FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Li, HQ Boiselle, PM Shepard, JAO TrotmanDickenson, B McLoud, TC AF Li, HQ Boiselle, PM Shepard, JAO TrotmanDickenson, B McLoud, TC TI Diagnostic accuracy and safety of CT-Guided percutaneous needle aspiration biopsy of the lung: Comparison of small and large pulmonary nodules SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID LESIONS AB OBJECTIVE. The purpose of this study was to compare the diagnostic accuracy and safety of CT-guided percutaneous needle aspiration biopsy of pulmonary nodules less than or equal to 1.5 cm in diameter with those of nodules greater than 1.5 cm in diameter. MATERIALS AND METHODS. We retrospectively reviewed a consecutive series of 97 patients who underwent CT-guided percutaneous needle aspiration biopsy of a lung nodule and then surgical resection (n = 95) or autopsy (n = 2). By examining CT images, we classified 27 nodules as small (less than or equal to 1.5 cm) and 70 nodules as large (>1.5 cm). Diagnostic accuracy was calculated by comparing cytologic diagnoses based on biopsy with final diagnoses based on histologic findings from surgery or autopsy. Each case was reviewed for possible complications, including pneumothorax and chest tube placement. RESULTS. The diagnostic accuracy of CT-guided percutaneous needle aspiration biopsy of large nodules was 96%. The diagnostic accuracy for small nodules was 74%, a statistically significant difference (p < .05). The prevalences of pneumothorax in our population were nearly identical for small and large nodules (22 and 21%, respectively). The prevalence of chest tube placement in our population was approximately 2%. The prevalences of chest tube placement were 0% for small nodules and 3% for large nodules. CONCLUSION. CT-guided percutaneous needle aspiration biopsy is significantly less accurate for small pulmonary nodules than for large pulmonary nodules, but the complication rates for both are low. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV CHEST,BOSTON,MA 02114. NR 12 TC 212 Z9 232 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1996 VL 167 IS 1 BP 105 EP 109 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UT684 UT WOS:A1996UT68400022 PM 8659351 ER PT J AU Lazar, EB Whitman, GJ Chew, FS AF Lazar, EB Whitman, GJ Chew, FS TI Lymphoma of bronchus-associated lymphoid tissue SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID LUNG C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Lazar, EB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 9 Z9 11 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1996 VL 167 IS 1 BP 116 EP 116 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UT684 UT WOS:A1996UT68400024 PM 8659353 ER PT J AU Cortell, ED Kaufman, JA Geller, SC Cambria, RP Rivitz, SM Waltman, AC AF Cortell, ED Kaufman, JA Geller, SC Cambria, RP Rivitz, SM Waltman, AC TI MR angiography of tibial runoff vessels: Imaging with the head coil compared with conventional arteriography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID MAGNETIC-RESONANCE ANGIOGRAPHY; OCCLUSIVE DISEASE; LOWER-EXTREMITY AB OBJECTIVE. We compared peripheral vascular MR angiography done with a standard transmit-receive head coil with conventional arteriography for identifying and evaluating runoff vessels below the knee. MATERIALS AND METHODS. We examined 55 legs in 31 symptomatic patients with both conventional contrast angiography and gradient-echo two-dimensional time-of-flight MR angiography. Both legs of patients were placed in a standard transmit-receive head coil for MR angiography and were imaged simultaneously, For evaluation of stenoses, images of vessels were divided into 10 segments, and each segment was graded on a four-point scale. RESULTS. In the 393 native vascular segments evaluated, the sensitivity of MR angiography in identifying normal vessels was 95% and the specificity was 98%. In detecting segmental occlusion, MR angiography was 98% sensitive and 97% specific, Sensitivity and specificity for stenoses greater than 75% were 98% and 96%, respectively, and for stenoses greater than 50%, they were 98% and 95%, respectively. Interpretative discrepancies were found in 35 vessel segments in 18 legs; none was of clinical relevance. Of all vessel segments shown as occluded by conventional angiography, 1% appeared patent on MR angiograms. No vessel segments shown as normal on MR angiograms were found to be occluded on conventional angiograms. CONCLUSION, When performed simultaneously on both legs of symptomatic patients, 2D time-of-flight MR angiography with a standard transmit-receive head coil provides a time-efficient and highly sensitive and specific means of evaluating below-knee runoff. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV VASC RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT VASC SURG,BOSTON,MA 02114. NR 21 TC 30 Z9 31 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1996 VL 167 IS 1 BP 147 EP 151 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UT684 UT WOS:A1996UT68400031 PM 8659360 ER PT J AU Nielsen, GP Rosenberg, AE Koerner, FC Young, RH Scully, RE AF Nielsen, GP Rosenberg, AE Koerner, FC Young, RH Scully, RE TI Smooth-muscle tumors of the vulva - A clinicopathological study of 25 cases and review of the literature SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE vulva; leiomyoma; leiomyosarcoma ID PROGESTERONE RECEPTORS; AGGRESSIVE ANGIOMYXOMA; ESTROGEN-RECEPTORS; MENSTRUAL-CYCLE; LEIOMYOSARCOMA; TISSUE; LEIOMYOMA; ESTRADIOL; NEOPLASM; BINDING AB The clinical and pathological features of 25 smooth-muscle tumors of the vulva were analyzed. The patients ranged in age from 17 to 67 (mean, 37.6) years; two were pregnant, Twenty-three tumors were 1.5 to 16 (mean, 5.2) cm in greatest dimension; the size of two tumors was unknown, Microscopic examination showed that 16 tumors were circumscribed, six had focally infiltrative margins, and the margins could not be evaluated in three tumors. Fourteen tumors were composed mainly of spindle cells; two of these tumors had prominent myxoid stroma. Seven tumors were predominantly epithelioid and had a prominent hyalinized or myxoid stroma; often the cells had a plexiform pattern. Four tumors contained an approximately equal number of epithelioid and spindle cells. Ten tumors had mild, nine moderate, and six severe cytologic atypia. Mitotic figures ranged from 0 to 10 (average, 1.8) per 10 high-power fields (hpf). Immunohistochemically, all the tumors stained for one or more muscle markers, Thirteen of 17 tumors were positive for estrogen receptors, and 16 of 18 were positive for progesterone receptors, Follow-up information ranging from 1 month to 19 years (average, 5 years) was available in 19 cases. Four tumors recurred locally, and one patient with recurrent tumor died of metastases 7 months after the initial operation. We propose an expanded criteria to distinguish between leiomyomas and leiomyosarcomas of the vulva. Tumors that manifest three or all of the four following features should be considered sarcomas: greater than or equal to 5 cm in greatest dimension, infiltrative margins, greater than or equal to 5 mitotic figures per 10 hpf, and moderate to severe cytologic atypia. Those that have only one of these characteristics should be diagnosed as leiomyoma, and those that exhibit only two of these features should be considered benign but atypical leiomyomas. The sarcomas should be excised with widely negative margins; the leiomyomas and the atypical leiomyomas should be excised conservatively, with long-term, careful follow-up. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 63 TC 64 Z9 69 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 1996 VL 20 IS 7 BP 779 EP 793 DI 10.1097/00000478-199607000-00001 PG 15 WC Pathology; Surgery SC Pathology; Surgery GA UU255 UT WOS:A1996UU25500001 PM 8669526 ER PT J AU Pins, MR Young, RH Daly, WJ Scully, RE AF Pins, MR Young, RH Daly, WJ Scully, RE TI Primary squamous cell carcinoma of the ovary - Report of 37 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; carcinoma; squamous cell; dermoid cyst; teratoma; endometriosis ID BENIGN CYSTIC TERATOMA; CANCER AB A total of 37 cases of ovarian primary squamous cell carcinoma (SCC)-19 associated with a dermoid cyst (SCCD), seven associated with endometriosis (SCCE), and 11 pure (SCCP)-are described. The last le cases belong within the new World Health Organization category of SCC in the surface epithelial-stromal category. The 19 patients with SCCD were 21-75 (mean, 52) years old; three of the carcinomas were in situ and seven, six, and three tumors were stages I, II, and III, respectively. The tumors and associated dermoid cysts were 6-35 cm in greatest dimension, usually forming mural nodules with intracavitary protrusion and focal necrosis and hemorrhage; two, seven, and seven tumors were grades 1, 2, and 3, respectively. SCCD was focally associated with a columnar epithelial cyst lining in 13 cases, suggesting an origin therein. One patient with stage I, grade 1 SCCD also had squamous cell carcinoma in situ (CIS) of the cervix. The seven patients with SCCE were 29-70 (mean, 49) years old, and one, three, one, and two tumors were stages I, II, III, and IV, respectively; all of the tumors were grade 3. One was associated with squamous cell carcinoma in situ of the cervix. The 11 patients with SCCP were 27-73 (mean, 56) years old, and one, four, five, and one tumors were stages I, II, III, and IV, respectively. The tumors were 6-26 cm in greatest diameter, usually solid with focal necrosis; one and 10 tumors were grades 2 and 3, respectively. Three patients with SCCP also had cervical squamous cell carcinoma in situ. The patients with SCCE had a poorer overall survival than those with SCCD. Five of the six patients with SCCE for whom adequate follow-up information was available died of their disease (mean survival, 5 months); also, in all five cases of SCCE reported in the literature, the patients died of their disease (mean survival, 4 months). The stage of the tumor and its grade correlated best with overall survival for all three types of SCC. C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 32 TC 70 Z9 73 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 1996 VL 20 IS 7 BP 823 EP 833 DI 10.1097/00000478-199607000-00005 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA UU255 UT WOS:A1996UU25500005 PM 8669530 ER PT J AU Qvist, J Peterfreund, RA Perlmutter, GS AF Qvist, J Peterfreund, RA Perlmutter, GS TI Transient compartment syndrome of the forearm after attempted radial artery cannulation SO ANESTHESIA AND ANALGESIA LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114. RP Qvist, J (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,FRUIT ST,BOSTON,MA 02114, USA. NR 15 TC 11 Z9 12 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 1996 VL 83 IS 1 BP 183 EP 185 DI 10.1097/00000539-199607000-00033 PG 3 WC Anesthesiology SC Anesthesiology GA UT702 UT WOS:A1996UT70200033 PM 8659734 ER PT J AU Jain, RK AF Jain, RK TI 1995 Whitaker lecture: Delivery of molecules, particles, and cells to solid tumors SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Review DE tumor microcirculation; angiogenesis; blood flow; vascular permeability; diffusion and convection; receptor-ligand binding; interstitial pressure; lymphatics; cell adhesion and deformation; cancer detection and treatment ID INTERSTITIAL FLUID PRESSURE; NATURAL-KILLER-CELLS; GROWTH-FACTOR-BETA; POSITRON EMISSION TOMOGRAPHY; HUMAN ADENOCARCINOMA LS174T; BLOOD-FLOW; MICROVASCULAR PERMEABILITY; NEOPLASTIC TISSUES; MONOCLONAL-ANTIBODIES; SCID MICE AB To reach cancer cells in a tumor, a blood-borne therapeutic agent must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, and finally migrate through