (r = -0.60; p < 0.001). In conclusion, in diabetic hemodialysis patients with a relative PTH deficiency (1) the use of a low calcium dialysate increases basal and maximal PTH levels, (2) the increased secretory capacity (maximal PTH) during treatment with a low calcium dialysate suggests the possibility of enhanced parathyroid gland growth, and (3) the inverse correlation between basal calcium and both the basal/maximal PTH ratio and the basal PTH suggests that the steady-state PTH level is largely determined by the prevailing serum calcium concentration. C1 Hosp Univ Reina Sofia, Dept Nephrol, Cordoba, Spain. Dialysis Serv Florida, Ft Walton Beach, FL USA. St Francis Hosp, Wichita, KS USA. Univ Chicago, Chicago, IL 60637 USA. Univ Calif Irvine, Irvine, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Hosp Univ Reina Sofia, Unit Invest, Cordoba, Spain. W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, Dept Med, Los Angeles, CA 90073 USA. RP Felsenfeld, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Rodriguez, teresa/H-5452-2011 NR 33 TC 23 Z9 23 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 MAY PY 2000 VL 15 IS 5 BP 927 EP 935 DI 10.1359/jbmr.2000.15.5.927 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 306PR UT WOS:000086605500016 PM 10804023 ER PT J AU Whitfield, JF Morley, P Willick, GE Isaacs, RJ MacLean, S Ross, V Barbier, JR Divieti, P Bringhurst, FR AF Whitfield, JF Morley, P Willick, GE Isaacs, RJ MacLean, S Ross, V Barbier, JR Divieti, P Bringhurst, FR TI Lactam formation increases receptor binding, adenylyl cyclase stimulation and bone growth stimulation by human parathyroid hormone (hPTH)(1-28)NH2 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE parathyroid hormone; osteoporosis; receptors; bone; trabecular ID OVARIECTOMIZED RATS; ANALOGS AB Human parathyroid hormone (1-28)NH2 [hPTH(1-28)NH2] is the smallest of the PTH fragments that can fully stimulate adenylyl cyclase in ROS 17/2 rat osteoblast-like osteosarcoma cells. This fragment has an IC50 of 110 nM for displacing I-125-[Nle(8,18)Tyr(34)]bovine PTH(1-34)NH2 from HKRK B7 porcine kidney cells, which stably express 950,000 human type 1 PTH/PTH-related protein (PTHrP) receptors (PTH1Rs) per cell. It also has an EC50 of 23.9 nM for stimulating adenylyl cyclase in ROS 17/2 cells. Increasing the amphiphilicity of the alpha-helix in the residue 17-28 region by replacing Lys(27) with Leu and stabilizing the helix by forming a lactam between Glu(22) and Lys(26) to produce the [Leu(27)]cyclo(Glu(22)-Lys(26))hPTH(1-28)NH2 analog dramatically reduced the IC50 for displacing I-125-[Nle(8,18),Tyr(34)]bPTH(1-34)NH2 from hPTH1Rs from 110 to 6 nM and dropped the EC50 for adenylyl cyclase stimulation in ROS 17/2 cells from 23.9 to 9.6 nM, These modifications also increased the osteogenic potency of hPTH(1-28)NH2, Thus, hPTH(1-28)NH2 did not significantly stimulate either femoral or vertebral trabecular bone growth in rats when injected daily at a dose of 5 nmol/100 g body weight for 6 weeks, beginning 2 weeks after ovariectomy (OVX), but it strongly stimulated the growth of trabeculae in the cancellous bone of the distal femurs and L5 vertebrae when injected at 25 nmol/100 g body weight. By contrast [Leu(27)]cyclo(Glu(22)-Lys(26))hPTH(1-28)NH2 significantly stimulated trabecular bone growth when injected at 5 nmol/100 g of body weight. Thus, these modifications have brought the bone anabolic potency of hPTH(1-28)NH2 considerably closer to the potencies of the larger PTH peptides and analogs. C1 Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. RP Whitfield, JF (reprint author), Natl Res Council Canada, Inst Biol Sci, 100 Sussex Dr, Ottawa, ON K1A 0R6, Canada. NR 14 TC 14 Z9 15 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 MAY PY 2000 VL 15 IS 5 BP 964 EP 970 DI 10.1359/jbmr.2000.15.5.964 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 306PR UT WOS:000086605500021 PM 10804028 ER PT J AU Schulz, JT Sheridan, RL Ryan, CM MacKool, B Tompkins, RG AF Schulz, JT Sheridan, RL Ryan, CM MacKool, B Tompkins, RG TI A 10-year experience with toxic epidermal necrolysis SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Burn-Association CY MAR 23-27, 1999 CL LAKE BUENA VISTA, FLORIDA SP Amer Burn Assoc ID STEVENS-JOHNSON SYNDROME; LYELL SYNDROME; SKIN DISEASES; MANAGEMENT; COMPLICATIONS AB Toxic epidermal necrolysis is a devastating medication-induced desquamation disorder with a reported mortality rate of 30% to 60% in adults. Data from previously reported series suggest that age, delay in referral to a burn center, total body surface area (TBSA) involvement, and systemic steroid treatment are poor prognostic indicators. We reviewed the records of 39 patients treated in our burn center over the past 10 years and found that the mortality rate was significantly correlated with age, thrombocytopenia, and delay in presentation. Steroid treatment and TBSA involvement were not significantly related to the mortality rate. Thirty-nine adult patients with greater than 20% TBSA epithelial necrosis mere cared for in our center from January 1987 to March 1998. Wounds were treated with topical antimicrobial medications and porcine xenografts in a bacteria-controlled nursing unit. We reviewed the records of these patients for 28 clinical characteristics and looked for clinical correlates of mortality by single analysis of variance. The mortality rate was 44% (17 of 39 patients); the cause of death was most commonly multiple-organ dysfunction syndrome, for which a microbial etiologic agent was not always identified. Autopsies were performed on 11 of the 17 patients who died; there was evidence of multiple-organ damage. The patients who survived and the patients who died did not differ significantly in TBSA epithelial necrosis (66% +/- 6% vs 72% +/- 5%, respectively), admission platelets, number of nosocomial infections, number of complications, preadmission exposure to steroids, or extent of mucosal involvement. When compared with the patients who died, the patients who survived were (1) 20 years younger (47.5 +/- 4.2 years vs 64.5 +/- 5.3 years), (2) admitted to the hospital sooner after the onset of their rash (3.5 +/- 0.4 days vs 5.9 +/- 1.0 days), (3) much less likely to experience early thrombocytopenia (platelet nadir, 154 +/- 24 vs 70 +/- 18), (4) more likely to be febrile on presentation, and (5) less Likely to have been treated with antibiotics before referral to our unit. These differences were statistically significant. The most common etiologic agents were antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs. Our results for a group of older patients with toxic epidermal necrolysis with extensive skin involvement suggest that age, delay in hospitalization, thrombocytopenia, and early empiric antibiotic treatment are associated with a poor prognosis. C1 Massachusetts Gen Hosp, Burn Trauma Serv, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Shriners Burns Hosp, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Schulz, JT (reprint author), Massachusetts Gen Hosp, Burn Trauma Serv, Dept Surg, 55 Fruit St,GRB 1302, Boston, MA 02114 USA. NR 25 TC 86 Z9 88 U1 1 U2 3 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 MAY-JUN PY 2000 VL 21 IS 3 BP 199 EP 204 DI 10.1097/00004630-200021030-00004 PG 6 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 318YH UT WOS:000087311900003 PM 10850900 ER PT J AU Kang, SJ Wang, SY Hara, H Peterson, EP Namura, S Amin-Hanjani, S Huang, ZH Srinivasan, A Tomaselli, KJ Thornberry, NA Moskowitz, MA Yuan, JY AF Kang, SJ Wang, SY Hara, H Peterson, EP Namura, S Amin-Hanjani, S Huang, ZH Srinivasan, A Tomaselli, KJ Thornberry, NA Moskowitz, MA Yuan, JY TI Dual role of caspase-11 in mediating activation of caspase-1 and caspase-3 under pathological conditions SO JOURNAL OF CELL BIOLOGY LA English DT Article DE caspase-11; initiator caspase; stroke; middle cerebral artery occlusion; apoptosis ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; CYTOCHROME-C; IL-1-BETA-CONVERTING ENZYME; COMBINATORIAL APPROACH; SIGNALING COMPLEX; MICE DEFICIENT; APOPTOSIS; PROTEASE; ICE; INHIBITION AB Caspase-11,a member of the murine caspase family, has been shown to be an upstream activator of caspase-1 in regulating cytokine maturation. We demonstrate here that in addition to its defect in cytokine maturation, caspase-11-deficient mice have a reduced number of apoptotic cells and a defect in caspase-3 activation after middle cerebral artery occlusion (MCAO), a mouse model of stroke. Recombinant procaspase-11 can autoprocess itself in vitro. Purified active recombinant caspase-11 cleaves and activates procaspase-3 very efficiently. Using a positional scanning combinatorial library method, we found that the optimal cleavage site of caspase-11 was (I/L/V/P)EHD, similar to that of upstream caspases such as caspase-8 and -9. Our results suggest that caspase-11 is a critical initiator caspase responsible for the activation of caspase-3, as well as caspase-1. under certain pathological conditions. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Charlestown, MA 02129 USA. Merck Res Labs, Dept Enzymol, Rahway, NJ 07065 USA. Idun Pharmaceut Inc, La Jolla, CA 92037 USA. RP Yuan, JY (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. RI Moskowitz, Michael/D-9916-2011 NR 35 TC 193 Z9 200 U1 1 U2 8 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 MAY 1 PY 2000 VL 149 IS 3 BP 613 EP 622 DI 10.1083/jcb.149.3.613 PG 10 WC Cell Biology SC Cell Biology GA 310MJ UT WOS:000086831700010 PM 10791975 ER PT J AU Hall, JE Lavoie, HB Marsh, EE Martin, KA AF Hall, JE Lavoie, HB Marsh, EE Martin, KA TI Decrease in gonadotropin-releasing hormone (GnRH) pulse frequency with aging in postmenopausal women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FREE ALPHA-SUBUNIT; FOLLICLE-STIMULATING-HORMONE; HUMAN MENSTRUAL-CYCLE; LUTEINIZING-HORMONE; DEFICIENT MEN; HYPOTHALAMIC FUNCTION; METABOLIC-CLEARANCE; PULSATILE SECRETION; SERUM GONADOTROPINS; LH-SECRETION AB Increasing evidence suggests that aging is associated with dynamic changes in the hypothalamic and pituitary components of the reproductive axis that are independent of changes in gonadal hormone secretion. This study was designed to-determine the effect of age on GnRH pulse frequency in women in the absence of gonadal feedback using gonadotropin free alpha-subunit (FAS) and LH as neuroendocrine markers of endogenous GnRH secretion. All studies were performed in healthy, euthyroid postmenopausal women (PMW) during daytime hours. The impact of sampling interval and duration on assessment of pulse frequency in PMW was first examined in 10 women with a mean age of 61.6 +/- 8 yr (mean +/- SD), in whom blood was sampled every 5 min for 12 h. Each 5-min series was then reduced to simulate a 10-min series and then a 15-min series for pulse analysis, and the effect of 8 h compared with 12 h of sampling was determined. To define the changes in the frequency and amplitude of pulsatile hormone secretion with aging, 11 younger (45-55 yr) and 11 older (70-80 yr) PMW were then studied over 8 h at a 6-min sampling interval. In the initial series, the mean interpulse intervals (IPIs) for FAS were 53.8 +/- 3.6, 69.2 +/- 3.9, and 87.6 +/- 7.3 min at sampling intervals of 5, 10, and 15 min, respectively (P < 0.0005). The LH IPI also increased progressively with sampling intervals of 5, 10, and 15 min (54.4 +/- 2.5, 70.4 +/- 2.3, and 91.1 +/- 4.4 min; P < 0.0001). At the 5-min sampling interval, the calculated number of pulses/24 h was not different between a 12-h series compared with an 8-h series for either FAS or LH. In the second series of studies, the older PMW had lower gonadotropin levels (LH,86.5 +/- 8.8 vs. 51.3 +/- 7.7 IU/L, P < 0.01; FSH, 171.6 +/- 16.9 vs. 108.2 +/- 10.5 IU/L, P < 0.005; FAS, 1021.5 +/- 147.4 vs. 425.6 +/- 89.6 ng/L, P < 0.005, in younger and older PMW, respectively) despite no differences in estrone or estradiol levels. The older PMW also demonstrated a slower FAS pulse frequency compared with their younger counterparts, as reflected in an increased FAS IPI (52.6 +/- 3.1 and 70.6 +/- 5.9 min; P < 0.002). The difference in IPIs between younger and older PMW was not statistically significant for LH (65.4 +/- 5.6 and 71.8 +/- 6.6 min for younger and older PMW, respectively). FAS pulse amplitude was decreased in older PMW compared with younger PMW (431.7 +/- 66.2 vs. 224.6 +/- 81.9 ng/L; P < 0.01), whereas the decrease in LH pulse amplitude with age was of borderline statistical significance (23.2 +/- 3.1 vs. 15.9 +/- 2.1 IU/L; P = 0.09). In conclusion: 1) the use of a 5-min sampling interval and measurement of FAS as the primary marker of GnRH pulse generator activity indicate that GnRH pulse frequency in younger PMW is faster than previously reported, but not increased over that seen in the late follicular phase and midcycle surge in women with intact ovarian function; and 2) the marked decrease in FAS pulse frequency with age provides evidence of age-related changes in the hypothalamic component of the reproductive axis that are independent of changes in gonadal function. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX-5,Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066]; NIA NIH HHS [R01-AG-13241, R01 AG013241]; NICHD NIH HHS [P30-HD-28138] NR 44 TC 58 Z9 63 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2000 VL 85 IS 5 BP 1794 EP 1800 DI 10.1210/jc.85.5.1794 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WZ UT WOS:000088387300011 PM 10843154 ER PT J AU Hanita, M AF Hanita, M TI Self-report measures of patient utility: should we trust them? SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE patient preference; expected utility; measurement; patient self-report; medical decision mailing; cognitive psychology ID DECISION-MAKING; CATEGORY ACCESSIBILITY; IMPRESSION-FORMATION; SOCIAL-PERCEPTION; POSITIVE AFFECT; JUDGMENT; INFORMATION; PREFERENCES; MEMORY; CHOICE AB As self-reports, measures of patient utility are susceptible to the effects of cognitive biases in patients. This article presents often overlooked problems in these measures by outlining cognitive processes involved in patient self-report. It is argued that these measures: 1) require overly complex mental operations: 2) fail to elicit thoughtful response by default; 3) may be biased by patients' mood; 4) are affected by both researchers' choice of measurement instruments and patients' choice of judgment strategies: 5) tend to reflect the disproportionate influence of patients' values that happen to be recallable at the time of measurement: and 6) are affected by patients' fear of regret. It is suggested that solutions for these problems should involve: a) improving the methods of administration; b) developing measures that are less taxing to patients; and c) redefining the concept of patient utility as judged. as opposed to retrieved. evaluation. Published by 2000 Elsevier Science Inc. All rights reserved. C1 Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Hanita, M (reprint author), Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 65 TC 19 Z9 21 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 2000 VL 53 IS 5 BP 469 EP 476 DI 10.1016/S0895-4356(99)00205-X PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 314UG UT WOS:000087075500004 PM 10812318 ER PT J AU Calvo, B Castano, L Marcus-Bagley, D Fici, DA Awdeh, Z Alper, CA AF Calvo, B Castano, L Marcus-Bagley, D Fici, DA Awdeh, Z Alper, CA TI The [HLA-B18, F1C30, DR3] conserved extended haplotype carries a susceptibility gene for IgD deficiency SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE IgD deficiency; MHC; extended haplotype; basques ID MAJOR HISTOCOMPATIBILITY COMPLEX; SERUM; IMMUNODEFICIENCY; COMPLOTYPES; SARDINIANS AB We showed previously that the conserved extended MHC haplotype [HLA-B8 SC01, DR3] carries recessive susceptibility genes for IgA and IgG4 deficiency and dominant genes for IgD and IgG3 deficiency. [HLA-B18: F1C30, DR3] has similar class II and III regions to [HLA-B8, SC01, DR3] and is common in the Basques. We therefore studied serum immunoglobulin concentrations in Basque homozygotes, heterozygotes, and noncarriers of (F1C30, DRB1*0301, DRB3*02, DQA1*0501, DQB1*0201) (FIC30, DR3). As shown by others, no subjects were deficient in IgA, IgM, or Ige subclasses. In contrast, 29% of homozygotes and three of seven double heterozygotes with (SC01, DRB1*0301, DRB3*0101, DQA1*0501, DQB1*0201) (presumed homozygotes for IgD deficiency susceptibility genes) were IgD deficient. Thus, 32% of presumed homozygotes were IgD deficient compared with 1.6% of noncarriers. Of haplotype heterozygotes, 25% were IgD deficient. The high frequency of IgD deficiency in both homozygotes and heterozygotes for (F1C30, DR3) suggests a partially penetrant dominant susceptibility gene far IgD deficiency on [HLA-B18, FlC30, DR3]. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Hosp Cruces, Barakaldo, Basque, Spain. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Alper, CA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Castano, Luis/C-3084-2009 FU NHLBI NIH HHS [HL-29583]; NIAID NIH HHS [AI-14157] NR 18 TC 9 Z9 9 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 2000 VL 20 IS 3 BP 216 EP 220 DI 10.1023/A:1006693614974 PG 5 WC Immunology SC Immunology GA 339BG UT WOS:000088457300009 PM 10941830 ER PT J AU Lau, T Owen, W Yu, YM Noviski, N Lyons, J Zurakowski, D Tsay, R Ajami, A Young, VR Castillo, L AF Lau, T Owen, W Yu, YM Noviski, N Lyons, J Zurakowski, D Tsay, R Ajami, A Young, VR Castillo, L TI Arginine, citrulline, and nitric oxide metabolism in. end-stage renal disease patients SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INTRAVENOUS TRACER; PROTEIN-METABOLISM; DIETARY ARGININE; PLASMA ARGININE; AMINO-ACIDS; ADULT MAN; LOCALIZATION; HEMODIALYSIS; FAILURE; LEUCINE AB The kidneys are thought to be a major site of net de novo arginine synthesis, but the quantitative status of arginine metabolism and its substrate precursor relationship to nitric oxide (NO) synthesis in end stage renal disease (ESRD) patients have not been characterized. We have investigated kinetic aspects of whole body arginine metabolism in six patients with ESRD. They received two pre- and two post-hemodialysis intravenous tracer infusion studies with L-[guanidino-N-15(2)]arginine and L-[C-13]leucine during the first study, and L-[5-C-13]arginine and L-[5-C-13-ureido,5,5,H-2(2)]citrulline during the second study. Arginine homeostasis in ESRD patients was found to be associated with a lower rate ofarginine oxidation, and despite the decrease in renal function, the rate of de novo arginine synthesis appeared to be preserved. Plasma citrulline concentrations and flux were also elevated in these subjects compared with healthy adults. The rate of whole body NO synthesis was increased in the ESRD patients, but apparently not different pre- and post-hemodialysis therapy. The anatomic site(s) responsible for the maintenance of net de novo arginine synthesis and for the elevated NO synthesis and its pathophysiological importance in ESRD remain to be established. C1 Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Shriners Burn Hosp, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. MIT, Human Nutr Lab, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. Childrens Hosp, Dept Res Comp, Boston, MA 02115 USA. MassTrace Inc, Woburn, MA USA. RP Castillo, L (reprint author), Childrens Hosp, Dept Anesthesia, Farley S17,300 Longwood Ave, Boston, MA 02115 USA. FU NCRR NIH HHS [RR88]; NIDDK NIH HHS [R01 DK015856, P30 DK040561, DK15856, P30DK40561] NR 35 TC 73 Z9 76 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 MAY PY 2000 VL 105 IS 9 BP 1217 EP 1225 DI 10.1172/JCI7199 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 311UR UT WOS:000086904500010 PM 10791996 ER PT J AU Nikolic, B Lee, S Bronson, RT Grusby, MJ Sykes, M AF Nikolic, B Lee, S Bronson, RT Grusby, MJ Sykes, M TI Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targets SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; CELL-SURFACE-MOLECULE; T-CELLS; INTERFERON-GAMMA; MONOCLONAL-ANTIBODY; HELPER-CELLS; MURINE MODEL; MICE; EXPRESSION; LEUKEMIA AB STAT4 and STAT6 are transcription factors that play crucial roles in responding to IL-12 and IL-4, respectively. STAT4 gene knockout (STAT(4/4)) mice have markedly reduced Th1 responses and enhanced Th2 responses. STAT6(-/-) mice show the inverse phenotype. We compared the ability of bone marrow transplantation (BMT) with the inclusion of spleen cells from STAT6(-/-), STAT4(-/-), and wildtype (WT) mice to produce graft-versus-host disease (GVHD) in lethally irradiated MHC-mismatched recipients. Acute GVHD mortality was more rapid when induced by cells from STAT6(-/-) mice than when induced by STAT4(-/-) cells. However, cells from STAT4-/- and STAT6(-/-) donors both induced delayed GVHD mortality compared with WT controls, or compared with combined STAT4(-/-) and STAT6(-/-) cells, indicating a contribution of both Th1 cells and Th2 cells to acute GVHD. Recipients of STAT6(-/-) BMT showed evidence of acute GVHD with severe diarrhea and marked weight loss. Recipients of STAT4(-/-) BMT showed signs of GVHD with only initial transient weight loss and later development of severe skin GVHD. Histopathology showed that Th2 responses were required for the induction of both hepatic and severe skin GVHD, In contrast, both Th1 cells and Th2 cells were capable of causing intestinal pathology of GVHD. Our studies demonstrate an additive role for Th1 and Th2 cells in producing acute GVHD, and suggest a cytokine-directed approach to treating end-organ manifestations of GVHD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, Boston, MA 02129 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL49915, R01 HL049915]; NIAID NIH HHS [AI40171, R01 AI040171] NR 57 TC 138 Z9 147 U1 1 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 MAY PY 2000 VL 105 IS 9 BP 1289 EP 1298 DI 10.1172/JCI7894 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 311UR UT WOS:000086904500018 PM 10792004 ER PT J AU Olszak, IT Poznansky, MC Evans, RH Olson, D Kos, C Pollak, MR Brown, EM Scadden, DT AF Olszak, IT Poznansky, MC Evans, RH Olson, D Kos, C Pollak, MR Brown, EM Scadden, DT TI Extracellular calcium elicits a chemokinetic response from monocytes in vitro and in vivo SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SENSING RECEPTOR; CA2+-SENSING RECEPTOR; CELL-LINE; EXPRESSION; PROTEIN; MIGRATION; INFLAMMATION; CYTOKINES; MODEL AB Recruitment of macrophages to sites of cell death is critical for induction of an immunologic response. Calcium concentrations in extracellular fluids vary markedly, and are particularly high at sites of injury or infection. We hypothesized that extracellular calcium participates in modulating the immune response, perhaps acting via the seven-transmembrane calcium-sensing receptor (CaR) on mature monocytes/macrophages. We observed a dose-dependent increase in monocyte chemotaxis in response to extracellular calcium or the selective allosteric CaR activator NPS R-467. In contrast, monocytes derived from mice deficient in CaR lacked the normal chemotactic response to a calcium gradient. Notably, CaR activation of monocytes bearing the receptor synergistically augmented the transmigration response of monocytes to the chemokine MCP-1 in association with increased cell-surface expression of its cognate receptor, CCR2. Conversely, stimulation of monocytes with MCP- 1 or SDF- 1 alpha reciprocally increased CaR expression, suggesting a dual-enhancing interaction of Ca2+ with chemokines in recruiting inflammatory cells. Subcutaneous administration in mice of Ca2+, MCP-1, or (more potently) the combination of Ca2+ and MCP-1, elicited an inflammatory infiltrate consisting of monocytes/macrophages. Thus extracellular calcium functions as an ionic chemokinetic agent capable of modulating the innate immune response in vivo and in vitro by direct and indirect actions on monocytic cells. Calcium deposition may be both consequence and cause of chronic inflammatory changes at sites of injury, infection, and atherosclerosis. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Endocrine Hypertens Div, Boston, MA 02115 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,Room 5212, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL44851, R01 HL044851]; NIDDK NIH HHS [DK41415, DK50234, R01 DK048330, R01 DK050234, R01 DK052005, R01 DK052479] NR 30 TC 74 Z9 75 U1 1 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 MAY PY 2000 VL 105 IS 9 BP 1299 EP 1305 DI 10.1172/JCI9799 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 311UR UT WOS:000086904500019 PM 10792005 ER PT J AU Boussiotis, VA Tsai, EY Yunis, EJ Thim, S Delgado, JC Dascher, CC Berezovskaya, A Rousset, D Reynes, JM Goldfeld, AE AF Boussiotis, VA Tsai, EY Yunis, EJ Thim, S Delgado, JC Dascher, CC Berezovskaya, A Rousset, D Reynes, JM Goldfeld, AE TI IL-10-producing T cells suppress immune responses in anergic tuberculosis patients SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VERSUS-HOST DISEASE; MYCOBACTERIUM-TUBERCULOSIS; INTERFERON-GAMMA; IN-VIVO; INFECTED MICE; IFN-GAMMA; ANTIGEN; INDUCTION; RECEPTOR; IL-10 AB The lethality of Mycobacterium tuberculosis remains the highest among infectious organisms and is linked to inadequate immune response of the host. Containment and cure of tuberculosis requires an effective cell-mediated immune response, and the absence, during active tuberculosis infection, of delayed-type hypersensitivity (DTH) responses to mycobacterial antigens, defined as anergy, is associated with poor clinical outcome. To investigate the biochemical events associated with this anergy, we screened 206 patients with pulmonary tuberculosis and identified anergic patients by their lack of dermal reactivity to tuberculin purified protein derivative (PPD). In vitro stimulation of T cells with PPD induced production of IL-10, IFN-gamma, and proliferation in PPD+ patients, whereas cells from anergic patients produced IL-10 but not IFN-gamma and failed to proliferate in response to this treatment. Moreover, in anergic patients IL-10-producing T cells were constitutively present, and T-cell receptor-mediated (TCR-mediated) stimulation resulted in defective phosphorylation of TCR zeta and defective activation of ZAP-70 and MAPK. These results show that T-cell anergy can be induced by antigen in vivo in the intact human host and provide new insights into mechanisms by which M, tuberculosis escapes immune surveillance. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Immunol & AIDS, Boston, MA 02115 USA. Cambodian Hlth Comm, Phnom Penh, Cambodia. Inst Pasteur Cambodge, Phnom Penh, Cambodia. RP Boussiotis, VA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Smith 852,44 Binney St, Boston, MA 02115 USA. RI Rousset, Dominique/A-4209-2009; Reynes, Jean-Marc/M-6108-2014 FU NHLBI NIH HHS [P50 HL054785, HL54785, R01 HL059838]; NIAID NIH HHS [AI41584, AI43552, R01 AI043552, R21 AI043552, R56 AI043552] NR 54 TC 282 Z9 297 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 MAY PY 2000 VL 105 IS 9 BP 1317 EP 1324 DI 10.1172/JCI9918 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 311UR UT WOS:000086904500021 PM 10792007 ER PT J AU Khan, ZU Kortom, M Marouf, R Chandy, R Rinaldi, MG Sutton, DA AF Khan, ZU Kortom, M Marouf, R Chandy, R Rinaldi, MG Sutton, DA TI Bilateral pulmonary aspergilloma caused by an atypical isolate of Aspergillus terreus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; IMMUNOCOMPROMISED HOSTS; EXPERIENCE; INFECTION; DIAGNOSIS AB A case of bilateral pulmonary aspergilloma caused by an atypical isolate of Aspergillus terreus is described. The diagnosis was established by the presence of septate, dichotomously branched fungal elements in freshly collected bronchoalveolar lavage and sputum specimens and by repeated isolation of the fungus in culture. Specific precipitating antibodies against the A. terreus isolate were demonstrated in the patient's serum. The isolate was atypical as it failed to produce fruiting structures on routine mycological media, but it did so on extended incubation on potato Rake agar and produced globose, relatively heavy-walled, hyaline accessory conidia (formerly termed aleurioconidia) on both vegetative and aerial mycelia. Also, it produced an intense yellow diffusing pigment in the medium. The report underscores the increasing importance of A. terreus in the etiology of pulmonary aspergillosis. It is suggested that A. terreus antigen be included in the battery of serodiagnostic reagents to facilitate the early diagnosis of infections caused by this species. C1 Kuwait Univ, Fac Med, Dept Microbiol, Safat 13110, Kuwait. Minist Publ Hlth, Mubarak Al Kabeer Hosp, Dept Med, Kuwait, Kuwait. Minist Publ Hlth, Mubarak Al Kabeer Hosp, Dept Hematol, Kuwait, Kuwait. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. RP Khan, ZU (reprint author), Kuwait Univ, Fac Med, Dept Microbiol, POB 24923, Safat 13110, Kuwait. NR 31 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2000 VL 38 IS 5 BP 2010 EP 2014 PG 5 WC Microbiology SC Microbiology GA 311TU UT WOS:000086902400060 PM 10790144 ER PT J AU Kaufman, D Raghavan, D Carducci, M Levine, EG Murphy, B Aisner, J Kuzel, T Nicol, S Oh, W Stadler, W AF Kaufman, D Raghavan, D Carducci, M Levine, EG Murphy, B Aisner, J Kuzel, T Nicol, S Oh, W Stadler, W TI Phase II trial of gemcitabine plus cisplatin in patients with metastatic urothelial cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TRANSITIONAL-CELL-CARCINOMA; ADVANCED BLADDER-CANCER; LUNG-CANCER; CHEMOTHERAPY; METHOTREXATE; VINBLASTINE; DOXORUBICIN; COMBINATION; PLATINUM; TUMORS AB Purpose: To assess the activity and toxicity of the combination of gemcitabine and cisplatin in the treatment of chemotherapy-naive patients with metastatic urothelial cancer. Patients and Methods: Forty-six patients with measurable stage IV carcinoma of the urothelium were enrolled onto this trial. Gemcitabine 1,000 mg/m(2) was administered intravenously for 30 to 60 minutes on days 1, 8, and 15 of each 28-day cycle. Cisplatin was administered after gemcitabine on day 1 of each cycle. The first 11 patients received an initial cisplatin dose of 100 mg/m(2). Due to the hematologic toxicity observed in several of these patients, the dose was reduced to 75 mg/m(2) in the remaining 35 patients. Patients were treated with six cycles, unless disease progression or severe toxicity necessitated earlier discontinuation. Results: Ten of the 46 patients achieved a complete response and nine showed a partial response. The overall response rate was 41%. The median time to treatment failure was 5.5 months. The median survival was 14.3 months, and the 1-year survival probability was 54%. Most of the toxicities were hematologic and, in general, easily manageable. Conclusion: Gemcitabine plus cisplatin is active in the treatment of metastatic urothelial cancer in chemotherapy-naive patients and has an acceptable clinical safety profile. Studies are under way to further define the place of gemcitabine in combination with other chemotherapeutic agents in the treatment of metastatic urothelial cancer. (C) 2000 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. Johns Hopkins Univ, Baltimore, MD USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Univ Chicago, Chicago, IL 60637 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Kaufman, D (reprint author), Massachusetts Gen Hosp, 1 Hawthorne Pl,Room 107, Boston, MA 02114 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 22 TC 136 Z9 140 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 2000 VL 18 IS 9 BP 1921 EP 1927 PG 7 WC Oncology SC Oncology GA 311FK UT WOS:000086873900014 PM 10784633 ER PT J AU Porteus, MH Narkool, P Neuberg, D Guthrie, K Breslow, N Green, DM Diller, L AF Porteus, MH Narkool, P Neuberg, D Guthrie, K Breslow, N Green, DM Diller, L TI Characteristics and outcome of children with Beckwith-Wiedemann syndrome and Wilms' tumor: A report from the National Wilms Tumor Study Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEMIHYPERTROPHY; RISK; ANIRIDIA AB Purpose: Children with Beckwith-Wiedemann syndrome (BWS) are at increased risk for developing Wilms' tumor (WT), We reviewed the National Wilms Tumor Study Group (NWTSG) records to assess clinical characteristics and outcome of patients with WT and BWS. Methods: In the NWTSG, treating clinicians were asked to report, for each enrolled patient, whether the patient had BWS. Between 1980 and 1995, 4,669 patients were treated on two consecutive NWTSG protocols (NWTS 3 and NWTS 4). We retrospectively reviewed the clinical characteristics and treatment outcomes of BWS patients compared with patients with WT without BWS. Results: Fifty-three children enrolled onto NWTS 3 and 4 were reported to have BWS. BWS patients were more likely to present with lower-stage tumors (P =.0001), with more than half (27 of 53) presenting with stage I disease. The overall treatment outcomes for the BWS patients were nearly identical to those without BWS, with overall survival at 4 years from diagnosis at 89% and 90%, respectively. Overall, 21% of the patients with BWS had bilateral disease, either at diagnosis (nine of 53) or as metachronous contralateral recurrence (two of 53). BWS patients enrolled onto NWTS 4 had smaller tumors than those enrolled onto NWTS 3 (P =.02), a trend not seen in the non-BWS patients. Conclusion: Like children without BWS, children with BWS and WT have an excellent prognosis with modern treatment regimens. There is a high risk of bilateral disease, and increasingly smaller rumors are being detected. This suggests that a national trial assessing the role of ultrasound screening followed by nephron-sparing surgery for some patients may be appropriate. J Clin Oncol 18:2026-2031. (C) 2000 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. Univ Washington, Natl Wilms Tumor Study Grp, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Roswell Pk Canc Inst, Dept Pediat, Buffalo, NY 14263 USA. Sch Med & Biomed Serv, Buffalo, NY USA. RP Diller, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, 44 Binney St, Boston, MA 02115 USA. NR 26 TC 37 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 2000 VL 18 IS 10 BP 2026 EP 2031 PG 6 WC Oncology SC Oncology GA 315YE UT WOS:000087139900004 PM 10811666 ER PT J AU Simpson, JF Gray, R Dressler, LG Cobau, CD Falkson, CI Gilchrist, KW Pandya, KJ Page, DL Robert, NJ AF Simpson, JF Gray, R Dressler, LG Cobau, CD Falkson, CI Gilchrist, KW Pandya, KJ Page, DL Robert, NJ TI Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: Results from the Eastern Cooperative Oncology Group companion study, EST 4189 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID S-PHASE FRACTION; TERM FOLLOW-UP; FLOW-CYTOMETRY; MITOTIC COUNT; CARCINOMA; CHEMOTHERAPY; MIB-1; METASTASES; SURVIVAL; KI-67 AB Purpose: The identification of a subset of patients with axillary lymph node-positive breast cancer with an improved prognosis would be clinically useful. We report the prognostic importance of histologic grading and proliferative activity in a cohort of patients with axillary lymph node-positive breast cancer and compare these parameters with other established prognostic factors. Patients and Methods: This Eastern Cooperative Oncology Group laboratory companion study (E4189) centered on 560 axillary lymph node-positive patients registered onto one of six eligible clinical protocols. Flow cytometric (ploidy and S-phase fraction [SPF]) and histopathologic analyses (Nottingham Combined Histologic Grade and mitotic index) were performed on paraffin-embedded tissue from 368 patients. Results: Disease recurred in 208 patients; in 161 (77%), within the first 5 years. Mitotic index and grade were associated with both ploidy and SPF (P less than or equal to.01). Within the first 5 years of follow-up, mitotic index (P =.004), grade (P =.004), ploidy (P =.006), and SPF (P =.05) were associated with time to recurrence; there was also a significant association with survival. The effect of mitotic index was largely a result of the difference between 0 to 2 mitoses/10 high-power fields (HPF; 5-year recurrence of 31%) and more than 2 mitoses/10 HPF (5-year recurrence of 52%). The 0 to 2 mitoses/10 HPF group was independently associated with improved prognosis at 5 years (P =.002) in regression models that included other standard prognostic factors. Conclusion: A subset of axillary lymph node-positive patients with improved prognosis may be identified using a lower (< 3 mitoses/10 HPF) mitotic count than is usually performed. J Clin Oncol 18:2059-2069. (C) 2000 by American Society of Clinical Oncology. C1 Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. Flower Mem Hosp, Sylvania, OH USA. Univ Pretoria, ZA-0002 Pretoria, South Africa. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Univ Rochester, Ctr Canc, Rochester, NY USA. Fairfax Hosp, Falls Church, VA 22046 USA. RP Simpson, JF (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, MCN C3321, Nashville, TN 37232 USA. FU NCI NIH HHS [CA49957, CA23318, CA59307] NR 44 TC 87 Z9 89 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 2000 VL 18 IS 10 BP 2059 EP 2069 PG 11 WC Oncology SC Oncology GA 315YE UT WOS:000087139900009 PM 10811671 ER PT J AU Dorval, M Patenaude, AF Schneider, KA Kieffer, SA DiGianni, L Kalkbrenner, KJ Bromberg, JI Basili, LA Calzone, K Stopfer, J Weber, BL Garber, JE AF Dorval, M Patenaude, AF Schneider, KA Kieffer, SA DiGianni, L Kalkbrenner, KJ Bromberg, JI Basili, LA Calzone, K Stopfer, J Weber, BL Garber, JE TI Anticipated versus actual emotional reactions to disclosure of results of genetic tests for cancer susceptibility: Findings from p53 and BRCA1 testing programs SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BREAST-OVARIAN CANCER; PSYCHOLOGICAL DISTRESS; HEREDITARY BREAST; FAMILIES; PREDISPOSITION; ATTITUDES AB Purpose: We examined the ability of individuals undergoing genetic testing for cancer susceptibility in two structured research protocols to accurately anticipate emotional reactions to disclosure of their test result. We explored whether accuracy of emotional anticipation was associated with postdisclosure psychologic adjustment. Methods: Data from 65 individuals were analyzed; 24 members of Li-Fraumeni cancer syndrome families were tested for p53 mutations (all 24 were unaffected), and 41 subjects with hereditary breast-ovarian cancer susceptibility were tested for BRCA1 mutations (34 were unaffected and seven were affected). Subjects were from families in which a germline mutation had been previously identified. At the pretest session, subjects rated the extent to which they anticipated feeling each of six emotional states (relief, happiness, sadness, guilt, anger, and worry) after disclosure that they did or did not carry the familial mutation. After receiving their test result, they rated their feelings on the same scale of emotions for the appropriate condition. Extent of accuracy and association with psychologic distress at 6 months, as assessed with standardized measures, were evaluated. Results: Overall, mean levels of emotional reactions after receiving test results were not different from those anticipated before result disclosure. However, affected BRCA1 carriers experienced higher levels of anger and worry than they had anticipated. Underestimation of subsequent distress emotions related to test result was associated with a significant increase in general psychologic distress at 6 months. Conclusion: Unaffected individuals in cancer-predisposition testing programs are generally accurate in anticipating emotional reactions to test results. However, cancer patients may underestimate their distress after disclosure of positive results and could benefit from intervention strategies. J Clin Oncol 18:2135-2142. (C) 2000 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Patenaude, AF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Populat Sci, 44 Binney St, Boston, MA 02115 USA. FU NHGRI NIH HHS [HG00725, HG12044] NR 29 TC 89 Z9 89 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 2000 VL 18 IS 10 BP 2135 EP 2142 PG 8 WC Oncology SC Oncology GA 315YE UT WOS:000087139900017 PM 10811679 ER PT J AU Hendrick, V Altshuler, LL Gitlin, MJ Delrahim, S Hammen, C AF Hendrick, V Altshuler, LL Gitlin, MJ Delrahim, S Hammen, C TI Gender and bipolar illness SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CYCLING AFFECTIVE-DISORDER; COMORBIDITY; FAMILY AB Background: For major depression and schizophrenia, gender differences have been reported in symptom expression and course of illness. Gender differences in bipolar disorder are becoming increasingly apparent, but have been less studied. Research data on these differences will help determine whether gender is important in influencing illness variables such as course, symptom expression, and likelihood of comorbidity. Method: Charts of 131 patients (63 women and 68 men) with a DSM-IV diagnosis of bipolar disorder admitted to the University of California Los Angeles Mood Disorders Program over a 3-year period were reviewed to gather data on demographic variables and course of illness and to assess differences in the illness across genders. Results: No significant gender differences were found in the rate of bipolar I or bipolar II diagnoses, although women were overrepresented in the latter category. Also, no significant gender differences emerged in age at onset, number of depressive or manic episodes, and number of hospitalizations for depression. Women, however, had been hospitalized significantly more often than men for mania. Further, whereas bipolar men were significantly more likely than bipolar women to have a comorbid substance use disorder, women with bipolar disorder had 4 times the rate of alcohol use disorders and 7 times the rate of other substance use disorders than reported in women from community-derived samples. Conclusion: For bipolar disorder, course of illness variables such as age at onset and number of affective episodes of each polarity do not seem to differ across genders. Women, however, may be more likely than men to be hospitalized for manic episodes. While both men and women with the illness have high rates of comorbidity with alcohol and other substance use disorders, women with bipolar disorder are at a particularly high risk for comorbidity with these conditions. C1 Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Hendrick, V (reprint author), 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. NR 15 TC 114 Z9 117 U1 2 U2 17 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 MAY PY 2000 VL 61 IS 5 BP 393 EP 396 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 321FP UT WOS:000087445700018 PM 10847318 ER PT J AU Daffner, KR Scinto, LFM Calvo, V Faust, R Mesulam, MM West, WC Holcomb, PJ AF Daffner, KR Scinto, LFM Calvo, V Faust, R Mesulam, MM West, WC Holcomb, PJ TI The influence of stimulus deviance on electrophysiologic and behavioral responses to novel events SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID EXPLORATORY EYE-MOVEMENTS; INTRACEREBRAL POTENTIALS; VISUAL-STIMULI; RARE TARGET; NOVELTY DETECTION; WORKING-MEMORY; ATTENTION; AMPLITUDE; CURIOSITY; SURPRISE AB This study investigated the role of stimulus deviance in determining electrophysiologic and behavioral responses to "novelty." Stimulus deviance was defined in terms of differences either from the immediately preceding context or from long-term experience. Subjects participated in a visual event-related potential (ERP) experiment, in which they controlled the duration of stimulus viewing with a button press, which Served as a measure of exploratory behavior. Each of the three experimental conditions included a frequent repetitive background stimulus and infrequent stimuli that deviated from the background stimulus. In one condition, both background and deviant stimuli were simple, easily recognizable geometric figures. In another condition, both background and deviant stimuli were unusual/unfamiliar figures, and in a third condition, the background stimulus was a highly unusual figure, and the deviant stimuli were simple, geometric shapes. Deviant stimuli elicited larger N2-P3 amplitudes and longer viewing durations than the repetitive background stimulus, even when the deviant stimuli were simple, familiar shapes and the background stimulus was a highly unusual figure. Compared to simple, familiar deviant stimuli, unusual deviant stimuli elicited larger N2-P3 amplitudes and longer viewing times. Within subjects, the deviant stimuli that evoked the largest N2-P3 responses also elicited the longest viewing durations. We conclude that deviance from both immediate context and long-term prior experience contribute to the response to novelty, with the combination generating the largest N2-P3 amplitude and the most sustained attention. The amplitude of the N2-P3 mag reflect how much "uncertainty" is evoked by a novel visual stimulus and signal the need for further exploration and cognitive processing. C1 Harvard Med Sch, Boston, MA USA. Northwestern Univ, Sch Med, Evanston, IL 60208 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Medford, MA 02155 USA. RP Daffner, KR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cognit & Behav Neurol, 221 Longwood Ave, Boston, MA 02115 USA. NR 66 TC 45 Z9 45 U1 1 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAY PY 2000 VL 12 IS 3 BP 393 EP 406 DI 10.1162/089892900562219 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 324XJ UT WOS:000087646900003 PM 10931766 ER PT J AU Somasundaran, P Simpson, S Jain, RK Ivanov, I Raghuraman, V AF Somasundaran, P Simpson, S Jain, RK Ivanov, I Raghuraman, V TI Investigation of thin aqueous films on silica using a modified interferometric technique SO JOURNAL OF COLLOID AND INTERFACE SCIENCE LA English DT Article DE micro-interferometric technique; free bubble method; disjoinning pressure; thin aqueous films; silica ID STABILITY AB The thinning behavior of liquid films between free bubbles and silica is investigated using the interferometric technique. Stable films were obtained at higher salt concentrations compared to previous studies because of the improved cleaning procedure. In contrast to the captive bubble technique used in the past, the free bubble method employed more closely approximates such processes as flotation. The results obtained for aqueous films at low and high ionic strengths are in better agreement with theoretical predictions than those in previous studies. (C) 2000 Academic Press. C1 Columbia Univ, Langmuir Ctr Colloids & Interfaces, Ctr Adv Studies Novel Surfactants, NSF,IUCR, New York, NY 10027 USA. Massachusetts Gen Hosp, Steele Lab Tumor Biol, Boston, MA 02114 USA. Rogers Corp, Rogers, CT 06263 USA. Univ Sofia, Fac Chem, Lab Thermodynam Physicochem Hydrodynam, BU-1126 Sofia, Bulgaria. RP Somasundaran, P (reprint author), Columbia Univ, Langmuir Ctr Colloids & Interfaces, Ctr Adv Studies Novel Surfactants, NSF,IUCR, 911 Mudd Bldg, New York, NY 10027 USA. NR 27 TC 7 Z9 7 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0021-9797 J9 J COLLOID INTERF SCI JI J. Colloid Interface Sci. PD MAY 1 PY 2000 VL 225 IS 1 BP 243 EP 246 DI 10.1006/jcis.2000.6735 PG 4 WC Chemistry, Physical SC Chemistry GA 309UC UT WOS:000086786800030 ER PT J AU Ho, C Zhou, JH Medina, M Goto, T Jacobson, M Bhide, PG Kosik, KS AF Ho, C Zhou, JH Medina, M Goto, T Jacobson, M Bhide, PG Kosik, KS TI delta-catenin is a nervous system-specific adherens junction protein which undergoes dynamic relocalization during development SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE ventricular zone; migration; dendrites; Arm-repeat family ID NEURONAL MIGRATION; TYROSINE PHOSPHORYLATION; CELL-ADHESION; LISSENCEPHALY GENE; E-CADHERIN; EXPRESSION; BRAIN; REELER; MICE; NEUROGENESIS AB delta-catenin is a member of the Armadillo repeat family and component of the adherens junction discovered in a two-hybrid assay as a bona fide interactor with presenilin-1 (Zhou et al., [1997], NeuroReport 8:2085-2090), a protein which carries mutations that cause familial Alzheimer's disease. The expression pattern of delta-catenin was mapped between embryonic day 10 (E10) and adulthood by Northern blots, in situ hybridization and immunohistochemistry in the mouse. In development, delta-catenin is dynamically regulated with respect to its site of expression. It is first expressed within proliferating neuronal progenitor cells of the neuroepithelium, becomes down-regulated during neuronal migration, and is later reexpressed in the dendritic compartment of postmitotic neurons. In the mouse, delta-catenin mRNA is expressed by E10, increases and peaks at postnatal day (P)7, with lower levels in adulthood. In the developing neocortex, delta-catenin mRNA is strongly expressed in the proliferative ventricular zone and the developing cortical plate, yet is conspicuously less prominent in the intermediate zone, which contains migrating cortical neurons, delta-catenin protein forms a honeycomb pattern in the neuroepithelium by labeling the cell periphery in a typical adherens junction pattern. By E18, delta-catenin expression shifts primarily to nascent apical dendrites, a pattern that continues through adulthood. The dynamic relocalization of delta-catenin expression during development, taken together with previously published data which described a role for delta-catenin in cell motility (Lu et al., [1999] J. Cell. Biol. 144:519-532), suggests the hypothesis that delta-catenin regulation is closely linked to neuronal migration and may play a role in the establishment of mature dendritic relationships in the neuropil. (C) 2000 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kosik, KS (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, 77 Ave Louis Pasteur,HIM 750, Boston, MA 02115 USA. FU NINDS NIH HHS [NS32657] NR 45 TC 57 Z9 59 U1 0 U2 7 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 MAY 1 PY 2000 VL 420 IS 2 BP 261 EP 276 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 300FW UT WOS:000086243300008 PM 10753311 ER PT J AU Huang, GT Rosowski, JJ Peake, WT AF Huang, GT Rosowski, JJ Peake, WT TI Relating middle-ear acoustic performance to body size in the cat family: measurements and models SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE hearing; middle ear; cat family; body size; acoustics ID REFLECTION COEFFICIENT; INPUT IMPEDANCE; LOCALIZATION; EVOLUTION; HEARING; LIONS AB Is the acoustic performance of the mammalian middle ear dependent on body size? We focus on the cat family, because of its qualitatively uniform (and distinctive) middle-ear structure, large size range, and the extensive data available from domestic cats which provide a framework for relating middle-ear acoustics to structure. We report measurements of acoustic admittance in 17 live adult ears of 11 exotic species, ranging in size from sand cat (3 kg) to tiger (180 kg). For low frequencies, the middle-ear response is compliant for all species and generally increases with size. The compliance of the middle-ear air space increases with size, but the compliance of the tympanic membrane and ossicular chain is not correlated with size. Structure-based rules are developed to represent some features of middle-ear performance: (I) low-frequency sensitivity increases with size; and (2) the frequency of a prominent notch in admittance decreases with size. Although some species deviate from the rules, the data generally support the idea that in larger felids the middle-ear response is shifted to lower frequencies. Thus, in the cat family, body size partly describes variations in auditory features. More speculatively, ethological pressures which might influence hearing performance are discussed. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM gthuang@mit.edu NR 66 TC 26 Z9 28 U1 1 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7594 EI 1432-1351 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD MAY PY 2000 VL 186 IS 5 BP 447 EP 465 DI 10.1007/s003590050444 PG 19 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 328ZH UT WOS:000087881300004 PM 10879948 ER PT J AU Murphy, M Signoretti, S Kadin, ME Loda, M AF Murphy, M Signoretti, S Kadin, ME Loda, M TI Detection of TCR-gamma gene rearrangements in early mycosis fungoides by non-radioactive PCR-SSCP SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; T-CELL LYMPHOMA; GRADIENT GEL-ELECTROPHORESIS; SEZARY-SYNDROME; CUTANEOUS LESIONS; DIAGNOSIS; CLONALITY AB Early mycosis fungoides (MF) can mimic numerous benign inflammatory dermatoses on routine histological examination. In this study, a recently developed non-radioactive polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) technique was used to assess T-cell clonality in paraffin-embedded skin biopsies clinically and pathologically suspicious for early MF, Non-radioactive PCR-SSCP is a simple, sensitive, reproducible and rapid procedure requiring minimal instrumentation. DNA was extracted from 22 skill biopsies of 20 patients with suspected patch stage MF and 15 skin biopsies of inflammatory dermatoses. V gamma 1-8, V gamma 9, V gamma 10, V gamma 11 and J gamma 1/J gamma 2 consensus primers were used for T-cell receptor (TCR)-gamma gene rearrangement amplification. PCR products were analyzed by non-radioactive SSCP. Clonal TCR-gamma gene rearrangements were detected in 17 of 22 (77%) suspected MF specimens. Clonal SSCP banding patterns were different among individual patients. In addition, identical banded patterns were demonstrated in serial skin biopsies from the same patient. No dominant T-cell clones were found in the inflammatory dermatoses studied. Therefore, non-radioactive PCR-SSCP is a useful molecular diagnostic tool for assessment of T-cell clonality in paraffin-embedded specimens suspicious for early MF. The SSCP imprint of PCR products is specific for each TCR-gamma gene rearrangement, and may be used to evaluate concurrent/recurrent disease in individual patients. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. Albany Med Ctr, Dept Pathol & Lab Med, Div Dermatopathol, Albany, NY USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. RP Loda, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 29 TC 27 Z9 29 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD MAY PY 2000 VL 27 IS 5 BP 228 EP 234 DI 10.1034/j.1600-0560.2000.027005228.x PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA 313MA UT WOS:000087002400004 PM 10847547 ER PT J AU Su, LD Duncan, LM AF Su, LD Duncan, LM TI Lymphoma- and leukemia-associated cutaneous atypical CD30+T-cell reactions SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID LARGE-CELL LYMPHOMA; LYMPHOPROLIFERATIVE DISORDERS; T-CELL; MYCOSIS-FUNGOIDES; CD30 EXPRESSION; PAPULOSIS; KI-1; TRANSLOCATION; RECOVERY; FEATURES AB Cutaneous CD30+ lymphoid infiltrates appear cytologically atypical and occasionally may be misinterpreted as recurrent disease when they occur in patients treated for other primary hematologic malignancies. We recently encountered two such cases and present our findings. One patient with B-cell lymphoma and another with myeloid leukemia developed cutaneous eruptions after chemotherapy displaying highly atypical perivascular lymphoid cells on histology that mimicked recurrent disease. In both cases, the lymphocytes were CD30+ T cells by immunohistochemistry. The skin lesions spontaneously resolved and have not recurred. Because one case was initially misinterpreted as recurrent leukemia, we conclude that close clinical correlation and immunophenotypic confirmation should be done for atypical cutaneous lymphoid infiltrates in patients with primary hematologic malignancies. We discuss the differential diagnosis of atypical CD30+ infiltrates in this setting, which include recurrent lymphoma or myeloid leukemia, primary cutaneous anaplastic large cell lymphoma (ALCL), lymphomatoid papulosis (LYP), carbamazepine-induced CD30+ pseudolymphoma, viral infection and an atypical eruption of lymphocyte recovery. C1 Univ Michigan Hosp, Dept Pathol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. RP Su, LD (reprint author), Univ Michigan Hosp, Dept Pathol, M5224 Med Sci 1,1301 Catherine Rd, Ann Arbor, MI 48109 USA. NR 42 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 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD MAY PY 2000 VL 27 IS 5 BP 249 EP 254 DI 10.1034/j.1600-0560.2000.027005249.x PG 6 WC Dermatology; Pathology SC Dermatology; Pathology GA 313MA UT WOS:000087002400007 PM 10847550 ER PT J AU Mehta, A Dreyer, K Boland, G Frank, M AF Mehta, A Dreyer, K Boland, G Frank, M TI Do picture archiving and communication systems improve report turnaround times? SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT 17th Symposium for Computer Applications in Radiology held at the Annual Meeting of the Society-for-Computer-Applications-in-Radiology (SCAR 2000) CY JUN 03-06, 2000 CL PHILADELPHIA, PENNSYLVANIA SP Soc Comp Applicat Radiol ID PACS AB Radiology departments are beginning to embrace new technologies to decrease operating budgets and improve services. One of these technologies is the picture archiving and communication system (PACS). PACS, through immediate availability of images to the radiologist, promises to decrease turnaround times of reports to the clinician. The purpose of this study was to determine if this technology actually decreases the time for referring clinicians to receive reports generated by the radiologist. The time to provide a preliminary report by a resident and time to finalize this report by a board-certified radiologist was retrospectively obtained for 6,022 abdominal and pelvic computed tomography (CT) scans over two 1-year periods from March 1, 1997 to March 1, 1998 and from March 1, 1998 to March 1, 1999. During the first year, interpretation was conducted using hard-copy film and during the second using PACS. In both 1-year periods, MedSpeak voice recognition software (IBM, White Plains, NY) was employed for dictation. The average time for a preliminary report for a abdominal and pelvic CT, dictated by a resident or fellow, to be available in alphanumeric form on the hospital information system using hard-copy film was 3.73 days. The installation of a PACS system decreased this turnaround time to 0.56 days, representing an 85.0% improvement. The time to availability of final reports, ie, signed by board-certified staff radiologists, was 5.49 days in the hard-copy interpretation subset and 5.97 days in the PACS subset. The addition of PACS into an academic gastrointestinal radiology division improves availability of alphanumeric preliminary reports of abdominal and pelvic CTs on the hospital information system (HIS), dictated by a resident or fellow, by 85.0%. There was no impact with a PACS on the time to final sign reports by a staff board certified radiologist as signing patterns remained relatively constant over the two interpretation formats. Copyright (C) 2000 by W.B. Saunders Company. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Mehta, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 2 TC 22 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD MAY PY 2000 VL 13 IS 2 SU 1 BP 105 EP 107 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 319KA UT WOS:000087339000026 PM 10847375 ER PT J AU Dreyer, KJ Mehta, A Thrall, J AF Dreyer, KJ Mehta, A Thrall, J TI Can radiologic images be incorporated into the electronic patient record? SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT 17th Symposium for Computer Applications in Radiology held at the Annual Meeting of the Society-for-Computer-Applications-in-Radiology (SCAR 2000) CY JUN 03-06, 2000 CL PHILADELPHIA, PENNSYLVANIA SP Soc Comp Applicat Radiol AB As radiology makes advances toward filmlessness, all of medicine is headed, just as rapidly, toward paperless transmission of patient information, While there are obvious advantages to this electronic approach, and several standards to conform to for the transmission of textual (Health Level 7 [HL-7]) and image (Digital Imaging and Communications in Medicine [DICOM]) data, it is the integration of these two data sets that is clinically essential and yet poorly defined, This report defines an approach for, and the successful implementation of, the integration of radiologic image data with textual data contained within the electronic patient record (EPR) through the use of standard internet protocols. Incorporation of medical images in the EPR has proven to be critical to the successful deployment of picture archiving and communications systems (PACS) and the reduction of film consumption at Massachusetts General Hospital (MGH). Since the installation of the first internet-based Image Data Repository (IDR) at MGH in 1995, the system has adequately served to meet the needs of clinical requests by both radiology-only browser users and users of the EPR. It has drastically reduced the need for film and provided concurrent display of images and text throughout the institution and beyond. Copyright (C) 2000 by W.B. Saunders Company. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Dreyer, KJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 0 Emerson,Suite 3E, Boston, MA 02114 USA. NR 0 TC 3 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 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD MAY PY 2000 VL 13 IS 2 SU 1 BP 138 EP 141 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 319KA UT WOS:000087339000034 PM 10847383 ER PT J AU Risken, MJ Nadel, ES Brown, DFM AF Risken, MJ Nadel, ES Brown, DFM TI Cough and shortness of breath SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; ETIOLOGY; LEGIONELLA C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Med Sch, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 14 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 MAY PY 2000 VL 18 IS 4 BP 457 EP 461 DI 10.1016/S0736-4679(00)00171-2 PG 5 WC Emergency Medicine SC Emergency Medicine GA 311TT UT WOS:000086902300011 PM 10802425 ER PT J AU Lechner, F Wong, DKH Dunbar, PR Chapman, R Chung, RT Dohrenwend, P Robbins, G Phillips, R Klenerman, P Walker, BD AF Lechner, F Wong, DKH Dunbar, PR Chapman, R Chung, RT Dohrenwend, P Robbins, G Phillips, R Klenerman, P Walker, BD TI Analysis of successful immune responses in persons infected with hepatitis C virus SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE acute infection; cytotoxic T lymphocytes; T helper cells; tetramer staining; interferon gamma ID CYTOTOXIC T-LYMPHOCYTES; MHC CLASS-I; CHORIOMENINGITIS VIRUS; PERIPHERAL-BLOOD; ANTIRETROVIRAL THERAPY; QUANTITATIVE-ANALYSIS; PHENOTYPIC ANALYSIS; VIRAL CLEARANCE; CELL RESPONSE; HIV-INFECTION AB Although hepatitis C virus (HCV) infection is very common, identification of patients during acute infection is rare. Consequently, little is known about the immune response during this critical stage of the disease. We analyzed the T lymphocyte response during and after acute resolving HCV infection in three persons, using interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) and human histocompatibility leukocyte antigen (HLA) peptide tetramer assays. Acute infection was associated with a broadly directed T helper and cytotoxic T lymphocyte (CTL) response, which persisted after resolution of clinical hepatitis and clearance of viremia. At the earliest time point studied, highly activated CTL populations were observed that temporarily failed to secrete IFN-gamma, a "stunned" phenotype, from which they recovered as viremia declined, in long-term HCV-seropositive persons, CTL responses were more common in persons who had cleared viremia compared with those with persistent viremia, although the frequencies of HCV-specific CTLs were lower than those found in persons during and after resolution of acute HCV infection. These studies demonstrate a strong and persistent CTL response in resolving acute HCV infection, and provide rationale to explore immune augmentation as a therapeutic intervention in chronic HCV infection. C1 Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England. Univ Oxford, John Radcliffe Hosp, MRC, Human Immunol Unit, Oxford OX3 9DU, England. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Klenerman, P (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Level 7, Oxford OX3 9DU, England. RI Robbins, Gregory/F-7988-2011; Yang, Chen/G-1379-2010; Dunbar, Rod/C-2570-2012 OI Dunbar, Rod/0000-0001-9626-2600 NR 63 TC 957 Z9 984 U1 2 U2 20 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 MAY 1 PY 2000 VL 191 IS 9 BP 1499 EP 1512 DI 10.1084/jem.191.9.1499 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 311LC UT WOS:000086884900007 PM 10790425 ER PT J AU Taraszka, KS Higgins, JMG Tan, KM Mandelbrot, DA Wang, JH Brenner, MB AF Taraszka, KS Higgins, JMG Tan, KM Mandelbrot, DA Wang, JH Brenner, MB TI Molecular basis for leukocyte integrin alpha(E)beta(7) adhesion to epithelial (E)-cadherin SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE cadherins; integrins; cell adhesion; T lymphocytes; protein binding ID FUNCTION-ASSOCIATED ANTIGEN-1; AMINO-ACID-RESIDUES; CELL-CELL-ADHESION; CRYSTAL-STRUCTURE; E-CADHERIN; BINDING-SITE; I-DOMAIN; T-LYMPHOCYTES; TERMINAL DOMAINS; RECEPTOR AB Cadherins are expressed in tissue-restricted patterns and typically mediate homophilic adhesion. Cadherins also mediate lymphocyte adhesion, providing the opportunity for lymphocyte attachment to parenchymal cells. The best characterized example of lymphocyte adhesion to a tissue-specific cell adhesion molecule, as opposed to a vascular endothelial adhesion molecule, is the interaction between integrin alpha(E)beta(7) on intraepithelial lymphocytes and E-cadherin on epithelial cells. However, the molecular basis for an integrin-cadherin interaction is not well defined. Realization that the cadherin domain adopts a topology similar to the immunoglobulin (Ig) fold suggested that integrin recognition of E-cadherin might be similar to recognition of Ig superfamily ligands. Thus, we modeled domain 1 of human E-cadherin and studied the role of solvent-exposed loops that connect Ig-like core-forming beta strands. Mutational analyses localized the integrin alpha(E)beta(7) recognition site to the top of domain 1 at the face formed by the BC and FG loops, a site distinct from the region recognized in intercellular adhesion molecule (ICAM)-1, -2, and -3, mucosal addressin cell adhesion molecule 1 (MAdCAM-1), vascular cell adhesion molecule 1 (VCAM-1), and fibronectin by their integrin ligands, Moreover, the integrin alpha(E)beta(7) binding site is distinct from the homophilic binding site on E-cadherin. These studies provide a conceptual basis for integrin-cadherin binding and extend the model that an Ig-like fold can serve as a scaffold for recognition. C1 Brigham & Womens Hosp, Dept Internal Med, Div Rheumatol Allergy & Immunol, Lymphocyte Biol Sect, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Brenner, MB (reprint author), Brigham & Womens Hosp, Dept Internal Med, Div Rheumatol Allergy & Immunol, Lymphocyte Biol Sect, 1 Jimmy Fund Way,Smith Bldg,Rm 552, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL048675, HL48675]; NIAID NIH HHS [AI01212] NR 51 TC 36 Z9 38 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 2000 VL 191 IS 9 BP 1555 EP 1567 DI 10.1084/jem.191.9.1555 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 311LC UT WOS:000086884900012 PM 10790430 ER PT J AU Aghi, M Hochberg, F Breakefield, XO AF Aghi, M Hochberg, F Breakefield, XO TI Prodrug activation enzymes in cancer gene therapy SO JOURNAL OF GENE MEDICINE LA English DT Review DE prodrug activation; gene therapy; cancer; review article ID VIRUS THYMIDINE KINASE; EXPERIMENTAL BRAIN-TUMORS; RABBIT LIVER CARBOXYLESTERASE; PYRIMIDINE NUCLEOSIDE ANALOGS; EXPRESS CYTOSINE DEAMINASE; RAT GLIOMA-CELLS; IN-VIVO; ESCHERICHIA-COLI; SUICIDE GENE; DEOXYCYTIDINE KINASE AB Among the broad array of genes that have been evaluated for tumor therapy, those encoding prodrug activation enzymes are especially appealing as they directly complement ongoing clinical chemotherapeutic regimes. These enzymes can activate prodrugs that have low inherent toxicity using both bacterial and yeast enzymes, or enhance prodrug activation by mammalian enzymes. The general advantage of the farmer is the large therapeutic index that can be achieved, and of the latter, the non-immunogenicity (supporting longer periods of prodrug activation) and the fact that the prodrugs will continue to have some efficacy after transgene expression is extinguished. This review article describes 13 different prodrug activation schemes developed over the last 15 years, two of which - activation of ganciclovir by viral thymidine kinase and activation of 5-fluorocytosine to 5-fluorouracil - are currently being evaluated in clinical trials. Essentially all of these prodrug activation enzymes mediate toxicity through disruption of DNA replication, which occurs at differentially high rates in tumor cells compared with most normal cells. In cancer gene therapy, vectors target delivery of therapeutic genes to tumor cells, in contrast to the use of antibodies in antibody-directed prodrug therapy. Vector targeting is usually effected by direct injection into the tumor mass or surrounding tissues, but the efficiency of gene delivery is usually low. Thus it is important that the activated drug is able to act on non-transduced tumor cells. This bystander effect may require cell-to-cell contact or be mediated by facilitated diffusion or extracellular activation to target neighboring tumor cells. Effects at distant sites are believed to be mediated by the immune system, which can be mobilized to recognize tumor antigens by prodrug-activated gene therapy. Prodrug activation schemes can be combined with each other and with other treatments, such as radiation, in a synergistic manner. Use of prodrug wafers for intratumoral drug activation and selective permeabilization of the tumor vasculature to prodrugs and vectors should further increase the value of this new therapeutic modality. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Med, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Dept Mol Neurogenet, 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69246-04] NR 129 TC 151 Z9 156 U1 1 U2 27 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAY-JUN PY 2000 VL 2 IS 3 BP 148 EP 164 DI 10.1002/(SICI)1521-2254(200005/06)2:3<148::AID-JGM105>3.0.CO;2-Q PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 321GL UT WOS:000087447700001 PM 10894261 ER PT J AU Chen, ZB Koralov, SB Gendelman, M Carroll, MC Kelsoe, G AF Chen, ZB Koralov, SB Gendelman, M Carroll, MC Kelsoe, G TI Humoral immune responses in Cr2(-/-) mice: Enhanced affinity maturation but impaired antibody persistence SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CENTER B-CELLS; FOLLICULAR DENDRITIC CELLS; COMPLEMENT RECEPTOR TYPE-2; T-DEPENDENT ANTIGEN; GERMINAL-CENTERS; IN-SITU; LYMPHOCYTES-B; GUINEA-PIGS; ACQUIRED-IMMUNITY; MOUSE COMPLEMENT AB Deficiency in CD21/CD35 by disruption of the Cr2 loci leads to impaired humoral immune responses. In this study, we detail the role of CD21/CD35 on Ab responses to the hapten (4-hydroxy-3-nitrophenyl)acetyl conjugated to chicken gamma-globulin. Surprisingly, Cr2(-/-) mice generate significant Ab responses and germinal center (GC) reactions to low doses of this Ag in alum, although the magnitude of their responses is much reduced in comparison with those of Cr2(+/-) and C57BL/6 controls. Increasing Ag dose partially corrected this deficit. In situ study of the somatic genetics of GC B cells demonstrated that VDJ hypermutation does not require CD21/CD35, and Cr2(-/-) mice exhibited enhanced affinity maturation of serum Ab in the post-GC phase of the primary response. On the other hand, Cr2(-/-) mice displayed accelerated loss of serum Ab and long-lived Ab-forming cells. These observations suggest that B-cell activation/survival signals mediated by CD21 and/or the retention of Ag by CD21/CD35 play important roles in the generation, quality, and maintenance of serum Ab. The Journal of Immunology, 2000, 164: 4522-4532. C1 Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Kelsoe, G (reprint author), Duke Univ, Med Ctr, Dept Immunol, Box 3010, Durham, NC 27710 USA. FU NIA NIH HHS [AG-13789]; NIAID NIH HHS [AI-24335, AI-39246] NR 74 TC 74 Z9 78 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 MAY 1 PY 2000 VL 164 IS 9 BP 4522 EP 4532 PG 11 WC Immunology SC Immunology GA 306XQ UT WOS:000086624300013 PM 10779753 ER PT J AU Ho, SC Chaudhuri, S Bachhawat, A McDonald, K Pillai, S AF Ho, SC Chaudhuri, S Bachhawat, A McDonald, K Pillai, S TI Accelerated proteasomal degradation of membrane Ig heavy chains SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HISTOCOMPATIBILITY COMPLEX-MOLECULES; CELL ANTIGEN RECEPTOR; ENDOPLASMIC-RETICULUM; BINDING-PROTEIN; T-CELL; ER DEGRADATION; P-GLYCOPROTEIN; CALNEXIN; BIP; ASSOCIATION AB Membrane IgG H chains turn over considerably more rapidly than secretory Ig H chains in the 18-81 A2 pre-B cell, line. This rapid degradation occurs in proteasomes. N-Glycosylated membrane Ig H chains accumulate in the endoplasmic reticulum in the presence of proteasomal inhibitors, suggesting that retrotranslocation and proteasomal degradation of membrane Ig H chains may be closely coupled processes. Accelerated proteasomal degradation of membrane Ig H chains was also observed in transfected nonlymphoid cells. At steady state, the membrane form of the H chain associates more readily with Bip and calnexin than its secretory counterpart. The preferential recognition of membrane, as opposed to secretory, Ig H chains by some endoplasmic reticulum chaperones, may provide an explanation for the accelerated proteasomal degradation of the former. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St,Charlestown Navy Yard, Boston, MA 02129 USA. FU NCI NIH HHS [CA 69618]; NIAID NIH HHS [AI 33507] NR 51 TC 10 Z9 10 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 MAY 1 PY 2000 VL 164 IS 9 BP 4713 EP 4719 PG 7 WC Immunology SC Immunology GA 306XQ UT WOS:000086624300037 PM 10779777 ER PT J AU Lin, Y Soares, MP Sato, H Csizmadia, E Robson, SC Smith, N Bach, FH AF Lin, Y Soares, MP Sato, H Csizmadia, E Robson, SC Smith, N Bach, FH TI Long-term survival of hamster hearts in presensitized rats SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DELAYED XENOGRAFT REJECTION; NATURAL-KILLER-CELLS; BABOON CARDIAC TRANSPLANTS; ACUTE VASCULAR REJECTION; VENOM FACTOR THERAPY; ENDOTHELIAL-CELLS; T-CELL; CONCORDANT XENOGRAFTS; HYPERACUTE REJECTION; MONONUCLEAR-CELLS AB We transplanted hamster hearts into rats that had been sensitized to hamster cardiac;grafts 5 days earlier as a model for discordant xenotransplantation, Sensitized rats had high serum levels of elicited anti-donor IgM and IgG that caused hyperacute rejection. Transient complement inhibition with cobra venom factor (CVF) plus daily and continuing cyclosporin A (CyA) prevented hyperacute rejection. However, grafts underwent delayed xenograft rejection (DXR). DXR involved IgG and associated Ab-dependent cell-mediated rejection, because depletion of IgG or Ab-dependent cell-mediated rejection-associated effector cells prolonged graft survival and the serum-mediated Ab-dependent cell-mediated cytotoxicity in vitro. Blood exchange in combination with CVF/CyA treatment dramatically decreased the level of preexisting Abs, but DXR still occurred in association with the return of Abs, Splenectomy and cyclophosphamide acted synergistically to delay Ab return, and when combined with blood exchange/ CVF/CyA facilitated long-term survival of grafts. These grafts survived in the presence of anti-donor IgM, IgG, and complement that precipitated rejection of naive hearts, indicating that accommodation (survival in the presence of anti-graft Abs and complement) had occurred. We attribute the long-term survival to the removal of preexisting anti-donor Abs and therapy that attenuated the rate of Ab return. Under such conditions, the surviving hearts showed expression in endothelial cells and smooth muscle cells of protective genes and an intragraft Th2 immune response. Th2 responses and protective genes are associated with resistance to IgM- and IgG-mediated, complement-dependent and -independent forms of rejection. 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 [R01HL 58688] NR 64 TC 31 Z9 39 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 MAY 1 PY 2000 VL 164 IS 9 BP 4883 EP 4892 PG 10 WC Immunology SC Immunology GA 306XQ UT WOS:000086624300058 PM 10779798 ER PT J AU Eron, JJ Smeaton, LM Fiscus, SA Gulick, RM Currier, JS Lennox, JL D'Aquila, RT Rogers, MD Tung, R Murphy, RL AF Eron, JJ Smeaton, LM Fiscus, SA Gulick, RM Currier, JS Lennox, JL D'Aquila, RT Rogers, MD Tung, R Murphy, RL TI The effects of protease inhibitor therapy on human immunodeficiency virus type 1 levels in semen (AIDS clinical trials group protocol 850) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 6th Conference on Retroviruses and Opportunistic Infections CY JAN 31-FEB 04, 1999 CL CHICAGO, ILLINOIS ID SEXUAL TRANSMISSION; REVERSE-TRANSCRIPTASE; SEMINAL PLASMA; PERINATAL TRANSMISSION; ANTIRETROVIRAL AGENTS; ANTIVIRAL TREATMENT; HIV-1 PROTEASE; VIRAL LOAD; RNA; ZIDOVUDINE AB Antiretroviral therapy may lead to decreased shedding of human immunodeficiency virus type 1 (HIV-1) in genital secretions. Thirty men, 19 receiving amprenavir and ii receiving amprenavir, zidovudine, and lamivudine, donated blood and semen while undergoing treatment, to evaluate the effects of these medications on HIV-1 shedding in semen. Before therapy, 4 men had HIV-1 RNA levels in seminal plasma >6.0 log(10) (1 million) copies/mL, markedly higher than levels in blood plasma. Most men (77%) had HIV-1 RNA levels in seminal plasma below the limit of quantification during therapy. Amprenavir alone suppressed I HIV-1 RNA levels to <400 copies/mL in seminal plasma in the majority of patients, the first direct demonstration of the antiretroviral effects of a protease inhibitor in the male genital tract. However, 8 men (27%) had measurable HIV-1 in seminal plasma at their last study visit, 4 with increasing levels. Persistent replication of HIV in the genital tract may have implications for the selection of resistant virus and sexual transmission of HIV-1. C1 Univ N Carolina, Dept Med, Sch Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Microbiol & Immunol, Sch Med, Chapel Hill, NC 27599 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Harvard Univ, Stat & Data Anal Ctr, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Vertex Pharmaceut, Cambridge, MA USA. NYU, Dept Med, New York, NY 10016 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Univ So Calif, Dept Med, Los Angeles, CA USA. Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Univ Calif Los Angeles, UCLA Care Ctr, Los Angeles, CA USA. RP Eron, JJ (reprint author), Univ N Carolina, Dept Med, Sch Med, 547 Burnett Womack, Chapel Hill, NC 27599 USA. RI Lennox, Jeffrey/D-1654-2014; OI Lennox, Jeffrey/0000-0002-2064-5565; Murphy, Robert/0000-0003-3936-2052 FU NIAID NIH HHS [AI38858, AI27659, AI25868] NR 35 TC 62 Z9 63 U1 0 U2 2 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 MAY PY 2000 VL 181 IS 5 BP 1622 EP 1628 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 319QV UT WOS:000087353700014 PM 10783117 ER PT J AU Kockro, RA Hampl, JA Jansen, B Peters, G Scheihing, M Giacomelli, R Kunze, S Aschoff, A AF Kockro, RA Hampl, JA Jansen, B Peters, G Scheihing, M Giacomelli, R Kunze, S Aschoff, A TI Use of scanning electron microscopy to investigate the prophylactic efficacy of rifampin-impregnated CSF shunt catheters SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID CEREBROSPINAL-FLUID SHUNTS; STAPHYLOCOCCUS-EPIDERMIDIS; INTRAVENOUS CATHETERS; IN-VITRO; INFECTIONS; COLONIZATION; PREVENTION; ADHERENCE; SLIME; SUBSTANCE AB Infection continues to be one of the major complications of cerebrospinal fluid (CSF) shunting procedures, and is caused mainly by skin-derived bacteria. Production of an extracellular biofilm plays an important role in the pathogenesis of shunt-associated infections by protecting bacteria from immune mechanisms and antibiotics. So far, removal of the original shunt and implantation of a new shunting device has been the only successful treatment for most patients, As an alternative strategy to prevent CSF infections, a rifampin-impregnated silicone catheter was designed to provide high initial and long-lasting (>60 days) release of bactericidal drug. To investigate the pathophysiological mechanism of its function, this new device was investigated both in vitro and in a rodent model of CSF infection by scanning electron microscopy (SER;I) and bacterial culture, Staphylococcus epidermidis (10(8) cfu/ml) and S, aureus (10(4) cfu/ml) served as test strains. SEM demonstrated that, in contrast to the unloaded catheters, initial bacterial adherence on the catheter surface could be reduced to a few single cells, which did not show visible signs of proliferation. Bacterial cultures obtained simultaneously were all sterile, showing that adherent bacteria were killed immediately by the rifampin released from the catheter, Although rifampin incorporation into silicone polymers was not able to prevent initial bacterial adhesion completely, subsequent colonisation could be prevented. C1 Univ Heidelberg, Dept Neurosurg, D-6900 Heidelberg, Germany. Univ Mainz, Dept Hyg & Environm Med, D-6500 Mainz, Germany. Univ Munster, Inst Med Microbiol, D-4400 Munster, Germany. RP Hampl, JA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 37 TC 87 Z9 88 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD MAY PY 2000 VL 49 IS 5 BP 441 EP 450 PG 10 WC Microbiology SC Microbiology GA 308VP UT WOS:000086733800009 PM 10798557 ER PT J AU McKay, JR Alterman, AI Cacciola, JS Mulvaney, FD O'Brien, CP AF McKay, JR Alterman, AI Cacciola, JS Mulvaney, FD O'Brien, CP TI Prognostic significance of antisocial personality disorder in cocaine-dependent patients entering continuing care SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID ADDICTION SEVERITY INDEX; SUBSTANCE-ABUSERS; RELIABILITY; ALCOHOL; DRINKING; RELAPSE; REHABILITATION; PSYCHOTHERAPY; INTERVIEW; VALIDITY AB This study examined the relationship of antisocial personality disorder (APD) to response to continuing care treatments in a sample of cocaine-dependent patients. Patients (N = 127) were randomly assigned to 20-week standard group or individualized relapse prevention continuing care interventions after the completion of an initial treatment episode and followed up at 3, 6, and 12 months. APD and non-APE patients did not differ on retention in continuing care, substance use outcomes, social function outcomes, or experiences before or during cocaine relapse episodes. A diagnosis of APD was also not a predictor of differential response to the two continuing care interventions in the study. However, APD patients had worse medical and psychiatric problem severity than non-APE patients at entrance to continuing care and during follow-up. These results suggest that cocaine patients with APD who are in the continuing care phase of outpatient rehabilitation might benefit from additional medical and psychiatric treatment services. C1 Univ Penn, Treatment Res Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP McKay, JR (reprint author), Univ Penn, Treatment Res Ctr, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA05186, DA08399, DA00361] NR 39 TC 39 Z9 39 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAY PY 2000 VL 188 IS 5 BP 287 EP 296 DI 10.1097/00005053-200005000-00006 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 313YZ UT WOS:000087028500006 PM 10830566 ER PT J AU Siffert, J Poussaint, TY Goumnerova, LC Scott, RM LaValley, B Tarbell, NJ Pomeroy, SL AF Siffert, J Poussaint, TY Goumnerova, LC Scott, RM LaValley, B Tarbell, NJ Pomeroy, SL TI Neurological dysfunction associated with postoperative cerebellar mutism SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE cerebellar mutism; akinetic mutism; medulloblastoma; posterior fossa syndrome; brain tumor ID POSTERIOR-FOSSA SURGERY; PERIOPERATIVE FACTORS; CHILDREN; TUMORS; PATHOPHYSIOLOGY; MEDULLOBLASTOMA; INTELLIGENCE; DYSARTHRIA; RESECTION; COGNITION AB Background and objectives. The postoperative cerebellar mutism syndrome (CMS) is an unique acute postoperative complication characterized by transient decrease in speech output (often mutism), apathy, irritability as well as global cerebellar dysfunction. As much as 25% of patients undergoing a resection of a cerebellar or IV ventricular tumor may develop such a syndrome. In this retrospective study we characterize the clinical features of the CMS and explore potential etiologic mechanisms. Methods. We conducted a retrospective analysis of medical records and imaging tests of 8 consecutive patients with the CMS identified through the database of the Children's Hospital and Dana-Farber Cancer Institute, Boston, and compared with a control group of 8 unaffected children undergoing a comparable tumor resection. Results. In contrast to the control group, children in the affected group had marked decrease in speech output and comprehension, apathy and lack of initiative, inattention, persistent eye closure, flaccid hemiparesis and a severe global cerebellar dysfunction. Swallowing difficulties and bowel and bladder dysfunction were also observed. The median duration of the syndrome as judged by the persistence of the communication abnormalities was 4 weeks. The recovery was near complete with exception for a persistent global cerebellar dysfunction. A comparison of CT and MRI scans of children in both groups failed to identify distinguishing features. Conclusion. A surgical lesion of the midline cerebellum can cause a complex neurological dysfunction such as the CMS. Thus, we postulate that the cerebellum and its connections function as a 'modulatory system' in control of both motor and non-motor functions, including attention and language. C1 Beth Israel Med Ctr, Hyman Newman Inst Neurol & Neurosurg, New York, NY 10028 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Radiat Oncol, Boston, MA USA. RP Siffert, J (reprint author), Beth Israel Med Ctr, Hyman Newman Inst Neurol & Neurosurg, 170 E End Ave, New York, NY 10028 USA. NR 33 TC 65 Z9 66 U1 1 U2 3 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 MAY PY 2000 VL 48 IS 1 BP 75 EP 81 DI 10.1023/A:1006483531811 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 351CA UT WOS:000089137400010 PM 11026700 ER PT J AU Pays, L Schwarting, G AF Pays, L Schwarting, G TI Gal-NCAM is a differentially expressed marker for mature sensory neurons in the rat olfactory system SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE olfactory; NCAM; glycolipid; maturation; rat ID CELL-ADHESION MOLECULE; POLYSIALIC ACID; N-CAM; MONOCLONAL-ANTIBODIES; TOPOGRAPHIC ORDER; VOMERONASAL AXONS; RECEPTOR NEURONS; ADULT-RATS; PROTEIN; GROWTH AB A new monoclonal antibody, 2E11, was produced by immunizing mice with the microsomal fraction of rat accessory olfactory bulb cells. This IgM recognizes a previously described complex alpha-galactosyl containing glycolipid, as well as N-linked glycoproteins at 170 and 210 kD. These proteins correspond to a new nerve cell adhesion molecule (NCAM) glycoform, Gal-NCAM, which contains a blood group B-like oligosaccharide, During embryonic development, the 2E11 epitope is expressed by a subset of mature olfactory sensory neurons randomly dispersed throughout the olfactory epithelium, whereas in the olfactory bulb, immunostaining is restricted to medial areas of the nerve layer. When compared to PSA-NCAM, another NCAM glycoform, Gal-NCAM has a mutually exclusive distribution pattern both in the olfactory epithelium and in the olfactory bulb. We propose a model for the hierarchy of neuronal maturation in the olfactory epithelium, including a switch from PSA-NCAM expression by immature neurons to the expression of Gal-NCAM by mature neurons, (C) 2000 John Wiley & Sons, Inc. J Neurobiol 43: 173-185, 2000. C1 Shriver Ctr, Waltham, MA 02452 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Pays, L (reprint author), Shriver Ctr, 200 Trapelo Rd, Waltham, MA 02452 USA. FU NIDCD NIH HHS [DC 00953] NR 46 TC 20 Z9 20 U1 1 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD MAY PY 2000 VL 43 IS 2 BP 173 EP 185 DI 10.1002/(SICI)1097-4695(200005)43:2<173::AID-NEU7>3.0.CO;2-# PG 13 WC Neurosciences SC Neurosciences & Neurology GA 308DT UT WOS:000086695800007 PM 10770846 ER PT J AU Schinkmann, KA Kim, TA Avraham, S AF Schinkmann, KA Kim, TA Avraham, S TI Glutamate-stimulated activation of DNA synthesis via mitogen-activated protein kinase in primary astrocytes: Involvement of protein kinase C and related adhesion focal tyrosine kinase SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE glutamate; primary astrocytes; mitogen-activated protein kinase; tyrosine kinase; related adhesion focal tyrosine kinase (RAFTK) ID LONG-TERM POTENTIATION; CULTURED ASTROCYTES; COUPLED RECEPTORS; INDUCED APOPTOSIS; GLIAL-CELLS; CALCIUM; PHOSPHORYLATION; PYK2; MEGAKARYOCYTES; BRAIN AB Glutamate is the major excitatory neurotransmitter in the CNS. Although its role in neurons has been studied extensively, little is known about its function in astrocytes. We studied the effects of glutamate on signaling pathways in primary astrocytes. We found that the tyrosine kinase related adhesion focal tyrosine kinase (RAFTK) is tyrosine phosphorylated in response to glutamate in a time- and dose-dependent manner. This phosphorylation was pertussis toxin (PTX) sensitive and could be attenuated by the depletion of Ca2+ from intracellular stores. RAFTK tyrosine phosphorylation was mediated primarily by class I/II metabotropic glutamate receptors and depends on protein kinase C (PKC) activation. Glutamate treatment of primary astrocytes also results in a significant increase in the activity of the mitogen-activated protein kinases [extracellular signal-related kinases 1/2 (ERK1/2)]. Like RAFTK phosphorylation, ERK1/2 activation is PTX sensitive and can be attenuated by the depletion of intracellular Ca2+ and by PKC inhibition, suggesting that RAFTK might mediate the glutamate-dependent activation of ERK1/2. Furthermore, we demonstrated that glutamate stimulation of primary astrocytes leads to a significant increase in DNA synthesis. Glutamate-stimulated DNA synthesis is PTX sensitive and can be inhibited by the MAP kinase kinase inhibitor PD98059, suggesting that in primary astrocytes, glutamate might signal via RAFTK and MAP kinase to promote DNA synthesis and cell proliferation. C1 Harvard Univ, Sch Med, Inst Med, BIDMC,Div Expt Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Avraham, S (reprint author), Harvard Univ, Sch Med, Inst Med, BIDMC,Div Expt Med, 4 Blackfan Circle,Rm 323, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 55445] NR 45 TC 30 Z9 32 U1 0 U2 3 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 MAY PY 2000 VL 74 IS 5 BP 1931 EP 1940 DI 10.1046/j.1471-4159.2000.0741931.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 304CY UT WOS:000086466200017 PM 10800936 ER PT J AU Jenkins, BG Klivenyi, P Kustermann, E Andreassen, OA Ferrante, RJ Rosen, BR Beal, MF AF Jenkins, BG Klivenyi, P Kustermann, E Andreassen, OA Ferrante, RJ Rosen, BR Beal, MF TI Nonlinear decrease over time in N-acetyl aspartate levels in the absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington's disease mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE spectroscopy; N-acetyl aspartate; glutamine; glucose; Huntington's disease transgenic mice ID MAGNETIC-RESONANCE SPECTROSCOPY; KETONE-BODY METABOLISM; PROTON MR SPECTROSCOPY; INTRANUCLEAR INCLUSIONS; IN-VIVO; RAT-BRAIN; ASTROGLIAL RELATIONSHIPS; MITOCHONDRIAL DISORDERS; NEUROLOGICAL PHENOTYPE; 3-NITROPROPIONIC ACID AB Mice transgenic for exon I of mutant huntingtin, with 141 CAG repeals, exhibit a profound symptomatology characterized by weight loss, motor disorders, and early death. We performed longitudinal analysis of metabolite levels in these mice using NMR spectroscopy in vivo and in vitro. These mice exhibited a large (53%), nonlinear drop in in vivo N-acetyl aspartate (NAA) levels over time, commencing at similar to 6 weeks of age, coincident with onset of symptoms. These drops in NAA levels occurred in the absence of neuronal death as measured by postmortem Nissl staining and neuronal counting but in the presence of nuclear inclusion bodies. In addition to decreased NAA, these mice showed a large elevation of glucose in the brain (600%) consistent with a diabetic profile and elevations in blood glucose levels both before and after glucose loading. In vitro NMR analysis revealed significant increases in glutamine (100%), taurine (95%) cholines (200%), and scyllo-inositol (333%) and decreases in glutamate (24%) and succinate (47%). These results lead to two conclusions. NAA is reflective of the health of neurons and thus is a noninvasive marker, with a temporal progression similar to nuclear inclusion bodies and symptoms, of neuronal dysfunction in transgenic mice. Second, the presence of elevated glutamine is evidence of a profound metabolic defect. We present arguments that the elevated glutamine results from a decrease in neuronal-glial glutamate-glutamine cycling and a decrease in glutaminase activity. C1 Cornell Univ, Coll Med, Dept Neurol & Neurosci, New York, NY 10021 USA. Dept Vet Affairs, Bedford, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Beal, MF (reprint author), Cornell Univ, Coll Med, Dept Neurol, 525 E 68th St, New York, NY 10021 USA. FU NINDS NIH HHS [NS16367, NS31579, NS39258] NR 82 TC 110 Z9 113 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2000 VL 74 IS 5 BP 2108 EP 2119 DI 10.1046/j.1471-4159.2000.0742108.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 304CY UT WOS:000086466200037 PM 10800956 ER PT J AU Weiner, HL Guttmann, CRG Khoury, SJ Orav, EJ Hohol, MJ Kikinis, R Jolesz, FA AF Weiner, HL Guttmann, CRG Khoury, SJ Orav, EJ Hohol, MJ Kikinis, R Jolesz, FA TI Serial magnetic resonance imaging in multiple sclerosis: correlation with attacks, disability, and disease stage SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; MRI; natural history; disability ID BRAIN MRI; HYPOINTENSE LESIONS; NATURAL-HISTORY; ENHANCED MRI; FOLLOW-UP; PROGRESSION; SPECTROSCOPY; VOLUME AB Serial MRI and clinical testing was performed on 45 well-defined untreated multiple sclerosis patients in different categories of disease (relapsing-remitting, progressive, stable). Up to 24 MRIs were scheduled over a 1-year period for each patient. Clinical evaluation was performed monthly and at times of attacks using the Expanded Disability Status Scale (EDSS) and the Ambulation Index (AI). MRI scans were performed both with and without gadolinium enhancement. MRI lesion volume was determined by computerized analysis and gadolinium-enhancing lesions were counted by radiologists. We observed an increase in lesion volume over 1 year in all patient groups except those classified clinically as stable. In relapsing-remitting patients there were correlations between increases in the number of gadolinium enhancing lesions and increases in EDSS and the occurrence of attacks. In chronic progressive patients, increases in lesion volume were correlated with both increases in EDSS and AI. These results demonstrate a linkage between MRI and clinical disease that depends both on the stage of MS and the MRI measures used and support the use of MRI as a surrogate marker of clinical disability in the study of multiple sclerosis. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Weiner, HL (reprint author), Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, 77 Ave Louis Pasteur,HIM 730, Boston, MA 02115 USA. OI khoury, samia/0000-0003-3198-6063 FU NCRR NIH HHS [NCRR GCRC M01]; NINDS NIH HHS [N01-NS-0-2397] NR 47 TC 59 Z9 60 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAY 1 PY 2000 VL 104 IS 2 BP 164 EP 173 DI 10.1016/S0165-5728(99)00273-8 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 297FL UT WOS:000086071200009 PM 10713356 ER PT J AU Hyman, BT Christie, R Carter, C Kajdasz, S Bacskai, B AF Hyman, BT Christie, R Carter, C Kajdasz, S Bacskai, B TI Multiphoton in vivo immuno-imaging of amyloid deposits in a transgenic model of Alzheimer's disease. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2000 VL 59 IS 5 MA 22 BP 424 EP 424 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 311EE UT WOS:000086871100032 ER PT J AU North, PE Mizeracki, A Waner, M Mihm, MC Mrak, RE AF North, PE Mizeracki, A Waner, M Mihm, MC Mrak, RE TI Do juvenile hemangiomas originate from endoneurial microvasculature? SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Arkansas Childrens Hosp, Dept Vet Affairs Med Ctr, Little Rock, AR 72202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2000 VL 59 IS 5 MA 39 BP 429 EP 429 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 311EE UT WOS:000086871100049 ER PT J AU Stemmer-Rachamimov, AO Murthy, V Haddad, L Roy, J Cutone, A Beauchamp, RL Smith, N Ramesh, V Louis, DN AF Stemmer-Rachamimov, AO Murthy, V Haddad, L Roy, J Cutone, A Beauchamp, RL Smith, N Ramesh, V Louis, DN TI Tuberin and hamartin are co-expressed in tissues and have similar developmental regulation. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2000 VL 59 IS 5 MA 82 BP 439 EP 439 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 311EE UT WOS:000086871100092 ER PT J AU Newell, KL Hobbs, W Srinidhi, L MacDonald, M Gusella, J Vonsattel, JP AF Newell, KL Hobbs, W Srinidhi, L MacDonald, M Gusella, J Vonsattel, JP TI Neuronal nuclear inclusions in asymptomatic subjects at risk for Huntington's disease. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2000 VL 59 IS 5 MA 178 BP 463 EP 463 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 311EE UT WOS:000086871100187 ER PT J AU Endres, M Meisel, A Biniszkiewicz, D Namura, S Prass, K Ruscher, K Lipski, A Jaenisch, R Moskowitz, MA Dirnagl, U AF Endres, M Meisel, A Biniszkiewicz, D Namura, S Prass, K Ruscher, K Lipski, A Jaenisch, R Moskowitz, MA Dirnagl, U TI DNA methyltransferase contributes to delayed ischemic brain injury SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cerebral ischemia; delayed cell death; DNA damage; DNA methylation; DNA methyltransferase; gene expression ID HISTONE ACETYLATION; CEREBRAL-ISCHEMIA; GERM-LINE; METHYLATION; GENE; CANCER; DAMAGE; CONSEQUENCES; EUKARYOTES; EXPRESSION AB DNA methylation is important for controlling the profile of gene expression and is catalyzed by DNA methyltransferase (MTase), an enzyme that is abundant in brain. Because significant DNA damage and alterations in gene expression develop as a consequence of cerebral ischemia, we measured MTase activity in vitro and DNA methylation in vivo after mild focal brain ischemia. After 30 min middle cerebral artery occlusion (MCAo) and reperfusion, MTase catalytic activity and the 190 kDa band on immunoblot did not change over time. However, [H-3]methyl-group incorporation into DNA increased significantly in wildtype mice after reperfusion, but not in mutant mice heterozygous for a DNA methyltransferase gene deletion (Dnmt(S/+)). Dnmt(S/+) mice were resistant to mild ischemic damage, suggesting that increased DNA methylation is associated with augmented brain injury after MCA occlusion. Consistent with this formulation, treatment with the MTase inhibitor 5-aza-2'-deoxycytidine and the deacetylation inhibitor trichostatin A conferred stroke protection in wild-type mice. In contrast to mild stroke, however, DNA methylation was not enhanced, and reduced dnmt gene expression was not protective in an ischemia model of excitotoxic/necrotic cell death. In conclusion, our results demonstrate that MTase activity contributes to poor tissue outcome after mild ischemic brain injury. C1 Humboldt Univ, Charite Hosp, Dept Neurol, Div Expt Neurol, D-10098 Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Endres, M (reprint author), Humboldt Univ, Charite Hosp, Dept Neurol, Div Expt Neurol, D-10098 Berlin, Germany. RI Moskowitz, Michael/D-9916-2011; OI Meisel, Andreas/0000-0001-7233-5342; Dirnagl, Ulrich/0000-0003-0755-6119 FU NINDS NIH HHS [NS10828] NR 51 TC 138 Z9 142 U1 1 U2 5 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 MAY 1 PY 2000 VL 20 IS 9 BP 3175 EP 3181 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 309RL UT WOS:000086783000015 PM 10777781 ER PT J AU Kourtzi, Z Kanwisher, N AF Kourtzi, Z Kanwisher, N TI Cortical regions involved in perceiving object shape SO JOURNAL OF NEUROSCIENCE LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Neuroscience CY OCT 23-28, 1999 CL MIAMI BEACH, FLORIDA SP Soc Neurosci DE shape perception; object recognition; neuroimaging; visual cortex; lateral and ventral occipital; adaptation ID INFERIOR TEMPORAL NEURONS; DEPTH-PERCEPTION; FUNCTIONAL MRI; CORTEX; RECOGNITION; MACAQUE; SELECTIVITY; FMRI; REPRESENTATION; MECHANISMS AB The studies described here use functional magnetic resonance imaging to test whether common or distinct cognitive and/or neural mechanisms are involved in extracting object structure from the different image cues defining an object's shape, such as contours, shading, and monocular depth cues. We found overlapping activations in the lateral and ventral occipital cortex [known as the lateral occipital complex (LOC)] for objects defined by different visual cues (e.g., grayscale photographs and line drawings) when each was compared with its own scrambled-object control. In a second experiment we found a reduced response when objects were repeated, independent of whether they appeared in the same or a different format (i.e., grayscale images vs line drawings). A third experiment showed that activation in the LOC was no stronger for three-dimensional shapes defined by contours or monocular depth cues, such as occlusion, than for two-dimensional shapes, suggesting that these regions are not selectively involved in processing three-dimensional shape information. These results suggest that common regions in the LOC are involved in extracting and/or representing information about object structure from different image cues. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Kourtzi, Z (reprint author), MIT, Dept Brain & Cognit Sci, NE20-4043,3 Cambridge Ctr,77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NIMH NIH HHS [NIMH 56037] NR 43 TC 402 Z9 405 U1 11 U2 22 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 MAY 1 PY 2000 VL 20 IS 9 BP 3310 EP 3318 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 309RL UT WOS:000086783000028 PM 10777794 ER PT J AU Harsh, GR Deisboeck, TS Louis, DN Hilton, J Colvin, M Silver, JS Qureshi, NH Kracher, J Finkelstein, D Chiocca, EA Hochberg, FH AF Harsh, GR Deisboeck, TS Louis, DN Hilton, J Colvin, M Silver, JS Qureshi, NH Kracher, J Finkelstein, D Chiocca, EA Hochberg, FH TI Thymidine kinase activation of ganciclovir in recurrent malignant gliomas: a gene-marking and neuropathological study SO JOURNAL OF NEUROSURGERY LA English DT Article DE gene therapy; brain neoplasm; ganciclovir; glioblastoma multiforme ID EXPERIMENTAL BRAIN-TUMORS; VECTOR PRODUCER CELLS; THERAPY; INVIVO AB Object. The gene therapy paradigm of intratumoral activation of ganciclovir (GCV) following transduction of tumor cells by retroviral vectors bearing the thymidine kinase (tk) gene has produced dramatic remissions of malignant gliomas in animal models. In human trials, although the technique has been deemed safe, little antitumor effect has been demonstrated. To evaluate the basis of this inefficacy in human gliomas, the authors conducted a gene-marking trial involving neuropathological and biochemical studies of treated tumor specimens. Methods. Five patients with malignant recurrent gliomas underwent stereotactic biopsy sampling and intratumoral implantation procedures with three aliquots of 10(6) vector-producing cells (VPCs) in columns. After 5 days, the tumor was resected and the tumor bed reimplanted with VPCs, and a course of GCV was given. Patients received clinical and radiological follow up for 6 months. Tumor specimens were analyzed neuropathologically and for tk gene expression by anti-TK immunohistochemistry and TK enzymatic activity. Four patients tolerated the treatment well but experienced tumor progression. The other developed an abscess after the second operation and died. Increased TK enzymatic activity was demonstrated in the one tumor specimen analyzed. Immunohistochemical evidence of tk gene expression was limited to VPCs. Transduction of tumor cells was not seen. Viable tumor cells were seen near VPCs containing TK. The lymphocytic immune response was mild. Conclusions. Except for the risk of infection inherent in reoperation, this tk-GCV paradigm was both feasible and safe. Pathological studies indicated that limited dissemination of VPCs and vector from the infusion site and failure to transduce tumor cells with the tk gene are major barriers to efficacy. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurol, Neurosurg Serv,Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA USA. RP Harsh, GR (reprint author), Stanford Med Ctr R227, Dept Neurosurg, Stanford, CA 94305 USA. FU NCI NIH HHS [5PO1CA69246] NR 20 TC 71 Z9 75 U1 0 U2 2 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 MAY PY 2000 VL 92 IS 5 BP 804 EP 811 DI 10.3171/jns.2000.92.5.0804 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 307VV UT WOS:000086675600009 PM 10794295 ER PT J AU Agostini, HT Ryschkewitsch, CF Baumhefner, RW Tourtellotte, WW Singer, EJ Komoly, S Stoner, GL AF Agostini, HT Ryschkewitsch, CF Baumhefner, RW Tourtellotte, WW Singer, EJ Komoly, S Stoner, GL TI Influence of TC virus coding region genotype on risk of multiple sclerosis and progressive multifocal leukoencephalopathy SO JOURNAL OF NEUROVIROLOGY LA English DT Article; Proceedings Paper CT Symposium on An Update on Multiple Sclerosis Research and Care CY MAY 03-05, 1999 CL MILAN, ITALY SP Dompe Biotec, Farmades s p a, Serono Pharma, Teva Pharm, Beckman Coulter, Int Lab, Celbio, Space Inport Export, Dasit, PBI Int DE polyomavirus; genotype; demyelination; nuclear factor-1 site ID POLYOMAVIRUS JC-VIRUS; BRAIN-TISSUE; CEREBROSPINAL-FLUID; REGULATORY REGIONS; TRANSGENIC MICE; SEQUENCES; DNA; INFECTION; PROTEIN; URINE AB Two features of the biology of JC virus make it a particularly suitable candidate for an agent in MS-like disease: its neurotropic capability targeting glial cells as evidenced in progressive multifocal leukoencephalopathy lesions, and its capacity for latency and persistence as illustrated by its behaviour in the kidney. TC virus is chronically or intermittently excreted in the urine by some 40% of the population. The existence of TC virus in multiple coding-region genotypes provides a unique approach to the study of JC virus-induced neurological disease. We have previously shown that a genotype originating in Asia but also present in Europe and the US, called Type 2B, is more frequently found in PML brain than expected based on its prevalence in urine samples from a control population. In contrast, we find that the excretion of JCV in MS patients is similar in both genotype and frequency to that of control individuals, and appears to be regulated by factors unrelated to those that control CNS disease activity. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. W Los Angeles Vet Affairs Med Ctr, Serv Neurol, Los Angeles, CA 90073 USA. John Ferenc Del Pesti Teaching Hosp, Budapest, Hungary. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-27,MSC-4126, Bethesda, MD 20892 USA. NR 41 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD MAY PY 2000 VL 6 SU 2 BP S101 EP S108 PG 8 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 326RN UT WOS:000087748700023 PM 10871796 ER PT J AU Gabuzda, D Wang, JB AF Gabuzda, D Wang, JB TI Chemokine receptors and mechanisms of cell death in HIV neuropathogenesis SO JOURNAL OF NEUROVIROLOGY LA English DT Article; Proceedings Paper CT Symposium on HIV and Nervous System: Emerging Issues CY APR 14-16, 1999 CL BETHESDA, MARYLAND SP Natl Inst Mental Hlth, Natl Inst Neurol DE HIV-1; chemokine receptor; microglia; brain; apoptosis ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; IN-VIVO DISTRIBUTION; BLOOD-BRAIN-BARRIER; ACQUIRED-IMMUNODEFICIENCY; TYPE-1 INFECTION; NEURONAL APOPTOSIS; CORECEPTORS CXCR4; ENDOTHELIAL-CELLS; AIDS DEMENTIA AB Several chemokine receptors are used as coreceptors for HIV-1 entry in the central nervous system (CNS). CCR5 is the major coreceptor together with CD4 for HIV-1 infection of microglia, the major target cells for HIV-1 infection in the CNS. CXCR4 and CCR3 are also expressed on microglia and can mediate infection by certain HIV-1 isolates but at lower efficiency than CCR5, Additional chemokine coreceptors are expressed in the brain, but their role in HIV-1 neuropathogenesis has not been defined. The expression of CXCR4, and possibly other chemokine receptors, on subpopulations of neurons and glial cells may render neurons vulnerable to mechanisms of CNS injury induced by the HIV-1 gp120 Env protein. HIV-1 viruses which use CXCR4 and emerge during the late stages of HIV-1 infection may impact disease progression in the CNS by inducing apoptosis of neurons and other cell types. The neurodegenerative mechanisms may involve infection of microglia by certain CXCR4 tropic viruses in addition to cellular dysfunction and apoptosis induced by HIV-1 gp120 binding to CXCR4. Understanding the role of CXCR4 and other chemokine receptors in HIV-1 neuropathogenesis will help to advance the development of new therapeutic strategies for the prevention and treatment of neurologic disorders associated with HIV-1 infection. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JF816,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 28691]; NINDS NIH HHS [NS35734, NS37277] NR 83 TC 67 Z9 70 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD MAY PY 2000 VL 6 SU 1 BP S24 EP S32 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 326RM UT WOS:000087748600004 PM 10871762 ER PT J AU Dougherty, DD Bonab, AA Biederman, J Spencer, TJ Rauch, SL Madras, BK Dragotakes, SD Alpert, NM Fischman, AJ AF Dougherty, DD Bonab, AA Biederman, J Spencer, TJ Rauch, SL Madras, BK Dragotakes, SD Alpert, NM Fischman, AJ TI Assessment of dopamine transporter density in patients with attention deficit hyperactivity disorder using I-123-altropane. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 104 BP 27P EP 27P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400105 ER PT J AU Alpert, NM Bonab, A Fischman, AJ AF Alpert, NM Bonab, A Fischman, AJ TI The simplified reference region model for parametric imaging: Domain of validity. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 226 BP 57P EP 58P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400227 ER PT J AU Aquino, SL Moore, RH Asmuth, J McLoud, TC Fischman, AJ AF Aquino, SL Moore, RH Asmuth, J McLoud, TC Fischman, AJ TI Non linear registration of FDG-PET and thoracic CT data sets. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 234 BP 60P EP 60P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400235 ER PT J AU Kimura, Y Ishii, K Senda, M Alpert, NH AF Kimura, Y Ishii, K Senda, M Alpert, NH TI Formation of FDG parametric images based on clustering and principal components. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Tokyo Metropolitan Inst Gerontol, Tokyo, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 397 BP 100P EP 101P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400398 ER PT J AU Brownell, AL Chen, YI Cicchetti, F Livni, E Jenkins, BG Isacson, O AF Brownell, AL Chen, YI Cicchetti, F Livni, E Jenkins, BG Isacson, O TI Is infammation a factor in neurodegeneration. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, McLean Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 407 BP 103P EP 103P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400408 ER PT J AU Madras, BK Babich, JW Livni, E Bonab, AA Fischman, AJ AF Madras, BK Babich, JW Livni, E Bonab, AA Fischman, AJ TI Pet imaging of the dopamine transporter: A window on dopamine neuron regeneration in Parkinsonian monkeys. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 410 BP 104P EP 104P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400411 ER PT J AU Jacobson, AF Haseley, DR AF Jacobson, AF Haseley, DR TI Reliability of left ventricular ejection fraction (LVEF) determinations from gated myocardial spect imaging (GMSI) with Tl-201. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 492 BP 125P EP 125P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400493 ER PT J AU Bonab, AA Meltzer, P Hillier, S Burker, M Barrow, SA Madras, BK Fischman, AJ AF Bonab, AA Meltzer, P Hillier, S Burker, M Barrow, SA Madras, BK Fischman, AJ TI Quantification of SPECT imaging with a highly selective DAT ligand; Tc-99m-(15)O05t. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Organix Inc, Woburn, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 839 BP 185P EP 185P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400733 ER PT J AU Dougherty, DD Bonab, AA Alpert, NM Rauch, SL Fava, M Ottowitz, W Livni, E Fischman, AJ AF Dougherty, DD Bonab, AA Alpert, NM Rauch, SL Fava, M Ottowitz, W Livni, E Fischman, AJ TI PET receptor studies of major depression with anger attacks. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Butler Hosp, Providence, RI 02906 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 899 BP 199P EP 199P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400793 ER PT J AU Bonab, AA Alpert, NM Livni, E Fischman, AJ AF Bonab, AA Alpert, NM Livni, E Fischman, AJ TI Measurement of DAT binding potential with C-11-Altropane. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 931 BP 207P EP 207P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400825 ER PT J AU Madras, BK Bonab, AA Livni, E Babich, JW Meltzer, PC Fischman, AJ AF Madras, BK Bonab, AA Livni, E Babich, JW Meltzer, PC Fischman, AJ TI [C-11]Tropoxene, a dopamine transport inhibitor that bears no amine nitrogens, accumulates in the dopamine-rich striatum of monkey: A PET study. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Organix Inc, Woburn, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 933 BP 208P EP 208P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400827 ER PT J AU Hillier, S Burker, M Meltzer, P Madras, BK Fischman, AJ AF Hillier, S Burker, M Meltzer, P Madras, BK Fischman, AJ TI Radiolabeling of the highly selective DAT ligand, O-(15)O5T, with Tc-99m: Choice of transchelation agent. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1067 BP 241P EP 242P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892400961 ER PT J AU Choi, NC Fischman, AJ Hunter, G Hamberg, L McLoud, T AF Choi, NC Fischman, AJ Hunter, G Hamberg, L McLoud, T TI Dose response relation between PET-FDG uptake after chemo-radiotherapy (CT plus rT) and histopathologic tumor control (PTCP) in stage III lung cancer. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1253 BP 287P EP 287P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401147 ER PT J AU Jacobson, AF Maisey, RN Fogelman, I Kuhn, D AF Jacobson, AF Maisey, RN Fogelman, I Kuhn, D TI Yield of FDG-PET scanning as a routine follow-up exam in patients with malignancy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Guys & St Thomas Hosp, London SE1 9RT, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1325 BP 304P EP 304P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401219 ER PT J AU Carter, EA Tompkins, RG Fischman, AJ AF Carter, EA Tompkins, RG Fischman, AJ TI Detection of Helicobacteria overgrowth ln the large intestine of rats. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1376 BP 316P EP 316P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401270 ER PT J AU Fischman, AJ Carter, EA Tompkins, RG AF Fischman, AJ Carter, EA Tompkins, RG TI Pulmonary sequestration of neutrophils is increased in severe but not in mild experimental pancreatitis. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1384 BP 318P EP + PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401278 ER PT J AU Carter, EA Tompkins, RG Fischman, AJ AF Carter, EA Tompkins, RG Fischman, AJ TI Thermal injury in rats is associated with increased replication and apoptosis in wound, intestine and spleen: Implications for radionuclide imaging. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1424 BP 328P EP 328P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401318 ER PT J AU Carter, EA Strauss, HW Tait, J Tompkins, RG Fischman, AJ AF Carter, EA Strauss, HW Tait, J Tompkins, RG Fischman, AJ TI Burn induced insulin resistance in rats is associated with increased in vivo uptake of I-125-annexin by skeletal muscle and bone. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Stanford Univ, Palo Alto, CA 94304 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2000 VL 41 IS 5 SU S MA 1428 BP 329P EP 329P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364KW UT WOS:000089892401322 ER PT J AU Huang, XD Cuajungco, MP Atwood, CS Moir, RD Tanzi, RE Bush, AI AF Huang, XD Cuajungco, MP Atwood, CS Moir, RD Tanzi, RE Bush, AI TI Alzheimer's disease, beta-amyloid protein and zinc SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Workshop on Zinc and Health - Current Status and Future Directions CY NOV 04-05, 1998 CL BETHESDA, MARYLAND SP NIH, Amer Dietet Assoc, Amer Soc Clin Nutrit, Ctr Dis Control & Prevent, FDA, US Dept Defense, Ctr Food Safety & Appl Nutrit DE Alzheimer's disease; amyloid precursor protein; A beta amyloid; zinc; homeostasis ID RECEPTOR-RELATED PROTEIN; PRECURSOR PROTEIN; FIBRIL FORMATION; CEREBROSPINAL-FLUID; TRANSGENIC MICE; HIPPOCAMPAL CULTURES; REACTIVE ASTROCYTES; OXIDATIVE STRESS; BINDING-SITE; RAT-BRAIN AB Alzheimer's disease (AD) is characterized by amyloid deposits within the neocortical parenchyma and the cerebrovasculature. The main component of these predominantly extracellular collections, A beta, which is normally a soluble component of all biological fluids, is cleaved out of a ubiquitously expressed parent protein, the amyloid protein precursor (APP), one of the type 1 integral membrane glycoproteins, Considerable evidence has indicated that there is zinc dyshomeostasis and abnormal cellular zinc mobilization in AD. We have characterized both APP and A beta as copper/zinc metalloproteins, Zinc, copper and iron have recently been reported to be concentrated to 0.5 to 1 mmol/L in amyloid plaque. In vitro, rapid A beta aggregation is mediated by Zn(ll), promoted by the alpha-helical structure of A beta, and is reversible with chelation, In addition, A beta produces hydrogen peroxide in a Cu(ll)/Fe(lll)-dependent manner, and the hydrogen peroxide formation is quenched by Zn(ll), Moreover, zinc preserves the nontoxic properties of A beta, Although the zinc-binding proteins apolipoprotein E epsilon 4 allele and alpha(2)-macroglobulin have been characterized as two genetic risk factors for AD, zinc exposure as a risk factor for AD has not been rigorously studied. Based on our findings, we envisage that zinc may serve twin roles by both initiating amyloid deposition and then being involved in mechanisms attempting to quench oxidative stress and neurotoxicity derived from the amyloid mass. Hence, it remains debatable whether zinc supplementation is beneficial or deleterious for AD until additional studies clarify the issue. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Genet & Aging Unit,Lab Oxidat Biol, Charleston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Unit,Lab Oxidat Biol, Charleston, MA 02129 USA. RP Bush, AI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Genet & Aging Unit,Lab Oxidat Biol, Charleston, MA 02129 USA. RI Cuajungco, Math/B-2647-2008; Bush, Ashley/A-1186-2007 OI Cuajungco, Math/0000-0003-0749-9564; Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [R29-AG12686, F32-AG05782] NR 94 TC 84 Z9 90 U1 2 U2 19 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2000 VL 130 IS 5 SU S BP 1488S EP 1492S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 311ZP UT WOS:000086917400025 PM 10801964 ER PT J AU Troulis, MJ Glowacki, J Perrott, DH Kaban, LB AF Troulis, MJ Glowacki, J Perrott, DH Kaban, LB TI Effects of latency and rate on bone formation in a porcine mandibular distraction model SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 80th Annual Meeting of AAOMS CY SEP, 1998 CL NEW ORLEANS, LOUISIANA ID GRADUAL DISTRACTION; INTERNAL DEVICES; OSTEOGENESIS; OSTEOTOMIES; MAXILLARY; MINIPIGS; SURGERY AB Purpose: Long treatment protocols currently limit the application of distraction osteogenesis (DO). The purpose of this study was to develop a porcine model for DO and to define the effects of latency and distraction rate on bone formation. Materials and Methods: Distracters were placed through submandibular incisions. For analysis of latency, mandibular osteotomies were distracted after 0 (n = 3) or 4 (n = 2) days at a rate of 1 mm/d (7 days) with 14 daps fixation. For analysis of rate, osteotomies were distracted at 1 mm (n = 4), 2 mm (n = 4), or 4 mm (n = 4) per day to produce a 12-mm gap with 24 days fixation.. DO mounds mere assessed in vivo with bimanual palpation to detect mobility across the gap. Harvested specimens were evaluated by gross appearance and bimanual palpation. Standardized radiographic techniques were used to estimate bone density. Results: During DO, animals showed normal activity. There were no infections, and no distracters were removed prematurely. Clinical and radiographic evaluation of the groups that underwent distraction after 0- or 4-day latency showed equivalent healing. In the comparison of distraction rates, stability was greatest in the group distracted at 1 mm/d. Conclusions: A porcine model for mandibular DO has been developed in which mandibular lengthening was successful performed without latency and at a rate of 1 mm/d. The relationships among latency, gap size, rate, and duration of fixation are poorly understood and can be defined with relevant animal models. (C) 2000 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Skeletal Biol Res Ctr, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Warren 1201, Boston, MA 02114 USA. NR 30 TC 70 Z9 73 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2000 VL 58 IS 5 BP 507 EP 513 DI 10.1016/S0278-2391(00)90012-0 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 308WC UT WOS:000086735000012 PM 10800906 ER PT J AU Zaleske, DJ AF Zaleske, DJ TI Localization of dominantly inherited isolated triphalangeal thumb SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zaleske, DJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 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 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAY PY 2000 VL 18 IS 3 BP 339 EP 339 DI 10.1002/jor.1100180302 PG 1 WC Orthopedics SC Orthopedics GA 338VJ UT WOS:000088443700001 PM 10937617 ER PT J AU Matsumura, T Whelan, MC Li, XQ Trippel, SB AF Matsumura, T Whelan, MC Li, XQ Trippel, SB TI Regulation by IGF-I and TGF-beta 1 of swarm-rat chondrosarcoma chondrocytes SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; PLATE CHONDROCYTES; CELL-PROLIFERATION; DNA-SYNTHESIS; TGF-BETA; PROTEOGLYCAN SYNTHESIS; OSTEO-SARCOMA; INSULIN; DIFFERENTIATION; FACTOR-BETA-1 AB The growth factors transforming growth factor-beta 1 and insulin-like growth factor-I influence a wide range of cellular actions, including the growth of several neoplastic cell types. Their role in the regulation of neoplastic chondrocytes remains unclear. We tested the hypotheses that transforming growth factor-beta 1 and insulin-like growth factor-I differentially regulate neoplastic chondrocytes and interact to modulate the mitotic and matrix synthetic activities of neoplastic chondrocytes. We used Swarm-rat chondrosarcoma chondrocytes to investigate the effect of each factor individually and of both factors in combination on [H-3]thymidine incorporation into DNA and on [S-35]sulfate incorporation into glycosaminoglycans. Each factor increased [H-3]thymidine incorporation 2.7-fold; transforming growth factor-beta 1 achieved this effect at a 20-fold lower concentration than insulin-like growth factor-I. In contrast, insulin-like growth factor-I stimulated [S-35]sulfate incorporation 3.5-fold; this was twice the maximal effect of transforming growth factor-beta 1. Transforming growth factor-beta 1 and insulin-like growth factor-I each decreased the proportion of newly synthesized glycosaminoglycans that were retained in the cells and pericellular matrix, indicating that the anabolic effect of these factors is only partly directed toward cell associated matrix production. The mitogenic and matrix synthetic actions of insulin-like growth factor-I and transforming growth factor-beta 1 were synergistic. In concert, they increased [H-3]thymidine incorporation approximately 12-fold, an effect three times greater than the sum of the maximal stimulation achieved by each factor individually. Similarly, transforming growth factor-beta 1 and insulin-like growth factor-I together increased glycosaminoglycan synthesis approximately two times more than the sum of their maximal individual effects. Taken together, these data indicate that these chondrosarcoma chondrocytes are positively regulated by insulin-like growth factor-I and transforming growth factor-beta 1 and that these growth factors interact to augment the mitotic and matrix synthetic actions of the chondrocytes. If supported in human models, the sensitivity to growth factors of these cells suggests that interventions directed toward growth factor inhibition may be of therapeutic value. C1 Massachusetts Gen Hosp, Orthopaed Res Labs, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Trippel, SB (reprint author), Massachusetts Gen Hosp, Orthopaed Res Labs, Dept Orthopaed Surg, Jackson 11th Floor, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR 31068] NR 29 TC 23 Z9 25 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAY PY 2000 VL 18 IS 3 BP 351 EP 355 DI 10.1002/jor.1100180305 PG 5 WC Orthopedics SC Orthopedics GA 338VJ UT WOS:000088443700004 PM 10937620 ER PT J AU Waber, DP Carpentieri, SC Klar, N Silverman, LB Schwenn, M Hurwitz, CA Mullenix, PJ Tarbell, NJ Sallan, SE AF Waber, DP Carpentieri, SC Klar, N Silverman, LB Schwenn, M Hurwitz, CA Mullenix, PJ Tarbell, NJ Sallan, SE TI Cognitive sequelae in children treated for acute lymphoblastic leukemia with dexamethasone or prednisone SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE acute lymphoblastic leukemia; central nervous system; cognitive; dexamethasone ID OSTERRIETH COMPLEX FIGURE; MENINGEAL LEUKEMIA; CHILDHOOD LEUKEMIA; DECLARATIVE MEMORY; CORTICOSTEROIDS; HIPPOCAMPUS; FLUORIDE; NEUROTOXICITY; INTELLIGENCE; PRODUCTIONS AB Purpose: The cognitive sequelae of treatment for childhood acute lymphoblastic leukemia (ALL) were compared in a group of patients who received dexamethasone during the intensification and maintenance phases of therapy with those in a historical control group for whom antileukemia therapy was similar, except that the corticosteroid component of therapy was prednisone. Methods: Patients treated for ALL on Dana-Farber Cancer Institute protocols 87-01 (n = 44) and 91-01 (n = 23) were evaluated by standard cognitive and achievement tests. Corticosteroid therapy was delivered in 5-day pulses given every 3 weeks during intensification acid continuation phases of therapy for a total of 2 years. Results: Children treated on protocol 87-01 received prednisone at a dose of 40 mg/m(2)/d (standard risk, SR) or 120 mg/ m(2)/d (high risk, HR); those treated on protocol 91-01 received dexamethasone at a dose of 6 mg/m(2) per day (SR) or 18 mg/m2 per day (HR). Children treated on protocol 91-01 performed less well on cognitive testing. Subsample analysis indicated that cranial radiation therapy and methotrexate dose did not account for differences in cognitive outcomes. Conclusions: The findings of this preliminary study are consistent with the hypothesis that dexamethasone therapy can increase risk for neurocognitive late effects in children treated for ALL and indicate that further investigation of this question is warranted. C1 Childrens Hosp, Dept Psychiat, Div Psychol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Dept Pediat, Amherst, MA 01003 USA. Maine Med Ctr, Maine Childrens Canc Program, Portland, ME 04102 USA. Maine Med Ctr, Barbara Bush Childrens Hosp, Portland, ME 04102 USA. RP Waber, DP (reprint author), Dept Psychiat, Learning Disabil Res Ctr, 300 Longwood Ave,Carnegie 2, Boston, MA 02115 USA. FU NCI NIH HHS [CA06516, CA68484]; NICHD NIH HHS [P30-HD18655] NR 44 TC 94 Z9 94 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAY-JUN PY 2000 VL 22 IS 3 BP 206 EP 213 DI 10.1097/00043426-200005000-00004 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 320HJ UT WOS:000087395500003 PM 10864051 ER PT J AU Parsons, SK Mayer, DK Alexander, SW Xu, RH Land, V Laver, J AF Parsons, SK Mayer, DK Alexander, SW Xu, RH Land, V Laver, J CA Economic Evaluation Working Grp Pe TI Growth factor practice patterns among pediatric oncologists: Results of a 1998 Pediatric Oncology Group survey SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 15-18, 1999 CL ATLANTA, GEORGIA SP Amer Soc Clin Oncol DE hematopoietic growth factors; neutropenia; febrile neutropenia; pediatric oncology; practice guide lines; evidence-based medicine ID COLONY-STIMULATING FACTOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; CELL LUNG-CANCER; CLINICAL-PRACTICE GUIDELINES; MYELOSUPPRESSIVE CHEMOTHERAPY; INDUCTION CHEMOTHERAPY; FEBRILE NEUTROPENIA; CHILDREN; TRIAL; FEVER AB The American Society of Clinical Oncology (ASCO) guidelines on growth factor (GF) use recommend applying adult-derived guidelines in pediatric oncology. An ASCO survey of adult oncology GF use determined the preference for first degree prophylaxis (use of GF when febrile neutropenia [FN] is expected to be high in untreated patients), second-degree prophylaxis (administration of GF after a documented episode of FN on a previous cycle of chemotherapy), and intervention in the treatment of FN. Similar preferences have not been evaluated in pediatrics. The purpose of this study was to (1) characterize GF use in pediatric oncology; (2) correlate use patterns with demographic factors; and (3) compare the Pediatric Oncology Group (POG) and ASCO surveys. The ASCO survey was revised for use within pediatric oncology and was mailed to the physician membership of FOG; 341 were returned (85% completion rate). Comparisons were made with the ASCO survey. Most (76%) physicians said GF use was determined by protocol requirements and most (70%) patients were entered on FOG protocols. GF use as first-degree prophylaxis was selected 40% of the time, which was significantly greater than in adults; this was most influenced by anticipated duration of neutropenia (greater than or equal to 7 days). The severity of the initial clinical course (eg, neutropenia, infection) influenced use in second-degree prophylaxis; dose reduction alone was never selected. For FN, GF use was 45%, with lower preferences in uncomplicated FN (16%-38%) compared with complicated FN (66%). FOG respondents endorse greater use of GF for first and second-degree prophylaxis but less use in uncomplicated FN than do ASCO respondents. These patterns may reflect different strategies, including the role of chemotherapy, value of dose intensity, and perceived toxicity of regimens. Given these differences, adult-based guidelines may not be appropriate for pediatrics. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat,Div Hematol Oncol, Boston, MA 02115 USA. POG Operat Off, Chicago, IL USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Parsons, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-69177, CA-30969, CA-41573] NR 57 TC 7 Z9 7 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAY-JUN PY 2000 VL 22 IS 3 BP 227 EP 241 DI 10.1097/00043426-200005000-00008 PG 15 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 320HJ UT WOS:000087395500006 PM 10864054 ER PT J AU Grabowski, EF Carter, CA Tsukurov, O Conroy, N Hsu, CY Abbott, WM Ingelfinger, JR Orkin, RW AF Grabowski, EF Carter, CA Tsukurov, O Conroy, N Hsu, CY Abbott, WM Ingelfinger, JR Orkin, RW TI Comparison of human umbilical vein and adult saphenous vein endothelial cells: Implications for newborn hemostasis and for laboratory models of endothelial cell function SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article ID TISSUE FACTOR PATHWAY; BLOOD-COAGULATION; EXPRESSION; INHIBITOR; TFPI C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Grabowski, EF (reprint author), Massachusetts Gen Hosp, Blake 255,Fruit St, Boston, MA 02114 USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAY-JUN PY 2000 VL 22 IS 3 BP 266 EP 268 DI 10.1097/00043426-200005000-00016 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 320HJ UT WOS:000087395500014 PM 10864062 ER PT J AU Cooper, RA AF Cooper, RA TI Wheelchairs and related technology for the millennium - Guest editorial SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Engn Mech, Pittsburgh, PA 15213 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. NR 11 TC 5 Z9 5 U1 1 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2000 VL 37 IS 3 BP XIII EP XVI PG 4 WC Rehabilitation SC Rehabilitation GA 370YB UT WOS:000165149900002 PM 10917256 ER PT J AU Cooper, RA Dvorznak, MJ Rentschler, AJ Boninger, ML AF Cooper, RA Dvorznak, MJ Rentschler, AJ Boninger, ML TI Displacement between the seating surface and hybrid test dummy during transitions with a variable configuration wheelchair: A technical note SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article ID SHEAR AB Changing seating posture can extend the amount of time a person can safely remain seated without damaging tissue or becoming fatigued. The Excelsior is an electrically powered wheelchair that utilizes sit-to-stand (STS) and sit-to-recline (STR) motions to aid in pressure relief. The motion of the wheelchair seating system must closely follow anatomical paths or ulcers may develop from the resulting shear forces. Displacement between the person and the wheelchair seating surface is one measure of these shear forces. The displacement between a Hybrid II 50th percentile anthropometric test dummy (ATD) and the seating surface of the Excelsior wheelchair was examined during STS and STR with two cushions, a Jay Active and a low-profile Roho cushion. The difference between the backrest and ATD back angles were 4.29 degrees +/- 2.13 degrees and 1.78 degrees +/- 1.73 degrees for the Roho and Jay cushions respectively during STS and 3.32 degrees +/- 4.21 degrees and 10.71 degrees + 6.20 degrees during STR. These were statistically significant at p<.05. During STS, shear displacement between the Hybrid II back and Excelsior backrest did not exceed 1.5 cm for either cushion. ATD thigh-to-seat displacements were 2.5 cm for the Jay and 3.0 cm for the Roho cushion. STR produced dummy thigh-to-seat displacements of 1.5 cm and 3.5 cm for the Jay and Roho cushions respectively. Shear displacement in the ATD back was about 3.5 cm for the Roho and 6 cm for the Jay. The latter displacement should be reduced; however, the other conditions are marginal or acceptable. Hysteresis was acceptable or better for all cushion/motion combinations, with the highest net displacement of about 2.5 cm. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151 R1, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151 R1, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 13 TC 3 Z9 3 U1 0 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2000 VL 37 IS 3 BP 297 EP 303 PG 7 WC Rehabilitation SC Rehabilitation GA 370YB UT WOS:000165149900007 PM 10917261 ER PT J AU Puniello, MS McGibbon, CA Krebs, DE AF Puniello, MS McGibbon, CA Krebs, DE TI Lifting characteristics of functionally limited elders SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE angular momentum; balance; biomechanics; elderly; jerk; lifting; strength ID ERECTOR SPINAE; FLEXION-RELAXATION; PASSIVE TISSUES; MUSCLE-ACTIVITY; JOINT MOMENTS; ARM MOVEMENTS; GAIT VELOCITY; BACK MUSCLES; CHAIR-RISE; MODEL AB Background. The purpose of this study was to investigate the lifting characteristics of elders with functional limitations using burden lifting smoothness, trunk angular momentum, and back and hip torque, and to correlate these characteristics with strength and functional measures. Methods. Thirty elders (65-89 years old) consented to biomechanical analysis of Lifting, gait, and chair rise, and to maximum isometric strength testing of the hip and knee extensors and shoulder flexors. Jerk, the rate of change of acceleration, is a measure of smoothness of motion. We calculated peak vertical jerk of the box at the beginning part of the lift. Momentum is the product of mass and velocity. HAT (head, arms, trunk) angular momentum was calculated during chair rise. Results, Hip extensor strength correlated positively with box jerk, as did box jerk and peak trunk angular momentum between subjects. There was an inverse correlation between peak upper body angular momentum when lifting a box from floor to knee height, and gait speed normalized to body weight. There was a positive correlation between trunk angular momentum during lifting and trunk angular momentum during chair rise. Conclusion. Stronger subjects used more peak vertical box jerk and more trunk peak angular momentum to lift a box from floor to knee height. Stronger subjects who used more HAT angular momentum during free speed chair rise also used more trunk peak angular momentum during the first phase of the lift, but lifting characteristics were independent of gait velocity. Weaker subjects used less peak momentum and peak jerk, choosing instead a more conservative, and apparently more stable, lifting strategy. Before counseling elderly patients on proper body mechanics for lifting, clinicians should assess strength and functional status. Weak elders should be taught a lifting strategy that allows them to maintain optimal balance, and to lift without jerking the load. C1 Massachusetts Gen Hosp, Biomat Lab, Boston, MA 02114 USA. MGH, Inst Hlth Profess, Boston, MA 02114 USA. RP Krebs, DE (reprint author), Massachusetts Gen Hosp, Biomat Lab, 101 Merrimac St, Boston, MA 02114 USA. NR 51 TC 13 Z9 13 U1 0 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2000 VL 37 IS 3 BP 341 EP 352 PG 12 WC Rehabilitation SC Rehabilitation GA 370YB UT WOS:000165149900012 PM 10917266 ER PT J AU Lin, T Guinan, JJ AF Lin, T Guinan, JJ TI Auditory-nerve-fiber responses to high-level clicks: Interference patterns indicate that excitation is due to the combination of multiple drives SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID COCHLEAR HAIR-CELLS; LOW-FREQUENCY TONES; GUINEA-PIG COCHLEA; BASILAR-MEMBRANE; RECEPTOR POTENTIALS; CHINCHILLA COCHLEA; IMPULSE RESPONSES; DAMAGED COCHLEA; SINGLE-FIBER; WAVE-FORM AB There has been no systematic study of auditory-nerve-fiber (ANF) responses to high-level clicks despite the advantages of clicks in revealing the natural resonances of a system. Cat single ANFs were studied using clicks up to 120 dB pSPL. Peri-stimulus-time (PST) histograms of responses were corrected for refractory effects, and compound PST (cPST) histograms were formed from rarefaction- and condensation-click PSTs. At low levels the responses followed the classic picture with each cPST appearing to be from a single resonant system followed by low-pass filtering that reduces high-frequency synchrony. In fibers across all characteristic frequencies, there were significantly different patterns at high click levels including several nonclassic features and "phase reversals," i.e., a peak in the rarefaction-click PST at low levels was replaced at high levels by a peak at the same latency in the condensation-click PST. There were two separate regions of nonclassic features and phase reversals, which indicates that auditory-nerve fibers are excited by the combination at some stage in the cochlea of at least three excitation drives derived from the acoustic stimulus. These data support the interpretation that the cochlear partition vibrates in multiple resonant modes with each mode producing one excitation drive and that the mix of modes varies with sound level. (C) 2000 Acoustical Society of America. [S0001-4966(00)00205-8]. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu FU NIDCD NIH HHS [5 RO1 DC 00235, T32 DC00038] NR 69 TC 47 Z9 47 U1 0 U2 0 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2000 VL 107 IS 5 BP 2615 EP 2630 DI 10.1121/1.428648 PN 1 PG 16 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 312WX UT WOS:000086967900032 PM 10830384 ER PT J AU Coffey, BJ Biederman, J Geller, DA Spencer, TJ Kim, GS Bellordre, CA Frazier, JA Cradock, K Magovcevic, M AF Coffey, BJ Biederman, J Geller, DA Spencer, TJ Kim, GS Bellordre, CA Frazier, JA Cradock, K Magovcevic, M TI Distinguishing illness severity from tic severity in children and adolescents with Tourette's disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE illness severity; tics; Tourette's disorder ID PSYCHOPATHOLOGY; RELIABILITY; SCHEDULE; MANIA AB Objective: To examine whether tic severity, comorbid disorders, or both are associated with illness morbidity in youths with Tourette's disorder (TD). Method: Subjects were 156 consecutively referred youths (aged 5-20 years) who met DSM-III-R criteria for Tourette's disorder at a major academic medical center. All subjects were evaluated with a clinical interview by a child and adolescent psychiatrist and an assessment battery that included the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version. Statistical analysis used chi(2) and multivariate logistic regression. Results: Nineteen (12%) of the 156 youths with TD required psychiatric hospitalization. Current age, TD severity, TD duration, obsessive-compulsive disorder, psychosis, major depression, bipolar disorder, panic disorder, and overanxious disorder were significant univariate predictors of psychiatric hospitalization (p < .01]. While tic severity was marginally significant as a predictor of psychiatric hospitalization (p < .05), major depression (p < .016) and bipolar disorder (p < .001) were robust predictors of psychiatric hospitalization, even after statistical adjustment far collinearity and correction for all other variables assessed. Conclusion: The findings indicate that comorbid mood disorders are strongly associated with illness morbidity in youths with TD, highlighting the importance of attention to comorbidity in patients with TD. C1 Harvard Univ, Sch Med, McLean Hosp, Joint Pediat Psychopharmacol Unit, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Joint Pediat Psychopharmacol Unit, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. RP Coffey, BJ (reprint author), Harvard Univ, Sch Med, McLean Hosp, Joint Pediat Psychopharmacol Unit, 115 Mill St, Belmont, MA 02478 USA. NR 25 TC 33 Z9 34 U1 0 U2 1 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 MAY PY 2000 VL 39 IS 5 BP 556 EP 561 DI 10.1097/00004583-200005000-00008 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 308DC UT WOS:000086694400008 PM 10802972 ER PT J AU Coffey, BJ Biederman, J Smoller, JW Geller, DA Sarin, P Schwartz, S Kim, GS AF Coffey, BJ Biederman, J Smoller, JW Geller, DA Sarin, P Schwartz, S Kim, GS TI Anxiety disorders and tic severity in juveniles with Tourette's disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE anxiety disorders; ties; juveniles; Tourette's disorder ID OBSESSIVE-COMPULSIVE DISORDER; DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; CHILDREN; PSYCHOPATHOLOGY; CLONIDINE; RELIABILITY; DESIPRAMINE; PARENTS; MANIA AB Objective: It was hypothesized that comorbidity with anxiety disorders would predict tic severity in youths with Tourette's disorder (TD). Method: Subjects were 190 youths meeting DSM-III-R diagnostic criteria for TD who were consecutively referred to a pediatric psychopharmacology program between 1994 and 1997. Subjects were initially evaluated with a clinical interview and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version. Statistical analysis used t tests, chi(2) tests, and logistic regression analysis. Results: One hundred thirty-four subjects were classified as mild/moderate and 56 as severe TD cases. No meaningful differences were found in socioeconomic status, gender distribution, or age at onset of TD between the 2 groups. The 2 groups could not be differentiated by the presence of comorbid mood or disruptive behavior disorders including attention-deficit hyperactivity disorder. Although obsessive-compulsive disorder (OCD) was overrepresented among the severe SD cases, the difference failed to reach statistical significance. Excluding social and simple phobias, all other anxiety disorders were more clearly overrepresented among subjects with severe TD; separation anxiety disorder most robustly predicted tic severity, irrespective of the presence of OCD or other anxiety disorders. Conclusion: Findings suggest that non-OCD anxiety disorders in general and separation anxiety disorder in particular may be significantly associated with tic severity in referred TD patients. C1 Harvard Univ, Sch Med, McLean Hosp, Joint Pediat Psychopharmacol, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Joint Pediat Psychopharmacol, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. RP Coffey, BJ (reprint author), Harvard Univ, Sch Med, McLean Hosp, Joint Pediat Psychopharmacol, 115 Mill St, Belmont, MA 02478 USA. NR 62 TC 67 Z9 69 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2000 VL 39 IS 5 BP 562 EP 568 DI 10.1097/00004583-200005000-00009 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 308DC UT WOS:000086694400009 PM 10802973 ER PT J AU Baim, DS AF Baim, DS TI Is it time to offer elective percutaneous treatment of the unprotected left main coronary artery? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID STENOSES; ANGIOPLASTY; RESTENOSIS; IMMEDIATE C1 Harvard Univ, Sch Med, Intervent Cardiol Sect, Beth Isreal Deaconess Med Ctr, Boston, MA 02215 USA. RP Baim, DS (reprint author), Harvard Univ, Sch Med, Intervent Cardiol Sect, Beth Isreal Deaconess Med Ctr, Boston, MA 02215 USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY PY 2000 VL 35 IS 6 BP 1551 EP 1553 DI 10.1016/S0735-1097(00)00598-2 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 310LB UT WOS:000086828700021 PM 10807459 ER PT J AU Scherrer-Crosbie, M Liel-Cohen, N Otsuji, Y Guerrero, JL Sullivan, S Levine, RA Picard, MH AF Scherrer-Crosbie, M Liel-Cohen, N Otsuji, Y Guerrero, JL Sullivan, S Levine, RA Picard, MH TI Myocardial perfusion and wall motion in infarction border zone: Assessment by myocardial contrast echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CORONARY-ARTERY DISEASE; BLOOD-FLOW; HIBERNATING MYOCARDIUM; EXTENT; MODEL; HEART; DOG; METABOLISM; STENOSIS AB Several mechanisms have been proposed to explain the decreased wall motion (WM) at the borders of myocardial infarction (MI), We used myocardial contrast echocardiography (MCE) to Investigate the relation of perfusion to WM in infarcted border zones (BZs) 6 weeks after MI in 5 sheep. After quantifying the extent of WM abnormality and the perfusion defect, normal (NL), infarcted, and BZs were defined. Peak intensity after contrast was measured in acoustic units (AU). Radiolabeled microspheres were injected to measure regional blood now. The heart was stained with 2,3,5-triphenyltetrazolium chloride (TTC). The perfusion defect on MCE was 33% +/- 7% of the total myocardial area and correlated well with TTC (r = 0.92, P <.03). The BZ was 8% +/- 5% of the total myocardial area. Peak intensity after contrast was decreased in MI compared with BZ and NL (MI: 2.5 +/- 1.9 AU, BZ: 8.0 +/- 3.8 AU, P <.005; NL: 10.2 +/- 6.9 AU, P <.02) and comparable in NL and BZ. The blood flow measured by microspheres was not different in NL and BZ but was decreased In MI (NL: 1.6 mL/g/min, st: 1.5 +/- 0.5 mL/g/min, MI: 0.7 +/- 0.5 mL/g/min; P <.0001). In this model of chronic ovine MI, the BZ was small and its perfusion was preserved. These findings support the hypothesis that tethering of normal myocardial segments explains the abnormal wall motion noted at the borders of MI. C1 Harvard Univ, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Sch Med,Div Cardiol, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Harvard Univ, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Sch Med,Div Cardiol, VBK 508,55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 25 TC 14 Z9 14 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAY PY 2000 VL 13 IS 5 BP 353 EP 357 DI 10.1016/S0894-7317(00)70004-6 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 316FB UT WOS:000087156000003 PM 10804432 ER PT J AU Lee, CW Kaufman, JA Fan, CM Geller, SC Brewster, D Cambria, RP Lamuraglia, GM Gertler, JP Abbott, WM Waltman, AC AF Lee, CW Kaufman, JA Fan, CM Geller, SC Brewster, D Cambria, RP Lamuraglia, GM Gertler, JP Abbott, WM Waltman, AC TI Clinical outcome of internal iliac artery occlusions during endovascular treatment of aortoiliac aneurysmal diseases SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE aneurysm, abdominal; aneurysm, therapy; endovascular stent-graft; iliac arteries, stenosis or obstruction; hypogastric artery, occlusion ID ABDOMINAL AORTIC-ANEURYSM; STENT-GRAFTS; REPAIR; SURGERY; BYPASS AB PURPOSE: To determine the clinical outcome of hypogastric artery occlusion in patients who underwent endovascular treatment of aortoiliac aneurysmal disease. MATERIAL AND METHODS: From January 1994 to March 1998, 94 patients underwent endovascular treatment of aneurysmal diseases involving the infra-abdominal aorta or iliac arteries. Preoperative and intraoperative radiologic data were reviewed. Discharge summaries, clinic visits, and phone calls formed the basis for clinical follow-up, with a mean follow-up period of 7.3 months (range, 1-24 months). RESULTS: Because of the anatomy of the aneurysms, 28 patients required occlusion of one or more hypogastric arteries. One of the 28 patients died of unrelated causes before follow-up. Seven (26%) of the remaining 27 patients developed symptoms attributable to the hypogastric artery occlusions. Five patients developed new buttock or thigh claudication; of these five patients, three with initially mild symptoms noted complete or near complete resolution of symptoms upon follow-up. One patient with originally significant claudication at 2-year follow-up noted near resolution of symptoms. The other patient with severe pain did not improve significantly on final 1-year follow-up before his death (of unrelated causes). Other clinical complications were worsening sexual function in one patient and a nonhealing sacral decubitus ulcer that developed in a debilitated patient in the postoperative setting, which required surgery. No bowel ischemia was observed. CONCLUSION: When treating aortoiliac aneurysmal disease through an endovascular approach, the occlusion of internal iliac artery is often necessary but carries with it a small but finite chance of morbidity. C1 Massachusetts Gen Hosp, Div Vasc & Intervent Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Div Vasc & Intervent Radiol, 32 Fruit St, Boston, MA 02114 USA. EM kaufmanfamily@sprintmail.com NR 13 TC 84 Z9 87 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAY PY 2000 VL 11 IS 5 BP 567 EP 571 DI 10.1016/S1051-0443(07)61607-8 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 315MU UT WOS:000087118200004 PM 10834486 ER PT J AU Shireman, PK Greisler, HP AF Shireman, PK Greisler, HP TI Mitogenicity and release of vascular endothelial growth factor with and without heparin from fibrin glue SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Midwestern-Vascular-Surgical-Society CY SEP 23-25, 1999 CL CHICAGO, ILLINOIS SP Midwestern Vascular Surg Soc ID INTIMAL HYPERPLASIA; CELL-PROLIFERATION; FACTOR TYPE-1; GRAFTS; SUSPENSIONS; INHIBITION AB Purpose: Fibrin glue (FG) has been used for local cytokine delivery on both vascular grafts and angioplasty sites. We measured the diffusive release of vascular endothelial growth factor (VEGF) and heparin from FG and the mitogenic activity of VEGF with and without heparin in FG on canine endothelial cells (ECs) and smooth muscle cells (SMCs). Methods: Release of VEGF labeled with iodine 125 and tritiated heparin from FG into the overlying media was serially measured over 96 hours, and the data are reported as the mean percent released +/- SD. Proliferation assays measuring tritiated thymidine incorporation were performed for ECs and SMCs plated in media with 10% serum on FG containing various concentrations of VEGF and heparin. Media was placed on the FG for 24 hours and removed before plating cells to minimize the effect of the released, soluble VEGF and heparin. Results: At 24 hams, 54% +/- 1% and 58% +/- 1% of the radioactive VEGF and heparin were released, respectively, with minimal release thereafter (58% +/- 1% and 66% +/- 1% at 96 hours). The ECs, SMCs, or media only (no cells) was plated an FG containing radioactive VEGF in an immediate or 24-hour delayed fashion for 72 hours to determine the percent release of VEGF into the media with the two different methods of plating. Cell type and the presence or absence of cells did not affect VEGF release, but there was three times more VEGF in the media for the immediate versus delayed plating (P < .001). Without heparin, VEGF at 100 ng/mL, or more in the FG was needed to induce EC proliferation. Heparin at 5 U/mL, enhanced EC proliferation at the VEGF dose of 100 ng/mL, as compared with no heparin (P < .001), but not at the VEGF dose of 1000 ng/mL, which Likely represents a maximal response. With heparin at 500 U/mL, the ECs died. In contrast, VEGF, in the presence or absence of heparin, did not affect SMC proliferation. Conclusions: We conclude that FG with VEGF at 1000 ng/mL, and heparin at 5 U/mL is the optimal concentration for in vivo use because this may encourage EC, but not SMC, proliferation. The VEGF at 1000 ng/mL, should leave mitogenic concentrations of VEGF intact after the initial, diffusive loss, and the addition of heparin at 5 U/mL may enhance VEGF mitogenic activity. C1 Loyola Univ, Med Ctr, Dept Surg, Div Peripheral Vasc Surg, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Cell Biol, Maywood, IL 60153 USA. Edward Hines Vet Adm Hosp, Dept Surg, Hines, IL 60141 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, Vasc Surg Sect, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Dept Surg, San Antonio, TX 78284 USA. RP Greisler, HP (reprint author), Loyola Univ, Med Ctr, Dept Surg, Div Peripheral Vasc Surg, 2160 S 1st Ave, Maywood, IL 60153 USA. FU NHLBI NIH HHS [R01 HL41272] NR 12 TC 20 Z9 22 U1 0 U2 2 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 MAY PY 2000 VL 31 IS 5 BP 936 EP 943 DI 10.1067/mva.2000.106420 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 315JG UT WOS:000087109900012 PM 10805884 ER PT J AU Alexander, L Weiskopf, E Greenough, TC Gaddis, NC Auerbach, MR Malim, MH O'Brien, SJ Walker, BD Sullivan, JL Desrosiers, RC AF Alexander, L Weiskopf, E Greenough, TC Gaddis, NC Auerbach, MR Malim, MH O'Brien, SJ Walker, BD Sullivan, JL Desrosiers, RC TI Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection SO JOURNAL OF VIROLOGY LA English DT Article ID LIMITING DILUTION ANALYSIS; CYTOTOXIC LYMPHOCYTES-T; LONG-TERM SURVIVOR; HIV-1 INFECTION; DISEASE PROGRESSION; REVERSE-TRANSCRIPTASE; GENETIC RESTRICTION; VIRAL REPLICATION; MOLECULAR CLONE; RHESUS-MONKEYS AB Factors accounting for long-term nonprogression may include infection with an attenuated strain of human immunodeficiency virus type 1 (HIV-1), genetic polymorphisms in the host, and virus-specific immune responses. In this study, we examined eight individuals with nonprogressing or slowly progressing HIV-1 infection, none of whom were homozygous for host-specific polymorphisms (CCR5-Delta 32, CCR2-64I, and SDF-1-3'A) which have been associated with slower disease progression. HTV-1 was recovered from seven of the eight, and recovered virus was used for sequencing the full-length HTV-1 genome; full-length HIV-1 genome sequences from the eighth were determined following amplification of viral sequences directly from peripheral blood mononuclear cells (PBMC), Longitudinal studies of one individual with HIV-1 that consistently exhibited a slow/low growth phenotype revealed a single amino acid deletion in a conserved region of the gp41 transmembrane protein that was not seen in any of 131 envelope sequences in the Los Alamos HIV-1 sequence database. Genetic analysis also revealed that five of the eight individuals harbored HIV-1 with unusual 1- or 2-amino-acid deletions in the Gag sequence compared to subgroup B Gag consensus sequences. These deletions in Gag have either never been observed previously or are extremely rare in the database. Three individuals had deletions in Nef, and one had a 4-amino-acid insertion in Vpu, The unusual polymorphisms in Gag, Env, and Nef described here were also found in stored PBMC samples taken 3 to 11 years prior to, or in one case 4 years subsequent to, the time of sampling for the original sequencing. In all, seven of the eight individuals exhibited one or more unusual polymorphisms; a total of 13 unusual polymorphisms were documented in these seven individuals. These polymorphisms may have been present from the time of initial infection or may have appeared in response to immune surveillance or other selective pressures. Our results indicate that unusual, difficult-to-revert polymorphisms in HIV-1 can be found associated with slow progression or nonprogression in a majority of such cases. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. Univ Massachusetts, Sch Med, Dept Pediat, Program Mol Med, Worcester, MA 01605 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. NCI, Lab Genet Divers, Frederick, MD 21702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Boston, MA 02114 USA. RP Desrosiers, RC (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, 1 Pine Hill Dr, Southborough, MA 01772 USA. OI Malim, Michael/0000-0002-7699-2064 FU NCRR NIH HHS [K26 RR000168, P51 RR000168]; NIAID NIH HHS [AI25328, AI28568, AI38559, R01 AI025328, R01 AI028568, R37 AI025328, R37 AI028568] NR 59 TC 120 Z9 120 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2000 VL 74 IS 9 BP 4361 EP 4376 DI 10.1128/JVI.74.9.4361-4376.2000 PG 16 WC Virology SC Virology GA 302KV UT WOS:000086365000048 PM 10756051 ER PT J AU Etemad-Moghadam, B Sun, Y Nicholson, EK Fernandes, M Liou, K Gomila, R Lee, J Sodroski, J AF Etemad-Moghadam, B Sun, Y Nicholson, EK Fernandes, M Liou, K Gomila, R Lee, J Sodroski, J TI Envelope glycoprotein determinants of increased fusogenicity in a pathogenic simian-human immunodeficiency virus (SHIV-KB9) passaged in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID HTLV-III/LAV ENVELOPE; AIDS-LIKE DISEASE; PERSISTENT INFECTION; CHEMOKINE RECEPTORS; RHESUS-MONKEYS; LYMPHOCYTE DEPLETION; ATOMIC-STRUCTURE; MACAQUE MONKEYS; AMINO-ACIDS; HIV-1 ENTRY AB Changes in the envelope glycoprotein ectodomains of a nonpathogenic simian-human immunodeficiency virus (SHIV-89.6) that was serially passaged in vivo have been shown to be responsible for the increased pathogenicity of the resulting virus, SHIV-KB9 (G. B. Karlsson, et al., J. Exp. Med. 188:1159-1171, 1998). The 12 amino acid changes in the envelope glycoprotein ectodomains resulted in increased chemokine receptor-binding and syncytium-forming abilities. Here we identify the envelope glycoprotein determinants of these properties. A single amino acid change in the gp120 third variable (V3) loop was both necessary and sufficient for the observed increase in the binding of the SHIV-KB9 gp120 glycoprotein to the CCR5 chemokine receptor. The increased syncytium-forming ability of SHIV-KB9 involved, in addition to the V3 loop change, changes in the second conserved (C2) region of gp120 (residue 225) and in the gp41 ectodomain (residues 564 and 567). The C2 and gp41 ectodomain changes influenced syncytium formation in a cooperative manner. Changes in the V1/V2 gp120 variable loops exerted a negative effect on syncytium formation and chemokine receptor binding, supporting a previously described role of these changes in immune evasion. The definition of the passage-associated changes that determine the efficiency of chemokine receptor binding and membrane fusogenicity will allow evaluation of the contribution of these properties to in vivo CD4-positive lymphocyte depletion. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol, JFB824,44 Binney St, Boston, MA 02115 USA. NR 61 TC 84 Z9 85 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2000 VL 74 IS 9 BP 4433 EP 4440 DI 10.1128/JVI.74.9.4433-4440.2000 PG 8 WC Virology SC Virology GA 302KV UT WOS:000086365000057 PM 10756060 ER PT J AU Yang, XZ Florin, L Farzan, M Kolchinsky, P Kwong, PD Sodroski, J Wyatt, R AF Yang, XZ Florin, L Farzan, M Kolchinsky, P Kwong, PD Sodroski, J Wyatt, R TI Modifications that stabilize human immunodeficiency virus envelope glycoprotein trimers in solution SO JOURNAL OF VIROLOGY LA English DT Article ID GP41 TRANSMEMBRANE GLYCOPROTEIN; MEMBRANE-FUSION; MONOCLONAL-ANTIBODIES; CHEMOKINE RECEPTORS; TYPE-1 GP41; INFLUENZA HEMAGGLUTININ; CRYSTAL-STRUCTURE; ATOMIC-STRUCTURE; DISULFIDE BONDS; COILED-COIL AB The functional unit of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins is a trimer composed of three gp120 exterior glycoproteins and three gp41 transmembrane glycoproteins. The lability of intersubunit interactions has hindered the production and characterization of soluble, homogeneous envelope glycoprotein trimers. Here we report three modifications that stabilize soluble forms of HIV-1 envelope glycoprotein trimers: disruption of the proteolytic cleavage site between gp120 and gp41, introduction of cysteines that form intersubunit disulfide bonds, and addition of GCN4 trimeric helices. Characterization of these secreted glycoproteins by immunologic and biophysical methods indicates that these stable trimers retain structural integrity. The efficacy of the GCN4 sequences in stabilizing the trimers, the formation of intersubunit disulfide bonds between appropriately placed cysteines, and the ability of the trimers to interact with a helical, C-terminal gp41 peptide (DP178) support a model in which the N-terminal gp41 coiled coil exists in the envelope glycoprotein precursor and contributes to intersubunit interactions within the trimer. The availability of stable, soluble HIV-1 envelope glycoprotein trimers should expedite progress in understanding the structure and function of the virion envelope glycoprotein spikes. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. RP Wyatt, R (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 815, Boston, MA 02115 USA. FU NIAID NIH HHS [AI24755, AI31783, AI39420, P30 AI028691, R01 AI031783, R01 AI039420, R37 AI024755] NR 61 TC 136 Z9 139 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2000 VL 74 IS 10 BP 4746 EP 4754 DI 10.1128/JVI.74.10.4746-4754.2000 PG 9 WC Virology SC Virology GA 306ZV UT WOS:000086629400035 PM 10775613 ER PT J AU Ikeda, K Wakimoto, H Ichikawa, T Jhung, S Hochberg, FH Louis, DN Chiocca, EA AF Ikeda, K Wakimoto, H Ichikawa, T Jhung, S Hochberg, FH Louis, DN Chiocca, EA TI Complement depletion facilitates the infection of multiple brain tumors by an intravascular, replication-conditional herpes simplex virus mutant SO JOURNAL OF VIROLOGY LA English DT Article ID DISCORDANT XENOGRAFT SURVIVAL; AMPHIPATHIC PEPTIDE ANALOGS; TYPE-1 GLYCOPROTEIN GC; THYMIDINE KINASE GENE; LONG-TERM SURVIVAL; IMMUNE EVASION; RIBONUCLEOTIDE REDUCTASE; INTRAARTERIAL DELIVERY; COMPLETE REGRESSION; CARDIAC XENOGRAFTS AB Intravascular routes of administration can provide a means to target gene- and virus-based therapies to multiple tumor foci located within an organ, such as the brain. However, we demonstrate here that rodent plasma inhibits cell transduction by replication-conditional (oncolytic) herpes simplex viruses (HSV), replication-defective HSV, and adenovirus vectors. In vitro depletion of complement with mild heat treatment or in vivo depletion by treatment of athymic rats with cobra venom factor (CVF) partially reverses this effect. Without CVF, inhibition of cell infection by HSV is observed at plasma dilution as high as 1:32, while plasma from CVF-treated animals displays anti-HSV activity at lower dilutions (1:8). When applied to the therapy of intracerebral brain tumors, in vivo complement depletion facilitates the initial infection (assayed at the 2 day time point) by an intra-arterial replication-conditional HSV of tumor cells, located within three separate and distinct human glioma masses. However, at the 4-day time point, no propagation of HSV from initially infected tumor cells could be observed. Previously, we have shown that the immunosuppressive agent, cyclophosphamide (CPA), facilitates the in vivo propagation of an oncolytic HSV, delivered intravascularly, within infected multiple intracerebral masses, by inhibition of both innate and elicited anti-HSV neutralizing antibody response (K. Ikeda et al., Nat. Med. 5:881-889, 1999). In this study, we thus show that the addition of CPA to the CVF treatment results in a significant increase in viral propagation within infected tumors, measured at the ii-day time period. The concerted action of CVF and CPA significantly increases the life span of athymic rodents harboring three separate and large glioma xenografts after treatment with intravascular, oncolytic HSV. Southern analysis of viral genomes analyzed by PCR reveals the presence of the oncolytic virus in the brains, livers, spleens, kidneys, and intestine of treated animals, although none of these tissues displays evidence of HSV-mediated gene expression. In light of clinical trials of oncolytic HSV for malignant brain tumors, these findings suggest that antitumor efficacy may be limited by the host innate and elicited humoral responses. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Labs,Neurosurg Serv, Charlestown, MA 02129 USA. RP Chiocca, EA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Labs,Neurosurg Serv, East Bldg,CNY6,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA 69246, P01 CA069246] NR 74 TC 100 Z9 102 U1 3 U2 6 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 MAY PY 2000 VL 74 IS 10 BP 4765 EP 4775 DI 10.1128/JVI.74.10.4765-4775.2000 PG 11 WC Virology SC Virology GA 306ZV UT WOS:000086629400037 PM 10775615 ER PT J AU Hsu, SIH Ramirez, SB Winn, MP Bonventre, JV Owen, WF AF Hsu, SIH Ramirez, SB Winn, MP Bonventre, JV Owen, WF TI Evidence for genetic factors in the development and progression of IgA nephropathy SO KIDNEY INTERNATIONAL LA English DT Review DE heredity; IgAN; familial nephropathy; glomerulonephritis; chronic renal failure; hematuria ID CONVERTING-ENZYME GENE; MESANGIAL PROLIFERATIVE GLOMERULONEPHRITIS; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; INSERTION DELETION POLYMORPHISM; POLYCYSTIC KIDNEY-DISEASE; SPONTANEOUS ANIMAL-MODEL; STAGE RENAL-DISEASE; DDY MICE; ANGIOTENSIN-II; NEPHROTIC SYNDROME AB Background IgA nephropathy (IgAN) is the most common glomerulonephritis in the world among patients undergoing renal biopsy. Once considered a relatively benign condition, longitudinal follow-up studies have revealed that in fact 9 to 50% of patients progress to end-stage renal disease within 20 years of disease onset. In the three decades since its first description by Jean Berger and Nicole Hinglais, clinical, epidemiologic, and immunologic studies of the pathogenesis of primary (idiopathic) mesangial glomerulonephritis with predominant IgA deposits have characterized the features of IgAN as a distinct glomerular disease entity. However, the basic molecular mechanism(s) underlying abnormal IgA deposition in the mesangium with ensuing extracellular matrix expansion and mesangial cell proliferation remains poorly understood. The task of elucidating the molecular basis of IgAN is made especially challenging by the fact that both environmental and genetic components likely contribute to the development and progression of IgAN. Methods and Results. We review here the evidence for genetic factors in the development and progression of IgAN, including a reappraisal of earlier conflicting results from small immunogenetic case-control studies, the evidence for racial differences in the prevalence of IgAN, a detailed summary of all reported occurrences of familial IgAN worldwide, and an exhaustive review of new insights gained through the study of two murine models of hereditary IgAN: the ddY and the uteroglobin-deficient mouse. Conclusions. With the development of powerful molecular genetic approaches to the study of both Mendelian and complex human genetic diseases, and the successful efforts of investigators to identify and clinically characterize large IgAN multiplex families, we propose that genetic analysis of familial IgAN is the most promising approach to the identification of IgAN disease/susceptibility genes. Alternatively, if the case-control study design is employed to identify associations between particular candidate genes or markers and the development of IgAN, spurious associations caused by the effects of population stratification should be ruled out by confirming the findings using powerful and sensitive family-based methodologies such as the transmission/dysequilibrium test (TDT). C1 Natl Univ Singapore, Fac Med, Dept Med, Singapore 117548, Singapore. Natl Univ Singapore, Fac Med, Dept Pediat, Singapore 117548, Singapore. Natl Kidney Fdn Singapore, Div Res, Singapore, Singapore. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Univ, Med Ctr, Duke Inst Renal Outcomes Res & Hlth Policy, Durham, NC USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Duke Univ, Med Ctr, Duke Ctr Human Genet, Durham, NC USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Hsu, SIH (reprint author), Natl Univ Singapore Hosp, Dept Med, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore. EM mdchsus@nus.edu.sg NR 146 TC 123 Z9 150 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2000 VL 57 IS 5 BP 1818 EP 1835 DI 10.1046/j.1523-1755.2000.00032.x PG 18 WC Urology & Nephrology SC Urology & Nephrology GA 310WL UT WOS:000086852000002 PM 10792601 ER PT J AU Poe, DS AF Poe, DS TI Laser-assisted endoscopic stapedectomy: A prospective study SO LARYNGOSCOPE LA English DT Review DE stapedectomy; laser; endoscopy ID CARBON-DIOXIDE LASER; ARGON-LASER; EAR SURGERY; YAG LASER; OTOSCLEROSIS SURGERY; STAPES SURGERY; ERBIUM-LASER; MIDDLE-EAR; CO2-LASER STAPEDOTOMY; OPTICAL FIBERS AB Objective: To improve the techniques required to perform a stapedotomy without prosthesis (stapedioplasty), Study Design: New infrared lasers were evaluated for potential use in otological surgery in guinea pigs, A prospective human trial of 34 primary stapes operations using the Argon ion laser was performed, with 11 stapedioplasties and 23 conventional stapedotomies as controls. Methods: Laser-tissue interactions were evaluated for temporal bone and live guinea pig tissues, measuring crater histology and labyrinthine temperature elevations. Patients undergoing stapedioplasty had Argon ion laser cuts with endoscopic assistance made in the anterior crus and footplate to mobilize the posterior segment of the stapes while the anterior portion remained fixed. Results: Diode laser (808-nm) vaporization craters and temperature elevations in the vestibule were suitable for clinical use. Overall, stapedioplasty patients' hearing was improved with air-bone gap closure to a mean of 8.3 dB (SD +/- 9.8 dB), Conclusions: Patients with anterior footplate otosclerosis are candidates for stapedioplasty preserving the annular ring and stapes tendon and eliminating prosthesis complications, High-resolution small endoscopes, coupled with Argon ion or diode lasers promise to improve stapes visualization, enhancing the ability to minimally invasive surgery on the stapes footplate. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Poe, DS (reprint author), Zero Emerson Pl,Suite 2C, Boston, MA 02114 USA. NR 182 TC 28 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2000 VL 110 IS 5 SU 95 BP 1 EP 37 DI 10.1097/00005537-200005001-00001 PN 2 PG 37 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 311YX UT WOS:000086915700001 PM 10807349 ER PT J AU Moller, MB Kania, PW Ino, Y Gerdes, AM Nielsen, O Louis, DN Skjodt, K Pedersen, NT AF Moller, MB Kania, PW Ino, Y Gerdes, AM Nielsen, O Louis, DN Skjodt, K Pedersen, NT TI Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma: prognostic significance of E2F-1 and p16(INK4A) SO LEUKEMIA LA English DT Article DE prognosis; E2F-1; retinoblastoma gene; p16; cyclin D3; lymphoma ID NON-HODGKINS-LYMPHOMAS; TUMOR-SUPPRESSOR GENE; RETINOBLASTOMA SUSCEPTIBILITY GENE; CYCLIN D1; IMMUNOHISTOCHEMICAL DETECTION; ALTERED EXPRESSION; POOR-PROGNOSIS; MESSENGER-RNA; LUNG-CANCER; HIGH-GRADE AB In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based lymphoma registry for alterations of the RB1 pathway at the genetic (RB1 and CDK4) and protein (pRb, cyclin D1, cyclin D3, CDK4, and E2F-1) level. The results were correlated with the data from our previous studies of CDKN2A deletion and hypermethylation, other p53 pathway components, p27(Klp1) expression, and proliferation, as well as with clinical outcome, including prognosis. We found aberrant pRb expression in four (12%) of 34 DLCLs. One of these had a point mutation in intron 3 10 bp downstream of exon 3 generating a novel splice signal. Seven tumours (21%) showed cyclin D3 overexpression, including all three thyroid lymphomas (P = 0.006). Cyclin D3 overexpression and p16(INK4A)/pRb aberrations were mutually exclusive, supporting an oncogenic role for cyclin D3 in DLCL, p16(INK4A) inactivation, cyclin D3 overexpression, or aberrant pRb expression was identified in 18 of 34 DLCLs (53%). Combining these results with our previous p53 pathway studies showed that 82% of the de novo DLCLs had alterations of these pathways, and that both pathways were altered in 13 cases (38%). Low E2F-1 expression was associated with treatment failure (P = 0.020), and multivariate analysis of overall survival identified both low E2F-1 expression (relative risk = 6.9; P = 0.0037) and p16(INK4A) inactivation (relative risk = 3.3; P = 0.0247) as independent prognostic markers. These data support a role of E2F-1 as tumour suppressor gene in lymphoma and strongly suggest that the RBI and p53 pathways are important in the development of de novo DLCL. Furthermore, low E2F-1 expression and p16(INK4A) inactivation may serve as prognostic markers for patients with this type of lymphoma. C1 Odense Univ, Univ So Denmark, Dept Pathol, DK-5000 Odense C, Denmark. Odense Univ, Univ So Denmark, Dept Clin Genet, DK-5000 Odense, Denmark. Odense Univ, Univ So Denmark, Dept Immunol & Microbiol, DK-5000 Odense C, Denmark. Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol Neuropathol & Neurol Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Moller, MB (reprint author), Odense Univ, Univ So Denmark, Dept Pathol, Winslowpk 15, DK-5000 Odense C, Denmark. RI Moller, Michael/G-8340-2016 OI Moller, Michael/0000-0003-2041-3630 NR 61 TC 53 Z9 53 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2000 VL 14 IS 5 BP 898 EP 904 DI 10.1038/sj.leu.2401761 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 310HA UT WOS:000086819400020 PM 10803523 ER PT J AU Paganetti, H Goitein, M AF Paganetti, H Goitein, M TI Radiobiological significance of beamline dependent proton energy distributions in a spread-out Bragg peak SO MEDICAL PHYSICS LA English DT Article DE proton beam; radiotherapy; relative biological effectiveness; spread-out Bragg peak ID RELATIVE BIOLOGICAL EFFECTIVENESS; WEIGHTING FUNCTIONS; 160-MEV PROTONS; BEAMS; MICRODOSIMETRY; SPECTRA; CELLS; THERAPY; DEPTH; RBE AB Similar target doses can be achieved with different mixed radiation fields, i.e., particle energy distributions, produced by a practical proton beam and a range modulator. The dose delivered in particle therapy can be described as the integral of fluence times the total mass stopping power over the particle energy distributions. We employed Monte Carlo simulations to explore the influence on the relative biological effectiveness (RBE) of the energy and the energy spread of the proton beam incident on a range modulator system. Using different beams, the conditions of beam delivery were adjusted so that similar spread out Bragg peak (SOBP) doses were delivered to a simulated water phantom. We calculated the RBE for inactivation of three different cell lines using the track structure model. The RBE depends on the details of the dose deposition and the biological characteristics of the irradiated tissue. Our calculations show that, for differing beam conditions, the corresponding differences in the total mass stopping power distributions are reflected in differences in the RBE. However, these differences are remarkable only at the very distal edge of the SOBP, for low doses, and/or fur large differences in beam setup. (C) 2000 American Association of Physicists in Medicine. [S0094-2405(00)04305-4]. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [CA21239] NR 33 TC 24 Z9 24 U1 2 U2 6 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2000 VL 27 IS 5 BP 1119 EP 1126 DI 10.1118/1.598977 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 317EA UT WOS:000087212200036 PM 10841418 ER PT J AU Gross, A Pilcher, K Blachly-Dyson, E Basso, E Jockel, J Bassik, MC Korsmeyer, SJ Forte, M AF Gross, A Pilcher, K Blachly-Dyson, E Basso, E Jockel, J Bassik, MC Korsmeyer, SJ Forte, M TI Biochemical and genetic analysis of the mitochondrial response of yeast to BAX and BCL-X-L SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PERMEABILITY TRANSITION PORE; CYTOCHROME-C RELEASE; PROAPOPTOTIC PROTEIN BAX; PROGRAMMED CELL-DEATH; SACCHAROMYCES-CEREVISIAE; MAMMALIAN-CELLS; SCHIZOSACCHAROMYCES-POMBE; ION-CHANNEL; APOPTOSIS; ACTIVATION AB The BCL-2 family includes both proapoptotic (e.g., BAX and BAK) and antiapoptotic (e.g., BCL-2 and BCL-X-L) molecules. The cell death-regulating activity of BCL-2 members appears to depend on their ability to modulate mitochondrial function, which may include regulation of the mitochondrial permeability transition pore (PTP). We examined the function of BAX and BCL-X-L using genetic and biochemical approaches in budding yeast because studies with yeast suggest that BCL-2 family members act upon highly conserved mitochondrial components. In this study we found that in wild-type yeast, BAX induced hyperpolarization of mitochondria, production of reactive oxygen species, growth arrest, and cell death; however, cytochrome c was not released detectably despite the induction of mitochondrial dysfunction. Coexpression of BCL-X-L prevented all BAX-mediated responses. We also assessed the function of BCL-X-L and BAX in the same strain of Saccharomyces cerevisiae with deletions of selected mitochondrial proteins that have been implicated in the function of BCL-2 family members. BAX-induced growth arrest was independent of the tested mitochondrial components, including voltage-dependent anion channel (VDAC), the catalytic beta subunit or the delta subunit of the F0F1-ATP synthase, mitochondrial cyclophilin, cytochrome c, and proteins encoded by the mitochondrial genome as revealed by [rho(0)] cells. In contrast, actual cell killing was dependent upon select mitochondrial components including the beta subunit of ATP synthase and mitochondrial genome-encoded proteins but not VDAC. The BCL-X-L protection from either BAX-induced growth arrest or cell killing proved to be independent of mitochondrial components. Thus, BAX induces two cellular processes in yeast which can each be abrogated by BCL-X-L: cell arrest, which does not require aspects of mitochondrial biochemistry, and cell killing, which does. C1 Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Oregon Hlth & Sci Univ, Vollum Inst, L474,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM Stanley_Korsmeyer@dfci.harvard.edu; forte@ohsu.edu NR 86 TC 126 Z9 130 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2000 VL 20 IS 9 BP 3125 EP 3136 DI 10.1128/MCB.20.9.3125-3136.2000 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 303LB UT WOS:000086422400018 PM 10757797 ER PT J AU Yang, L Embree, LJ Hickstein, DD AF Yang, L Embree, LJ Hickstein, DD TI TLS-ERG leukemia fusion protein inhibits RNA splicing mediated by serine-arginine proteins SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CARBOXY-TERMINAL DOMAIN; HUMAN MYELOID-LEUKEMIA; POLYMERASE-II; BINDING PROTEIN; IN-VIVO; CHROMOSOMAL TRANSLOCATION; LARGEST SUBUNIT; NUCLEAR MATRIX; TRANSCRIPTION; GENE AB The translocation liposarcoma (TLS) gene is fused to the ETS-related gene (ERG) in human myeloid leukemia, resulting in the generation of a TLS-ERG protein. We demonstrate that both TLS and the TLS-ERG leukemia fusion protein bind to RNA polymerase II through the TLS N-terminal domain, which is retained in the fusion protein; however, TLS recruits members of the serine-arginine (SR) family of splicing factors through its C-terminal domain, whereas the TLS-ERG fusion protein lacks the ability to recruit SR proteins due to replacement of the C-terminal domain by the fusion partner ERG. In transient-transfection assays, the TLS-ERG fusion protein inhibits E1A pre-mRNA splicing mediated by these TLS-associated SR proteins (TASR), and stable expression of the TLS-ERG fusion protein in K562 cells alters the splicing profile of CD44 mRNA. These results suggest that TLS fusion proteins may lead to cellular abnormalities by interfering with the splicing of important cellular regulators. C1 Univ Washington, Sch Med, Div Oncol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Div Mol Med, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. RP Hickstein, DD (reprint author), Univ Washington, Sch Med, Dept Med Oncol, 1660 S Columbian Way,GMR 151, Seattle, WA 98108 USA. NR 52 TC 97 Z9 103 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2000 VL 20 IS 10 BP 3345 EP 3354 DI 10.1128/MCB.20.10.3345-3354.2000 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 308ET UT WOS:000086698100002 PM 10779324 ER PT J AU Gangolli, EA Belyamani, M Muchinsky, S Narula, A Burton, KA McKnight, GS Uhler, MD Idzerda, RL AF Gangolli, EA Belyamani, M Muchinsky, S Narula, A Burton, KA McKnight, GS Uhler, MD Idzerda, RL TI Deficient gene expression in protein kinase inhibitor alpha null mutant mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHOENOLPYRUVATE CARBOXYKINASE; CATALYTIC SUBUNIT; REGULATORY SUBUNITS; SOMATOSTATIN GENE; BETA-ISOFORMS; PKI-ALPHA; LOCALIZATION; TRANSCRIPTION; CREB; PHOSPHORYLATION AB Protein kinase inhibitor (PKI) is a potent endogenous inhibitor of the cyclic AMP (cAMP)-dependent protein kinase (PKA). It functions by binding the free catalytic (C) subunit with a high affinity and is also known to export nuclear C subunit to the cytoplasm. The significance of these actions with respect to PKI's physiological role is not well understood. To address this, we have generated by homologous recombination mutant mice that are deficient in PKI alpha, one of the three isoforms of PKI. The mice completely lack PKI activity in skeletal muscle and, surprisingly, shelf decreased basal and isoproterenol-induced gene expression in muscle, Further examination revealed reduced levels of the phosphorylated (active) form of the transcription factor CREB (cAMP response element binding protein) in the knockouts. This phenomenon sterns, at least in part, from lower basal PKA activity levels in the mutants, arising from a compensatory increase in the level of the RI alpha subunit of PKA. The deficit in gene induction, however, is not easily explained by current models of PKI function and suggests that PKI may play an as yet undescribed role in PKA signaling. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Michigan, Mental Hlth Res Inst, Ann Arbor, MI 48109 USA. RP Idzerda, RL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NICHD NIH HHS [HD 33057]; NIDDK NIH HHS [T32 DK007247, T32 DK07247]; NIGMS NIH HHS [GM 32875, R01 GM032875] NR 34 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2000 VL 20 IS 10 BP 3442 EP 3448 DI 10.1128/MCB.20.10.3442-3448.2000 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 308ET UT WOS:000086698100012 PM 10779334 ER PT J AU Fong, IC Zarrin, AA Wu, GE Berinstein, NL AF Fong, IC Zarrin, AA Wu, GE Berinstein, NL TI Functional analysis of the human RAG 2 promoter SO MOLECULAR IMMUNOLOGY LA English DT Article DE RAG2; BSAP; promoter ID B-CELL DEVELOPMENT; LEUCINE ZIPPER PROTEINS; GENE-EXPRESSION; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION; V(D)J RECOMBINATION; NUCLEAR-PROTEIN; C/EBP FAMILY; MOLECULAR-CLONING; ACTIVATOR PROTEIN AB Recombination activating genes RAGI and RAG2 are essential components of V(D)J recombination, a process that generates the specific antigen receptors in lymphocytes. To understand the mechanisms underlying the lineage and developmental regulation of transcription of RAG2, we have characterized the human RAG2 exon 1A promoter. In this study, a series of deletion constructs were used to isolate the promoter while a linker scanning approach was taken to assess functionally relevant cis elements within the promoter. Two regulatory domains were identified. The - 140 to - 123 region is critical for promoter activity in all cell lines tested. Mutations to the putative Ets (- 122 to - 118) or to the C/EBP (- 137 to - 129) consensus core sequences did abrogate promoter activity, although specific DNA/protein interactions remained, as determined by EMSA. The - 69 to - 48 region demonstrates lineage specific promoter activity. Mutations to an overlapping, BSAP-myb-Ikaros-myb site (- 65 to - 39) resulted in differential promoter activity in human B and T cells. EMSA analysis of this region showed a B cell specific protein complex. Transfection of BSAP into cell lines trans-activates the human RAG2 promoter. We conclude that transcriptional regulation of the human RAG2 gene is complex, involving both tissue specific and ubiquitous factors, and both proximal and distal regulatory elements. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Ontario Canc Inst, Inst Med Sci, Toronto, ON M5G 2M9, Canada. Harvard Univ, Sch Med, Dept Immunol, Ctr Blood Res, Boston, MA 02115 USA. Ontario Canc Inst, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. Toronto Sunnybrook Reg Canc Ctr, Dept Med, Toronto, ON M4N 3M5, Canada. RP Fong, IC (reprint author), Ontario Canc Inst, Inst Med Sci, 610 Univ Ave,Room 8-111, Toronto, ON M5G 2M9, Canada. NR 62 TC 15 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY PY 2000 VL 37 IS 7 BP 391 EP 402 DI 10.1016/S0161-5890(00)00056-0 PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 372XU UT WOS:000165260000006 PM 11074256 ER PT J AU Kahn, CR AF Kahn, CR TI Triglycerides and toggling the tummy SO NATURE GENETICS LA English DT Editorial Material ID TRANSGENIC MICE; ADIPOSE-TISSUE; OBESITY; LEPTIN; GENE; PEPTIDES; RECEPTOR AB Multiple-mechanisms regulate adipose mass and body weight. In addition to factors controlling appetite and energy expenditure, mechanisms controlling adipocyte number, triglyceride synthesis and triglyceride breakdown have important functions. But recent studies challenge our concepts concerning each of these. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. NR 19 TC 14 Z9 15 U1 0 U2 3 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 MAY PY 2000 VL 25 IS 1 BP 6 EP 7 DI 10.1038/75610 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 311KU UT WOS:000086884000004 PM 10802641 ER PT J AU Marin, MC Jost, CA Brooks, LA Irwin, MS O'Nions, J Tidy, JA James, N McGregor, JM Harwood, CA Yulug, IG Vousden, KH Allday, MJ Gusterson, B Ikawa, S Hinds, PW Crook, T Kaelin, WG AF Marin, MC Jost, CA Brooks, LA Irwin, MS O'Nions, J Tidy, JA James, N McGregor, JM Harwood, CA Yulug, IG Vousden, KH Allday, MJ Gusterson, B Ikawa, S Hinds, PW Crook, T Kaelin, WG TI A common polymorphism acts as an intragenic modifier of mutant p53 behaviour SO NATURE GENETICS LA English DT Article ID HUMAN LUNG-CANCER; CERVICAL-CANCER; CELL-LINES; WILD-TYPE; GENE; MUTATIONS; P73; SUPPRESSION; GROWTH; RISK AB The p73 protein, a homologue of the tumour-suppressor protein p53, can activate p53-responsive promoters and induce apoptosis in p53-deficient cells. Here we report that some tumour-derived p53 mutants can bind to and inactivate p73. The binding of such mutants is influenced by whether TP53 (encoding p53) codon 72, by virtue of a common polymorphism in the human population, encodes Arg or Pro. The ability of mutant p53 to bind p73, neutralize p73-induced apoptosis and transform cells in cooperation with EJ-Ras was enhanced when codon 72 encoded Arg. We found that the Arg-containing allele was preferentially mutated and retained in squamous cell tumours arising in Arg/Pro germline heterozygotes. Thus, inactivation of p53 family members may contribute to the biological properties of a subset of p53 mutants, and a polymorphic residue within p53 affects mutant behaviour. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. London Sch Hyg & Trop Med, London WC1, England. Inst Canc Res, Sect Cell Biol & Expt Pathol, London SW3 6JB, England. Univ Sheffield, No Gen Hosp, Dept Gynecol Oncol, Sheffield S5 7AU, S Yorkshire, England. Univ Birmingham, CRC, Inst Canc Studies, Birmingham, W Midlands, England. Ctr Cutaneous Res, London, England. NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. St Marys Hosp, Imperial Coll Sci Technol & Med, Ludwig Inst Canc Res, London, England. Tohoku Univ, Inst Dev Aging & Canc, Dept Cell Biol, Sendai, Miyagi 980, Japan. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI gusterson, barry/D-3752-2009; Marin Vieira, Maria del Carmen/B-8108-2015; 井川, 俊太郎/L-5911-2015 OI Marin Vieira, Maria del Carmen/0000-0002-7149-287X; NR 49 TC 396 Z9 405 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 MAY PY 2000 VL 25 IS 1 BP 47 EP 54 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 311KU UT WOS:000086884000015 PM 10802655 ER PT J AU McGinty, D Szymusiak, R AF McGinty, D Szymusiak, R TI The sleep-wake switch: A neuronal alarm clock SO NATURE MEDICINE LA English DT Editorial Material ID WAKING DISCHARGE; RATS; HYPOTHALAMUS; WAKEFULNESS AB A 70-year-old hypothesis that a rostral hypothalamic area is essential for maintaining sleep is re-awakened by the demonstration that the sleep-active ventrolateral preoptic neurons interact with wake-promoting systems in the upper brainstem. C1 Vet Adm Greater Los Angeles Healthcare Syst, Neurophysiol & Sleep Physiol Res Sepulveda Ctr, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Psychol, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Sepulveda, CA 91343 USA. RP McGinty, D (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Neurophysiol & Sleep Physiol Res Sepulveda Ctr, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 16 TC 56 Z9 56 U1 1 U2 6 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 MAY PY 2000 VL 6 IS 5 BP 510 EP 511 DI 10.1038/74988 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 309YB UT WOS:000086796200028 PM 10802704 ER PT J AU Fox, JG Beck, P Dangler, CA Whary, MT Wang, TC Shi, HN Nagler-Anderson, C AF Fox, JG Beck, P Dangler, CA Whary, MT Wang, TC Shi, HN Nagler-Anderson, C TI Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces helicobacter-induced gastric atrophy SO NATURE MEDICINE LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; PYLORI INFECTION; C57BL/6 MICE; HELIGMOSOMOIDES-POLYGYRUS; T-LYMPHOCYTES; SOUTH-AFRICA; EXPRESSION; FELIS; CELLS; CANCER AB Helicobacter pylori is causally associated with gastritis and gastric cancer. Some developing countries with a high prevalence of infection have high gastric cancer rates, whereas in others, these rates are low. The progression of helicobacter-induced gastritis and gastric atrophy mediated by type 1 T-helper cells may be modulated by concurrent parasitic infection. Here, in mice with concurrent helminth infection, helicobacter-associated gastric atrophy was reduced considerably despite chronic inflammation and high helicobacter colonization. This correlated with a substantial reduction in mRNA for cytokines and chemokines associated with a gastric inflammatory response of type 1 T-helper cells. Thus, concurrent enteric helminth infection can attenuate gastric atrophy, a premalignant lesion. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med, Mucosal Immunol Lab, Pediat Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Mucosal Immunol Lab, Gastroenterol Unit, Boston, MA 02114 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NCI NIH HHS [CA7529, CA74463]; NIAID NIH HHS [AI37740] NR 39 TC 329 Z9 339 U1 0 U2 9 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 MAY PY 2000 VL 6 IS 5 BP 536 EP 542 DI 10.1038/75015 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 309YB UT WOS:000086796200037 PM 10802709 ER PT J AU Poznansky, MC Olszak, IT Foxall, R Evans, RH Luster, AD Scadden, DT AF Poznansky, MC Olszak, IT Foxall, R Evans, RH Luster, AD Scadden, DT TI Active movement of T cells away from a chemokine SO NATURE MEDICINE LA English DT Article ID PROTEIN-COUPLED-RECEPTOR; AXON GUIDANCE; SIGNALING PATHWAYS; ATTRACTION; REPULSION; CHEMOTAXIS; CLONING; RANTES; GROWTH; SDF-1 AB Movement towards or away from a given stimulus guides the directional migration of prokaryotes, simple eukaryotes and neurons. As bi-directional cues may influence entry and exit of immune effector cells from tissue sites, we evaluated the migratory responses of T-cell subsets to varying concentrations of the chemokine stromal cell derived factor-1 (SDF-1). There was selective repulsion of subpopulations of T cells at high concentrations of recombinant SDF-1 or naturally occurring bone marrow-derived SDF-1, which could be inhibited by pertussis toxin and antibody against the chemokine receptor CXCR4. Distinct sensitivity profiles to genistein, herbimycin and 8-Br-cAMP biochemically distinguished movement of cells towards or away from an SDF-1 gradient. In vivo, antigen-induced T-cell recruitment into the peritoneal cavity was reversed by high but not low concentrations of SDF-1. The phenomenon of movement away from a chemokine represents a previously unknown mechanism regulating the localization of mature T cells. It adds to the functional repertoire of chemokines that may participate in immune physiology and may be applied therapeutically to alter the immune response. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr AIDS Res, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr AIDS Res, Boston, MA 02129 USA. OI Foxall, Russell/0000-0001-9821-0708 NR 33 TC 184 Z9 205 U1 0 U2 4 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 MAY PY 2000 VL 6 IS 5 BP 543 EP 548 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 309YB UT WOS:000086796200038 PM 10802710 ER PT J AU Sapirstein, A Bonventre, JV AF Sapirstein, A Bonventre, JV TI Phospholipases A(2) in ischemic and toxic brain injury SO NEUROCHEMICAL RESEARCH LA English DT Review DE phospholipase A(2); knockout mice; cerebral infarction; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; brain ID ACTIVATED PROTEIN-KINASE; ARACHIDONIC-ACID RELEASE; LONG-TERM POTENTIATION; RAT CEREBRAL-CORTEX; QUISQUALATE RECEPTORS; SIGNAL-TRANSDUCTION; PRIMARY CULTURES; DENTATE GYRUS; FATTY-ACIDS; CYTOSOLIC PHOSPHOLIPASE-A(2) AB Phospholipases A(2) (PLA(2)s) regulate hydrolysis of fatty acids, including arachidonic acid, from the sn-2 position of phospholipid membranes. PLA(2) activity has been implicated in neurotoxicity and neurodegenerative processes secondary to ischemia and reperfusion and other oxidative stresses. The PLA(2)s constitute a superfamily whose members have diverse functions and patterns of expression. A large number of PLA(2)s have been identified within the central nervous systems of rodents and humans. We postulated that group IV large molecular weight, cytosolic phospholipase A(2) (cPLA(2)) has a unique role in neurotoxicity associated with ischemic or toxin stress. We created mice deficient in cPLA(2) and tested this hypothesis in two injury models, ischemia/reperfusion and MPTP neurotoxicity. In each model cPLA(2) deficient mice are protected against neuronal injury when compared to their wild type littermate controls. These experiments support the hypothesis that cPLA(2) is an important mediator of ischemic and oxidative injuries in the brain. C1 Massachusetts Gen Hosp, Anesthesia & Crit Care Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Anesthesiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Massachusetts Gen Hosp E, Suite 4002,149 13th St, Charlestown, MA 02129 USA. EM sapirste@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK39773, DK38452]; NINDS NIH HHS [NS10828] NR 107 TC 54 Z9 58 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 EI 1573-6903 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 2000 VL 25 IS 5 BP 745 EP 753 DI 10.1023/A:1007583708713 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 328NQ UT WOS:000087857300026 PM 10905638 ER PT J AU Rao, VLR Rao, AM Dogan, A Bowen, KK Hatcher, J Rothstein, JD Dempsey, RJ AF Rao, VLR Rao, AM Dogan, A Bowen, KK Hatcher, J Rothstein, JD Dempsey, RJ TI Glial glutamate transporter GLT-1 down-regulation precedes delayed neuronal death in gerbil hippocampus following transient global cerebral ischemia SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE delayed neuronal death; gerbil; global cerebral ischemia; glutamate transporters; hippocampus; immunoblotting ID FOREBRAIN ISCHEMIA; SELECTIVE VULNERABILITY; MESSENGER-RNA; BRAIN INJURY; CA1 NEURONS; DAMAGE; EXPRESSION; EXCITOTOXICITY; MODEL; GABA AB Glial (GLT-1 and GLAST) and neuronal (EAAC1) high-affinity transporters mediate the sodium dependent glutamate reuptake in mammalian brain, Their dysfunction leads to neuronal damage by allowing glutamate to remain in the synaptic cleft for a longer duration. The purpose of the present study is to understand their contribution to the ischemic delayed neuronal death seen in gerbil hippocampus following transient global cerebral ischemia. The protein levels of these three transporters were studied by immunoblotting as a function of reperfusion time (6 h to 7 days) following a 10 min occlusion of bilateral common carotid arteries in gerbils. In the vulnerable hippocampus, there was a significant decrease in the protein levels of GLT-1 (by 36-46%, P < 0.05; between 1 and 3 days of reperfusion) and EAAC1 (by 42-68%, P < 0.05; between 1 and 7 days of reperfusion). Histopathological evaluation showed no neuronal loss up to 2 days of reperfusion but an extensive neuronal loss (by similar to 84%, P < 0.01) at 7 days of reperfusion in the hippocampal CA1 region. The time frame of GLT-1 dysfunction (1-3 days of reperfusion) precedes the initiation of delayed neuronal death (2-3 days of reperfusion). This suggests GLT-1 dysfunction as a contributing factor for the hippocampal neuronal death following transient global cerebral ischemia. Furthermore, decreased EAAC1 levels may contribute to GABAergic dysfunction and excitatory/inhibitory imbalance following transient global ischemia. (C) 2000 Published by Elsevier Science Ltd, All rights reserved. C1 Univ Wisconsin, Dept Neurol Surg, Clin Sci Ctr F4 309, Madison, WI 53792 USA. Univ Wisconsin, Cardiovasc Res Ctr, Madison, WI USA. William S Middleton Mem Vet Adm Hosp, Madison, WI USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Rao, VLR (reprint author), Univ Wisconsin, Dept Neurol Surg, Clin Sci Ctr F4 309, 600 Highland Ave, Madison, WI 53792 USA. RI rothstein, jeffrey/C-9470-2013 NR 41 TC 61 Z9 62 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD MAY PY 2000 VL 36 IS 6 BP 531 EP 537 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 296YK UT WOS:000086054200007 ER PT J AU Stern, CE Owen, AM Tracey, I Look, RB Rosen, BR Petrides, M AF Stern, CE Owen, AM Tracey, I Look, RB Rosen, BR Petrides, M TI Activity in ventrolateral and mid-dorsolateral prefrontal cortex during nonspatial visual working memory processing: Evidence from functional magnetic resonance imaging SO NEUROIMAGE LA English DT Article ID LATERAL FRONTAL-CORTEX; SENSORY STIMULATION; ACTIVATION; TASKS; ORGANIZATION; DISSOCIATION; OBJECT; PET AB Whole-brain functional magnetic resonance imaging was used to study five healthy human subjects while they performed two nonspatial visual working memory tasks and one control task. In the first memory task, the subjects were required to view a sequence of three pattern stimuli, randomly selected from a familiar set of four stimuli, and then identify which one of three simultaneously presented stimuli was the one that had not been presented in the previous array. In the other task, the subjects were required to observe an identical sequence of three randomly selected pattern stimuli and then to respond by Selecting those same stimuli in the order presented. In comparison to a baseline control task, increases in signal intensity were observed, bilaterally, in the mid-dorsolateral frontal cortex and in the right ventrolateral frontal cortex in both memory tasks. When the two tasks were compared directly, however, the first memory task, which had the higher monitoring requirement, yielded significantly greater signal intensity changes in area 9/46 of the right mid-dorsolateral frontal cortex. These results provide further evidence for the precise functional contribution made by the mid-dorsolateral frontal cortex in visual working memory tasks and concur closely with findings in nonhuman primates. (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Boston Univ, Dept Psychol, Cognit Neuroimaging Lab, Boston, MA 02215 USA. MRC, Cognit & Brain Sci Unit, Cambridge CB2 2EF, England. Univ Oxford, John Radcliffe Hosp, Dept Clin Neurol, Ctr Funct MRI Brain, Oxford OX3 9DU, England. McGill Univ, Montreal Neurol Inst, Cognit Neurosci Lab, Montreal, PQ H3A 2B4, Canada. RP Stern, CE (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Owen, Adrian/B-4997-2015 NR 25 TC 79 Z9 80 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2000 VL 11 IS 5 BP 392 EP 399 DI 10.1006/nimg.2000.0569 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 318EG UT WOS:000087270500006 PM 10806026 ER PT J AU Postle, BR Stern, CE Rosen, BR Corkin, S AF Postle, BR Stern, CE Rosen, BR Corkin, S TI An fMRI investigation of cortical contributions to spatial and nonspatial visual working memory SO NEUROIMAGE LA English DT Article ID PRIMATE PREFRONTAL CORTEX; LATERAL FRONTAL-CORTEX; FUNCTIONAL-ORGANIZATION; PARKINSONS-DISEASE; EMPIRICAL ANALYSES; NULL-HYPOTHESIS; HUMAN-BRAIN; OBJECT; DISSOCIATION; LOCALIZATION AB The experiments presented in this report were designed to test the hypothesis that visual working memory for spatial stimuli and for object stimuli recruits separate neuronal networks in prefrontal cortex. We acquired BOLD fMRI data from subjects while they compared each serially presented stimulus to the one that had appeared two or three stimuli previously. Three experiments failed to reject the null hypothesis that prefrontal cortical activity associated with spatial working memory performance cannot be dissociated from prefrontal cortical activity associated with nonspatial working memory performance. Polymodal regions of parietal cortex (inferior and superior parietal lobules), as well as cortex surrounding the superior frontal sulcus (and encompassing the frontal eye fields), also demonstrated equivalent levels of activation in the spatial and object conditions. Posterior cortical regions associated with the ventral visual processing stream (portions of lingual, fusiform, and inferior temporal gyri), however, demonstrated greater object than spatial working memory-related activity, particularly when stimuli varied only along spatial or featural dimensions. These experiments, representing fMRI studies of spatial and object working memory in which the testing procedure and the stimuli were identical in the two conditions, suggest that domain-specific visual working memory processing may be mediated by posterior regions associated with domain-specific sensory processing. (C) 2000 Academic Press. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Boston Univ, Dept Psychol, Cognit Neuroimaging Lab, Boston, MA 02215 USA. RP Postle, BR (reprint author), Univ Penn, Med Ctr, Dept Neurol, Area 9, 3 West Gates,3400 Spruce St, Philadelphia, PA 19104 USA. FU NIA NIH HHS [AG13483]; NINDS NIH HHS [NS01762] NR 57 TC 141 Z9 141 U1 3 U2 9 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 MAY PY 2000 VL 11 IS 5 BP 409 EP 423 DI 10.1006/nimg.2000.0570 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 318EG UT WOS:000087270500008 PM 10806028 ER PT J AU Behar, O Mizuno, K Neumann, S Woolf, CJ AF Behar, O Mizuno, K Neumann, S Woolf, CJ TI Putting the spinal cord together again SO NEURON LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; AXON REGENERATION; WHITE-MATTER; ADULT; GROWTH; INJURY; SCAR; CNS C1 Massachusetts Gen Hosp, Dept Anesthesia, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Neural Plast Res Grp, Charlestown, MA 02129 USA. NR 19 TC 18 Z9 24 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 2000 VL 26 IS 2 BP 291 EP 293 DI 10.1016/S0896-6273(00)81162-9 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 318QZ UT WOS:000087296500006 PM 10839348 ER PT J AU Kim, HA Pomeroy, SL Whoriskey, W Pawlitzky, I Benowitz, LI Sicinski, P Stiles, CD Roberts, TM AF Kim, HA Pomeroy, SL Whoriskey, W Pawlitzky, I Benowitz, LI Sicinski, P Stiles, CD Roberts, TM TI A developmentally regulated switch directs regenerative growth of Schwann cells through cyclin D1 SO NEURON LA English DT Article ID AXONALLY TRANSPORTED PROTEINS; RETINAL GANGLION-CELLS; TRANSCRIPTION FACTOR; ESTROGEN-RECEPTOR; SCIATIC-NERVE; EXPRESSION; PROLIFERATION; GAP-43; AXONS; RAT AB Sciatic nerve axons in cyclin D1 knockout mice develop normally, become properly ensheathed by Schwann cells, and appear to function normally. However, in the Wallerian degeneration model of nerve injury, the mitotic response of Schwann cells is completely inhibited. The mitotic block is Schwann cell autonomous and developmentally regulated. Rescue analysis (by "knockin" of cyclin E) indicates that D1 protein, rather than regulatory elements of the D1 gene, provides the essential Schwann cell function. Genetic inhibition of the Schwann cell cycle shows that neuronal responses to nerve injury are surprisingly independent of Schwann cell mitotic responses. Even axonal regrowth into the distal zone of a nerve crush injury is not markedly impaired in cyclin D1(-/-) mice. C1 Childrens Hosp, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Stiles, CD (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. FU NICHD NIH HHS [HD24926]; NINDS NIH HHS [NS35701] NR 40 TC 51 Z9 51 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 2000 VL 26 IS 2 BP 405 EP 416 DI 10.1016/S0896-6273(00)81173-3 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 318QZ UT WOS:000087296500017 PM 10839359 ER PT J AU Kaddurah-Daouk, R Matthews, R Beal, MF AF Kaddurah-Daouk, R Matthews, R Beal, MF TI Amyotrophic lateral sclerosis: Transgenic model and novel neuroprotective agent SO NEUROSCIENCE RESEARCH COMMUNICATIONS LA English DT Article DE Amyotrophic Lateral Sclerosis; animal models; creatine; kinase ID CU,ZN SUPEROXIDE-DISMUTASE; MITOCHONDRIAL CREATINE-KINASE; MOTOR-NEURON DISEASE; HYDROGEN-PEROXIDE; ENERGY-METABOLISM; OXIDATIVE DAMAGE; MOUSE MODELS; FAMILIAL ALS; ANIMAL-MODEL; MICE AB The discovery of mutations in the human SOD1 gene encoding (Cu, Zn SOD) in patients with familial amyotrophic lateral sclerosis (ALS) has made possible the development of etiological models of the disease. Expression of mutant SOD1 genes in transgenic mice (FALS mice) causes progressive paralytic disease whose general features resemble ALS in humans. Extensive studies strongly suggest that Cu, Zn SOD mutations cause an adverse gain of function that results in enhanced generation of damaging oxygen radicals. Mitochondria are particularly vulnerable to oxidative stress, and mitochondrial swelling and vacuolization are among the earliest pathologic features in the FALS mice harboring the SOD mutations. Mitochondrial dysfunction may lead to ATP depletion, which may contribute to cell death. Creatine buffers against ATP depletion and inhibits the opening of the mitochondrial transition pore, a complex of proteins implicated in apoptosis. We found that oral administration of creatine to FALS mice expressing the G93A mutation produced a dose-dependent improvement in motor performance, extended survival and protected against loss of motor neurons and substantia nigra neurons. Additionally creatine protected against increases in biochemical indices of oxidative damage. The development of the FALS mice enables drug discovery studies in ALS. C1 Avicena Grp Inc, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Div Pharmacol, Boston, MA 02115 USA. Yale Univ, Sch Med, Neurobiol Sect, New Haven, CT 06510 USA. Cornell Univ, Coll Med, Dept Neurol & Neurosci, New York, NY 10021 USA. RP Kaddurah-Daouk, R (reprint author), Avicena Grp Inc, 1 Broadway,Suite 600, Cambridge, MA 02142 USA. NR 38 TC 1 Z9 1 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0893-6609 J9 NEUROSCI RES COMMUN JI Neurosci. Res. Commun. PD MAY-JUN PY 2000 VL 26 IS 3 BP 215 EP 226 DI 10.1002/1520-6769(200005/06)26:3<215::AID-NRC9>3.0.CO;2-Z PG 12 WC Neurosciences SC Neurosciences & Neurology GA 327QA UT WOS:000087803200009 ER PT J AU Kilic, T Pamir, MN Kullu, S Eren, F Ozek, MM Black, PM AF Kilic, T Pamir, MN Kullu, S Eren, F Ozek, MM Black, PM TI Expression of structural proteins and angiogenic factors in cerebrovascular anomalies SO NEUROSURGERY LA English DT Article DE angiogenesis; arteriovenous malformation; cavernous malformation; fibroblast growth factor; fibronectin; laminin; structural proteins; transforming growth factor; vascular endothelial growth factor; venous angioma ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; CEREBRAL ARTERIOVENOUS-MALFORMATIONS; INDUCED TRANSCRIPTIONAL ACTIVATION; SMOOTH-MUSCLE CELLS; CAVERNOUS MALFORMATIONS; EXTRACELLULAR-MATRIX; NATURAL-HISTORY; CAPILLARY TELANGIECTASIA; VENOUS MALFORMATIONS AB OBJECTIVE: The goal of this study was to describe the expression of matrix proteins and angiogenic factors in cerebrovascular malformations. METHODS: Forty-six cerebrovascular malformations were immunohistochemically investigated with a battery of staining for five structural proteins (collagen IV collagen III, smooth muscle actin, fibronectin, and laminin), and three angiogenic factors (vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF], and transforming growth factor alpha[TGF alpha]). The lesions consisted of 34 arteriovenous malformations (AVMs), 10 cavernous malformations (CMs), and 2 venous angiomas. Expression intensity for each histological layer in the abnormal vessel wall was graded and compared. RESULTS: AVM endothelia and subendothelia expressed move laminin and collagen IV than the same layers of CMs. Conversely, CMs expressed move fibronectin than AVMs. CM endothelia exhibited more prominent staining for smooth muscle actin than AVM endothelia. AVMs and CMs expressed VEGF in the endothelium and subendothelium, and TGF alpha in endothelial and perivascular layers. However, unlike AVMs, CMs expressed bFGF in the endothelium as well. The brain tissue intermingled within AVMs also expressed growth factors. Modified glial cells in the brain tissue adjacent to CMs expressed bFGF and TGF alpha, but not VEGF. Venous angiomas did not express the studied growth factors and mainly consisted of structural proteins of angiogenically mature tissue. CONCLUSION: Expression characteristics of structural proteins reveal that AVMs and CMs have different immunohistological properties. This study provides strong confirmation of previous findings of VEGF and bFGF immunoexpression in AVMs and CMs. It adds new information on TGF alpha expression in these malformations and on expression of the angiogenic factors in venous angiomas. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Neurosurg Serv, Boston, MA 02115 USA. Marmara Univ, Fac Med, Dept Pathol, Istanbul, Turkey. Marmara Univ, Fac Med, Inst Neurol Sci, Dept Neurosurg, Istanbul, Turkey. RP Black, PM (reprint author), Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. NR 71 TC 117 Z9 126 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 2000 VL 46 IS 5 BP 1179 EP 1191 DI 10.1097/00006123-200005000-00032 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 310JK UT WOS:000086822600076 PM 10807251 ER PT J AU Powell, S AF Powell, S TI Biological basis of radiation sensitivity Part 2: Cellular and molecular determinants of radiosensitivity - Reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID ATM C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Mol Radiat Biol,Dept Radiat Oncol, Boston, MA 02115 USA. RP Powell, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Mol Radiat Biol,Dept Radiat Oncol, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 2000 VL 14 IS 5 BP 765 EP 766 PG 2 WC Oncology SC Oncology GA 368QN UT WOS:000090129200026 ER PT J AU Remulla, HD Gliklich, RE Metson, R Rubin, PAD AF Remulla, HD Gliklich, RE Metson, R Rubin, PAD TI Delayed orbital infection after endoscopic orbital decompression for dysthyroid orbitopathy SO OPHTHALMOLOGY LA English DT Article ID TRANSNASAL AB Objective: To present a delayed complication of endoscopic orbital decompression that has not been reported previously in the literature. Design: Retrospective non-comparative small case series. Participants: Three patients with dysthyroid orbitopathy. Intervention: The medical records of patients with dysthyroid orbitopathy who underwent endoscopic orbital decompression and subsequently developed orbital infection were reviewed. Results: Three patients with dysthyroid orbitopathy developed orbital infection (cellulitis or abscess) originating from the frontal sinus more than 2 years after their endoscopic orbital decompression surgery. Management required drainage of the abscess, administration of antibiotics, and creation of adequate frontal sinus drainage. Conclusions: Delayed orbital infection can occur after endoscopic orbital decompression for dysthyroid orbitopathy when the frontal sinus ostium is obstructed by orbital fat or scar tissue, infection within the frontal sinus can cause secondary orbital cellulitis or abscess. Early signs and symptoms of a frontal sinus infection can be easily misdiagnosed as progression of the patient's thyroid eye disease. Awareness of this possible complication followed by appropriate early intervention will prevent a potentially blinding condition. Furthermore, ever since this complication was observed, the authors' surgical technique of endoscopic decompression has been modified to leave the most anterosuperior portion of the lamina papyracea to prevent fat prolapse and scar formation into the region of the frontal recess. (C) 2000 by the American Academy of Ophthalmology. C1 Harvard Univ, Ophthalm Plast & Orbital Surg Serv, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Med Sch, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otorhinolaryngol, Boston, MA USA. RP Rubin, PAD (reprint author), Harvard Univ, Ophthalm Plast & Orbital Surg Serv, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Med Sch, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2000 VL 107 IS 5 BP 947 EP 950 DI 10.1016/S0161-6420(00)00031-2 PG 4 WC Ophthalmology SC Ophthalmology GA 310JM UT WOS:000086822800038 PM 10811088 ER PT J AU Kocher, MS Jupiter, JB AF Kocher, MS Jupiter, JB TI Enchondroma versus chondrosarcoma of the phalanx SO ORTHOPEDICS LA English DT Article C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg,Upper Extrem Serv, Boston, MA USA. RP Kocher, MS (reprint author), Childrens Hosp, Dept Orthoped Surg, 300 Longwood Ave, Boston, MA 02115 USA. NR 5 TC 4 Z9 6 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD MAY PY 2000 VL 23 IS 5 BP 493 EP 494 PG 2 WC Orthopedics SC Orthopedics GA 314PT UT WOS:000087065200023 PM 10825118 ER PT J AU Corey, JP Kemker, BJ Branca, JT Kuo, F Chang, YC Gliklich, RE AF Corey, JP Kemker, BJ Branca, JT Kuo, F Chang, YC Gliklich, RE TI Health status in allergic rhinitis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 102nd Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 12-16, 1998 CL SAN ANTONIO, TEXAS SP Amer Acad Otolaryngol Head & Neck Surg ID CHRONIC SINUSITIS AB Although valid and reliable instruments exist to measure the quality of life of allergic rhinitis patients, a statistically sensitive and clinically meaningful way to evaluate patients undergoing immunotherapy has not been reported. A 21-site prospective, observational study was performed in a population of consecutive patients with allergic rhinitis, Baseline general health measures revealed significant (P < 0.05) decrements from reported normative levels in 8 domains for patients choosing to undergo immunotherapy and 5 domains for patients choosing not to undergo immunotherapy. The General Health Survey was less sensitive in detecting change than the Nasal Health Survey (Chronic Sinusitis Survey) and allergy-specific (Rhinoconjunctivitis Quality of Life Questionnaire and Allergy Outcome Survey) surveys. Severity of symptoms was associated with both the likelihood to choose immunotherapy and the likelihood for early improvement. We conclude that general and condition-specific measures can be used to observe patients after immunotherapy; however, obtaining baseline data and controlling for seasonality are important considerations. C1 Univ Chicago, Pritzker Sch Med, Dept Surg, Otolaryngol Sect, Chicago, IL 60637 USA. Massachusetts Eye & Ear Infirm, Clin Outcomes Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Outcome Sci LLC, Boston, MA USA. RP Corey, JP (reprint author), Univ Chicago, Pritzker Sch Med, Dept Surg, Otolaryngol Sect, 5841 S Maryland Ave,MC 1035, Chicago, IL 60637 USA. NR 8 TC 7 Z9 7 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 MAY PY 2000 VL 122 IS 5 BP 681 EP 685 DI 10.1016/S0194-5998(00)70196-3 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 315TT UT WOS:000087129600011 PM 10793346 ER PT J AU Drummond, IA AF Drummond, IA TI The zebrafish pronephros: a genetic system for studies of kidney development SO PEDIATRIC NEPHROLOGY LA English DT Review DE zebrafish pronephros; nephrogenesis; mutant phenotypes ID MUTATIONS AFFECTING DEVELOPMENT; DORSOVENTRAL PATTERN-FORMATION; CARDIOVASCULAR-SYSTEM; XENOPUS-LAEVIS; CELL-MIGRATION; IN-VIVO; EXPRESSION; EMBRYO; MESODERM; DIFFERENTIATION AB The zebrafish, as a model system for vertebrate development, offers distinct experimental advantages for studies of organogenesis. The simplicity of the zebrafish pronephros, the feasibility of isolating large numbers of mutants, and the growth in infrastructure for genomics makes the zebrafish an attractive system for the analysis of kidney development. Mutants affecting several aspects of nephrogenesis, including differentiation of the intermediate mesoderm, nephron patterning, epithelial polarity, and angiogenesis, have been isolated. Analysis of mutant phenotypes and the cloning of mutant genes has revealed: (1) a role for bone morphogenetic proteins in patterning the ventral mesoderm, (2) an essential role for the pax2.1 gene in pronephric develop ment, (3) multiple loci required for establishing epithelial polarity in the pronephric duct, (4) a central role for podocytes in directing glomerulogenesis, and (5) 15 loci associated with cystic maldevelopment in the pronephros. The striking similarities of pronephric cell types to those found in higher vertebrates, as well as the conservation of kidney-specific gene expression patterns, suggest that insights gained from studies in zebrafish will be broadly applicable to cell differentiation in the kidney. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [R01 DK53093] NR 63 TC 46 Z9 48 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD MAY PY 2000 VL 14 IS 5 BP 428 EP 435 PG 8 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 311HM UT WOS:000086878700015 PM 10805474 ER PT J AU Rocco, MV Frankenfield, DL Frederick, PR Pugh, J McClellan, WM Owen, WF AF Rocco, MV Frankenfield, DL Frederick, PR Pugh, J McClellan, WM Owen, WF CA Natl ESRD Core Indicators Workgrou TI Intermediate outcomes by race and ethnicity in peritoneal dialysis patients: Results from the 1997 ESRD Core Indicators project SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article DE demographics; race; ethnicity; outcome; Health Care Financing Administration; Medicare, Hispanics ID NON-HISPANIC WHITES; MEXICAN-AMERICANS; HEMODIALYSIS-PATIENTS; HYPERTENSION; PREVALENCE; DISEASE; COHORT; HEALTH; RISK AB Background: Hispanics are the fastest growing minority group in the United States, and approximately 10% of all end-stage renal disease (ESRD) patients are Hispanic. Few data are available, however, regarding dialysis adequacy and anemia management in Hispanic patients receiving peritoneal dialysis in the U.S. Methods: Data from the Health Care Financing Administration (HCFA) ESRD Core Indicators Project were used to assess racial and ethnic differences in selected intermediate outcomes for peritoneal dialysis patients. Results: Of the 1219 patients for whom data were available from the 1997 sample, 9% were Hispanic, 24% were non-Hispanic blacks, and 59% were non-Hispanic whites. Hispanics were more likely to have diabetes mellitus as a cause of ESRD compared to blacks or whites, and both Hispanics and blacks were younger than white patients (both p < 0.001). Although whites had higher weekly Kt/V and creatinine clearance values compared to blacks or Hispanics (p < 0.05), blacks had been dialyzing longer (p < 0.01) and were more likely to be anuric compared to the other two groups (p < 0.001). Blacks had significantly lower mean hematocrit values (p < 0.001) and a greater proportion of patients who had a hematocrit level less than 28% (p < 0.05) compared to Hispanics or whites, despite receiving significantly larger weekly mean epoetin alfa doses (p < 0.05) and having significantly higher mean serum ferritin concentrations (p < 0.01). Multivariate logistic regression analysis revealed significant differences by race/ethnicity for experiencing a weekly Kt/V urea < 2.0 and hypertension, but not for other intermediate outcomes examined (weekly creatinine clearance < 60 L/week/1.73 m(2), Hct < 30%, and serum albumin < 3.5/3.2 g/dL). Conclusion: Hispanics had adequacy values similar to blacks and anemia parameters similar to whites. Additional studies are needed to determine the etiologies of the differences in intermediate outcomes by racial and ethnic groupings in peritoneal dialysis patients. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Nephrol Sect, Winston Salem, NC 27157 USA. US Hlth Care Financing Adm, Off Clin Stand & Qual, Baltimore, MD 21207 USA. S Texas Vet Hlth Care Syst, Disseminat & Implementat Ctr, San Antonio, TX USA. Emory Univ, Sch Med, Div Renal, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Program Hypertens & Renal Dis Hlth Serv Res, Atlanta, GA USA. Duke Univ, Inst Renal Outcomes Res & Hlth Policy, Durham, NC USA. RP Rocco, MV (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Nephrol Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. NR 33 TC 11 Z9 12 U1 0 U2 0 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD MAY-JUN PY 2000 VL 20 IS 3 BP 328 EP 335 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 330KM UT WOS:000087961300010 PM 10898051 ER PT J AU Friedl, L Bernardini, J Piraino, B AF Friedl, L Bernardini, J Piraino, B TI Latrogenic peritonitis: the need for prophylaxis SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article ID DIALYSIS PATIENTS; ANTIBIOTIC-PROPHYLAXIS; COLONOSCOPY; ENDOCARDITIS; POLYPECTOMY; PREVENTION C1 Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Friedl, L (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. NR 19 TC 13 Z9 14 U1 0 U2 0 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD MAY-JUN PY 2000 VL 20 IS 3 BP 343 EP 345 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 330KM UT WOS:000087961300014 PM 10898055 ER PT J AU Bergeron, B AF Bergeron, B TI Touch points SO PHYSICIAN AND SPORTSMEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0091-3847 J9 PHYSICIAN SPORTSMED JI Physician Sportsmed. PD MAY PY 2000 VL 28 IS 5 BP A46 EP A46 PG 1 WC Primary Health Care; Orthopedics; Sport Sciences SC General & Internal Medicine; Orthopedics; Sport Sciences GA 315CM UT WOS:000087095100015 ER PT J AU Pfefer, TJ Chan, KF Hammer, DX Welch, AJ AF Pfefer, TJ Chan, KF Hammer, DX Welch, AJ TI Dynamics of pulsed holmium : YAG laser photocoagulation of albumen SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID TEMPERATURE-DEPENDENCE; EGG-WHITE; IN-VITRO; TISSUE; COAGULATION; RADIATION; BIREFRINGENCE; DENATURATION; MECHANISMS; PARAMETERS AB The pulsed holmium:YAG laser(lambda = 2.12 mu m, tau(p) = 250 mu s) has been investigated as a method for inducing localized coagulation for medical procedures, yet the dynamics of this process are not well understood. In this study, photocoagulation of albumen (egg white) was analysed experimentally and results compared with optical-thermal simulations to investigate a rate process approach to thermal damage and the role of heat conduction and dynamic changes in absorption. The coagulation threshold was determined using probit analysis, and coagulum dynamics were documented with fast flash photography. The nonlinear computational model, which included a Beer's law optical component, a finite difference heat transfer component and an Arrhenius equation-based damage calculation, was verified against data from the literature. Moderate discrepancies between simulation results and our experimental data probably resulted from the use of a laser beam with an irregular spatial profile. This profile produced a lower than expected coagulation threshold and an irregular damage distribution within a millisecond after laser onset. After 1 ms, heat conduction led to smoothing of the coagulum. Simulations indicated that dynamic changes in absorption led to a reduction in surface temperatures. The Arrhenius equation was shown to be effective for simulating transient albumen coagulation during pulsed holmium:YAG laser irradiation. Greater understanding of pursed laser-tissue interactions may lead to improved treatment outcome and optimization of laser parameters for a variety of medical procedures. C1 Univ Texas, Biomed Engn Program, Austin, TX 78712 USA. Univ Texas, Dept Elect & Comp Engn, Austin, TX 78712 USA. RP Pfefer, TJ (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St,Bartlett 722, Boston, MA 02114 USA. RI Pfefer, Josh/I-9055-2012 NR 35 TC 9 Z9 9 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY PY 2000 VL 45 IS 5 BP 1099 EP 1114 DI 10.1088/0031-9155/45/5/302 PG 16 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 319CG UT WOS:000087321900003 PM 10843093 ER PT J AU Ratts, VS Tao, XJ Webster, CB Swanson, PE Smith, SD Brownbill, P Krajewski, S Reed, JC Tilly, JL Nelson, DM AF Ratts, VS Tao, XJ Webster, CB Swanson, PE Smith, SD Brownbill, P Krajewski, S Reed, JC Tilly, JL Nelson, DM TI Expression of BCL-2, BAX and BAK in the trophoblast layer of the term human placenta: a unique model of apoptosis within a syncytium SO PLACENTA LA English DT Article ID PROGRAMMED CELL-DEATH; VILLOUS TROPHOBLAST; HUMAN ENDOMETRIUM; HOMOLOG BAK; GENE FAMILY; IN-VIVO; MEMBERS; DIFFERENTIATION; PROTOONCOGENE; INHIBITION AB The regulation of apoptosis in the syncytiotrophoblast is of particular interest because this is the only true syncytial epithelium in human cell biology. Nuclei characteristic of apoptotic cells have been localized to this syncytium especially in association with fibrin-containing fibrinoid deposits. The factors responsible for regulating cell death-like features in the trophoblast syncytium are unknown. We tested the hypothesis that fibrin was required for trophoblast apoptosis. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP end-labelling) staining to detect DNA fragmentation typical of apoptosis was performed in term human placentae revealing labelled nuclei associated with fibrin-type fibrinoid, as well as labelled nuclei in discrete areas of syncytiotrophoblast without fibrin. We also hypothesized that members of the BCL-2 family of apoptosis-associated proteins contribute to the regulation of syncytiotrophoblast apoptosis. To identify members of this protein family that might regulate trophoblast apoptosis, we assessed expression of three important members of the bcl-2 gene family. We used immunohistochemistry with monoclonal antisera against human BCL-2 and polyclonal antisera against human BAX and BAK to study paraffin-embedded sections of human term placentae (n=5) from uncomplicated pregnancies. The anti-apoptotic BCL-2 protein was expressed throughout the syncytium of normal villi with much less staining in cytotrophoblast. Staining was also seen adjacent to fibrin deposits and in syncytium overlying fibrin deposits. Expression of the pro-apoptotic BAX protein was undetectable in the syncytiotrophoblast, was expressed in rare cytotrophoblast and was prominent in connective tissue and perivascular cells within the villous core. Localization of a second pro-apoptotic protein, BAK, revealed immunoreactivity in isolated areas of intact syncytium of normal villi. Additionally, fibrin deposits were associated with intense BAK staining in both syncytiotrophoblast and cytotrophoblast. From these data, we speculate that modulation of BAK expression is one factor regulating apoptosis in human trophoblast. (C) 2000 Harcourt Publishers Ltd. C1 Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63108 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63108 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02115 USA. St Marys Hosp, Dept Child Hlth, Manchester M13 0JH, Lancs, England. Burnham Inst, La Jolla, CA 92037 USA. RP Nelson, DM (reprint author), Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63108 USA. RI Brownbill, Paul/I-2412-2015 OI Brownbill, Paul/0000-0002-8328-7072 FU NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R01-HD29190, R01-HD34226] NR 35 TC 71 Z9 75 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD MAY PY 2000 VL 21 IS 4 BP 361 EP 366 DI 10.1053/plac.1999.0486 PG 6 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 325FR UT WOS:000087666000009 PM 10833371 ER PT J AU Marler, JJ Guha, A Rowley, J Koka, R Mooney, D Upton, J Vacanti, JP AF Marler, JJ Guha, A Rowley, J Koka, R Mooney, D Upton, J Vacanti, JP TI Soft-tissue augmentation with injectable alginate and syngeneic fibroblasts SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID VESICOURETERAL REFLUX; PMMA MICROSPHERES; MANNURONIC ACID; IN-VITRO; TRANSPLANTATION; BIOCOMPATIBILITY; MICROCAPSULES; COLLAGEN; GRAFT; IMPLANTATION AB Tissue engineering, a field that combines polymer scaffolds with isolated cell populations to create new tissue, may be applied to soft-tissue augmentation-an area in which polymers and cell populations have been injected independently. We have developed an inbred rat model in which the subcutaneous injection of a hydrogel, a form of polymer, under vacuum permits direct comparison of different materials in terms of both histologic behavior and their ability to maintain the specific shape and volume of a construct. Using this model, we compared three forms of calcium alginate, a synthetic hydrogel, over an 8-week period-standard alginate that was gelled following injection into animals (alginate post-gel), standard alginate that was gelled before injection into animals (alginate pre-gel) and alginate-RGD, to which the cell adhesion tripeptide RGD was linked covalently (RGD post-gel). Parallel groups that included cultured syngeneic fibroblasts suspended within each of these three gels were also evaluated (arginate post-gel plus cells, alginate pre-gel plus cells, and RGD post-gel plus cells). The study used 54 inbred Lewis rats (n = 9 for each of the six groups). Construct geometry was optimally maintained in the alginate post-gel group in which 58 percent of the original volume was preserved at 8 weeks and increased to 88 percent at 8 weeks when syngeneic fibroblasts were included within the gel. Volume was not as well preserved in the RGD post-gel group (25 percent of original volume at 8 weeks), but again increased when syngeneic fibroblasts were included (41 percent of original volume at 8 weeks). Maintenance of volume was poorest in the alginate pre-gel group (31 percent of original volume at 8 weeks) and failed to be augmented by the addition of fibroblasts (19 percent of original volume at 8 weeks). Histologically, the gel remained a uniform sheet surrounded by a fibrous capsule in the alginate post-gel groups. In the alginate pre-gel and RGD post-gel groups, there was significant ingrowth of a fibrovascular stroma into the gel with fragmentation of the construct In constructs in which syngeneic fibroblasts were included, cells were visualized throughout the gel but did not extend processes or appear to contribute to new tissue formation. Material compression testing indicated that the alginate and RGD post-gel constructs became stiffer over a 12-week period, particularly in the cell-containing groups. Our results suggest that calcium alginate could be a suitable agent for soft-tissue augmentation when gelled subcutaneously following injection. The addition of syngeneic fibroblasts enhanced the ability of the gel to maintain the volume of a construct; this seems to be mediated by increased gel stiffness rather than by de novo tissue formation. Our animal model, in combination with material testing data, permits rigorous comparison of different materials used for soft-tissue augmentation. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Beth Israel Hosp, Dept Surg, Boston, MA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Marler, JJ (reprint author), Childrens Hosp, Dept Surg, Enders 1008,300 Longwood Ave, Boston, MA 02115 USA. NR 52 TC 83 Z9 92 U1 0 U2 15 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 MAY PY 2000 VL 105 IS 6 BP 2049 EP 2058 DI 10.1097/00006534-200005000-00020 PG 10 WC Surgery SC Surgery GA 308QU UT WOS:000086725000020 PM 10839402 ER PT J AU Lein, M Jung, K Le, DK Hasan, T Ortel, B Borchert, D Winkelmann, B Schnorr, D Loenings, SA AF Lein, M Jung, K Le, DK Hasan, T Ortel, B Borchert, D Winkelmann, B Schnorr, D Loenings, SA TI Synthetic inhibitor of matrix metalloproteinases (batimastat) reduces prostate cancer growth in an orthotopic rat model SO PROSTATE LA English DT Article DE prostate cancer treatment; R3327 Dunning tumor; inhibition of tumor progression ID TISSUE INHIBITOR; COLORECTAL-CANCER; NUDE-MICE; CARCINOMA; EXPRESSION; BB-94; GELATINASE; SURVIVAL; SPREAD; BENIGN AB BACKGROUND. Increased concentrations of metalloproteinases are associated with the invasive and metastatic behavior of several human malignant tumors. Normally, enzymatic activity is tightly regulated by nonspecific mechanisms and specific inhibitors. The aim of the study was to determine the potential of a synthetic metalloproteinase inhibitor, batimastat, to show its in vitro effect on MatLyLu cancer cells and its in vivo effect on tumor growth in orthotopic cancer (R3327 Dunning tumor) in rats. METHODS. In vitro, a dose response curve of batimastat was generated over 4 days using the MTT assay. Prostate cancer was injected in vivo in male Copenhagen rats by inoculating R3327 Dunning tumor cells (MatLyLu) into the ventral prostatic lobe of 30 rats. Each of 10 rats received batimastat (30 mg/kg body weight) or vehicle administered once a day by i.p. application beginning the day of cell inoculation. Ten rats remained untreated. The effect on local tumor growth was evaluated by measuring tumor weights 20 days after tumor cell inoculation. RESULTS. Significant inhibition of tumor cell proliferation in vitro occurred at 400 and 4,000 ng/ml batimastat. After orthotopic cell inoculation, tumors grew to mean weights of 18.9 g in the control group without treatment, to 22.3 g in the vehicle group, and to 11.1 g in the treated group. Ln comparison to the control group and to the vehicle group, tumor weights increased significantly less under treatment with batimastat. CONCLUSIONS. Batimastat is able to reduce tumor growth in the standard prostate cancer model. Using this model, activity against cancer progression of future inhibitory agents can be reliably assessed. (C) 2000 Wiley-Liss, Inc. C1 Humboldt Univ, Univ Hosp Charite, Dept Urol, D-10117 Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP Lein, M (reprint author), Humboldt Univ, Univ Hosp Charite, Dept Urol, Schumannstr 20-21, D-10117 Berlin, Germany. NR 36 TC 24 Z9 27 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 0270-4137 J9 PROSTATE JI Prostate PD MAY 1 PY 2000 VL 43 IS 2 BP 77 EP 82 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 304VN UT WOS:000086505000001 PM 10754522 ER PT J AU Davis, JM Caroff, SN Mann, SC AF Davis, JM Caroff, SN Mann, SC TI Treatment of neuroleptic malignant syndrome SO PSYCHIATRIC ANNALS LA English DT Article ID ELECTROCONVULSIVE-THERAPY; LETHAL CATATONIA; RISK-FACTORS; DANTROLENE; SUCCINYLCHOLINE; PROGRESSION C1 Univ Illinois, Illinois State Psychiat Inst, Chicago, IL USA. Univ Penn, Dept Psychiat, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Davis, JM (reprint author), UIC, Dept Psychiat, 1601 W Taylor St, Chicago, IL 60612 USA. NR 36 TC 19 Z9 20 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 MAY PY 2000 VL 30 IS 5 BP 325 EP 331 PG 7 WC Psychiatry SC Psychiatry GA 313TJ UT WOS:000087015100008 ER PT J AU Fricchione, G Mann, SC Caroff, SN AF Fricchione, G Mann, SC Caroff, SN TI Catatonia, lethal catatonia, and neuroleptic malignant syndrome SO PSYCHIATRIC ANNALS LA English DT Article ID ELECTROCONVULSIVE-THERAPY; PREFRONTAL CORTEX; SERUM IRON; LORAZEPAM; DOPAMINE; METABOLISM; DIAZEPAM; SCHIZOPHRENIA; BROMOCRIPTINE; APOMORPHINE C1 Carter Ctr, Atlanta, GA 30307 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Fricchione, G (reprint author), Carter Ctr, 1 Copenhill,453 Freedom Pkwy, Atlanta, GA 30307 USA. NR 61 TC 24 Z9 25 U1 2 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD MAY PY 2000 VL 30 IS 5 BP 347 EP 355 PG 9 WC Psychiatry SC Psychiatry GA 313TJ UT WOS:000087015100010 ER PT J AU Mann, SC Caroff, SN Fricchione, G Campbell, EC AF Mann, SC Caroff, SN Fricchione, G Campbell, EC TI Central dopamine hypoactivity and the pathogenesis of neuroleptic malignant syndrome SO PSYCHIATRIC ANNALS LA English DT Article ID GANGLIA-THALAMOCORTICAL CIRCUITS; CONDITIONED AVOIDANCE-RESPONSE; FRONTAL-SUBCORTICAL CIRCUITS; PREFRONTAL CORTEX; BASAL GANGLIA; PARKINSONS-DISEASE; NUCLEUS ACCUMBENS; CAUDATE-NUCLEUS; SCHIZOPHRENIA; CATATONIA C1 Vet Adm Med Ctr 116A, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Carter Ctr, Atlanta, GA USA. RP Mann, SC (reprint author), Vet Adm Med Ctr 116A, Univ Ave, Philadelphia, PA 19104 USA. NR 47 TC 26 Z9 29 U1 1 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD MAY PY 2000 VL 30 IS 5 BP 363 EP 374 PG 12 WC Psychiatry SC Psychiatry GA 313TJ UT WOS:000087015100012 ER PT J AU Murphy, JM Laird, NM Monson, RR Sobol, AM Leighton, AH AF Murphy, JM Laird, NM Monson, RR Sobol, AM Leighton, AH TI Incidence of depression in the Stirling County Study: historical and comparative perspectives SO PSYCHOLOGICAL MEDICINE LA English DT Article ID DIAGNOSTIC-INTERVIEW-SCHEDULE; NATIONAL COMORBIDITY SURVEY; PSYCHIATRIC-DISORDERS; GENERAL-POPULATION; SEX-DIFFERENCES; LIFETIME PREVALENCE; MAJOR DEPRESSION; ANXIETY; EPIDEMIOLOGY; MORTALITY AB Background, The Stirling County Study provides a 40-year perspective on the epidemiology of psychiatric disorders in an adult population in Atlantic Canada. Across samples selected in 1952, 1970 and 1992 current prevalence of depression was stable. This paper concerns time trends in annual incidence as assessed through cohorts selected from the first two samples. Methods. Consistent interview data were analysed by a computerized diagnostic algorithm. The cohorts consisted of subjects at risk for a first depression: Cohort-1 (N = 575) was followed 1952-1970; Cohort-2 (N = 639) was followed 1970-1992. Life-table methods were used to calculate incidence rates and proportional hazards procedures were used for statistical assessment. Results, Average annual incidence of depression was 4.5 per 1000 for Cohort-1 and 3.7 for Cohort 2. Differences by gender, age and time were not statistically significant. The stability of incidence and the similarity of distribution by gender and age in these two cohorts corresponds to findings about the two early samples. In contrast, current prevalence in the recent sample was distributed differently and showed an increase among women under 45 years. Conclusions, The stability of the incidence of depression emphasizes the distinctive characteristics of current prevalence in the recent sample and suggests that the dominance of women in rates of depression may have occurred among those born after the Second World War. The results offer partial support for the interpretation of an increase in depression based on retrospective data in other recent studies but they indicate that the increase is specific to women. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Room 9155,149 13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH 39576] NR 46 TC 61 Z9 61 U1 5 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD MAY PY 2000 VL 30 IS 3 BP 505 EP 514 DI 10.1017/S0033291799002044 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 329LP UT WOS:000087908700003 PM 10883707 ER PT J AU Cohen, LM Steinberg, MD Hails, KC Dobscha, SK Fischel, SV AF Cohen, LM Steinberg, MD Hails, KC Dobscha, SK Fischel, SV TI Psychiatric evaluation of death-hastening requests - Lessons from dialysis discontinuation SO PSYCHOSOMATICS LA English DT Review ID PHYSICIAN-ASSISTED SUICIDE; OF-LIFE CARE; TERMINALLY ILL; ADVANCE DIRECTIVES; MEDICAL-TREATMENT; PATIENT REQUESTS; CRITICALLY ILL; DYING PATIENTS; UNITED-STATES; EUTHANASIA AB The authors aim to facilitate the psychiatric evaluation of death-hastening decisions, such as cessation of life-support treatment or physician-assisted suicide, by deriving principles for evaluating patients from a literature review and a recently completed prospective study on dialysis discontinuation conducted by consultation psychiatrists. Factors are delineated and suggestions are provided for the evaluation of requests to accelerate dying. Included are the authors' method for determining major depression in the context of terminal illness and their "vector analysis " in assessing patient requests to stop dialysis. As our society heatedly examines the care provided to the terminally ill, psychiatry also needs to reconsider whether actions that foreshorten life can be normative and permissible. Familiarity with competency, psychiatric diagnosis, and ease in communication and negotiation between patient, family, and staff are resources that psychiatrists can bring to these complicated assessments. Challenging areas include diagnosing depression, establishing the adequacy of palliative care, and appreciating issues related to personality features, family dynamics, and ethnic differences. C1 Baystate Med Ctr, Dept Psychiat, Springfield, MA 01199 USA. Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. Portland VA Med Ctr, Portland, OR USA. RP Cohen, LM (reprint author), Baystate Med Ctr, Dept Psychiat, Springfield, MA 01199 USA. NR 111 TC 18 Z9 18 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2000 VL 41 IS 3 BP 195 EP 203 DI 10.1176/appi.psy.41.3.195 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 318GR UT WOS:000087276000002 PM 10849450 ER PT J AU Tanielian, TL Pincus, HA Dietrich, AJ Williams, JW Oxman, TE Nutting, P Marcus, SC AF Tanielian, TL Pincus, HA Dietrich, AJ Williams, JW Oxman, TE Nutting, P Marcus, SC TI Referrals to psychiatrists - Assessing the communication interface between psychiatry and primary care SO PSYCHOSOMATICS LA English DT Article ID MANAGED CARE; DEPRESSION; PHYSICIANS AB The Study of Outpatient Referral Patterns was conducted in 1998 to examine the nature of the communication relationship between psychiatrists and primary care physicians regarding outpatient referrals. Nationally representative psychiatrists were surveyed (N = 542) regarding their aggregate experience with outpatient referrals from non-psychiatric physicians in the previous 60 clays. Data regarding frequency and type of information and mode of communication were gathered. Results indicate that primary care physicians represent a significant source of referrals to psychiatrists and that psychiatrists are generally satisfied with the communication interface with the referring physicians. Psychiatrists' level of satisfaction was related to the quantity and quality of information provided by referring physicians. C1 RAND Corp, Arlington, VA 22202 USA. Amer Psychiat Assoc, Washington, DC 20005 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH USA. S Texas Vet Healthcare Syst, Div Gen Internal Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Ctr Res Strategies, Denver, CO USA. RP Tanielian, TL (reprint author), RAND Corp, 1200 S Hayes St, Arlington, VA 22202 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 12 TC 26 Z9 27 U1 0 U2 1 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 MAY-JUN PY 2000 VL 41 IS 3 BP 245 EP 252 DI 10.1176/appi.psy.41.3.245 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 318GR UT WOS:000087276000009 PM 10849457 ER PT J AU Burhenne, LJW Wood, SA D'Orsi, CJ Feig, SA Kopans, DB O'Shaughnessy, KF Sickles, EA Tabar, L Vyborny, CJ Castellino, RA AF Burhenne, LJW Wood, SA D'Orsi, CJ Feig, SA Kopans, DB O'Shaughnessy, KF Sickles, EA Tabar, L Vyborny, CJ Castellino, RA TI Potential contribution of computer-aided detection to the sensitivity of screening mammography SO RADIOLOGY LA English DT Article; Proceedings Paper CT 86th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) CY NOV 26-DEC 01, 2000 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE breast neoplasms; breast neoplasms, diagnosis; cancer screening; computers, diagnostic aid ID BREAST-CANCER; QUALITY ASSURANCE; AMERICAN-COLLEGE; PROGRAM; INTERVAL; BENEFIT; TRIAL; AGE; VARIABILITY; GUIDELINES AB PURPOSE: To determine the false-positive rate in screening mammography, the capability of computer-aided detection (CAD) to identify these missed lesions, and whether or not CAD increases the radiologists' recall rate. MATERIALS AND METHODS: All available screening mammograms that led to the detection of biopsy-proved cancer (n = 1,083) and the most recent corresponding prior mammograms (n = 427) were collected from 13 facilities. Panels of radiologists evaluated the retrospectively visible prior mammograms by means of blinded review. All mammograms were analyzed by a CAD system that marks features associated with cancer. The recall rates of 14 radiologists were prospectively measured before and after installation of the CAD system. RESULTS: At retrospective review, 67% (286 of 427) of screening mammography detected breast cancers were visible on the prior mammograms. At independent, blinded review by panels of radiologists, 27% (115 of 427) were interpreted as warranting recall on the basis of a statistical evaluation index; and the CAD system correctly marked 77% (89 of 115) of these cases. The original attending radiologists' sensitivity was 79% (427 of [427 + 115]). There was no statistically significant increase in the radiologists' recall rate when comparing the values before (8.3%) with those after (7.6%) installation of the CAD system. CONCLUSION: The original attending radiologists had a false-negative rate of 21% (115 of [427 + 115]). CAD prompting could have potentially helped reduce this false-negative rate by 77% (89 of 115) without an increase in the recall rate. C1 R2 Technol, Altos, CA 94022 USA. Univ British Columbia, Dept Radiol, Vancouver, BC, Canada. Univ Massachusetts, Med Ctr, Dept Radiol, N Worcester, MA 01606 USA. Thomas Jefferson Univ Hosp, Breast Imaging Ctr, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. Cent Hosp, Dept Mamog, Falun, Sweden. Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. RP Castellino, RA (reprint author), R2 Technol, 325 Distel Circle, Altos, CA 94022 USA. NR 40 TC 353 Z9 362 U1 2 U2 9 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2000 VL 215 IS 2 BP 554 EP 562 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 306CG UT WOS:000086578500037 PM 10796939 ER PT J AU Nokes, KM Holzemer, WL Corless, IB Bakken, S Brown, MA Powell-Cope, GM Inouye, J Turner, J AF Nokes, KM Holzemer, WL Corless, IB Bakken, S Brown, MA Powell-Cope, GM Inouye, J Turner, J TI Health-related quality of life in persons younger and older than 50 who are living with HIV/AIDS SO RESEARCH ON AGING LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; OF-LIFE; HIV-INFECTION; AIDS; DISEASE; AGE; VALIDATION; ADHERENCE; PATIENT; ADULTS AB Mortality rates are higher in older persons with AIDS. The Wilson and Cleary health-related quality-of-life model was used to explore whether there were differences on health-related quality-of-life variables between persons aged 50 or older (n = 73) and younger persons (n = 640) in a national sample. Depending on the level of the data, either independent t tests or chi-squares were calculated. Older participants reported significantly more medical conditions such as diabetes or hypertension (p = .000), more limitations in physical functioning (p = .006), and self-disclosure of HIV infection to fewer people (p = .000). There were no significant differences on any of the other variables. There are relatively few differences in older as compared to younger persons living with HIV/AIDS, yet mortality rates are higher in older samples. The relationship between the areas where there are differences and whether they affect morbidity and mortality need further exploration. C1 CUNY Hunter Coll, Hunter Bellevue Sch Nursing, Community Hlth Nursing Program, New York, NY 10021 USA. Univ Calif San Francisco, Sch Nursing, Dept Community Hlth Syst, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Univ Washington, Womens Primary Care Clin, Seattle, WA 98195 USA. James A Haley Vet Hosp, Tampa, FL 33612 USA. Univ Hawaii Manoa, Sch Nursing, Grad Program, Honolulu, HI 96822 USA. Univ Alabama, Sch Nursing, Birmingham, AL USA. RP Nokes, KM (reprint author), CUNY Hunter Coll, Hunter Bellevue Sch Nursing, Community Hlth Nursing Program, New York, NY 10021 USA. OI Corless, Inge/0000-0003-0438-2037; Powell-Cope, Gail/0000-0002-4608-0128 NR 39 TC 38 Z9 38 U1 3 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0164-0275 J9 RES AGING JI Res. Aging PD MAY PY 2000 VL 22 IS 3 BP 290 EP 310 DI 10.1177/0164027500223004 PG 21 WC Gerontology SC Geriatrics & Gerontology GA 309LU UT WOS:000086769900004 ER PT J AU Basile, JN AF Basile, JN TI Combination agents as a means of improving adherence and other aspects of the Sixth Joint National Committee report SO SOUTHERN MEDICAL JOURNAL LA English DT Article; Proceedings Paper CT 3rd Annual Conference on Hypertension - Improving Outcomes in Primary Care CY JUN 11-13, 1999 CL KIAWAH ISL, SOUTH CAROLINA SP SO Med Assoc C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Basile, JN (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. NR 9 TC 1 Z9 2 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD MAY PY 2000 VL 93 IS 5 BP 534 EP 536 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 316YA UT WOS:000087194700023 PM 10832960 ER PT J AU Lee, SJ Zelen, M AF Lee, SJ Zelen, M TI Clinical trials and sample size considerations: Another perspective SO STATISTICAL SCIENCE LA English DT Article DE Type I and II error probabilities; posterior error probabilities; clinical trials; Bayesian inferences ID FREQUENTIST AB We propose a Bayesian formulation of the sample size problem for planning clinical trials. The frequentist paradigm for calculating sample sizes for clinical trials is to prespecify the type I and II error probabilities. These error probabilities are conditional on the true hypotheses. Instead we propose prespecifying posterior probabilities which are conditional on the outcome of the trial. Our method is easy to implement and has intuitive interpretations. We illustrate an application of our method to the planning of cancer clinical trials for the Eastern Cooperative Oncology Group (ECOG). C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. NR 9 TC 42 Z9 43 U1 1 U2 3 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 7, 3401 INVESTMENT BLVD, HAYWARD, CA 94545 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 2000 VL 15 IS 2 BP 95 EP 103 PG 9 WC Statistics & Probability SC Mathematics GA 348CT UT WOS:000088967700001 ER PT J AU Ostergaard, L Sorensen, AG Chesler, DA Weisskoff, RM Koroshetz, WJ Wu, O Gyldensted, C Rosen, BR AF Ostergaard, L Sorensen, AG Chesler, DA Weisskoff, RM Koroshetz, WJ Wu, O Gyldensted, C Rosen, BR TI Combined diffusion-weighted and perfusion-weighted flow heterogeneity magnetic resonance imaging in acute stroke SO STROKE LA English DT Article DE cerebral blood flow; magnetic resonance imaging, diffusion-weighted magnetic resonance imaging, perfusion-weighted microcirculation ID CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; CEREBROVASCULAR-DISEASE; ARTERY OCCLUSION; CONTRAST AGENTS; MR CONTRAST; SUSCEPTIBILITY; VOLUME AB Background and Purpose-The heterogeneity of microvascular flows is known to be an important determinant of the efficacy of oxygen delivery to tissue. Studies in animals have demonstrated decreased flow heterogeneity (FH) in states of decreased perfusion pressure. The purpose of the present study was to assess microvascular FH changes in acute stroke with use of a novel perfusion-weighted MRI technique and to evaluate the ability of combined diffusion-weighted MRI and FH measurements to predict final infarct size. Methods-Cerebral blood flow, FH, and plasma mean transit time (MTT) were measured in 11 patients who presented with acute (<12 hours after symptom onset) stroke. Final infarct size was determined with follow-up MRI or CT scanning. Results In normal brain tissue, the distribution of relative flows was markedly skewed toward high capillary flow velocities. Within regions of decreased cerebral blood flow, plasma MTT was prolonged. Furthermore, subregions were identified with significant loss of the high-flow component of the flow distribution, thereby causing increased homogeneity of flow velocities. In parametric maps that quantify the acute deviation of FH from that of normal tissue, areas of extreme homogenization of capillary flows predicted final infarct size on follow-up scans of 10 of 11 patients. Conclusions-Flow heterogeneity and MTT can be rapidly assessed as part of a routine clinical MR examination and may provide a tool for planning of individual stroke treatment, as well as in targeting and evaluation of emerging therapeutic strategies. C1 Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard MIT Div Hlth Sci, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Neurol, Stroke Unit, Boston, MA 02114 USA. Arhus Univ Hosp, Dept Neuroradiol, Arhus, Denmark. RP Ostergaard, L (reprint author), Aarhus Kommune Hosp, Dept Neuroradiol, Norrebrogade 44, DK-8000 Aarhus C, Denmark. RI Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 NR 30 TC 50 Z9 50 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2000 VL 31 IS 5 BP 1097 EP 1103 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 310HN UT WOS:000086820600013 PM 10797171 ER PT J AU Zaroff, JG Rordorf, GA Titus, JS Newell, JB Nowak, NJ Torchiana, DF Aretz, T Picard, MH AF Zaroff, JG Rordorf, GA Titus, JS Newell, JB Nowak, NJ Torchiana, DF Aretz, T Picard, MH TI Regional myocardial perfusion after experimental subarachnoid hemorrhage SO STROKE LA English DT Article DE angiography; cerebrovascular disorders; echocardiography; regional blood flow; dogs ID ABNORMALITIES; DOGS AB Background and Purpose-The pathophysiology of cardiac injury after subarachnoid hemorrhage (SAH) remains controversial. Data from animal models suggest that catecholamine-mediated injury is the most likely cause of cardiac injury after SAH. However, researchers also have proposed myocardial ischemia to be the under lying cause, as a result of coronary artery disease, coronary artery spasm, or hypertension and tachycardia. To test the hypothesis that SAM-induced cardiac injury occurs in the absence of myocardial hypoperfusion, we developed an experimental canine model that reproduces the clinical and pathological cardiac lesions of SAH and defines the epicardial and microvascular coronary circulation. Methods-Serial EGG, hemodynamic measurements, coronary angiography, regional myocardial blood now measurements by radiolabeled microspheres. 2D echocardiography, and myocardial contrast echocardiography were performed in 9 dogs with experimental SAH and 5 controls. Results-Regional wall motion abnormalities were identified in 8 of 9 SAH dogs and 1 of 5 controls (Fisher's Exact Test, P=0.02) but no evidence was seen of coronary artery disease or spasm by coronary angiography and of significant myocardial hypoperfusion by either regional myocardial blood flow or myocardial contrast echocardiography. Conclusions-In this experimental model of SAH, a unique form of regional left ventricular dysfunction occurs in the absence of myocardial hypoperfusion. Future studies are justified to determine the cause of cardiac injury after SAH. C1 Massachusetts Gen Hosp, Cardiac Unit, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Cardiac Ultrasound Lab, VBK-508,55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 22 TC 42 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2000 VL 31 IS 5 BP 1136 EP 1142 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 310HN UT WOS:000086820600020 PM 10797178 ER PT J AU Page, CW Barnes, SA Fisher, WE AF Page, CW Barnes, SA Fisher, WE TI Ulcer necessitans: A forgotten entity SO SURGERY LA English DT Article C1 Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. RP Fisher, WE (reprint author), Houston VAMC, Surg Serv 112, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2000 VL 127 IS 5 BP 593 EP 594 DI 10.1067/msy.2000.104405 PG 2 WC Surgery SC Surgery GA 312HQ UT WOS:000086938000021 PM 10819071 ER PT J AU Sever, S Damke, H Schmid, SL AF Sever, S Damke, H Schmid, SL TI Garrotes, springs. ratchets, and whips: Putting dynamin models to the test SO TRAFFIC LA English DT Review ID CLATHRIN-MEDIATED ENDOCYTOSIS; COATED VESICLE FORMATION; PLECKSTRIN HOMOLOGY DOMAIN; GTPASE-ACTIVATING PROTEINS; REVERSIBLE BLOCKAGE; MEMBRANE RETRIEVAL; NERVE-TERMINALS; PINCHASE ACTION; SH3 DOMAIN; AMPHIPHYSIN AB The GTPase dynamin is essential for clathrin-mediated endocytosis, Numerous new and exciting discoveries regarding dynamin function in vivo and in vitro have led to various models in which dynamin functions directly in membrane fission and the release of clathrin-coated vesicles from the plasma membrane. This would make dynamin unique among GTPases in its ability to act as a mechanochemical enzyme. Here we review the various models and their supporting data. We then discuss new findings that raise doubts as to whether dynamin breaks the paradigm that governs regulatory GTPases. C1 Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Scripps Res Inst, Dept Cell Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM slschmid@scripps.edu FU NIGMS NIH HHS [GM42455] NR 58 TC 176 Z9 178 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-9219 EI 1600-0854 J9 TRAFFIC JI Traffic PD MAY PY 2000 VL 1 IS 5 BP 385 EP 392 DI 10.1034/j.1600-0854.2000.010503.x PG 8 WC Cell Biology SC Cell Biology GA 325ZH UT WOS:000087706800003 PM 11208124 ER PT J AU Dzik, S Moroff, G Dumont, L AF Dzik, S Moroff, G Dumont, L CA ISBT TI A multicenter study evaluating three methods for counting residual WBCs in WBC-reduced blood components: Nageotte hemocytometry, flow cytometry, and microfluorometry SO TRANSFUSION LA English DT Article ID VOLUMETRIC CAPILLARY CYTOMETRY; WHITE CELLS; LOW NUMBERS; VALIDATION; LEUKOCYTES; PLATELETS; PRODUCTS AB BACKGROUND: A multicenter study was conducted to evaluate the performance characteristics of flow cytometry and microfluorimetry for counting low concentrations of WBCs and to compare the results with Nageotte hemocytometry. STUDY DESIGN AND METHODS: A two-phase study involving 10 centers located in the United States and in Europe was performed. coded samples of RBCs and platelets were distributed by 24-hour (Phase 1) or 2-day (Phase 2) courier service to each test site for analysis. Samples were prepared to include concentrations of WBCs slightly above and below the concentration corresponding to the threshold standards for WBC-reduced RBCs and platelets. All centers tested samples by Nageotte hemocytometry plus one or both of two automated methods. RESULTS: Both flow cytometry and microfluorometry gave better results than Nageotte hemocytometry in testing freshly prepared samples. At WBC concentrations >5 per mu L (RBCs) or >3 per mu L (platelets), the intersite CV was <20 percent for the automated methods but >30 percent for the Nageotte hemocytometer method (p<0.001). Accuracy was greater for the automated methods than for the Nageotte hemocytometer method (p<0.001). Nageotte hemocytometry showed a bias to underestimation relative to the results obtained with the automated methods. All methods had poorer performance in testing samples that required 12 days' shipment than in testing of those requiring overnight shipment. CONCLUSION: Automated methods for counting residual donor WBCs in WBC-reduced cellular components offer advantages of improved precision and greater accuracy than are seen with the Nageotte hemocytometer method. Automated methods are less labor-intensive but more costly than microscopic methods. Preparation and shipping methods will need further refinement for samples to be counted more than 24 hours after sample collection. C1 Massachusetts Gen Hosp, Blood Transfus Serv J224, Boston, MA 02114 USA. Amer Red Cross, Jerome H Holland Lab Biomed Sci, Rockville, MD USA. COBE BCT Inc, Lakewood, CO USA. RP Dzik, S (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv J224, 55 Fruit St, Boston, MA 02114 USA. RI Dumont, Larry/B-3994-2011; Selogie, Eileen/L-3628-2016 OI Dumont, Larry/0000-0002-1715-0748; NR 12 TC 34 Z9 36 U1 1 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2000 VL 40 IS 5 BP 513 EP 520 DI 10.1046/j.1537-2995.2000.40050513.x PG 8 WC Hematology SC Hematology GA 316BK UT WOS:000087147300004 PM 10827252 ER PT J AU Marciniak, RA Johnson, FB Guarente, L AF Marciniak, RA Johnson, FB Guarente, L TI Dyskeratosis congenita, telomeres and human ageing SO TRENDS IN GENETICS LA English DT Article ID HUMAN-CELLS; INACTIVATION; FIBROBLASTS; INHIBITION; CARRIERS; CANCER; MICE; RNA AB As normal humans age, telomeres shorten in tissues that contain dividing cells, and this has been proposed both as a cause of ageing and as a tumor-suppressor mechanism. The surprising finding that cells from individuals with the rare inherited disorder dyskeratosis congenita (DKC) have reduced levels of telomerase and shortened telomeres might provide the first direct genetic test of the function of telomeres in intact humans. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Marciniak, RA (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 32 TC 39 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAY PY 2000 VL 16 IS 5 BP 193 EP 195 DI 10.1016/S0168-9525(00)01984-3 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 310GE UT WOS:000086817500002 PM 10782108 ER PT J AU Way, KJ Chou, E King, GL AF Way, KJ Chou, E King, GL TI Identification of PKC-isoform-specific biological actions using pharmacological approaches SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID PROTEIN-KINASE-C; ANTISENSE OLIGONUCLEOTIDE INHIBITOR; IN-VIVO; SELECTIVE INHIBITOR; ALPHA EXPRESSION; PHORBOL ESTERS; BETA INHIBITOR; DIABETIC RATS; NUDE-MICE; ISOZYMES AB The protein kinase C (PKC) family consists of at least 12 isoforms that possess distinct differences in structure, substrate requirement, expression and localization. To date, identification of the physiological function of individual PKC isoforms has been restricted by the availability of few agents that inhibitor activate the isoforms with specificity. More recent approaches that are used to modulate PKC isoforms include oligonucleotide antisense technology, and peptide fragments to either inhibit or promote translocation of PKC isoforms to specific anchoring proteins. In this review, several currently available inhibitors and activators of PKC that display varying degrees of selectivity for the PKC isoforms will be discussed. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. FU NEI NIH HHS [EY5110] NR 50 TC 343 Z9 352 U1 0 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAY PY 2000 VL 21 IS 5 BP 181 EP 187 DI 10.1016/S0165-6147(00)01468-1 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 314NG UT WOS:000087061700012 PM 10785652 ER PT J AU Shipp, TD Bromley, B Benacerraf, B AF Shipp, TD Bromley, B Benacerraf, B TI The Prognostic significance of hyperextension of the fetal head detected antenatally with ultrasound SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE hyperextension; fetal head; attitude ID BREECH PRESENTATION AB Objectives The purpose of this study was to evaluate the clinical significance of hyperextension of the fetal head detected by ultrasound prior to the onset of labour. Methods Over a 10-year period, we retrospectively identified all fetuses who had hyperextension of the fetal head reported on antenatal ultrasound. Hyperextension referred to persistence of the cervical spine in extreme extension, with an extension angle of at least 150 degrees persisting for the duration of the scan. Follow-up information was obtained from Hospital medical records and obstetrical care providers. Results Follow-up was obtained on 57 of the 65 fetuses (87.7%) identified over the study period. Ten of the 57 fetuses had normal structural fetal surveys and had sonographically identified resolution prior to delivery. All 10 patients delivered at term and had newborns with normal neonatal courses. Twenty-six of 57 fetuses had no sonographic findings other than persistent hyperextension, and 19 of these 26 fetuses (73%) had normal neonatal courses. Twenty-one of 57 fetuses (37%) had structural anomalies sonographically identified in addition to hyperextension of the fetal head. All 21 of these pregnancies ended in either termination or fecal or neonatal demize. Conclusions Although resolution of isolated hyperextension of the fetal head is associated with a normal neonatal outcome, persistent isolated hyperextension of the fetal head can be associated with either a normal or an abnormal neonatal outcome. Fetuses with hyperextended heads and antenatally diagnosed structural anomalies have dismal outcomes. The identification of a fetus with hyperextension of the fetal head should prompt a detailed search for structural abnormalities. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Shipp, TD (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave,Suite 400, Boston, MA USA. NR 13 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD MAY PY 2000 VL 15 IS 5 BP 391 EP 396 DI 10.1046/j.1469-0705.2000.00120.x PG 6 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 350GK UT WOS:000089092500009 PM 10976480 ER PT J AU Spencer, BA Wood, BJ Dretler, SP AF Spencer, BA Wood, BJ Dretler, SP TI Helical CT and ureteral colic SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE FLANK PAIN; SPIRAL COMPUTERIZED-TOMOGRAPHY; TISSUE RIM SIGN; URINARY CALCULI; FILLING DEFECTS; CHEMICAL-COMPOSITION; EXCRETORY UROGRAPHY; PLAIN RADIOGRAPHY; DIAGNOSIS; NUMBERS AB Helical CT has many advantages over intravenous urography and ultrasound, making it the gold standard for the evaluation of flank pain that is suspicious for ureteral colic. Technological advances, important radiographic diagnostic methods, and a review of the literature supporting the use of helical CT are presented. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol,Wang Ambulatory Care Ctr 486, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20007 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Dretler, SP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol,Wang Ambulatory Care Ctr 486, Boston, MA 02114 USA. NR 41 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 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD MAY PY 2000 VL 27 IS 2 BP 231 EP + DI 10.1016/S0094-0143(05)70253-6 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 302PC UT WOS:000086373200005 PM 10778466 ER PT J AU Chakravarti, A Zehr, EM Zietman, AL Shipley, WU Goggins, WB Finkelstein, DM Young, RH Chang, EL Wu, CL AF Chakravarti, A Zehr, EM Zietman, AL Shipley, WU Goggins, WB Finkelstein, DM Young, RH Chang, EL Wu, CL TI Thymosin beta-15 predicts for distant failure in patients with clinically localized prostate cancer - Results from a pilot study SO UROLOGY LA English DT Article ID RADIATION-THERAPY; CARCINOMA; ADENOCARCINOMA; RADIOTHERAPY; EXPRESSION; PROTEINS AB Objectives. To report the results of a pilot study on the prognostic value of a newly identified actin-binding protein, thymosin beta-15 (T beta 15), in predicting prostate-specific Antigen (PSA) and bone failure in patients with Gleason 6/10 clinically localized prostate cancer. Methods. Thirty-two patients (median age 70 years) with clinically localized, moderately differentiated [Gleason 6/10) prostate cancer treated by external beam radiotherapy alone (68.4 Gy) with available paraffin blocks at the Massachusetts General Hospital were evaluated for this pilot study. All patients had clinical Stage MO disease at initial presentation, which was documented by bone scan (T1c-4,NX). Their corresponding biopsy specimens were stained immunohistochemically for T beta 15, which was then correlated with the clinical outcome in a blinded manner. The median follow-up was 6 years (range 1 to 19) for all of the patients. Results. The outcomes of the 32 patients can be grouped into three categories: patients with no evidence of disease (n = 11), patients with PSA failure without documented bone failure (n = 1 I), and patients with PSA failure and documented bone failure (n = 10]. T beta 15 staining intensity strongly correlated with clinical outcome. Of those patients whose specimens stained 3+ (strongest staining), 62% developed bone failure compared with 13% of those patients whose specimens stained 1+ (weakest staining) (P = 0.01). The 5-year freedom from PSA failure was only 25% for those patients with 3+ staining compared with 83% for those with 1+ staining (P = 0.02). Conclusions. The results of this pilot study have demonstrated that T beta 15 staining intensity may be a potentially important marker to identify high-risk patients with moderately differentiated, clinically localized prostate cancer. UROLOGY 55: 635-638, 2000. (C) 2000, Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. RP Chakravarti, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox Bldg Basement, Boston, MA 02114 USA. NR 15 TC 25 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 0090-4295 J9 UROLOGY JI UROLOGY PD MAY PY 2000 VL 55 IS 5 BP 635 EP 638 DI 10.1016/S0090-4295(00)00462-3 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 310NJ UT WOS:000086834000007 PM 10792068 ER PT J AU D'Amico, AV Weinstein, M Li, XD Richie, JP Fujimoto, J AF D'Amico, AV Weinstein, M Li, XD Richie, JP Fujimoto, J TI Optical coherence tomography as a method for identifying benign and malignant microscopic structures in the prostate gland SO UROLOGY LA English DT Article ID RADICAL RETROPUBIC PROSTATECTOMY; ADENOCARCINOMA; FAILURE; CANCER; BIOPSY AB Objectives. Optical coherence tomography (OCT) is a new optical imaging technique capable of providing cross-sectional imaging of tissue microstructure in vivo and in real time. OCT was used in the setting of the human prostate ex vivo, and the images acquired were compared with those obtained using standard histopathologic methods. Methods. Multiple samples (3 to 6) were obtained from the radical prostatectomy specimens of 7 men with clinically localized (T1c-2, N0, M0) adenocarcinoma of the prostate. These specimens were 1 cm in length and 1 mm x 1 mm in rectangular cross section. Specimens were first imaged using OCT and then embedded and stained in preparation for histopathologic evaluation. Co-registration of the images obtained using OCT and standard histopathologic evaluation provided the basis for comparison. Results. Structural architecture on the order of 50 to 150 mu m within benign glandular epithelium, fibro-adipose tissue, and malignant glandular epithelium could be resolved to a depth of approximately 0.5 mm using OCT. Conclusions. Microscopic resolution is possible in human prostatic tissue using OCT. Further studies using this technique to improve the detection and staging of adenocarcinoma of the prostate are ongoing. UROLOGY 55: 783-787, 2000. (C) 2000, Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Dept Elect Engn & Comp Sci, Boston, MA USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02215 USA. RI Li, Xingde/F-7663-2012 NR 17 TC 49 Z9 52 U1 1 U2 5 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 MAY PY 2000 VL 55 IS 5 BP 783 EP 787 DI 10.1016/S0090-4295(00)00475-1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 310NJ UT WOS:000086834000040 PM 10792101 ER PT J AU Arterburn, DE Richardson, WS AF Arterburn, DE Richardson, WS TI Evidence-based case review - Should we look further for cancer in a patient with venous thromboembolism? SO WESTERN JOURNAL OF MEDICINE LA English DT Review ID DEEP-VEIN THROMBOSIS; OCCULT CANCER; PULMONARY-EMBOLISM; CLINICAL COURSE; MALIGNANCY; SEARCH; SIGN; RISK AB A 71-year-old woman with venous thromboembolism was referred to us to determine whether a workup for cancer was indicated. She had been hospitalized because of deep venous thrombosis of her left leg and pulmonary embolism; she had no history of venous thromboembolism or cancer. For the past few months, she had the feeling of being "full" before she had eaten much but had no other constitutional or gastrointestinal symptoms. On physical examination, she was found to be obese (body mass index*=33), and there was fibrocystic nodularity in both breasts. She also had a trace of symmetric edema in her ankles. Laboratory test values showed mild normocytic anemia, but routine chemistry test results were normal, as were those of her liver function tests, urinalysis, activated protein C resistance, proteins C and S and antithrombin III concentrations, antiphospholipid antibody, and a chest film. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Off Educ Programs, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Arterburn, DE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Off Educ Programs, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU B M J PUBLISHING INC PI SAN FRANCISCO PA 221 MAIN ST, PO BOX 7690, SAN FRANCISCO, CA 94120-7690 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD MAY PY 2000 VL 172 IS 5 BP 325 EP 328 DI 10.1136/ewjm.172.5.325 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 313VR UT WOS:000087020300021 PM 10832425 ER PT J AU Fishman, JA AF Fishman, JA TI Xenotransplantation from swine: making a list, checking it twice ... SO XENOTRANSPLANTATION LA English DT Editorial Material ID ENDOGENOUS RETROVIRUS; PIG; INFECTION C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. NR 12 TC 7 Z9 8 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 2000 VL 7 IS 2 BP 93 EP 95 DI 10.1034/j.1399-3089.2000.00051.x PG 3 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 343XB UT WOS:000088726800004 PM 10961292 ER PT J AU Zhao, Y Swenson, K Wekerle, T Rodriguez-Barbosa, JI Arn, JS Sykes, M AF Zhao, Y Swenson, K Wekerle, T Rodriguez-Barbosa, JI Arn, JS Sykes, M TI The critical role of mouse CD4(+) cells in the rejection of highly disparate xenogeneic pig thymus grafts SO XENOTRANSPLANTATION LA English DT Article DE CD4 cells; immune response; thymus grafts; xenogeneic transplantation ID II-DEFICIENT MICE; T-CELLS; XENOGRAFT REJECTION; TOLERANCE INDUCTION; ISLET XENOGRAFTS; EFFECTOR-CELLS; HUMAN ADULT; IMMUNODEFICIENCY; SURVIVAL; BARRIER AB Long-term survival of fetal pig thymus (FP THY) grafts and efficient repopulation of mouse CD4(+) T cells is achieved in thymectomized (ATX) B6 mice that receive T and NK cell depletion by injection of a cocktail of mAbs (GK1.5, 2.43, 30-H12, and PK136) and fetal pig thymus/liver (FP THY/LIV) grafts. The requirement for each mAb in this conditioning regimen in order to avoid the rejection of FP THY grafts has not yet been defined. In our present studies, CD4 cell-depleted ATX B6 mice and euthymic MHC class II-deficient (IIKO) mice were employed to investigate the role of mouse CD4(+) cells in the rejection of FP THY grafts in vivo. After grafting FP THY/LIV to CD4(+) cell-depleted ATX B6 mice, efficient repopulation of mouse CD4(+) T cells was observed in the periphery. However, only two of four mice had remaining FP THY grafts by 17 weeks post-implantation, and these were of poor quality, whereas four of four T and NK cell-depleted ATX B6 mice had well-developed FP THY grafts. Furthermore, three of four FP THY/LIV-grafted, CD4(+) cell-depleted ATX B6 mice rejected donor MHC-matched pig skin grafts. In contrast, three of three FP THY/LIV grafted, T and NK cell-depleted, ATX B6 mice accepted donor MHC-matched pig skin grafts, suggesting that optimal tolerance to xenogeneic pig antigens was not achieved in mice conditioned only with anti-CD4 mAb. ATX B6 mice treated with only anti-CD8 mAb rejected FP THY completely by 6 weeks post-grafting, a time when CD4(+) cell-depleted ATX B6 mice had well-vascularized FP THY grafts. In addition, when euthymic IIKO mice were pre-treated with the standard conditioning regimen that includes four different mAbs, FP THY grafts survived and supported the repopulation of mouse CD4(+) T cells in the periphery, while high levels of mouse CD8(+) T cells developed in host thymi. These studies suggest that mouse CD4(+) T cells play a critical role in the acute rejection of xenogeneic FP THY grafts. Without help from CD4(+) cells, mouse CD8(+) cells, NK, NK/T, and TCR(gamma/delta)(+) T cells do not mediate acute rejection of FP THY grafts. Furthermore, our results suggest that other cell subsets besides CD4(+) T cells play a role in the delayed rejection of highly disparate xenogeneic FP THY grafts. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011; OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [HL186461]; NIAID NIH HHS [P01-AI39755] NR 42 TC 14 Z9 16 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 2000 VL 7 IS 2 BP 129 EP 137 DI 10.1034/j.1399-3089.2000.00048.x PG 9 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 343XB UT WOS:000088726800009 PM 10961297 ER PT J AU Onions, D Cooper, DKC Alexander, TJL Brown, C Claassen, E Foweraker, JE Harris, DL Mahy, BWJ Minor, PD Osterhaus, ADME Pastoret, PP Yamanouchi, K AF Onions, D Cooper, DKC Alexander, TJL Brown, C Claassen, E Foweraker, JE Harris, DL Mahy, BWJ Minor, PD Osterhaus, ADME Pastoret, PP Yamanouchi, K TI An approach to the control of disease transmission in pig-to-human xenotransplantation SO XENOTRANSPLANTATION LA English DT Article DE endogenous retroviruses; pigs; prions; viruses; xenozoonosis ID PORCINE ENDOGENOUS RETROVIRUS; ACCELERATING FACTOR CD55; HEPATITIS-E VIRUS; HUMAN-CELLS; HUMAN SERUM; ORGAN-TRANSPLANTATION; INFECTIOUS-DISEASE; TRANSGENIC PIGS; NIPAH-VIRUS; NO EVIDENCE AB Although several major immunologic hurdles need to be overcome, the pig is currently considered the most likely source animal of cells, tissues and organs for transplantation into humans. Concerns have been raised with regard to the potential for the transfer of infectious agents with the transplanted organ to the human recipient. This risk is perceived to be increased as it is likely that the patient will be iatrogenically immunocompromised and the organ-source pig may be genetically engineered in such a way to render its organs particularly susceptible to infection with human viruses. Furthermore, the risk may not be restricted to the recipient, but may have consequences for the health of others in the community, The identification of porcine endogenous retroviruses and of hitherto unknown viruses have given rise to the most concern, We document here the agents we believe should be excluded from the organ-source pigs. We discuss the likelihood of achieving this aim and outline the potential means by which it may best be achieved. C1 Q One Biotech Ltd, Glasgow G20 0XA, Lanark, Scotland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Univ Cambridge, Dept Clin Vet Med, Cambridge CB3 0ES, England. Univ Georgia, Coll Vet Med, Dept Pathol, Athens, GA 30602 USA. DLO, Inst Anim Sci & Hlth, Lelystad, Netherlands. Papworth Hosp, Publ Hlth Lab Serv, Microbiol Lab, Cambridge CB3 8RE, England. Iowa State Univ, Coll Agr, Dept Microbiol, Ames, IA USA. Iowa State Univ, Coll Vet Med, Dept Vet Diagnost & Prod Anim Med, Ames, IA USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. Erasmus Univ, Dept Virol, NL-3000 DR Rotterdam, Netherlands. Univ Liege, Fac Med Vet, Liege, Belgium. Nippon Inst Biol Sci, Tokyo, Japan. RP Q One Biotech Ltd, W Scotland Sci Pk,Todd Campus,Maryhill Rd, Glasgow G20 0XA, Lanark, Scotland. NR 73 TC 82 Z9 84 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 2000 VL 7 IS 2 BP 143 EP 155 DI 10.1034/j.1399-3089.2000.00047.x PG 13 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 343XB UT WOS:000088726800011 PM 10961299 ER PT J AU Auchincloss, H AF Auchincloss, H TI Literature update 1999, part 3 SO XENOTRANSPLANTATION LA English DT Review ID HYPERACUTE XENOGRAFT REJECTION; PORCINE ENDOTHELIAL-CELLS; SERUM-MEDIATED CYTOLYSIS; NATURAL-KILLER-CELLS; ATHYMIC NUDE-MICE; BONE-MARROW; EX-VIVO; TRANSGENIC PIGS; IN-VITRO; PROLONGS SURVIVAL C1 Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, GRB 504, Boston, MA 02114 USA. NR 129 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 2000 VL 7 IS 2 BP 156 EP 162 DI 10.1034/j.1399-3089.2000.00062.x PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 343XB UT WOS:000088726800012 PM 10961300 ER PT J AU Dalesio, O van Tinteren, H Clarke, M Peto, R Schroder, FH Dechering, I Evans, V Godwin, J Blumenstein, BA Crawford, ED Denis, L Hall, R Hill, C Iversen, P Shipley, WU Soloway, M Sylvester, R AF Dalesio, O van Tinteren, H Clarke, M Peto, R Schroder, FH Dechering, I Evans, V Godwin, J Blumenstein, BA Crawford, ED Denis, L Hall, R Hill, C Iversen, P Shipley, WU Soloway, M Sylvester, R CA Prostate Canc Trialists Collaborat TI Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials SO LANCET LA English DT Article ID PLUS CYPROTERONE-ACETATE; FINAL ANALYSIS; BILATERAL ORCHIECTOMY; METASTATIC CARCINOMA; MULTICENTER TRIAL; COMBINATION; NILUTAMIDE; FLUTAMIDE; CASTRATION; METAANALYSIS AB Background In advanced prostate cancer, androgen suppression (AS) by surgery or drugs controls testicular hormone secretion, and the further addition of an antiandrogen such as nitutamide, flutamide, or cyproterone acetate is referred to as maximum androgen blockade (MAB), The aim of this overview was to compare the effects on the duration of survival of MAB and of AS alone. Methods The collaborative meta-analysis of 27 randomised trials involved central reanalysis of the data on each of 8275 men (98% of those ever randomised in trials of MAB vs AS) with metastatic (88%) or locally advanced (12%) prostate cancer. Half were over 70 years of age, and follow-up was typically for about 5 years. Findings 5932 (72%) men have died; of the deaths for which causes were provided, about 80% were attributed to prostate cancer. 5-year survival was 25.4% with MAB versus 23.6% with AS alone, a non-significant gain of 1.8% (SE 1.3; logrank 2p=0.11). There was no significant heterogeneity in the treatment effect (MAB vs AS) with respect to age or disease stage. The results for cyproterone acetate, which accounted for only a fifth of the evidence, appeared slightly unfavourable to MAB (5-year survival 15.4% MAB vs 18.1% AS alone; difference -2.8% [SE 2.4]; logrank 2p=0.04 adverse), whereas those for nilutamide and flutamide appeared slightly favourable (5-year survival 27.6% MAB vs 24.7% AS alone; difference 2.9% [SE 1.3]; logrank 2p=0.005). Non-prostate-cancer deaths (although not clearly significantly affected by treatment) accounted for some of the apparently adverse effects of cyproterone acetate. Interpretation In advanced prostate cancer, addition of an antiandrogen to AS improved the 5-year survival by about 2% or 3% (depending on whether the analysis includes or excludes the cyproterone acetate trials), but the range of uncertainty as to the true size of this benefit runs from about 0% to about 5%. C1 Netherlands Canc Inst, Biometr Dept, PCTCG Secretariat, NL-1066 CX Amsterdam, Netherlands. Univ Oxford, Clin Trial Serv Unit, Oxford, England. Univ Oxford, Epidemiol Studies Unit, Oxford, England. Erasmus Univ, Rotterdam, Netherlands. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Colorado, Denver, CO 80202 USA. Middelheim Gen Hosp, Antwerp, Belgium. Freeman Rd Hosp, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England. Inst Gustave Roussy, Villejuif, France. Rigshosp, DK-2100 Copenhagen, Denmark. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Miami, FL 33152 USA. Eortc Data Ctr, Brussels, Belgium. RP Dalesio, O (reprint author), Netherlands Canc Inst, Biometr Dept, PCTCG Secretariat, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. NR 43 TC 428 Z9 437 U1 1 U2 11 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 29 PY 2000 VL 355 IS 9214 BP 1491 EP 1498 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 310LR UT WOS:000086830100010 ER PT J AU Klivenyi, P Andreassen, OA Ferrante, RJ Lancelot, E Reif, D Beal, MF AF Klivenyi, P Andreassen, OA Ferrante, RJ Lancelot, E Reif, D Beal, MF TI Inhibition of neuronal nitric oxide synthase protects against MPTP toxicity SO NEUROREPORT LA English DT Article DE MPTP; nitric oxide; peroxynitrite, Parkinson's disease ID INDUCED NEUROTOXICITY; SUPEROXIDE-DISMUTASE; SUBSTANTIA-NIGRA; IN-VIVO; 7-NITROINDAZOLE; PEROXYNITRITE; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; NITRATION; STRIATUM; MICE AB Previous work showed that several relatively specific inhibitors of neuronal nitric oxide synthase (nNOS) produce protection against MPTP induced dopaminergic toxicity. We examined whether a highly specific novel inhibitor of nNOS, ARR1 7338, could also protect against MPTP toxicity. ARR17338 produced dose-dependent significant protection against MPTP induced depletion of dopamine and protected against MPTP induced depletions of tyrosine hydroxylase immunostained neurons in the substantia nigra. These results provide further evidence that inhibitors of nNOS may be useful for the treatment of Parkinson's disease. NeuroReport 11:1265-1268 (C) 2000 Lippincott Williams & Wilkins. C1 Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol Pathol & Psychiat, Boston, MA 02118 USA. Bedford VA Med Ctr, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. AstraZeneca R&D Boston, Worcester, MA USA. Albert Szent Gyorgyi Med Sch, Dept Neurol, Szeged, Hungary. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Cornell Med Ctr, New York Hosp, New York, NY 10021 USA. RP Beal, MF (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, 525 E 68th St, New York, NY 10021 USA. FU NIA NIH HHS [AG13846]; NINDS NIH HHS [NS37102, NS35255] NR 20 TC 52 Z9 53 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 27 PY 2000 VL 11 IS 6 BP 1265 EP 1268 DI 10.1097/00001756-200004270-00024 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 312FB UT WOS:000086931600025 PM 10817604 ER PT J AU Berger, DL Zalis, ME Scully, RE Ott, MJ Mohammadkhani, MS AF Berger, DL Zalis, ME Scully, RE Ott, MJ Mohammadkhani, MS TI A 26-year-old woman with bouts of abdominal pain, vomiting, and diarrhea. Intussusception of the appendix into the cecum due to endometriosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COLONIC ENDOMETRIOSIS; VERMIFORM APPENDIX; SIGMOID COLON; LARGE-BOWEL; DIAGNOSIS; MANAGEMENT; CARCINOMA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 41 TC 9 Z9 9 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 27 PY 2000 VL 342 IS 17 BP 1272 EP 1278 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 307NZ UT WOS:000086660600008 ER PT J AU Alexander, SI Sykes, M McAfee, S Hope, J Preffer, F Sackstein, R Saidman, SL Dombkowski, D Sachs, DH Spitzer, TR AF Alexander, SI Sykes, M McAfee, S Hope, J Preffer, F Sackstein, R Saidman, SL Dombkowski, D Sachs, DH Spitzer, TR TI Can mixed chimerism be achieved without GVHD across HLA barriers using non-myeloablative conditioning with exhaustive in vivo T cell depletion? Preliminary experience in patients with hematological malignancies. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, BioTransplant Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 704 BP S295 EP S295 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800702 ER PT J AU Allan, JS Wain, JC Schwarze, ML Madsen, JC Sachs, DH AF Allan, JS Wain, JC Schwarze, ML Madsen, JC Sachs, DH TI Obliterative bronchiolitis develops in miniature swine transplanted across a minor histocompatibility barrier. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Div Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 110 BP S140 EP S140 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800111 ER PT J AU Alwayn, IPJ Basker, M Buhler, L Rieben, R Harper, D Appel, JZ Awwad, M Down, J White-Scharf, M Sachs, DH Thall, A Cooper, DKC AF Alwayn, IPJ Basker, M Buhler, L Rieben, R Harper, D Appel, JZ Awwad, M Down, J White-Scharf, M Sachs, DH Thall, A Cooper, DKC TI Porcine hematopoietic progenitor cells are rapidly cleared by the phagocytic reticuloendothelial system in baboons. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Bio Transplant Inc, Boston, MA USA. Univ Hosp Bern, Bern, Switzerland. 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1176 BP S420 EP S420 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911801174 ER PT J AU Appel, JZ Alwayn, IPJ Goepfert, C Buhler, L Cooper, DKC Robson, SC AF Appel, JZ Alwayn, IPJ Goepfert, C Buhler, L Cooper, DKC Robson, SC TI Pig leukocytes induce platelet aggregation in baboons: Implications for mixed chimerism and discordant organ transplantation SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Immunol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 545 BP S252 EP S253 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800543 ER PT J AU Baid, S Cosimi, AB Farrell, M Rubin, N Chung, R Feng, S Pascual, M AF Baid, S Cosimi, AB Farrell, M Rubin, N Chung, R Feng, S Pascual, M TI Post-transplant diabetes mellitus and recurrent graft hepatitis in hepatitis C(+) liver transplant recipients. SO TRANSPLANTATION LA English English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Unit, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 602 BP S267 EP S267 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800600 ER PT J AU Barth, RN Utsugi, R O'Neil, J Kitamura, H Edge, A Weir, G Sachs, DH Yamada, K AF Barth, RN Utsugi, R O'Neil, J Kitamura, H Edge, A Weir, G Sachs, DH Yamada, K TI Functional vascularized islet allografts in miniature swine SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RI Barth, Rolf/B-2542-2014 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 362 BP S207 EP S207 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800360 ER PT J AU Buhler, L Basker, M Alwayn, I Awwad, M Appel, J Thall, A White-Scharf, M Sachs, DH Cooper, DKC AF Buhler, L Basker, M Alwayn, I Awwad, M Appel, J Thall, A White-Scharf, M Sachs, DH Cooper, DKC TI CD40L blockade requires host macrophages to induce humoral unresponsiveness to pig hematopoietic cells in baboons. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. BioTransplant Inc, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1159 BP S415 EP S415 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911801157 ER PT J AU Buhler, L Alwayn, I Basker, M Awwad, M Ericson, T Huang, C Thall, A Down, J White-Scharf, ME Sachs, DH Cooper, DKC AF Buhler, L Alwayn, I Basker, M Awwad, M Ericson, T Huang, C Thall, A Down, J White-Scharf, ME Sachs, DH Cooper, DKC TI Engraftment of pig peripheral blood progenitor cells in baboons conditioned with a nonmyeloablative regimen and CD40L blockade. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. BioTransplant Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 658 BP S283 EP S283 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800656 ER PT J AU Busch, A Volk, HD Marasco, WA Mhashilkar, AM Ritter, T Doebis, C Seifert, M AF Busch, A Volk, HD Marasco, WA Mhashilkar, AM Ritter, T Doebis, C Seifert, M TI Generation of keratinocytes displaying a MHC class I 'knock-out' phenotype by intrabody expression: New perspectives for skin transplantation? SO TRANSPLANTATION LA English DT Meeting Abstract C1 Humboldt Univ, Bereich Med Charite, Inst Med Immunol, D-1040 Berlin, Germany. Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 147 BP S151 EP S151 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800148 ER PT J AU Collins, BH Kendall, WF Hobbs, HA Darrabie, MD Opara, EC AF Collins, BH Kendall, WF Hobbs, HA Darrabie, MD Opara, EC TI Non-immunologic mechanisms of islet allograft dysfunction: Effect of diabetes control on islet allograft dysfunction SO TRANSPLANTATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Islet Transplantat Lab, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 370 BP S209 EP S209 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800368 ER PT J AU Cook, JW Yin, Q De La Melena, VT Malinow, MR Orloff, SL AF Cook, JW Yin, Q De La Melena, VT Malinow, MR Orloff, SL TI Diet-induced hyperhomocyst(e)inemia accelerates transplant vascular sclerosis in a rat cardiac transplant chronic rejection model. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Oregon Reg Primate Res Ctr, Portland, OR 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 924 BP S351 EP S351 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800922 ER PT J AU Crespo, M Pascual, M Mauiyyedi, S Collins, AB Tolkoff-Rubin, N Delmonico, FL Cosimi, AB Colvin, RB Saidman, SL AF Crespo, M Pascual, M Mauiyyedi, S Collins, AB Tolkoff-Rubin, N Delmonico, FL Cosimi, AB Colvin, RB Saidman, SL TI Incidence of acute humoral rejection (AHR) in patients with steroid resistant renal allograft rejection. SO TRANSPLANTATION LA English DT Meeting Abstract C1 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, Transplant Unit, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 969 BP S363 EP S363 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800967 ER PT J AU De La Melena, VT Yin, Q Cook, JW Kreklywich, CN Streblow, DN Nelson, JA Orloff, SL AF De La Melena, VT Yin, Q Cook, JW Kreklywich, CN Streblow, DN Nelson, JA Orloff, SL TI The kinetics and development of CMV-accelerated transplant vascular sclerosis in rat cardiac allografts is linked to early presence of virus in the graft. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 909 BP S347 EP S347 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800907 ER PT J AU Dong, VM Kishimoto, K Exeni, A Yamanda, A Waaga, AM Briscoe, DM Auchincloss, H Grusby, MJ Khoury, SJ Sayegh, MH AF Dong, VM Kishimoto, K Exeni, A Yamanda, A Waaga, AM Briscoe, DM Auchincloss, H Grusby, MJ Khoury, SJ Sayegh, MH TI The differential role of CD28-B7 versus CD40L-CD40 in regulating alloimmune responses in STAT 4 versus STAT 6 gene knockout mice. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1027 BP S379 EP S379 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911801025 ER PT J AU Guckelberger, O Imai, M Michael, MD Sevigny, J Kahn, CR Robson, SC AF Guckelberger, O Imai, M Michael, MD Sevigny, J Kahn, CR Robson, SC TI Impaired hepatic regeneration in liver-specific insulin receptor knockout SO TRANSPLANTATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr, Boston, MA USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RI Sevigny, Jean/E-8039-2012 OI Sevigny, Jean/0000-0003-2922-1600 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 334 BP S200 EP S200 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800332 ER PT J AU Ito, H Kurtz, J Shaffer, J Sykes, M AF Ito, H Kurtz, J Shaffer, J Sykes, M TI One injection of anti-CD40L mAb overcomes CD4 T cell-mediated resistance to fully MHC-mismatched allogeneic marrow engraftment. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 995 BP S371 EP S371 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800993 ER PT J AU Kauffman, HM Cherikh, WS Delmonico, FL AF Kauffman, HM Cherikh, WS Delmonico, FL TI Unos report on cadaveric kidney graft survival: Multivariate analysis of discharge immunosuppressive drug regimens. SO TRANSPLANTATION LA English DT Meeting Abstract C1 United Network Organ Sharing, Richmond, VA USA. Massachusetts Gen Hosp, Dept Surg, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 13 BP S114 EP S114 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800014 ER PT J AU Kawai, T Abrahamian, G Sogawa, H Wee, SL Boskovic, S Nadazdin, O Andrews, D Mauiyyedi, S Hong, H Wu, D Phelan, J Weymouth, D Ko, D Colvin, RB Sachs, DH Cosimi, AB AF Kawai, T Abrahamian, G Sogawa, H Wee, SL Boskovic, S Nadazdin, O Andrews, D Mauiyyedi, S Hong, H Wu, D Phelan, J Weymouth, D Ko, D Colvin, RB Sachs, DH Cosimi, AB TI Costimulatory blockade for induction of mixed chimerism and renal allograft tolerance in nonhuman primates. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 991 BP S370 EP S370 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800989 ER PT J AU Kawai, T Sogawa, H Koulmada, M Ko, D Oneal, J Wee, SL Smith, RN Hong, H Wu, D Colvin, RB Sachs, DH Auchincloss, H Cosimi, AB AF Kawai, T Sogawa, H Koulmada, M Ko, D Oneal, J Wee, SL Smith, RN Hong, H Wu, D Colvin, RB Sachs, DH Auchincloss, H Cosimi, AB TI Successful induction of tolerance of pancreatic islets between MHC-mismatched nonhuman primates. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Joslin Clin, Dept Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 740 BP S304 EP S305 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800738 ER PT J AU Kishimoto, K Sho, MY Yamada, A Dong, VM Ariyan, C Fecteau, S Basadonna, GP Auchincloss, H Rothstein, DM Sayegh, MH AF Kishimoto, K Sho, MY Yamada, A Dong, VM Ariyan, C Fecteau, S Basadonna, GP Auchincloss, H Rothstein, DM Sayegh, MH TI Synergy between signal 1 plus signal 2 blockade in a stringent model of allograft rejection. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 998 BP S372 EP S372 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800996 ER PT J AU Kurtz, J Ito, H Shaffer, J Sykes, M AF Kurtz, J Ito, H Shaffer, J Sykes, M TI Synergistic effect of costimulatory blockade and cyclosporin treatment in the establishment of early mixed hematapoietic chimerism. SO TRANSPLANTATION 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 993 BP S370 EP S370 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800991 ER PT J AU Lee, RS Rusche, JR Sachs, DH Sayegh, MH Madsen, JC AF Lee, RS Rusche, JR Sachs, DH Sayegh, MH Madsen, JC TI CTLA4Ig induces regulatory T cells that mediate linked regulation of allogeneic T cell responses. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1101 BP S399 EP S399 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911801099 ER PT J AU Lee, RS Yamada, K Maloney, M Houser, S Womer, KL Sayegh, MH Madsen, JC AF Lee, RS Yamada, K Maloney, M Houser, S Womer, KL Sayegh, MH Madsen, JC TI Indirect recognition of donor class I peptides induces and accelerates cardiac allograft vasculopathy in the miniature swine. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1004 BP S373 EP S373 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911801002 ER PT J AU Makhlouf, I Koulmanda, M Auchincloss, H Sayegh, MH AF Makhlouf, I Koulmanda, M Auchincloss, H Sayegh, MH TI Mechanisms of islet allograft rejection: Role of autoimmunity and effect of T cell costimulatory blockade. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Islet Transplantat Lab, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 898 BP S344 EP S345 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800896 ER PT J AU Mathes, DW Rubin, JP Gazelle, GS Randolph, MA Wu, A Sachs, DH Lee, WPA AF Mathes, DW Rubin, JP Gazelle, GS Randolph, MA Wu, A Sachs, DH Lee, WPA TI In utero induction of transplantation tolerance in a swine model. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 505 BP S242 EP S243 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800503 ER PT J AU Mauiyyedi, S Crespo, M Pascual, M Collins, AB Saidman, S Rubin, N Williams, W Cosimi, AB Schneeberger, E Colvin, RB AF Mauiyyedi, S Crespo, M Pascual, M Collins, AB Saidman, S Rubin, N Williams, W Cosimi, AB Schneeberger, E Colvin, RB TI C4d deposition in peritubular capillaries of renal allografts: The morphology and immunophenotype of acute humoral rejection. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1114 BP S402 EP S402 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911801112 ER PT J AU McKay, DB Tao, L Sawasdikosol, S Burakoff, SJ AF McKay, DB Tao, L Sawasdikosol, S Burakoff, SJ TI Allopeptide/MHC-TCR affinity determines phosphorylation kinetics. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Med & Renal Div, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 77 BP S131 EP S131 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800078 ER PT J AU Odorico, JS Jacobson, LM Lumelsky, N Hullett, DA Thomson, JA Kahan, BW AF Odorico, JS Jacobson, LM Lumelsky, N Hullett, DA Thomson, JA Kahan, BW TI Pancreatic gene expression in differentiating embryonic stem cells. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Wisconsin, Sch Med, Dept Surg, Madison, WI USA. Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 707 BP S296 EP S296 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800705 ER PT J AU Pascual, M Crespo, M Rubin, NE Saidman, SL Williams, WW Mauiyyedi, S Collins, AB Farrell, M Colvin, RB Cosimi, AB Delmonico, FL AF Pascual, M Crespo, M Rubin, NE Saidman, SL Williams, WW Mauiyyedi, S Collins, AB Farrell, M Colvin, RB Cosimi, AB Delmonico, FL TI Treatment of refractory acute humoral rejection in kidney transplantation. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 672 BP S286 EP S286 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800670 ER PT J AU Rodriguez-Barbosa, JI Zhao, Y Zhao, GL Swenson, K Sachs, DH Sykes, M AF Rodriguez-Barbosa, JI Zhao, Y Zhao, GL Swenson, K Sachs, DH Sykes, M TI Improved CD4 reconstitution in thymectomized, T/NK cell depleted mice grafted in alternative sites with neonatal porcine thymus tissue. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 561 BP S257 EP S257 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800559 ER PT J AU Schuchert, MJ Wright, RD Colson, YL AF Schuchert, MJ Wright, RD Colson, YL TI The CD3/TCR beta/FCp33 complex on the facilitating cell is capable of receptor signaling and is required for the facilitation of allogeneic stem cell engraftment. SO TRANSPLANTATION LA English DT Meeting Abstract C1 UPMC, Hlth Syst, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 654 BP S282 EP S282 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800652 ER PT J AU Sogawa, H Kawai, T Wee, S Boskovic, S Abrahamian, G Ko, DSC Hon, H Winn, H Colvin, RB Sachs, DH Cosimi, AB AF Sogawa, H Kawai, T Wee, S Boskovic, S Abrahamian, G Ko, DSC Hon, H Winn, H Colvin, RB Sachs, DH Cosimi, AB TI Comparison of horse antithymocyte globulin with other T-cell depleting agents for induction of chimerism and renal allograft tolerance in nonhuman primates. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 519 BP S246 EP S246 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800517 ER PT J AU Tkaczuk, J Milford, EL Carpenter, CB Yu, CL Baksh, S Burakoff, SJ McKay, DB AF Tkaczuk, J Milford, EL Carpenter, CB Yu, CL Baksh, S Burakoff, SJ McKay, DB TI Intracellular signaling by the intermediate-affinity IL-2R chains after treatment with daclizumab. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Med & Renal Div, Boston, MA 02115 USA. RI Yu, Chao-Lan/D-1834-2011 OI Yu, Chao-Lan/0000-0002-9381-6011 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1096 BP S397 EP S397 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911801094 ER PT J AU Utsugi, R Lee, RS Barth, RN Kitamura, H Sachs, DH Yamada, K AF Utsugi, R Lee, RS Barth, RN Kitamura, H Sachs, DH Yamada, K TI Mechanisms of tacrolmius induced tolerance to fully MHC-mismatched renal allografts in miniature swine: Donor antigen specific regulatory mechanisms. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RI Barth, Rolf/B-2542-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 51 BP S124 EP S125 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800052 ER PT J AU Wekerle, T Kurtz, J Ito, H Shaffer, J Sykes, M AF Wekerle, T Kurtz, J Ito, H Shaffer, J Sykes, M TI A one-day protocol of bone marrow transplantation with costimulatory blockade for the rapid induction of donor-specific skin graft tolerance without pre-conditioning. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, TBRC,BMT Sect, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 994 BP S370 EP S370 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800992 ER PT J AU Wu, A Lerino, FL Yamada, K Sachs, DH AF Wu, A Lerino, FL Yamada, K Sachs, DH TI Regulatory mechanisms of tolerance in the class I mismatched renal allograft model: Specific suppression of anti-donor lymphocyte proliferative responses during the maintenance phase of tolerance. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 536 BP S250 EP S250 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800534 ER PT J AU Yamada, A Kishimoto, K Anosova, NG Mandelbrot, DA Dong, VM Sho, M Benichou, G Peach, R Auchincloss, H Sayegh, MH AF Yamada, A Kishimoto, K Anosova, NG Mandelbrot, DA Dong, VM Sho, M Benichou, G Peach, R Auchincloss, H Sayegh, MH TI B7-1 is the dominant ligand for CTLA-4 down regulation of alloimmune responses in vivo. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Unit, Surg Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Schepens Eye Res Inst, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Bristol Myers Squibb Pharmacol Res Inst, Princeton, NJ 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 1157 BP S414 EP S414 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911801155 ER PT J AU Yamada, A Gerth, AJ Laufer, TM Kishimoto, K Dong, VM Sho, M Sayegh, MH Auchincloss, H AF Yamada, A Gerth, AJ Laufer, TM Kishimoto, K Dong, VM Sho, M Sayegh, MH Auchincloss, H TI Role of CD4 and CD8 T cells in vascularized cardiac allograft rejection mediated by direct and indirect allorecognition. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Surg Serv, Transpantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 498 BP S240 EP S241 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800496 ER PT J AU Yamada, K Utsugi, R Barth, RN Kitamura, H Shimizu, A Huang, CA Neville, DM Sachs, DH AF Yamada, K Utsugi, R Barth, RN Kitamura, H Shimizu, A Huang, CA Neville, DM Sachs, DH TI Vascularized thymic grafts induce stable tolerance across fully MHC-mismatched allogeneic barriers in miniature swine. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RI Barth, Rolf/B-2542-2014 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2000 VL 69 IS 8 SU S MA 999 BP S372 EP S372 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 311XQ UT WOS:000086911800997 ER PT J AU Lin, LF Houng, AY Reed, GL AF Lin, LF Houng, AY Reed, GL TI Epsilon amino caproic acid inhibits streptokinase-plasminogen activator complex formation and substrate binding through kringle-dependent mechanisms SO BIOCHEMISTRY LA English DT Article ID MOLECULAR-WEIGHT FORM; HUMAN PLASMINOGEN; CONFORMATIONAL CHANGE; UROKINASE; DOMAINS; REGION; LIGAND; KINETICS; FIBRIN; GENERATION AB Lysine side chains induce conformational changes in plasminogen (Pg) that regulate the process of fibrinolysis or blood clot dissolution. A lysine side-chain mimic, epsilon amino caproic acid (EACA), enhances the activation of Pg by urinary-type and tissue-type Pg activators but inhibits Pg activation induced by streptokinase (SK). Our studies of the mechanism of this inhibition revealed that EACA (IC50 10 mu M) also potently blocked amidolytic activity by SK and Pg at doses nearly 10000-fold lower than that required to inhibit the amidolytic activity of plasmin. Different Pg fragments were used to assess the role of the kringles in mediating the inhibitory effects of EACA: mini-Pg which lacks kringles 1-4 of Glu-Pg and micro-Pg which lacks all kringles and contains only the catalytic domain. SK bound with similar affinities to Glu-Pg (K-A 2.3 x 10(9) M-1) and to mini-Pg (K-A 3.8 x 10(9) M-1) but with significantly lower affinity to micro-Pg (K-A = 6 X 10(7) M-1). EACA potently inhibited the binding of Glu-Pg to SK (Ki = 5.7 mu M), but was less potent (K-i = 81.1 mu M) for inhibiting the binding of mini-Pg to SK and had no significant inhibitory effects on the binding of micro-Pg and SK. In assays simulating substrate binding, EACA also potently inhibited the binding of Glu-Pg to the SK-Glu-Pg activator complex, but had negligible effects on micro-Pg binding. Taken together, these studies indicate that EACA inhibits Pg activation by blocking activator complex formation and substrate binding, through a kringle-dependent mechanism. Thus, in addition to interactions between SK and the protease domain, interactions between SK and the kringle domain(s) play a key role in Pg activation. C1 Harvard Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reed, GL (reprint author), Harvard Sch Publ Hlth, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 58496] NR 47 TC 29 Z9 31 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 25 PY 2000 VL 39 IS 16 BP 4740 EP 4745 DI 10.1021/bi992028x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308XG UT WOS:000086737700020 PM 10769130 ER PT J AU Albers, GW Lansberg, MG Norbash, AM Tong, DC O'Brien, MW Woolfenden, AR Marks, MP Moseley, ME AF Albers, GW Lansberg, MG Norbash, AM Tong, DC O'Brien, MW Woolfenden, AR Marks, MP Moseley, ME TI Yield of diffusion-weighted MRI for detection of potentially relevant findings in stroke patients SO NEUROLOGY LA English DT Article DE stroke; diffusion-weighted MRI; cerebral ischemia; clinical relevance ID ISCHEMIC STROKE; PATHOGENESIS; EXPERIENCE; UTILITY; TIME AB Objective: To determine whether diffusion-weighted imaging (DWI) could identify potentially clinically relevant findings in patients presenting more than 6 hours after stroke onset when compared with conventional MRI. Methods: MRI with both conventional (T2 and proton density images) and echoplanar imaging (DWI and apparent diffusion coefficient maps) was performed 6 to 48 hours after symptom onset (mean, 27 hours) in 40 consecutive patients with acute stroke. All acute lesions were identified first on conventional images, then on DWI, by a neuroradiologist who was provided with the suspected lesion location, based on a neurologist's examination before imaging. Abnormalities were rated as potentially clinically relevant if they were detected only on DWI and 1) confirmed the acute symptomatic lesion to be in a different vascular territory than suspected clinically, 2) revealed multiple lesions in different vascular territories suggestive of a proximal source of embolism, or 3) clarified that a lesion, thought to be acute on conventional imaging, was not acute. Results: The initial clinical impression of lesion localization was incorrect in 12 patients (30%), Clinically significant findings were detected by DWI alone in 19 patients (48%). DWI demonstrated the symptomatic lesion in a different vascular territory than suspected clinically or by conventional MRI in 7 patients (18%) and showed acute lesions in multiple vascular distributions in 5 patients (13%). In 8 patients (20%), DWI clarified that lesions thought to be acute on conventional MRI were actually old. Conclusion: In patients imaged 6 to 48 hours after stroke onset, DWI frequently provided potentially clinically relevant findings that were not apparent on conventional MRI. C1 Stanford Stroke Ctr, Palo Alto, CA 94304 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. RP Albers, GW (reprint author), Stanford Stroke Ctr, 701 Welch Rd,Bldg B,Suite 325, Palo Alto, CA 94304 USA. FU NINDS NIH HHS [5R01NS34866] NR 29 TC 78 Z9 79 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 25 PY 2000 VL 54 IS 8 BP 1562 EP 1567 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 307FD UT WOS:000086642000007 PM 10762494 ER PT J AU Ezzeddine, MA Primavera, JM Rosand, J Hedley-Whyte, ET Rordorf, G AF Ezzeddine, MA Primavera, JM Rosand, J Hedley-Whyte, ET Rordorf, G TI Clinical characteristics of pathologically proved cholesterol emboli to the brain SO NEUROLOGY LA English DT Article DE cholesterol emboli; stroke; border zone infarcts AB Cholesterol emboli (CE) to the brain are an important but often unrecognized cause of stroke. The authors reviewed 29 cases of brain CE identified on autopsy. Most patients were elderly (mean age, 74 years) and presented with encephalopathy and acute renal failure. Ten patients developed symptoms spontaneously, 19 after a procedure involving manipulation of the aorta. Brain imaging revealed multiple, small ischemic lesions and border zone infarcts in 11 of 17 patients. Pathology in most patients demonstrated multiple CE mixed with emboli of other types. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol Neuropathol, Boston, MA 02114 USA. RP Rordorf, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 55 Fruit St,Blake 1291, Boston, MA 02114 USA. NR 7 TC 24 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 25 PY 2000 VL 54 IS 8 BP 1681 EP 1683 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 307FD UT WOS:000086642000026 PM 10762515 ER PT J AU Ivanov, IP Rohrwasser, A Terreros, DA Gesteland, RF Atkins, JF AF Ivanov, IP Rohrwasser, A Terreros, DA Gesteland, RF Atkins, JF TI Discovery of a spermatogenesis stage-specific ornithine decarboxylase antizyme: Antizyme 3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL-SPECIFIC EXPRESSION; POLYAMINE HOMEOSTASIS; GENE; RAT; TISSUES; TRANSPORT; CLONING; GROWTH; LINE; CDNA AB Previous studies with mice overproducing ornithine decarboxylase have demonstrated the importance of polyamine homeostasis for normal mammalian spermatogenesis. The present study introduces a likely key player in the maintenance of proper polyamine homeostasis during spermatogenesis. Antizyme 3 is a paralog of mammalian ornithine decarboxylase antizymes. Like its previously described counterparts, antizymes 1 and 2, it inhibits ornithine decarboxylase, which catalyzes the synthesis of putrescine. Earlier work has shown that the coding sequences for antizymes 1 and 2 are in two different, partially overlapping reading frames. Ribosomes translate the first reading frame, and just before the stop codon for that frame, they shift to the second reading frame to synthesize a trans-frame product. The efficiency of this frameshifting depends on polyamine concentration, creating an autoregulatory circuit. Antizyme 3 cDNA has the same arrangement of reading frames and a potential shift site with definite, although limited, homology to its evolutionarily distant antizyme 1 and 3 counterparts. In contrast to antizymes 1 and 2, which are widely expressed throughout the body, antizyme 3 transcription is restricted to testis germ cells. Expression starts early in spermiogenesis and finishes in the late spermatid phase. The potential significance of antizyme 3 expression during spermatogenesis is discussed in this paper. C1 Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. US Dept Vet Affairs, Salt Lake City, UT 84148 USA. RP Atkins, JF (reprint author), Univ Utah, Dept Human Genet, 15 North 2030 East, Salt Lake City, UT 84112 USA. FU NIGMS NIH HHS [R01 GM048152, R01-GM48152] NR 45 TC 97 Z9 104 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 25 PY 2000 VL 97 IS 9 BP 4808 EP 4813 DI 10.1073/pnas.070055897 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 308GW UT WOS:000086703000075 PM 10781085 ER PT J AU Lin, AE Semina, EV Daack-Hirsch, S Roeder, ER Curry, CJR Rosenbaum, K Weaver, DD Murray, JC AF Lin, AE Semina, EV Daack-Hirsch, S Roeder, ER Curry, CJR Rosenbaum, K Weaver, DD Murray, JC TI Exclusion of the branchio-oto-renal syndrome locus (EYA1) from patients with branchio-oculo-facial syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE aplasia cutis congenita; branchial arch syndromes; branchio-otic (BO) syndrome; branchio-oculo-facial (BOF) syndrome; branchio-oto-renal ID BRANCHIOOCULOFACIAL SYNDROME; BOR SYNDROME; GENE AB In addition to craniofacial, auricular, ophthalmologic, and oral anomalies, the distinctive phenotype of the branchio-oculo-facial (BOF) syndrome (MIM 113620) includes skin defects in the neck or infra/supra-auricular region. These unusual areas of thin, erythematous wrinkled skin differ from the discrete cervical pits, cysts, and fistulas of the branchio-oto-renal (BOR) syndrome (MIM 113650), Although the BOF and BOR syndromes are sufficiently distinctive that they should not be confused, both can be associated with nasolacrimal duct stenosis, deafness, prehelical pits, malformed pinna, and renal anomalies. Furthermore, a reported father and son [Legius et al,, 1990, Clin Genet 37:347-500] had features of both conditions. It was not clear whether they had an atypical presentation of either BOR or BOF syndrome, or represented a private syndrome. In light of these issues, we selected the BOR locus (EYA1) as a possible gene mutation for the BOF syndrome. In five BOF patients, there were no mutations detected in the EYA1 gene, suggesting that it is not allelic to the BOR syndrome, (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Univ Iowa, Dept Pediat & Biol Sci, Iowa City, IA USA. Valley Childrens Hosp, Madera, CA USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. RP Lin, AE (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Warren 801,55 Fruit St, Boston, MA 02114 USA. FU NIDCR NIH HHS [DE08559] NR 16 TC 15 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD APR 24 PY 2000 VL 91 IS 5 BP 387 EP 390 DI 10.1002/(SICI)1096-8628(20000424)91:5<387::AID-AJMG13>3.0.CO;2-1 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 301GF UT WOS:000086301800013 PM 10767004 ER PT J AU Fava, M Vuolo, RD Wright, EC Nierenberg, AA Alpert, JE Rosenbaum, JF AF Fava, M Vuolo, RD Wright, EC Nierenberg, AA Alpert, JE Rosenbaum, JF TI Fenfluramine challenge in unipolar depression with and without anger attacks SO PSYCHIATRY RESEARCH LA English DT Article DE aggression; depression; fenfluramine; prolactin; serotonin ID FLUOXETINE TREATMENT; PROLACTIN RESPONSE; DISORDERS; QUESTIONNAIRE; AGGRESSION AB We have previously hypothesized that patients with major depression and anger attacks may have a greater central serotonergic dysregulation than depressed patients without such attacks. We wanted to compare the prolactin response to fenfluramine challenge, as an indirect measure of central serotonergic function, in depressed patients with and without anger attacks. We recruited 37 outpatients (22 men and 15 women; mean age: 39.5 +/- 10.5) with DSM-III-R major depressive disorder, diagnosed with the SCID-F, Their initial 17-item Hamilton Rating Scale for Depression score was greater than or equal to 16. Patients were classified as either having or not having anger attacks with the Anger Attacks Questionnaire. All patients received a single-blind placebo challenge followed by a fenfluramine challenge (60 mg orally) the next day. Plasma prolactin measurements were obtained with double antibody radioimmunoassay before and after both placebo and fenfluramine challenges, and fenfluramine and norfenfluramine blood levels after each challenge were determined by gas chromatography. Of the 37 study participants, 17 (46%) were classified as having anger attacks. There were no significant differences in age, Sender, fenfluramine, or norfenfluramine blood levels between depressed patients with and without anger attacks. Depressed patients with anger attacks showed a significantly blunted prolactin response to fenfluramine challenge compared to patients without anger attacks. As previous studies have shown blunted prolactin responses to fenfluramine in impulsive aggression among patients with personality disorders, our results support our hypothesis that depressed patients with anger attacks may have a relatively greater serotonergic dysregulation than depressed patients without these attacks. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 21 TC 55 Z9 56 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 24 PY 2000 VL 94 IS 1 BP 9 EP 18 DI 10.1016/S0165-1781(00)00120-7 PG 10 WC Psychiatry SC Psychiatry GA 316JQ UT WOS:000087164000002 PM 10788673 ER PT J AU Giovanni, A Keramaris, E Morris, EJ Hou, ST O'Hare, M Dyson, N Robertson, GS Slack, RS Park, DS AF Giovanni, A Keramaris, E Morris, EJ Hou, ST O'Hare, M Dyson, N Robertson, GS Slack, RS Park, DS TI E2F1 mediates death of B-amyloid-treated cortical neurons in a manner independent of p53 and dependent on Bax and caspase 3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALZHEIMERS-DISEASE BRAIN; ABL TYROSINE KINASE; CELL-CYCLE; RETINOBLASTOMA PROTEIN; BETA-PEPTIDE; TRANSCRIPTION FACTOR; INDUCED APOPTOSIS; TRANSGENIC MICE; NERVOUS-SYSTEM; RB AB Although B-amyloid (AB) is suggested to play an important role in Alzheimer's disease, the mechanisms that control AB-evoked toxicity are unclear. We demonstrated previously that the cell cycle-related cyclin-dependent kinase 4/6/retinoblastoma protein pathway is required for AB-mediated death. However, the downstream target(s) of this pathway are unknown. We show here that neurons lacking E2F1, a transcription factor regulated by the retinoblastoma protein, are significantly protected from death evoked by AB, Moreover, p53 deficiency does not protect neurons from death, indicating that E2F1-mediated death occurs independently of p53. Neurons protected by E2F1 deficiency have reduced Bax-dependent caspase 3-like activity. However, protection afforded by E2F1, Bax, or caspase 3 deficiency is transient. In the case of E2F1, but not with Bax or caspase 3 deficiency, delayed death is accompanied by DEVD-AFC cleavage activity. Taken together, these results demonstrate the required role of E2F1, Bax, and caspase 3 in AB evoked death, but also suggest the participation of elements independent of these apoptosis regulators. C1 Univ Ottawa, Neurosci Res Inst, Ottawa, ON K1H 8M5, Canada. Hoechst Marion Roussel, Neurosci, Bridgewater, NJ 08807 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. Merck Frosst, Pointe Claire, PQ H9R 4P8, Canada. RP Park, DS (reprint author), Univ Ottawa, Neurosci Res Inst, Ottawa, ON K1H 8M5, Canada. NR 49 TC 159 Z9 166 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 21 PY 2000 VL 275 IS 16 BP 11553 EP 11560 DI 10.1074/jbc.275.16.11553 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308DP UT WOS:000086695500004 PM 10766769 ER PT J AU Cahill, CJ Nayak, RC AF Cahill, CJ Nayak, RC TI Immunoelectron microscopic detection of tissue ganglioside antigens SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE immunoelectron microscopy; ganglioside; monoclonal antibody; lowicryl ID LOCALIZATION; GLYCOLIPIDS; ANTIBODY AB Glycolipid antigens are emerging as important markers of differentiated cells in vitro and in vivo. The study of the expression of these antigens in whole tissues by immunoelectron microscopy, using standard techniques, does not give acceptable results. We have established conditions for the specific demonstration of antibody binding to tissue glycolipid antigens by immunoelectron microscopy. Dehydration of tissues with alcohol is to be avoided as it extracts the glycolipid antigen out of the tissue. Dehydration in acetone provides good results. Embedding of the tissue in Araldite 512 results in high non-specific binding of the primary antibody and a decreased effective titre of the primary antibody. Embedding of tissues in Lowicryl HM20 resin resulted in low non-specific binding. We also describe a method of curing the Lowicryl resin that does not require a purpose built curing chamber. Quantitative analysis of immunogold binding reveals that acetone dehydration of tissues and embedding in Lowicryl gives greatly superior results in comparison with dehydration in alcohol and embedding in Araldite. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Nayak, RC (reprint author), Tufts Univ, New England Med Ctr, Sch Med, Box 8103,750 Washington St, Boston, MA 02111 USA. FU NIDDK NIH HHS [DK36836, DKRO139783] NR 15 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR 21 PY 2000 VL 238 IS 1-2 BP 45 EP 53 DI 10.1016/S0022-1759(00)00149-6 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 305ZR UT WOS:000086572100005 PM 10758234 ER PT J AU Agarwal, S Avni, O Rao, A AF Agarwal, S Avni, O Rao, A TI Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A924 EP A924 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100071 ER PT J AU Barrington, RA Zafari, M Fischer, M Pozdyakova, O Benjamin, C Carroll, MC AF Barrington, RA Zafari, M Fischer, M Pozdyakova, O Benjamin, C Carroll, MC TI Role of complement and Fc receptors in maintenance of B lymphocyte memory SO FASEB JOURNAL LA English DT Meeting Abstract C1 Ctr Blood Res, Boston, MA 02115 USA. Biogen Inc, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1189 EP A1189 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101632 ER PT J AU Barrington, RA Zhang, M Carroll, MC AF Barrington, RA Zhang, M Carroll, MC TI Complement-ligand requirement B lymphocyte survival in germinal centers SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1189 EP A1189 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101629 ER PT J AU Chen, ZE Gramaglia, I Panoskaltis-Mortari, A Murphy, WJ Zeller, J Roncarolo, M Boussiotis, VA Blazar, BR AF Chen, ZE Gramaglia, I Panoskaltis-Mortari, A Murphy, WJ Zeller, J Roncarolo, M Boussiotis, VA Blazar, BR TI Alloreactive CD4+T cells can be renderd anergic by a combination of IL-10+TGF beta due to a failure of cell cycle progression SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN 55455 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Hosp San Raffaele, TIGET, I-20132 Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1089 EP A1089 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101044 ER PT J AU Exley, M Bigley, N Cheng, O Tahir, SMA Koezuka, Y Alt, FW Snapper, S Balk, S AF Exley, M Bigley, N Cheng, O Tahir, SMA Koezuka, Y Alt, FW Snapper, S Balk, S TI Resistance to acute viral infection mediated by CD1-reactive T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Wright State Univ, Dayton, OH 45435 USA. Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, HHMI, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Kirin Brewery Corp, Gunma, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A984 EP A984 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100426 ER PT J AU Freeman, GJ Long, AJ Iwai, Y Bourque, K Chernova, T Nishimura, H Fitz, L Malenkovich, N Okazaki, T Byrne, M Horton, H Fouser, L Carter, L Carreno, B Collins, M Wood, CR Honjo, T AF Freeman, GJ Long, AJ Iwai, Y Bourque, K Chernova, T Nishimura, H Fitz, L Malenkovich, N Okazaki, T Byrne, M Horton, H Fouser, L Carter, L Carreno, B Collins, M Wood, CR Honjo, T TI The B7-homologue, PD-L, is the ligand of the PD-1 immunoinhibitory receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Genet Inst, Cambridge, MA 02140 USA. Kyoto Univ, Grad Sch Med, Dept Med Chem, Kyoto 6063501, Japan. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1170 EP A1170 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101520 ER PT J AU Garven, GJ Sato, AK Santambrogio, L Strominger, JL Stern, LJ AF Garven, GJ Sato, AK Santambrogio, L Strominger, JL Stern, LJ TI Dendritic cells secrete a protease activity capable of processing intact antigen into antigenic peptides for extracellular presentation to T cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 MIT, Dept Chem, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1048 EP A1048 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100801 ER PT J AU Gong, J Nikrui, N Chen, D Koido, S Wu, Z Tanaka, Y Avigan, D Kufe, D AF Gong, J Nikrui, N Chen, D Koido, S Wu, Z Tanaka, Y Avigan, D Kufe, D TI Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce anti-tumor immunity SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A947 EP A947 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100205 ER EF