the interstitium. Unfortunately, tumors often develop in ways that hinder each of these steps. Our research goals are to analyze each of these steps experimentally and theoretically, and then to integrate the resulting information in a unified theoretical framework. This paradigm of analysis and synthesis has allowed us to obtain a better understanding of physiological barriers in solid tumors, and to develop novel strategies to exploit and/or to overcome these barriers for improved cancer detection and treatment. RP HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT RADIAT ONCOL, BOSTON, MA 02114 USA. NR 132 TC 69 Z9 71 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 EI 1573-9686 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JUL-AUG PY 1996 VL 24 IS 4 BP 457 EP 473 DI 10.1007/BF02648108 PG 17 WC Engineering, Biomedical SC Engineering GA UY780 UT WOS:A1996UY78000001 PM 8841721 ER PT J AU Leape, LL Hilborne, LH Schwartz, JS Bates, DW Rubin, HR Slavin, P Park, RE Witter, DM Panzer, RJ Brook, RH Kelly, J Bluth, E KrouselWood, T Komaroff, A Matchar, D Kahn, K Tobacman, J AF Leape, LL Hilborne, LH Schwartz, JS Bates, DW Rubin, HR Slavin, P Park, RE Witter, DM Panzer, RJ Brook, RH Kelly, J Bluth, E KrouselWood, T Komaroff, A Matchar, D Kahn, K Tobacman, J TI The appropriateness of coronary artery bypass graft surgery in academic medical centers SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE coronary artery bypass; academic medical centers; regional health planning; angina pectoris; coronary disease AB Objective: To compare the appropriateness of use of coronary artery bypass graft (CABG) surgery in Academic Medical Center Consortium hospitals as judged 1) according to criteria developed by an expert panel, 2) according to revisions of those criteria made by cardiac surgeons from the Academic Medical Center Consortium, and 3) by review of cases by the surgeons responsible for those cases. Design: Retrospective, randomized medical record review. Setting: 12 Academic Medical Center Consortium hospitals. Patients: Random sample of 1156 patients who had had isolated CABG surgery in 1990. Main Outcome Measures: 1) Percentage of patients with indications for which CABG surgery was classified as appropriate, inappropriate, or of uncertain appropriateness and 2) percentage of cases in which CABG surgery was judged inappropriate or uncertain for which ratings changed after local case review. Results: Data were retrieved from medical records by trained abstractors using an explicit data collection instrument. Cases in which CABG surgery was judged to be inappropriate or uncertain were individually reviewed by the responsible surgeons. According to the expert panel ratings, 83% of the CABG operations (95% CI, 81% to 85%) were necessary, 9% (CI, 8% to 10%) were appropriate, 7% (CI, 5% to 8%) were uncertain, and 1.6% (CI, 0.6% to 2.5%) were inappropriate. These rates are almost identical to those found in a previous study that was done in New York State and that used the same criteria (in that study, 91% of operations were classified as necessary or appropriate, 7% were classified as uncertain, and 2.4% were classified as inappropriate). Rates of inappropriate procedures varied from 0% to 5% among the 12 member hospitals (P = 0.02). The Academic Medical Center Consortium cardiac surgeons revised 568 (24%) of the indications used by the expert panel. However, because those revisions altered the appropriateness ratings in both directions and affected only 50 cases (4%), the net effect of the revisions was slight: The rate of inappropriate CABG surgery increased from 1.6% to 1.9%. Local review found that data collection errors had caused erroneous ratings in 12.5% of 64 cases in which surgery had been classified as inappropriate or uncertain. Conclusions: The Academic Medical Center Consortium hospitals had low rates of inappropriate and uncertain use of CABG surgery, regardless of the criteria used for assessment. Even though surgeons from the Consortium revised the appropriateness ratings extensively, their revisions had a negligible effect on the overall assessment of appropriateness. However, because of potential data collection errors, appropriateness criteria should be used for individual case audits only if supplemented by subsequent physician review. C1 ACAD MED CTR CONSORTIUM,ROCHESTER,NY 14643. AMER MED ASSOC,CHICAGO,IL 60610. ALTON OCHSNER MED INST,NEW ORLEANS,LA. BRIGHAM & WOMENS HOSP,DEPT GEN MED,BOSTON,MA 02115. DUKE UNIV,MED CTR,DURHAM,NC. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,CTR EVALUAT MED PRACT,BOSTON,MA 02114. MAYO CLIN & MAYO FDN,ROCHESTER,MI. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. UNIV IOWA HOSP & CLIN,IOWA CITY,IA 52242. UNIV PENN,MED CTR,PHILADELPHIA,PA 19104. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. RAND CORP,SANTA MONICA,CA 90406. RI Bluth, Edward/A-8613-2011 NR 12 TC 34 Z9 34 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 1 PY 1996 VL 125 IS 1 BP 8 EP & PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA UT399 UT WOS:A1996UT39900002 PM 8644996 ER PT J AU Hyman, BT GomezIsla, T Briggs, M Chung, H Nichols, S Kohout, F Wallace, R AF Hyman, BT GomezIsla, T Briggs, M Chung, H Nichols, S Kohout, F Wallace, R TI Apolipoprotein E and cognitive change in an elderly population SO ANNALS OF NEUROLOGY LA English DT Article ID ONSET ALZHEIMERS-DISEASE; E ALLELE EPSILON-4; E POLYMORPHISM; RISK FACTOR; E GENOTYPE; ASSOCIATION; FREQUENCY AB The apolipoprotein E (apoE) epsilon 4 allele is overrepresented, and the apoE epsilon 2 allele underrepresented, in Alzheimer's disease. To assess the risk of cognitive impairment in individuals with these genotypes in the general population, we studied a population-based sample of 1,899 individuals 65 years and older as a follow-up to the Iowa 65+ Rural Health Study. Multiple regression and logistic regression analyses demonstrated significant effects of apoE epsilon 4 and apoE epsilon 2 in predicting performance on a delayed recall task over a 4- to 7-year period. The magnitude of this effect was, however, fairly modest, with odds ratios for developing impairment of approximately 1.37 (95% confidence interval: 1.007, 1.850; p = 0.045) for apoE epsilon 4 and 0.53 (95% confidence interval: 0.368, 0.777; p = 0.001) for apoE epsilon 2. These effects were more pronounced in women than men. Importantly, 85% of elderly apoE epsilon 4/4 individuals (average age, 81) scored in the unimpaired range on a screening mental status test. Thus, many individuals reach old age without cognitive impairment despite inheritance of one or two apoE epsilon 4 alleles. This suggests that apoE genotyping will have limited utility as a diagnostic or prognostic indicator of cognitive decline in individuals. C1 UNIV IOWA,COLL MED,DEPT PREVENT MED,IOWA CITY,IA. UNIV IOWA,COLL MED,DEPT PERIODONT,IOWA CITY,IA. RP Hyman, BT (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,NEUROL SERV,FRUIT ST,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG 12406, AG-02106, AG10127] NR 49 TC 148 Z9 149 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 1996 VL 40 IS 1 BP 55 EP 66 DI 10.1002/ana.410400111 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UW805 UT WOS:A1996UW80500010 PM 8687193 ER PT J AU Kieburtz, K McDermott, M Shoulson, I Fahn, S Brin, M Goetz, C Lang, A Olanow, CW LeWitt, P Mistura, K Waters, C Welsh, M Rodnitzky, R Dobson, J Argatoff, P Tanner, C Lewis, P Watts, R Bryan, B Comella, C Jaglin, JA Shults, C Fontaine, D Bressman, SB Moskowitz, C Hurtig, HI Shallow, K Hubble, J Barter, R Bennett, JP RostRuffner, E Perlmutter, JS McGeeMinnich, L Hauser, R Gauger, L Rajput, AH Sutton, A Trinidad, K Gardiner, IF Singer, C Sheldon, C Fink, JS Tennis, M Baker, D Bourgeois, K Casaceli, C Claude, K Hickey, G Nobel, R Oakes, D Orme, C Pelusio, RM Plumb, S Rudolph, A Randolph, P Sotack, J Watts, A Tariot, PN Golbe, LI Miller, P Hall, WJ Herndon, R Dorflinger, E Myl, D Modi, M Oarsley, L Yoo, K Eliahou, E Shimoun, G Colletta, S Siegel, J Pedder, S Dupuis, D AF Kieburtz, K McDermott, M Shoulson, I Fahn, S Brin, M Goetz, C Lang, A Olanow, CW LeWitt, P Mistura, K Waters, C Welsh, M Rodnitzky, R Dobson, J Argatoff, P Tanner, C Lewis, P Watts, R Bryan, B Comella, C Jaglin, JA Shults, C Fontaine, D Bressman, SB Moskowitz, C Hurtig, HI Shallow, K Hubble, J Barter, R Bennett, JP RostRuffner, E Perlmutter, JS McGeeMinnich, L Hauser, R Gauger, L Rajput, AH Sutton, A Trinidad, K Gardiner, IF Singer, C Sheldon, C Fink, JS Tennis, M Baker, D Bourgeois, K Casaceli, C Claude, K Hickey, G Nobel, R Oakes, D Orme, C Pelusio, RM Plumb, S Rudolph, A Randolph, P Sotack, J Watts, A Tariot, PN Golbe, LI Miller, P Hall, WJ Herndon, R Dorflinger, E Myl, D Modi, M Oarsley, L Yoo, K Eliahou, E Shimoun, G Colletta, S Siegel, J Pedder, S Dupuis, D TI Effect of lazabemide on the progression of disability in early Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; SELEGILINE; DEPRENYL; MPTP AB Lazabemide (Ro 19-6327) is a relatively short-acting, reversible, and selective type B monoamine oxidase inhibitor that is not metabolized to amphetamines or other active compounds. We previously found lazabemide to be safe and well tolerated at dosages of up to 400 mg/day during a 6-week study of 201 patients with early untreated Parkinson's disease (PD). We now assess whether or not lazabemide influences the progression of disability in untreated PD. Patients (N = 321) were assigned by randomization to one of five treatment groups (placebo, 25 mg, 50 mg, 100 mg, or 200 mg/day) and followed systematically for up to 1 year. The risk of reaching the primary end point (the onset of disability sufficient to require levodopa therapy) was reduced by 51% for the patients who received lazabemide compared with placebo-treated subjects. This effect was consistent among all dosages. The frequency of adverse experiences did not differ among the treatment groups. At dosages ranging from 25 to 200 mg/day, lazabemide was well tolerated and delayed the need for levodopa in early, otherwise untreated PD. The magnitude and pattern of benefits were similar to those observed after 1 year of deprenyl (selegiline) treatment in the DATATOP clinical trial. C1 COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY 10032. MT SINAI MED CTR,NEW YORK,NY 10029. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. TORONTO HOSP,TORONTO,ON M5T 2S8,CANADA. UNIV S FLORIDA,TAMPA,FL. SINAI HOSP,DETROIT,MI 48235. UNIV SO CALIF,LOS ANGELES,CA. UNIV IOWA,IOWA CITY,IA. UNIV CALGARY,MED CTR,CALGARY,AB,CANADA. PARKINSONS INST,SUNNYVALE,CA. EMORY UNIV,SCH MED,ATLANTA,GA. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. UNIV PENN,GRAD HOSP,PHILADELPHIA,PA 19104. UNIV KANSAS,KANSAS CITY,KS. UNIV VIRGINIA,CHARLOTTESVILLE,VA. WASHINGTON UNIV,ST LOUIS,MO. UNIV S FLORIDA,TAMPA,FL. UNIV SASKATCHEWAN,SASKATOON,SK,CANADA. UNIV ROCHESTER,ROCHESTER,NY. UNIV MIAMI,MIAMI,FL 33152. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,NEW BRUNSWICK,NJ. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. UNIV ROCHESTER,ROCHESTER,NY. HOSP GOOD SAMARITAN,PORTLAND,OR. RP Kieburtz, K (reprint author), UNIV ROCHESTER,MED CTR,DEPT NEUROL,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 1996 VL 40 IS 1 BP 99 EP 107 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UW805 UT WOS:A1996UW80500015 ER PT J AU Grillo, HC AF Grillo, HC TI Irreversible tetraplegia after tracheal resection - Invited Commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material RP Grillo, HC (reprint author), MASSACHUSETTS GEN HOSP,DEPT THORAC SURG,THORAC SURG UNIT,WARREN 1101,55 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 1996 VL 62 IS 1 BP 280 EP 280 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA UV817 UT WOS:A1996UV81700072 ER PT J AU Blankensteijn, JD Abbott, WM AF Blankensteijn, JD Abbott, WM TI Continuous pulse amplitude monitoring of infrainguinal bypass grafts in the first 24 postoperative hours SO ANNALS OF VASCULAR SURGERY LA English DT Article ID SAPHENOUS-VEIN BYPASSES; PATENCY; EXPERIENCE; PALPATION; IMPACT AB To evaluate continuous pulse amplitude monitoring (CPAM) as a method for early postoperative graft surveillance following infrainguinal bypass surgery, a prospective observational study was carried out in 34 consecutive infrainguinal bypass grafts. CPAM tracings were compared with pre- and postoperative pulse palpation, ankle/brachial index (ABI) measurements, and pulse volume recordings (PVR). The utility of each method was defined by its ability to demonstrate graft patency in the first 24 hours. Pulse palpation was considered a useful monitoring tool if a postoperative pedal pulse was found in the absence of palpable preoperative pulses. The ABI qualified in this respect if a postoperative increase of at least 0.25 could be demonstrated; for PVR tracings an increase of at least one category was required, The utility of CPAM was established by an increase of at least 5 mm compared to the preoperative values. There were no early graft failures. We were therefore unable to calculate the ability of the studies to predict graft failure. The percentages (95% confidence limits) for which pulse palpation, ABI, and PVR were found capable of demonstrating graft patency were 50% (range 34% to 65%), 53% (range 36% to 70%), and 71% (range 54% to 83%), respectively. CPAM appeared to be far superior to these three methods with a utility of 94% (range 81% to 98%; p <0.05). Patient and operator acceptability of CPAM was high. Skin pressure problems are a potential risk if the CPAM probe is left attached to the skin for more than 24 hours. CPAM was a valuable and reliable means of monitoring infrainguinal vascular reconstructions. Apart from being inexpensive, continuous, objective, and simple, CPAM is noninvasive and painless. It is advisable to remove the probe 24 hours after surgery, when the most crucial period for graft monitoring has passed. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,VASC LAB,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV VASC SURG,BOSTON,MA. RI Blankensteijn, Jan/Q-9291-2016 OI Blankensteijn, Jan/0000-0002-2062-8749 NR 20 TC 1 Z9 1 U1 0 U2 1 PU QUALITY MEDICAL PUBLISHING INC PI ST LOUIS PA 11970 BORMAN DR, STE 222, ST LOUIS, MO 63146 SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JUL PY 1996 VL 10 IS 4 BP 378 EP 384 DI 10.1007/BF02286784 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA VH504 UT WOS:A1996VH50400010 PM 8879395 ER PT J AU LaMuraglia, GM McGovern, FJ AF LaMuraglia, GM McGovern, FJ TI Gerota's fascia flap: An alternative for aortic graft coverage SO ANNALS OF VASCULAR SURGERY LA English DT Article ID AORTODUODENAL FISTULA; MANAGEMENT AB The greater omentum is commonly used when there is a surgical indication for a barrier between an aortic graft and the abdominal contents. There are few other options when the omentum is not available. A novel approach is described for this purpose-Gerota's fascia flap. It is a simple, durable technique that can readily be used to provide extra tissue in the retroperitoneum for coverage of an aortic graft or possibly an aortic stump. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV VASC SURG,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,UROL SERV,BOSTON,MA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU QUALITY MEDICAL PUBLISHING INC PI ST LOUIS PA 11970 BORMAN DR, STE 222, ST LOUIS, MO 63146 SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD JUL PY 1996 VL 10 IS 4 BP 405 EP 408 DI 10.1007/BF02286788 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA VH504 UT WOS:A1996VH50400014 PM 8879399 ER PT J AU Leaf, DA Kleinman, MT AF Leaf, DA Kleinman, MT TI Urban ectopy in the mountains: Carbon monoxide exposure at high altitude SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article ID CORONARY-ARTERY DISEASE; ISCHEMIC HEART-DISEASE; EXERCISE PERFORMANCE; ANGINA-PECTORIS; ARRHYTHMIAS; CARBOXYHEMOGLOBIN; MANAGEMENT; BLOOD AB Environmental exposure to inhaled carbon monoxide (CO) increases coronary artery disease risk. Sudden cardiac death, a frequent manifestation of coronary artery disease, is usually a result of ventricular dysrhythmia. The effect of exposure to CO at sea level (CO/SL) and simulated high (2.1 km) altitudes (CO/HA) on the incidence of cardiac ectopy in subjects with coronary artery disease was investigated. A double-blind crossover study was conducted, with random-order assignment, and each subject served as his own control. Seventeen men with documented coronary artery disease and stable angina pectoris performed cardiopulmonary exercise stress tests after random exposure to either CO or clean air (CA) at sea level (CA/SL) or at a simulated 2.1-km high altitude (CA/HA). The individual CO and HA exposure conditions were each selected to reduce the percentage of oxygen saturation of the subjects(1) arterial blood by 4%. Subjects(1) blood carboxyhemoglobin levels were increased from an average of 0.62% after clean-air exposure to 3.91% of saturation after CO exposure. The percentage of oxygen saturation in arterial blood was reduced from a baseline level of 98% to approximately 94% after CO/SL or CA/HA and to approximately 90% after CO/HA. Compared with the CA/SL (i.e., 10 premature ventricular contractions [PVCs]), the average incidence of exercise-induced ventricular ectopy was approximately doubled after all exposures (CO/SL = 18 PVCs, CA/HA = 16 PVCs, and CO/HA = 19 PVCs), and a significant trend (p < .05) of increased ectopy with decreased oxygen saturation in arterial blood was observed. Yet, among subjects who were free from ectopy (n = 11) on CA/SL, only 2 subjects developed ectopy after CO/HA. No episodes of ventricular tachycardia or fibrillation occurred. The findings indicated that exposure to increased levels of hypoxemia, resulting from hypoxic and/or CO exposures, increased the susceptibility to ventricular ectopy during exercise in individuals with stable angina pectoris; however, this risk was nominal for those without ectopy. C1 UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. UNIV CALIF IRVINE,DEPT COMMUNITY & ENVIRONM MED,IRVINE,CA 92717. RP Leaf, DA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIV GEN INTERNAL MED 691 111G,DEPT MED,LOS ANGELES,CA 90073, USA. NR 26 TC 9 Z9 9 U1 0 U2 0 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD JUL-AUG PY 1996 VL 51 IS 4 BP 283 EP 290 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA VC547 UT WOS:A1996VC54700004 PM 8757408 ER PT J AU Breiter, HC Rauch, SL Kwong, KK Baker, JR Weisskoff, RM Kennedy, DN Kendrick, AD Davis, TL Jiang, AP Cohen, MS Stern, CE Belliveau, JW Baer, L OSullivan, RL Savage, CR Jenike, MA Rosen, BR AF Breiter, HC Rauch, SL Kwong, KK Baker, JR Weisskoff, RM Kennedy, DN Kendrick, AD Davis, TL Jiang, AP Cohen, MS Stern, CE Belliveau, JW Baer, L OSullivan, RL Savage, CR Jenike, MA Rosen, BR TI Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID GLUCOSE METABOLIC RATES; CEREBRAL BLOOD-FLOW; HUMAN BRAIN; PET IMAGES; SENSORY STIMULATION; SIGNAL CHANGES; VISUAL-CORTEX; TIME; TOMOGRAPHY; ACTIVATION AB Background: The new technique of functional magnetic resonance imaging was used to investigate the mediating neuroanatomy of obsessive-compulsive disorder symptoms. Methods: Ten patients with obsessive-compulsive disorder and 5 normal subjects were studied via functional magnetic resonance imaging during control and provoked conditions. Data analysis entailed parametric and nonparametric statistical mapping. Results: Statistical maps (nonparametric; P<10(-3)) showed activation for 70% or more of patients with obsessive-compulsive disorder in medial orbitofrontal, lateral frontal, anterior temporal, anterior cingulate, and insular cortex, as well as caudate, lenticulate, and amygdala. No normal subjects exhibited activation in any brain region. Conclusions: Results of functional magnetic resonance imaging were consistent with past studies of obsessive-compulsive disorder that used other functional neuroimaging modalities. However, paralimbic and limbic activations were more prominent in the present study. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,NUCL MAGNET RESONANCE CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV CALIF LOS ANGELES,MED CTR,DEPT NEUROL,LOS ANGELES,CA 90024. RI Kennedy, David/H-3627-2012; Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU NCI NIH HHS [5T32CA0936211] NR 70 TC 427 Z9 432 U1 2 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 1996 VL 53 IS 7 BP 595 EP 606 PG 12 WC Psychiatry SC Psychiatry GA UW182 UT WOS:A1996UW18200005 PM 8660126 ER PT J AU Jenike, MA Breiter, HC Baer, L Kennedy, DN Savage, CR Olivares, MJ OSullivan, RL Shera, DM Rauch, SL Keuthen, N Rosen, BR Caviness, VS Filipek, PA AF Jenike, MA Breiter, HC Baer, L Kennedy, DN Savage, CR Olivares, MJ OSullivan, RL Shera, DM Rauch, SL Keuthen, N Rosen, BR Caviness, VS Filipek, PA TI Cerebral structural abnormalities in obsessive-compulsive disorder - A quantitative morphometric magnetic resonance imaging study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DEVELOPING VISUAL-CORTEX; CORPUS-CALLOSUM; WHITE MATTER; TRANSITORY MACROPHAGES; PSYCHIATRIC-DISORDERS; POSTNATAL-DEVELOPMENT; OPERCULUM SYNDROME; CAUDATE-NUCLEUS; HUMAN-BRAIN; FOLLOW-UP AB Background: A previous pilot study of only posterior brain regions found lower white-matter volume in pao tients with obsessive-compulsive disorder than in normal control subjects. We used new cohorts of patients and matched normal control subjects to study whole-brain volume differences between these groups with magnetic resonance imaging-based morphometry. Methods: Ten female patients with obsessive-compulsive disorder and 10 female control subjects, matched for handedness, age, weight, education, and verbal IQ, underwent magnetic resonance imaging with a 3-dimensional volumetric protocol. Scans were blindly normalized and segmented by means of well-characterized semiautomated intensity contour mapping and differential intensity contour algorithms. Brain structures investigated included the cerebral hemispheres, cerebral cortex, diencephalon, caudate, putamen, globus pallidus, hippocampus, amygdala, third and fourth ventricles, corpus callosum, operculum, cerebellum, and brain stem. Anterior to posterior neocortical regions, including precallosum, anterior pericallosum, posterior pericallosum, and retrocallosum, with adjacent white matter were also measured. Volumes found different between groups were correlated with Yale-Brown Obsessive Compulsive Scale score and Rey-Osterieth Complex Figure Test measures. Results: Confirming results of our earlier pilot study and expanding the findings to the whole brain, patients with obsessive-compulsive disorder had significantly less total white matter but, in addition, significantly greater total cortex and opercular volumes. Severity of obsessive-compulsive disorder and nonverbal immediate memory correlated with opercular volume. Conclusions: Replication of volumetric white-matter differences suggests a widely distributed structural brain abnormality in obsessive-compulsive disorder. Whereas determining the etiogenesis may require research at a microscopic level, understanding its functional significance can be further explored via functional neuroimaging and neuropsychological studies. C1 MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, NUCL MAGNET RESONANCE CTR, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. RI Kennedy, David/H-3627-2012 FU NICHD NIH HHS [HD 27802]; NINDS NIH HHS [NS 20489, NS 24279] NR 99 TC 174 Z9 178 U1 12 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 1996 VL 53 IS 7 BP 625 EP 632 PG 8 WC Psychiatry SC Psychiatry GA UW182 UT WOS:A1996UW18200008 PM 8660129 ER PT J AU George, MS Parekh, PI Rosinsky, N Ketter, TA Kimbrell, TA Heilman, KM Herscovitch, P Post, RM AF George, MS Parekh, PI Rosinsky, N Ketter, TA Kimbrell, TA Heilman, KM Herscovitch, P Post, RM TI Understanding emotional prosody activates right hemisphere regions SO ARCHIVES OF NEUROLOGY LA English DT Article ID LANGUAGE; PET; COMPREHENSION; ORGANIZATION; APROSODIAS; ANATOMY; WORDS AB Background: Defects in expressing or understanding the affective or emotional tone of speech (aprosodias) have been associated with right hemisphere dysfunction, while defects of propositional language have been linked to left hemisphere disease. The brain regions involved in recognition of emotional prosody in healthy subjects is less clear. Objectives: To investigate the brain regions involved in understanding emotional prosody and to determine whether these differ from those involved in understanding emotion based on propositional content. Methods: We studied 13 healthy subjects using water labeled with radioactive oxygen 15 and positron emission tomography while they listened to 3 similar sets of spoken English sentences. In different tasks, their responses were based on the emotional propositional content, on the emotional intonation of the sentence (prosody), or on their ability to repeat the second word in the sentence (control). Results: Understanding propositional content activated the prefrontal cortex bilaterally, on the left more than on the right. In contrast, responding to the emotional prosody activated the right prefrontal cortex. Conclusion: Neurologically healthy subjects activate right hemisphere regions during emotional prosody recognition. C1 NIMH,BIOL PSYCHIAT BRANCH,DIV INTRAMURAL RES PROGRAMS,BETHESDA,MD 20892. NIH,PET DEPT,CTR CLIN,BETHESDA,MD. UNIV FLORIDA,DEPT NEUROL,GAINESVILLE,FL 32611. MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT NEUROL,CHARLESTON,SC 29425. RALPH H JOHNSON VET ADM MED CTR,CHARLESTON,SC. RP George, MS (reprint author), MED UNIV S CAROLINA,DEPT RADIOL,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 40 TC 175 Z9 178 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 1996 VL 53 IS 7 BP 665 EP 670 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA UW177 UT WOS:A1996UW17700013 PM 8929174 ER PT J AU Levy, ML Miller, BL Cummings, JL Fairbanks, LA Craig, A AF Levy, ML Miller, BL Cummings, JL Fairbanks, LA Craig, A TI Alzheimer disease and frontotemporal dementias - Behavioral distinctions SO ARCHIVES OF NEUROLOGY LA English DT Article ID FRONTAL-LOBE DEGENERATION; SPECT CHARACTERISTICS; CLINICAL PICTURE; DIAGNOSIS AB Background: Frontotemporal dementia (FTD) is a syndrome produced by lobar degeneration of the temporal and/or frontal lobes. Objectives: To quantify the behavioral disturbances of FTD and compare them with behavioral changes observed in Alzheimer disease (AD). Design: Cross-sectional comparison of 2 groups defined by research diagnostic criteria and single photon emission computed tomography. Behaviors were assessed using a standardized rating scale-Neuropsychiatric Inventory. Groups were matched for dementia severity. Setting: Patients were seen at 2 university-based outpatient dementia clinics and a Veterans Affairs medical center. Participants: Twenty-two patients with FTD and 30 patients with AD. Results: Patients with FTD had significantly greater total Neuropsychiatric Inventory scores than patients with AD and exhibited more apathy, disinhibition, euphoria, and aberrant motor behavior. The Neuropsychiatric Inventory accurately assigned 77% of patients with FTD and 77% of patients with AD to the correct diagnostic group using disinhibition, apathy, and depression. Patients with FTD had higher levels of disinhibition and apathy with relatively lower levels of depression compared with patients with AD. Conclusions: The Neuropsychiatric Inventory provides a behavioral profile that differentiates patients with FTD from patients with AD. Patients with FTD are more behaviorally disturbed but are often less depressed than patients with AD relative to their level of apathy. C1 UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,SCH MED,PSYCHIAT SERV,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT NEUROL,LOS ANGELES,CA 90024. FU NIA NIH HHS [AG10123] NR 21 TC 205 Z9 208 U1 0 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 1996 VL 53 IS 7 BP 687 EP 690 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA UW177 UT WOS:A1996UW17700017 PM 8929178 ER PT J AU Krzystolik, MG Kuperwasser, M Dreyer, EB AF Krzystolik, MG Kuperwasser, M Dreyer, EB TI Anterior-segment ultrasound biomicroscopy in a patient with AIDS and bilateral angle-closure glaucoma secondary to uveal effusions SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 5 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 1996 VL 114 IS 7 BP 878 EP 879 PG 2 WC Ophthalmology SC Ophthalmology GA UX515 UT WOS:A1996UX51500018 PM 8660176 ER PT J AU Meara, JG Li, KK Shah, SS Cunningham, MJ AF Meara, JG Li, KK Shah, SS Cunningham, MJ TI Odontogenic keratocysts in the pediatric population SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SURGICAL-MANAGEMENT; CYSTS; EXPRESSION; DIAGNOSIS; GROWTH; AID AB Objective: To review the characteristics and treatment of odontogenic keratocysts in the pediatric population at our institution in light of a comprehensive literature review of odontogenic keratocysts in the general population in the hope of elucidating clinical, radiological, or pathological factors that would suggest a different therapeutic approach to odontogenic keratocysts in the pediatric as opposed to the adult population. Design: A 19-year retrospective medical chart review of children with mandibular or maxillary masses of odontogenic keratocyst origin. Setting: Two academic tertiary care institutions. Patients: Eleven children had pathologically confirmed odontogenic keratocysts. Age at diagnosis ranged from 8 to 18 years (mean, 13.4 years). Results: A cystic mass with dentition displacement was characteristic clinically and radiographically. Treatment principally consisted of enucleation with or without extraction of teeth. Follow-up ranged from 1 to 8 years. Seven patients remained free of disease. Recurrences or second primary lesions occurred in 4 patients, all of whom had a family history of nevoid basal cell carcinoma syndrome or multiple cysts suggestive of this diagnosis. The maximum 8-year interval between initial treatment and recurrence is noteworthy. Conclusions: The diagnosis of odontogenic keratocyst deserves consideration in children who have a mass of the mandible or maxilla. The clinical behavior of this lesion in its initial occurrence and response to conservative treatment seems to be similar to that reported in adults. Odontogenic keratocysts, especially those that are multiple or recurrent, should alert the clinician to the possible underlying diagnosis of nevoid basal cell carcinoma syndrome. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. NR 25 TC 17 Z9 17 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 1996 VL 122 IS 7 BP 725 EP 728 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA UX513 UT WOS:A1996UX51300005 PM 8663943 ER PT J AU Kerrigan, DC Deming, LC Holden, MK AF Kerrigan, DC Deming, LC Holden, MK TI Knee recurvatum in gait: A study of associated knee biomechanics SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID GENU-RECURVATUM; BIOFEEDBACK TREATMENT; STROKE; SIGNAL AB Objectives: To quantitatively evaluate peak knee extensor torque values imparted to the posterior knee structures during gait in patients with knee recurvatum compared with torque values observed in control subjects, and to assess the predictive value of the degree of knee hyperextension and other clinical factors in estimating peak knee extensor torque. Design: A retrospective analysis of clinical and quantitative gait data obtained from patients and control subjects. Settings: A gait laboratory. Subjects: Forty-one consecutive patients with neurologically based impairments presenting with knee hyperextension during gait (52 limbs) and 46 able-bodied control subjects. Main Outcome Measure: Peak knee extensor torque during the stance period of the gait cycle. Results: Although overall, the patient average peak extensor torque was significantly greater (p < .001) than the control subjects' average value, knee extensor torques were within or below a +/- 1 standard deviation range for control subjects in 25% (13) of limbs tested. Peak knee hyperextension angle was a poor predictor of peak extensor torque; there was statistical significance (coefficient .061, p < .001) only for hyperextension angles of less than or equal to 4 degrees. Multiple regression incorporating hyperextension angle and other clinical variables to predict peak knee extensor torque resulted in an adjusted r(2) of .53. Conclusion: Patients with knee recurvatum have variable peak extensor torque values associated with their knee hyperextension. Knowledge of knee hyperextension angle and other clinical factors are only partially useful in predicting a patient's peak knee extensor torque imparted to the posterior knee structures during walking. (C) 1996 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation C1 SPAULDING REHABIL HOSP,BOSTON,MA. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. RP Kerrigan, DC (reprint author), HARVARD UNIV,SCH MED,DEPT PHYS MED & REHABIL,125 NASHUA ST,BOSTON,MA 02114, USA. NR 26 TC 34 Z9 35 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 1996 VL 77 IS 7 BP 645 EP 650 DI 10.1016/S0003-9993(96)90002-7 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA UY347 UT WOS:A1996UY34700003 PM 8669989 ER PT J AU Scaglioni, PP Melegari, M Wands, JR AF Scaglioni, PP Melegari, M Wands, JR TI Recent advances in the molecular biology of hepatitis B virus SO BAILLIERES CLINICAL GASTROENTEROLOGY LA English DT Article ID PROTEIN-KINASE-C; LIVER PLASMA-MEMBRANES; ARGININE-RICH DOMAIN; TATA-BINDING PROTEIN; X-GENE PRODUCT; REVERSE TRANSCRIPTION; CORE PROTEIN; DNA-SYNTHESIS; VIRAL REPLICATION; TRANSGENIC MICE C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOL HEPATOL LAB,CHARLESTOWN,MA 02129. RP Scaglioni, PP (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,MCH E,149 13TH ST,BOSTON,MA 02129, USA. OI Scaglioni, Pier Paolo/0000-0002-6036-5138 FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-08169] NR 96 TC 15 Z9 16 U1 1 U2 3 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3528 J9 BAILLIERE CLIN GASTR JI Baillieres Clin. Gastroenterol. PD JUL PY 1996 VL 10 IS 2 BP 207 EP 225 DI 10.1016/S0950-3528(96)90003-2 PG 19 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VC658 UT WOS:A1996VC65800003 PM 8864030 ER PT J AU Frueh, BC Turner, SM Beidel, DC Mirabella, RF Jones, WJ AF Frueh, BC Turner, SM Beidel, DC Mirabella, RF Jones, WJ TI Trauma management therapy: A preliminary evaluation of a multicomponent behavioral treatment for chronic combat-related PTSD SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; PSYCHOPHYSIOLOGICAL ASSESSMENT; EMOTIONAL IMAGERY; EXPOSURE THERAPY; SOCIAL PHOBIA; ANXIETY; SYMPTOMS; RESPONSES; MEMORIES AB The development and initial evaluation of a new, comprehensive and multicomponent behavioral treatment (Trauma Management Therapy, or TMT) for chronic combat-related Post-Traumatic Stress Disorder (PTSD) is described. The program utilizes elements of intensive exposure therapy, programmed practice, and structured social and emotional skills training to target the multiple aspects of chronic combat-related PTSD. The treatment was found to be effective in alleviating a broad spectrum of difficulties in combat veterans with chronic PTSD, most of whom had co-occuring Axis I and/or Axis II disorders. The results are discussed with respect to the implementation of the new treatment and the general need for a comprehensive approach to treating combat-related PTSD. Implications for the potential cost-effectiveness of the treatment program also are discussed. Copyright (C) 1996 Elsevier Science Ltd. C1 MED UNIV S CAROLINA, DEPT PSYCHIAT & BEHAV SCI, ANXIETY PREVENT & TREATMENT RES CTR, CHARLESTON, SC 29425 USA. JOHNS HOPKINS MED CTR, KENNEDY KRIEGER INST, DEPT BEHAV PSYCHOL, BALTIMORE, MD USA. MED UNIV S CAROLINA, DEPT HLTH POLICY & ADM, CHARLESTON, SC 29425 USA. RP Frueh, BC (reprint author), RALPH H JOHNSON VET AFFAIRS MED CTR, 109 BEE ST, CHARLESTON, SC 29401 USA. NR 69 TC 55 Z9 57 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD JUL PY 1996 VL 34 IS 7 BP 533 EP 543 DI 10.1016/0005-7967(96)00020-4 PG 11 WC Psychology, Clinical SC Psychology GA VE455 UT WOS:A1996VE45500003 PM 8826760 ER PT J AU Kyriakis, JM Avruch, J AF Kyriakis, JM Avruch, J TI Protein kinase cascades activated by stress and inflammatory cytokines SO BIOESSAYS LA English DT Review ID HEAT-SHOCK PROTEINS; C-JUN; MAP KINASE; SIGNAL-TRANSDUCTION; MEK KINASE; PHOSPHORYLATION; TRANSCRIPTION; DOMAIN; YEAST; RAS AB Signal transduction pathways constructed around a core module of three consecutive protein kinases, the most distal being a member of the extracellular signal-regulated kinase (ERK) family, are ubiquitous among eukaryotes. Recent work has defined two cascades activated preferentially by the inflammatory cytokines TNF-alpha and IL-1-beta, as well as by a wide variety of cellular stresses such as UV and ionizing radiation, hyperosmolarity, heat stress, oxidative stress, etc, One pathway converges on the ERK subfamily known as the 'stress activated' protein kinases (SAPKs, also termed Jun N-terminal kinases, JNKs), whereas the second pathway recruits the p38 kinases, Upstream inputs are diverse, and include small GTPases (primarily Rac and Cdc42; secondarily Ras) acting through mammalian homologs of the yeast Ste20 kinase, other kinase subfamilies (e.g. GC kinase) and ceramide, a putative second messenger for certain TNF-alpha actions. These two cascades signal cell cycle delay, cellular repair or apoptosis in most cells, as well as activation of immune and reticuloendothelial cells. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP EAST,DEPT MED,CHARLESTOWN,MA 02129. RP Kyriakis, JM (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,DIABET UNIT,CHARLESTOWN,MA 02129, USA. NR 68 TC 604 Z9 618 U1 0 U2 14 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JUL PY 1996 VL 18 IS 7 BP 567 EP 577 DI 10.1002/bies.950180708 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA UY013 UT WOS:A1996UY01300007 PM 8757935 ER PT J AU Hotamisligil, S Toner, M Powers, RD AF Hotamisligil, S Toner, M Powers, RD TI Changes in membrane integrity, cytoskeletal structure, and developmental potential of murine oocytes after vitrification in ethylene glycol SO BIOLOGY OF REPRODUCTION LA English DT Article ID UNFERTILIZED MOUSE OOCYTES; EMBRYOS; SURVIVAL; ORGANIZATION; CRYOPRESERVATION; FERTILIZATION; DIMETHYLSULFOXIDE; CRYOPROTECTANT; TOXICITY; EXPOSURE AB A systematic approach was taken to assess and optimize a protocol for intracellular vitrification by introducing high concentrations of the cryoprotectant agent (CPA) ethylene glycol (EG) into unfertilized murine oocytes. The effects of EG on membrane integrity, microfilament organization, and developmental potential were evaluated. During exposure to 0.5-2 M EG, oocytes showed maximum shrinkage to 55.5% of the isotonic volume within the first minute and reexpanded to their initial volume within 15 min. Transferral of oocytes to higher concentrations of EG (4-8 M EG) for 1-5 min after 15 min of equilibration at 2 M EC was tolerated well. Microfilament organization appeared normal after this equilibration period. During prolonged exposure (> 5 min) to high concentrations of EC (> 4 M), membrane blebs were noticed on the surface of the cells, and microfilament distribution was disturbed. After treatment with 6 M EG and vitrification with 6 M EG+0.5 M sucrose, there were no significant differences in development to the two-cell and blastocyst stages between CPA-treated, vitrified, and control oocytes. These results indicate that EC is an effective CPA for mouse oocyte vitrification protocols without any observed compromise in morphology and developmental functions. C1 BOSTON COLL,DEPT BIOL,CHESTNUT HILL,MA 02167. MASSACHUSETTS GEN HOSP,CTR ENGN MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. NR 31 TC 72 Z9 78 U1 1 U2 5 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 1996 VL 55 IS 1 BP 161 EP 168 DI 10.1095/biolreprod55.1.161 PG 8 WC Reproductive Biology SC Reproductive Biology GA VE873 UT WOS:A1996VE87300022 PM 8793071 ER PT J AU Cannon, SC AF Cannon, SC TI Slow inactivation of sodium channels: More than just a laboratory curiosity SO BIOPHYSICAL JOURNAL LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP Cannon, SC (reprint author), HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114, USA. NR 7 TC 17 Z9 17 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1996 VL 71 IS 1 BP 5 EP 7 PG 3 WC Biophysics SC Biophysics GA UV908 UT WOS:A1996UV90800004 PM 8804584 ER PT J AU Munn, LL Melder, RJ Jain, RK AF Munn, LL Melder, RJ Jain, RK TI Role of erythrocytes in leukocyte-endothelial interactions: Mathematical model and experimental validation SO BIOPHYSICAL JOURNAL LA English DT Article ID BLOOD-FLOW; CONCENTRATED SUSPENSIONS; PARTICLE MOTIONS; SMALL TUBES; CELLS; SHEAR; MIGRATION; ADHESION; ARTERIOLES; TRANSPORT AB The binding of circulating cells to the vascular wall is a central process in inflammation, metastasis, and therapeutic cell delivery. Previous in vitro studies have identified the adhesion molecules on various circulating cells and the endothelium that govern the process under static conditions. Other studies have attempted to simulate in vivo conditions by subjecting adherent cells to shear stress as they interact with the endothelial cells in vitro. These experiments are generally performed with the cells suspended in Newtonian solutions. However, in vivo conditions are more complex because of the non-Newtonian flow of blood, which is a suspension consisting of 20-40% erythrocytes by volume. The forces imparted by the erythrocytes in the flow can contribute to the process of cell adhesion. A number of experimental and theoretical studies have suggested that the rheology of blood can influence the binding of circulating leukocytes by increasing the normal and axial forces on leukocytes or the frequency of their collision with the vessel wall, but there have been no systematic investigations of these phenomena to date, The present study quantifies the contribution of red blood cells (RBCs) in cell capture and adhesion to endothelial monolayers using a combination of mathematical modeling and in vitro studies. Mathematical modeling of the flow experiments suggested a physical mechanism involving REC-induced leukocyte dispersion and/or increased normal adhesive contact. Flow chamber studies performed with and without RBCs in the suspending medium showed increases in wall collision and binding frequencies, and a decrease in rolling velocity in the presence of erythrocytes. Increased fluid viscosity alone did not influence the binding frequency,and the differences could not be attributed to large near-wall excesses of the lymphocytes. The results indicate that RBCs aid in the transport and initial engagement of lymphocytes to the vascular wall, modifying the existing paradigm for immune cell surveillance of the vascular endothelium by adding the erythrocyte as an essential contributor to this process. C1 HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114. RP Munn, LL (reprint author), MASSACHUSETTS GEN HOSP,COX 7,FRUIT ST,BOSTON,MA 02114, USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R35-CA-56591, F32 CA-61631] NR 41 TC 93 Z9 95 U1 2 U2 6 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1996 VL 71 IS 1 BP 466 EP 478 PG 13 WC Biophysics SC Biophysics GA UV908 UT WOS:A1996UV90800049 PM 8804629 ER PT J AU Cardoso, AA Schultze, JL Boussiotis, VA Freeman, GJ Seamon, MJ Laszlo, S Billet, A Sallan, SE Gribben, JG Nadler, LM AF Cardoso, AA Schultze, JL Boussiotis, VA Freeman, GJ Seamon, MJ Laszlo, S Billet, A Sallan, SE Gribben, JG Nadler, LM TI Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen SO BLOOD LA English DT Article ID LIMITING DILUTION ANALYSIS; CLONAL ANERGY; LYMPHOCYTES-T; IMMUNE DEVIATION; COSTIMULATION; CD28; INTERLEUKIN-2; CTLA-4; B7/BB1; PROLIFERATION AB Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity, These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC, Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy, In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T-cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance. (C) 1996 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED & PEDIAT,BOSTON,MA. RP Cardoso, AA (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,D-740,44 BINNEY ST,BOSTON,MA 02115, USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [CA68484, CA66996]; NIAID NIH HHS [AI35225] NR 47 TC 143 Z9 148 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1996 VL 88 IS 1 BP 41 EP 48 PG 8 WC Hematology SC Hematology GA UV297 UT WOS:A1996UV29700003 PM 8704200 ER PT J AU Champseix, C Marechal, V Khazaal, I Schwartz, O Fournier, S Schlegel, N Dranoff, G Danos, O Blot, P Vilmer, E Heard, JM Peault, B Lehn, P AF Champseix, C Marechal, V Khazaal, I Schwartz, O Fournier, S Schlegel, N Dranoff, G Danos, O Blot, P Vilmer, E Heard, JM Peault, B Lehn, P TI A cell surface marker gene transferred with a retroviral vector into CD34(+) cord blood cells is expressed by their T-cell progeny in the SCID-hu thymus SO BLOOD LA English DT Article ID TRANSPLANTATION; RECONSTITUTION; PATIENT; MOUSE AB Gene transduction into immature hematopoietic cells collected at birth from the umbilical cord could be useful for the treatment of genetic or acquired disorders of the hematopoietic system diagnosed during pregnancy, The SCID-hu mouse is a convenient model to investigate T-cell lineage gene therapy, since it allows replication of human intrathymic T-cell development. CD34(+) cells isolated from cord blood were cocultured with GRIP MFG-murine CD2 (mCD2) cells that produce recombinant retroviruses encoding the mCD2 antigen, a cell surface marker easily detectable by flow cytometry. After 3 and 4 days in coculture, a mean of 19% and 39% human hematopoietic cells, respectively, expressed the mCD2 antigen. CD34(+) cells cocultured for 4 days were used to reconstitute human fetal thymus implanted in SCID mice. Five to 10 weeks later, the mCD2 antigen was detected on approximately 10% of human thymocytes repopulating the thymic grafts in four of nine SCID mouse chimeras. Vector genomes were detected in graft cell DNA by Southern blot. Analysis of vector integration indicated that positive cells were of polyclonal origin in three animals and predominantly monoclonal in the other one. Our data show that foreign genes can he transduced into CD34(+) cord blood cells endowed with T-cell differentiation potential, and suggest strategies for T-cell lineage gene therapy in the neonate. (C) 1996 by The American Society of Hematology. C1 CNRS,INST EMBRYOL CELLULAIRE & MOLEC,F-94736 NOGENT SUR MARNE,FRANCE. COLL FRANCE,CNRS UMR 9924,NOGENT SUR MARNE,FRANCE. INST PASTEUR,LAB RETROVIRUS & TRANSFERT GENET,CNRS URA 1157,PARIS,FRANCE. HOP ROBERT DEBRE,SERV HEMATOL CLIN,INSERM U120,F-75019 PARIS,FRANCE. HOP ROBERT DEBRE,SERV BIOL & MATERN,INSERM U120,F-75019 PARIS,FRANCE. DANA FARBER CANC INST,BOSTON,MA 02115. NR 25 TC 27 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1996 VL 88 IS 1 BP 107 EP 113 PG 7 WC Hematology SC Hematology GA UV297 UT WOS:A1996UV29700011 PM 8704164 ER PT J AU Diacovo, TG Roth, SJ Buccola, JM Bainton, DF Springer, TA AF Diacovo, TG Roth, SJ Buccola, JM Bainton, DF Springer, TA TI Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta(2)-integrin CD11b/CD18 SO BLOOD LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; TRANSENDOTHELIAL MIGRATION; COUNTER-RECEPTOR; MONOCLONAL-ANTIBODIES; LEUKOCYTE FUNCTION; LFA-1; MAC-1; DEFICIENCY; RECOGNITION; ENDOTHELIUM AB Platelets bound to thrombogenic surfaces have been shown to support activation-dependent firm adhesion of neutrophils in flow following selectin-mediated tethering and rolling, The specific receptor(s) responsible for mediating adhesion-strengthening interactions between neutrophils and platelets has not previously been identified. Furthermore, the ability of adherent platelets to support the migration of bound neutrophils has not been tested. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte binding in vascular shear flow and emigration at thrombogenic sites. Our results demonstrate that the beta(2)-integrin Mac-1 (CD11b/CD18) is required for both firm attachment to and transmigration of neutrophils across surface-adherent platelets. In flow assays, neutrophils from patients with leukocyte adhesion deficiency-1 (LAD-I), which lack beta(2)-integrin receptors, formed P-selectin-mediated rolling interactions, but were unable to develop firm adhesion to activated platelets, in contrast to healthy neutrophils, which developed firm adhesion within 5 to 30 seconds after initiation of rolling. Furthermore, the adhesion-strengthening interaction observed for healthy neutrophils could be specifically inhibited by monoclonal antibodies (mAbs) to Mac-1, but not to lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) or intercellular adhesion molecule-2 (ICAM-2; CD102). Further evidence for a beta(2)-integrin-dependent neutrophil/platelet interaction is demonstrated by the complete inhibition of interleukin (IL)-8-induced neutrophil transmigration across platelets bound to fibronectin-coated polycarbonate filters by mAbs to Mac-1. Thus, Mac-1 is required for firm adhesion of neutrophils to activated, adherent platelets and may play an important role in promoting neutrophil accumulation on and migration across platelets deposited at sites of vascular injury. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,DIV NEWBORN MED,CTR BLOOD RES,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CARDIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA. FU NCI NIH HHS [CA 31799] NR 60 TC 373 Z9 380 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1996 VL 88 IS 1 BP 146 EP 157 PG 12 WC Hematology SC Hematology GA UV297 UT WOS:A1996UV29700016 PM 8704169 ER PT J AU Zukerberg, LR Benedict, WF Arnold, A Dyson, N Harlow, E Harris, NL AF Zukerberg, LR Benedict, WF Arnold, A Dyson, N Harlow, E Harris, NL TI Expression of the retinoblastoma protein in low-grade B-cell lymphoma: Relationship to cyclin D1 SO BLOOD LA English DT Article ID GENE-PRODUCT; TRANSCRIPTION FACTOR; SUSCEPTIBILITY GENE; BINDING PROTEIN; ADENOVIRUS E1A; RB PROTEIN; PHOSPHORYLATION; PROGRESSION; E2F; TRANSITION AB The product of the retinoblastoma tumor-suppressor gene (pRB), a nuclear phosphoprotein that regulates transcription factors such as E2F, is involved in cell cycle control and differentiation. Its activity is regulated by phosphorylation; the underphosphorylated form inhibits transcription whereas the highly phosphorylated form is inactive. Cyclin D1 and its associated kinase (CDK 4/6) phosphorylate pRB in vitro, and therefore are thought to contribute to the regulation of pRB function. To examine the effect of cyclin D1 overexpression on pRB in primary tumor tissue, we studied pRB expression in low-grade B-cell neoplasms, with particular regard to mantle cell lymphoma, which is characterized by cyclin D1 (bcl-1) overexpression. pRB expression was studied by immunostaining with a well-characterized anti-pRB antibody; the phosphorylation status of pRB was examined by immunoblots; and the functional binding capacity of pRB was examined by in vitro binding to adenovirus E1A protein. We studied 3 reactive lymph nodes, 28 low grade B-cell lymphomas, 4 cases of hairy cell leukemia (HCL) and 3 plasmacytomas. Reactive lymph nodes showed intense pRB staining of germinal centers, with strongest (2+) staining in the large cells (centroblasts) of the proliferating (dark) zone and weak or no staining of small lymphocytes, including those of the mantle zone. In B-chronic lymphocytic leukemia (B-CLL) (4 cases), follicular lymphoma (3 cases) and mucosa-associated (MALT) lymphoma (3 cases) strong (2+) pRB staining was limited to centroblasts in reactive and neoplastic follicles and occasional proliferation centers, with only faint staining of small lymphoid cells. In contrast, 15 of 16 cases of mantle cell lymphoma showed strong (1-2+) staining of most cells; one blastoid mantle cell lymphoma showed only faint pRB staining. All cases of (HCL) and plasmacytoma showed strong pRB staining. Although most lymphomas with strong PRE expression were cyclin D1(+), three cyclin D1(+) cases showed only weak pRB expression (1 B-CLL, 1 blastoid mantle cell, 1 unclassifiable low grade B-cell lymphoma). Conversely, of the 4 pRB(+) HCLs and 3 pRB(+) plasmacytomas, only 1 of each was cyclin D1(+). pRB appeared to exist primarily in the underphosphorylated (fastest migrating) form on Western blot, despite the fact that cyclin D1 was complexed to CDK4, a form in which it normally phosphorylates pRB. In addition, pRB appeared to be unmutated, because it bound normally to the adenovirus E1A protein and showed nuclear localization by immunostaining. We conclude that most cases of mantle cell lymphoma, HCL, and plasmacytoma show high levels of pRB in contrast to follicle center lymphoma and small lymphocytic lymphoma; however, pRB expression does not appear to be consistently related to cyclin D1 overexpression. The pRB appears to be unmutated and underphosphorylated, and therefore should be in its active form. Our data from primary lymphoma tissue suggests that overexpression of cyclin D1, whereas tumorigenic, does not lead to pRB loss or hyperphosporylation. Thus, the mechanism by which cyclin D1 contributes to tumorigenesis and the significance of the restricted expression of pRB in low-grade lymphoid neoplasms remain to be determined. (C) 1996 by The American Society of Hematology. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,ENDOCRINE ONCOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BAYLOR COLL MED,CTR BIOTECHNOL,THE WOODLANDS,TX 77381. FU NCI NIH HHS [CA55909, CA54672] NR 53 TC 48 Z9 49 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1996 VL 88 IS 1 BP 268 EP 276 PG 9 WC Hematology SC Hematology GA UV297 UT WOS:A1996UV29700030 PM 8704183 ER PT J AU Giannobile, WV AF Giannobile, WV TI Periodontal tissue engineering by growth factors SO BONE LA English DT Article; Proceedings Paper CT Portland Bone Symposium CY AUG 02-05, 1995 CL PORTLAND, OR ID BONE MORPHOGENETIC PROTEIN; LIGAMENT FIBROBLASTIC CELLS; RECEPTOR MESSENGER-RNAS; SKIN EPITHELIAL-CELLS; FREEZE-DRIED BONE; FACTOR-BETA; FACTOR-I; GINGIVAL FIBROBLASTS; CRANIOTOMY DEFECTS; REPARATIVE DENTIN AB Polypeptide growth factors (GFs) have been shown to modulate the wound healing response in both hard and soft tissues. During the past decade, many investigators have demonstrated the anabolic effects of these wound healing molecules on the promotion of periodontal attachment structures, namely alveolar bone, periodontal ligament and tooth root cementum. The molecular cloning and large scale purification of GFs has allowed expanded in vivo studies on periodontal tissue regeneration. This review will outline specific effects of these factors at both the in vitro and in vivo level on the promotion of periodontal and peri-implant bone wound healing, This paper will conclude with a future perspective of ongoing studies in the human clinical trial arena using growth and osteoinductive factors to promote periodontal tissue regeneration and alveolar bone repair in the oral cavity. C1 HARVARD UNIV,SCH DENT MED,DEPT PERIODONTOL,BOSTON,MA 02115. RP Giannobile, WV (reprint author), DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,188 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [K16 DE 00275] NR 117 TC 73 Z9 78 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD JUL PY 1996 VL 19 IS 1 SU S BP S23 EP S37 DI 10.1016/S8756-3282(96)00127-5 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UW664 UT WOS:A1996UW66400003 PM 8830996 ER PT J AU McPherson, SE Cummings, JL AF McPherson, SE Cummings, JL TI Neuropsychological aspects of vascular dementia SO BRAIN AND COGNITION LA English DT Article; Proceedings Paper CT Annual Conference on the Dementias - Diagnosis and Implications for Management CY MAR, 1994 CL TORONTO, CANADA SP Baycrest Ctr Geriatr Care, Rotman Res Inst, Univ Calif Los Angeles, Alzheimers Res Ctr ID SUBCORTICAL ARTERIOSCLEROTIC ENCEPHALOPATHY; PARAMEDIAN THALAMIC INFARCTION; WHITE MATTER LUCENCIES; SCAN LEUKO-ARAIOSIS; ALZHEIMERS-DISEASE; BINSWANGERS DISEASE; NEUROLOGIC FINDINGS; CLINICAL-FEATURES; LANGUAGE; IMPAIRMENT AB Vascular dementia (VaD) is the second most common cause of dementia in the elderly. Neuropsychologically, VaD has been characterized traditionally as having a ''patchy'' pattern of cognitive deficits. Newly developed diagnostic criteria for VaD suggest that this ''patchy'' pattern is associated with one type of VaD - multiple cortical infarctions, and that several additional subtypes of VaD exist, each featuring a characteristic pattern of neuropsychological deficits. Strategic infarct de mentias have unique features that reflect the specific brain region affected. Lacunar state and Binswanger's disease produce subcortical dementia with disproportionate executive dysfunction. The profile of neuropsychological disturbances observed in VaD patients provides important insight into the localization and pathophysiology of the underlying cerebrovascular disease. (C) 1996 Academic Press, Inc. C1 UNIV CALIF LOS ANGELES,ALZHEIMERS DIS CTR,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,BEHAV NEUROSCI SECT,PSYCHIAT SERV,LOS ANGELES,CA. FU NIA NIH HHS [AG10123] NR 60 TC 33 Z9 33 U1 2 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD JUL PY 1996 VL 31 IS 2 BP 269 EP 282 DI 10.1006/brcg.1996.0045 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA UX223 UT WOS:A1996UX22300011 PM 8812007 ER PT J AU Louis, DN AF Louis, DN TI Clinicopatho-genetic subsets of glioblastoma multiforme: From both sides now SO BRAIN PATHOLOGY LA English DT Editorial Material ID ASTROCYTIC TUMORS; PATHWAYS; GLIOMAS C1 MASSACHUSETTS GEN HOSP,CS KUBIK LAB NEUROPATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Louis, DN (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02114, USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI ZURICH PA ISN JOURNAL PO BOX, CH-8033 ZURICH, SWITZERLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 1996 VL 6 IS 3 BP 223 EP 224 DI 10.1111/j.1750-3639.1996.tb00849.x PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UY659 UT WOS:A1996UY65900005 ER PT J AU Bigatello, LM Zapol, WM AF Bigatello, LM Zapol, WM TI New approaches to acute lung injury SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE lung, damage; complications, acute respiratory distress syndrome; complications, barotrauma; pharmacology, nitric oxide; airway, pressure ID RESPIRATORY-DISTRESS-SYNDROME; INHALED NITRIC-OXIDE; CRITICALLY ILL PATIENTS; MECHANICAL VENTILATION; OXYGEN DELIVERY; PULMONARY HEMODYNAMICS; AIRWAY PRESSURES; CLINICAL-TRIAL; FAILURE; ARDS C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Bigatello, LM (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02114, USA. NR 62 TC 31 Z9 32 U1 0 U2 0 PU PROF SCI PUBL PI LONDON PA TAVISTOCK HOUSE EAST, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUL PY 1996 VL 77 IS 1 BP 99 EP 109 PG 11 WC Anesthesiology SC Anesthesiology GA UW581 UT WOS:A1996UW58100011 PM 8703635 ER PT J AU Kaelin, WG AF Kaelin, WG TI Tumor suppressor proteins as leading compounds for drug discovery SO BRITISH JOURNAL OF CANCER LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1996 VL 74 SU 28 BP SP21 EP SP21 PG 1 WC Oncology SC Oncology GA UX776 UT WOS:A1996UX77600014 ER PT J AU Hallek, M DanhauserRiedl, S Herbst, R Warmuth, M Winkler, A Kolb, HJ Druker, B Griffin, JD Emmerich, B Ullrich, A AF Hallek, M DanhauserRiedl, S Herbst, R Warmuth, M Winkler, A Kolb, HJ Druker, B Griffin, JD Emmerich, B Ullrich, A TI Interaction of the receptor tyrosine kinase p145(c-kit) with the p210(bcr/abl) kinase in myeloid cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE bcr/abl; c-kit; oncogene; chronic myeloid leukaemia; pathogenesis ID COLONY-STIMULATING FACTOR; ACUTE MYELOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; C-KIT LIGAND; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; BCR-ABL; PHILADELPHIA-CHROMOSOME; FUNCTIONAL EXPRESSION; PROGENITOR CELLS AB The chimaeric bcr/abl oncogene is detected in virtually all cases of chronic myelogenous leukaemia (CML). It encodes a constitutively active tyrosine kinase of 210 kDalton, p210(bcr/abl), which stimulates a variety of cytosolic signalling intermediates, The effects of (bcr/abl) on the activity of growth factor receptors are less well known. In order to investigate interaction of p210(bcr/abl) with the receptor tyrosine kinase p145(c-kit), we used two myeloid, factor-dependent cell lines, MO7 and 32D, to generate bcr/abl positive sublines, MO7p210 and 32Dp210, by transfection with the bcr/abl gene, Since 32D and 32Dp210 cells did not express p145(c-kit), a c-kit retrovirus was used to generate c-kit positive cell lines (32Dkit, 32Dp210kit). In contrast to MO7 and 32Dkit cells, MO7p210 and 32Dp210kit cells were factor independent and did not respond to the growth-promoting effects of recombinant human Steel factor (rhSF), Preincubation with a monoclonal antibody (MAb) neutralizing the binding of SP to p145(c-kit) did not affect the growth of MO7p210 cells, thus eliminating the possibility of an autocrine SF secretion. 32Dkit cells transfected with bcr/abl containing an inactivating point mutation (Iys-->Arg271) in the Abl kinase domain (32Dp210(Arg271)kit) retained their responsiveness to the effects of rhSF, Immune complex kinase assays showed that the kinase activity of p145(c-kit) was several-fold higher in MO7p210 and 32Dp210kit cells than in MO7, 32Dkit and 32Dp210(Arg271)kit cells, suggesting that Abl kinase activity was necessary to activate p145(c-kit). Co-immunoprecipitation experiments with anti-Kit and anti-Abl MAbs demonstrated that p145(c-kit) and p210(bcr/abl) were associated in an intracellular complex in human bcr/abl positive, c-kit positive cell lines (MO7p210; GM/SO). Finally, colony assays with bone marrow from bcr/abl positive CML patients showed that the haemopoietic progenitors of three of four patients did not respond to rhSF. Taken together, the results suggest that p145(c-kit) can be activated by p210(bcr/abl) via an Abl-kinase dependent mechanism involving the complex formation of both proteins, These findings could explain some clinical features (basophilia, increase of immature myeloid cells) of chronic-phase CML. C1 MAX PLANCK INST BIOCHEM, D-82152 MARTINSRIED, GERMANY. UNIV MUNICH, KLINIKUM GROSSHADERN, MED KLIN 3, D-8000 MUNICH, GERMANY. OREGON HLTH SCI UNIV, PORTLAND, OR 97201 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. RP Hallek, M (reprint author), UNIV MUNICH, KLINIKUM INNENSTADT, MED KLIN, ZIEMSSENSTR 1, D-80336 MUNICH, GERMANY. NR 52 TC 38 Z9 38 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1996 VL 94 IS 1 BP 5 EP 16 DI 10.1046/j.1365-2141.1996.6102053.x PG 12 WC Hematology SC Hematology GA UX112 UT WOS:A1996UX11200002 PM 8757502 ER PT J AU Dedera, DA Urashima, M Chauhan, D LeBrun, DP Bronson, RT Anderson, KC AF Dedera, DA Urashima, M Chauhan, D LeBrun, DP Bronson, RT Anderson, KC TI Interleukin-6 is required for pristane-induced plasma cell hyperplasia in mice SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE interleukin-6; pristane; plasmacytosis; plasmacytoma; interleukin-6 knockout mice ID TUMOR-NECROSIS-FACTOR; HUMAN B-CELLS; TRANSGENIC MICE; C-MYC; MONOCLONAL-ANTIBODY; GENE-EXPRESSION; MESSENGER-RNAS; LYMPHOCYTE-B; CD40 LIGAND; INDUCTION AB Intraperitoneal injection of pristane induces production of interleukin-6 (IL-6) and either plasmacytosis or plasmacytoma in mice, depending upon the genetic background Pristane does not induce plasmacytoma in IL-6 knockout (IL-6-/-) mice, suggesting that IL-6 is required for this process. In the present study we determined whether IL-6 is also required for pristane-induced hyperplasia of normal plasma cells. Pristane was injected intraperitoneally into IL-6-/- and IL-6 wild-type (IL-6+/+) mice. Overall there were more deaths in IL-6+/+ mice (85%) than in IL-6-/- mice (40%), P = 0.024, Hyperplastic lymph node and spleen weight did not differ (P = 0.82 and P = 0.15, respectively) in IL-6-/- versus IL-6+/+ mice. Lymphocytosis with similar patterns of expression of B-cell (B220) and T-cell (Thy-1) antigens was noted in both IL-6-/- and IL-6+/+ mice. However, morphological studies, dual fluorescent staining for Syn-1 and B220 antigens (syn-1(+) B220(+) cells), and intracytoplasmic Ig staining revealed plasma cell hyperplasia in lymph node and spleen from IL-6+/+, but not IL-6-/-, mice. These plasma cells from IL-6+/+ mice were polyclonal and unable to induce tumour formation in severe combined immunodeficient mice. These data demonstrate that IL-6 is required for pristane-induced hyperplasia of polyclonal plasma cells in mice. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON,CANADA. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. FU NCI NIH HHS [CA 50947] NR 47 TC 17 Z9 18 U1 1 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 1996 VL 94 IS 1 BP 53 EP 61 DI 10.1046/j.1365-2141.1996.6282074.x PG 9 WC Hematology SC Hematology GA UX112 UT WOS:A1996UX11200008 PM 8757508 ER PT J AU Dion, LD Goldsmith, KT Garver, RI AF Dion, LD Goldsmith, KT Garver, RI TI Quantitative and in vivo activity of adenoviral-producing cells made by cotransduction of a replication-defective adenovirus and a replication-enabling plasmid SO CANCER GENE THERAPY LA English DT Article DE neoplasms; genetic vectors; adenoviridae; adenovirus E1 proteins ID BRAIN-TUMORS; GENE; SEQUENCES; THERAPY; GLIOMA; MODEL AB Achieving limited recombinant viral replication may provide a means of amplifying viral-mediated gene transfer in vivo. We have previously shown that cotransduction of an El-defective adenovirus with a plasmid containing the deleted El functions into prostate carcinoma cells resulted in El-defective virus production by those cells. The studies described here have extended these findings to more firmly establish the capacity of the trans complementation approach to achieve amplification of recombinant viral transgene expression. The recombinant virus used for all the studies was AdCMV-luc which contained a luciferase expression cassette; the replication-enabling plasmid, pE1, encoded the El functions deleted from AdCMV-luc. Quantitative in vitro studies with the HeLa cell line showed that for each plaque forming unit of AdCMV-luc originally exposed to the cells, 0.54 x 10(3) new replication-defective viruses were detected in supernatants and lysates over the following 3 days. Multiple cell lines were shown to support new virus production following cotransduction of AdCMV-luc and pE1. Small numbers of replication-competent viruses were detected in the lysates and supernatants from the cotransduced cells such that for every 10(5) replication-defective viruses approximately two replication-competent viruses were produced. Tumor nodules produced by engrafting a mixture of AdCMV-luc/pE1-cotransduced HeLa cells with uninfected HeLa cells yielded much higher levels of luciferase expression than control rumors containing mixtures of cells infected with AdCMV-luc alone. In total, these results demonstrate new virus production by cells receiving a replication-defective adenovirus and a replication-enabling plasmid are capable of amplifying recombinant viral transgene expression in vivo. C1 UNIV ALABAMA,SCH MED,DIV PULM & CRIT CARE MED,BIRMINGHAM,AL 35294. BIRMINGHAM VAMC,BIRMINGHAM,AL. NR 11 TC 16 Z9 16 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JUL-AUG PY 1996 VL 3 IS 4 BP 230 EP 237 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA VA441 UT WOS:A1996VA44100002 PM 8853547 ER PT J AU Hirschi, KK Xu, CE Tsukamoto, T Sager, R AF Hirschi, KK Xu, CE Tsukamoto, T Sager, R TI Gap junction genes Cx26 and Cx43 individually suppress the cancer phenotype of human mammary carcinoma cells and restore differentiation potential SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID C6 GLIOMA-CELLS; EPITHELIAL-CELLS; CONNEXIN43 CDNA; GROWTH; COMMUNICATION; EXPRESSION; PROTEINS; CHANNEL; PHOSPHORYLATION; TRANSFECTION AB Normal human mammary epithelial cells express hCx43 and hCx26 proteins, which form functional gap junction channels. Both Cx genes are transcriptionally downregulated in mammary carcinoma cell lines; consequently, no protein is made and gap junctions are absent, This result suggests that the loss of gap junctional communication may play an important role in carcinogenesis, To address this question, two sets of stable transfectants were produced in a recloned line of human mammary carcinoma cells (MDA-MB-435), One set expressed hCx26, and the other expressed hCx43. Studies of transfectants that contain functional gap junctions showed that they grew more slowly in culture than controls, and that their tumor-forming ability was strongly suppressed, In studies designed to examine their differentiation capacity, these transfectants were found to have regained the capacity to form three-dimensional structures in a matrigel matrix, This property is characteristic of normal mammary epithelial cells, but it is lost in the parental tumor cells and neo-transfectant controls. Thus, junctional communication is shown here to play a decisive role in the morphogenesis of mammary gland structures. The hCx26 and hCx43 genes behave as classical tumor suppressor genes both in culture and in animal tests in restoring growth regulatory properties to metastatic mammary carcinoma cells, Expression of these genes further induces the ability to differentiate as shown by the formation of three-dimensional structures when transfected cells are embedded in a matrigel matrix. These findings suggest that the reexpression of gap junctions may play a vital role in normalizing tumor cell behavior. C1 DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. FU NCI NIH HHS [CA57517] NR 45 TC 222 Z9 234 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUL PY 1996 VL 7 IS 7 BP 861 EP 870 PG 10 WC Cell Biology SC Cell Biology GA UV513 UT WOS:A1996UV51300002 PM 8809403 ER PT J AU Alpan, RS Pardee, AB AF Alpan, RS Pardee, AB TI p21 (WAF1/CIP1/SDI1) is elevated through a p53-independent pathway by mimosine SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID CELL-CYCLE; P53; DNA; PROTEIN; HYDROXYUREA; INITIATION; PHASE; GENE AB Tumor suppressor p53 is a nuclear protein that is induced by DNA damage and is involved in G(1) and G(2) phase control of the cell cycle. p21(WAF1/CIP1/SDI1) (p21), a cyclin-dependent kinase inhibitor, is a downstream target and effector of p53 to induce G(1) arrest. Mimosine is a potent reversible late G(1) phase blocker of the cell cycle. In this study, we showed that mimosine can increase both p21 mRNA and protein levels, indirectly inhibit cyclin E-associated kinase activity without affecting the cyclin E protein level, block human breast cancer cells (21PT) in the late G(1) phase of the cell cycle, and induce a p53-independent pal pathway in these cells, These results support the possibility of restoring a G(1) checkpoint by use of mimosine. They also suggest that the mechanism of the effect of mimosine is complex and may have more than one target in the cell. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIGMS NIH HHS [5-R01 GM24571-15] NR 61 TC 71 Z9 71 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUL PY 1996 VL 7 IS 7 BP 893 EP 901 PG 9 WC Cell Biology SC Cell Biology GA UV513 UT WOS:A1996UV51300006 PM 8809407 ER PT J AU Vatner, DE Sato, N Galper, JB Vatner, SF AF Vatner, DE Sato, N Galper, JB Vatner, SF TI Physiological and biochemical evidence for coordinate increases in muscarinic receptors and G(i) during pacing-induced heart failure SO CIRCULATION LA English DT Article DE receptors; proteins; heart failure; nervous system, autonomic; signal transduction ID HUMAN VENTRICULAR MYOCARDIUM; FAILING HUMAN-HEART; ADENYLATE-CYCLASE; CONSCIOUS DOGS; G-PROTEIN; DILATED CARDIOMYOPATHY; REGULATORY PROTEIN; DOWN-REGULATION; ALPHA; INHIBITION AB Background It is not clear whether the increase in the myocardial guanylyl nucleotide inhibitory protein (G(i)), frequently observed in heart failure, is associated with any functional effects. Methods and Results Eight sham-operated dogs and 10 dogs were studied with pacing-induced heart failure (240 bpm for 4 to 7 weeks), characterized by reduced (P < .05) left ventricular dP/dt (from 2926 +/- 99 to 1303 +/- 126 mm Hg/s). The muscarinic agonist acetylcholine (10 mu g/kg IV) in the presence of ganglionic blockage reduced left ventricular dP/dt more (P < .05) in heart failure (-23 +/- 2%) than before heart failure (-8 +/- 2%), despite lesser reductions in arterial pressure. G(i alpha 2) was increased by 55% in heart failure. Dose-response curves for carbachol (10(-8) to 10(-3) mol/L) inhibition of isoproterenol-stimulated adenylyl cyclase demonstrated Significantly greater (P < .05) inhibition in heart failure compared with sham-operated dogs. These changes were associated with a coordinate increase in muscarinic receptor density, determined by antagonist binding with H-3-quinuclidinyl benzilate, in heart failure (153 +/- 6.2 fmol/mg protein) compared with sham-operated dogs (124 +/- 7.4 fmol/mg protein). Agonist binding with carbachol also revealed an increase in total muscarinic receptors in heart failure without a change in fraction of high- and low-affinity receptors. Conclusions These data, in the aggregate, provide physiological and biochemical evidence to support the concept that the coordinate increases in muscarinic receptor number and G(i) levels in heart failure are coupled to increased inhibition of adenylyl cyclase activity and an increased inhibition of myocardial contractility. C1 NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-45332, HL-38070, HL-37404] NR 43 TC 36 Z9 38 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 1 PY 1996 VL 94 IS 1 BP 102 EP 107 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UU208 UT WOS:A1996UU20800016 PM 8964109 ER PT J AU Slater, GJ Saini, S MayoSmith, WW Sharma, P Eisenberg, PJ HaHn, PF AF Slater, GJ Saini, S MayoSmith, WW Sharma, P Eisenberg, PJ HaHn, PF TI Mn-DPDP enhanced MR imaging of the liver: Analysis of pulse sequence performance SO CLINICAL RADIOLOGY LA English DT Article ID CONTRAST AB Aim: To compare liver enhancement and lesion-liver contrast on T1-weighted (T1W) gradient recalled echo (GRE), spin-echo (SE) and fat-suppressed SE (FS-SE) pulse sequences at Manganese-DPDP (Mn-DPDP) enhanced magnetic resonance (MR) imaging of the liver. Patients and Methods: Twenty-one patients with known liver lesions were administered 5 mu mol/kg of Mn-DPDP. TIW GRE (78/2.3/80 degrees), SE and F-SE (300/12) images were obtained before and 15 min after Mn-DPDP. Signal/noise ratio (SNR) and lesion-liver contrast/noise ratio (CNR) were calculated for each pulse sequence. Results: Liver SNR (n = 21) and lesion-liver CNR (n = 10) increased significantly after Mn-DPDP on all three pulse sequences (P < 0.0001). Liver SNR was highest on the FS-SE and GRE pulse sequences (FS-SE = 43.8, GRE = 38.4, SE = 29.2). Lesion-liver CNR was highest on the FS-SE pulse sequence (FS-SE = -29.3, SE = -23.2, GRE- -19.8), which was significantly higher than the GRE pulse sequence (P < 0.05). Conclusion: The T1-weighted fat-suppressed SE (FS-SE) pulse sequence provides highest liver enhancement and lesion-liver contrast and is recommended for Mn-DPDP enhanced NBR imaging. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 8 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD JUL PY 1996 VL 51 IS 7 BP 484 EP 486 DI 10.1016/S0009-9260(96)80187-5 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UX116 UT WOS:A1996UX11600005 PM 8689823 ER PT J AU Krosnick, A AF Krosnick, A TI Editorial comment SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP Krosnick, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD JUL-AUG PY 1996 VL 18 IS 4 BP 561 EP 561 DI 10.1016/S0149-2918(96)80206-2 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VG941 UT WOS:A1996VG94100001 ER PT J AU Krosnick, A AF Krosnick, A TI Comparative efficacy of oral and intravenous granisetron for the prevention of acute chemotherapy-induced emesis - Editorial comment SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP Krosnick, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD JUL-AUG PY 1996 VL 18 IS 4 BP 577 EP 577 DI 10.1016/S0149-2918(96)80208-6 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VG941 UT WOS:A1996VG94100003 ER PT J AU Krosnick, A AF Krosnick, A TI Changing antipsychotic medication: Guidelines on the transition to treatment with risperidone - Editorial comment SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP Krosnick, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD JUL-AUG PY 1996 VL 18 IS 4 BP 591 EP 591 DI 10.1016/S0149-2918(96)80210-4 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VG941 UT WOS:A1996VG94100005 ER PT J AU Christenson, G OSullivan, R AF Christenson, G OSullivan, R TI Trichotillomania - Rational treatment options SO CNS DRUGS LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; CLINICAL CHARACTERISTICS; BEHAVIORAL TREATMENT; ACRAL LICK; CLOMIPRAMINE; FLUOXETINE; AUGMENTATION; FENFLURAMINE; DEPRESSION; THERAPY AB Trichotillomania is a psychiatric condition characterised by chronic hair pulling, which is often associated with considerable comorbidity. Typically striking during critical developmental periods in childhood or early adolescence, the disorder tends to follow a chronic course. Trichotillomania is currently classified in DSM-IV as an impulse control disorder. However, phenomenological observations, neurobiological investigations and pharmacological responsivity have suggested similarities between hair pulling and affective states, compulsions, ties, and displacement activities involving excessive grooming. These findings indicate that the classification and theories of the aetiology of trichotillomania may need to be reconsidered. Few pharmacological treatment studies have been conducted for trichotillomania, and among those that have been published several discrepant results have been noted. Nonetheless, certain clinical guidelines can be offered. The usual recommended pharmacological approach is to initiate treatment with an antidepressant that has serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibiting properties, This should be administered for 8 to 12 weeks. Depending on the clinical context, augmentation with anxiolytics, thymoleptics, antipsychotics, topical corticosteroids and other agents may be useful. Behavioural treatment is also an important treatment approach and should be considered either as the initial intervention or in concert with medication. Although rational options for the treatment of trichotillomania can be recommended based on the currently available literature, further controlled studies of pharmacological and nonpharmacological interventions are clearly needed. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP EAST,TRICHOTILLOMANIA CLIN,PSYCHIAT NEUROSCI PROGRAM,CHARLESTOWN,MA. RP Christenson, G (reprint author), UNIV MINNESOTA,BOYNTON HLTH CTR,DEPT PSYCHIAT,410 CHURCH ST SE,MINNEAPOLIS,MN 55455, USA. NR 84 TC 15 Z9 15 U1 1 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PD JUL PY 1996 VL 6 IS 1 BP 23 EP 34 PG 12 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UY669 UT WOS:A1996UY66900003 ER PT J AU Tronni, C Welebob, E AF Tronni, C Welebob, E TI End-user satisfaction of a patient education tool manual versus computer-generated tool SO COMPUTERS IN NURSING LA English DT Article DE user-computer interface; computer systems; nursing evaluation research; software; patient education AB This article reports a nonexperimental comparative study of end-user satisfaction before and after implementation of a vendor supplied computerized system (Micromedex, Inc.) for providing up-to-date patient instructions regarding diseases, injuries, procedures, and medications. The purpose of this research was to measure the satisfaction of nurses who directly interact with a specific patient educational software application and to compare user satisfaction with manual versus computer generated materials. A computing satisfaction questionnaire that uses a scale of 1 to 5 (1 being the lowest) was used to measure end-user computing satisfaction in five constructs: content, accuracy, format, ease of use, and timeliness. Summary statistics were used to calculate mean ratings for each of the questionnaire's 12 items and for each of the five constructs. Mean differences between the ratings before and after implementation of the five constructs were significantly paired t test. Total user satisfaction improved with the computerized system, and the computer generated materials were given a higher rating than were the manual materials. Implications of these findings are discussed. RP Tronni, C (reprint author), MASSACHUSETTS GEN HOSP,WHITE 122,55 FRUIT ST,BOSTON,MA 02114, USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0736-8593 J9 COMPUT NURS JI Comput. Nurs. PD JUL-AUG PY 1996 VL 14 IS 4 BP 235 EP 238 DI 10.1097/00024665-199607000-00012 PG 4 GA UZ226 UT WOS:A1996UZ22600010 PM 8718844 ER PT J AU Saladino, RA Stack, AM Thompson, C Sattler, F Novitsky, TJ Siber, GR Fleisher, GR AF Saladino, RA Stack, AM Thompson, C Sattler, F Novitsky, TJ Siber, GR Fleisher, GR TI High-dose recombinant endotoxin neutralizing protein improves survival in rabbits with Escherichia coli sepsis SO CRITICAL CARE MEDICINE LA English DT Article DE shock, septic; bacterial infection; endotoxin; lipo-polysaccharide; tumor necrosis factor; cytokine; endotoxin neutralizing protein; animal model; critical illness ID ANTI-LPS FACTOR; LIMULUS ANTILIPOPOLYSACCHARIDE FACTOR; TUMOR NECROSIS FACTOR; HORSESHOE-CRAB; TACHYPLEUS-TRIDENTATUS; LIPOPOLYSACCHARIDE; SHOCK; ANTICOAGULANT; ACTIVATION AB Objective: To assess the benefit of a recombinant endotoxin neutralizing protein from Limulus polyphemus in treating Gramnegative bacterial sepsis in rabbits, Design: Prospective, blinded, controlled, laboratory trial, Setting: Animal research laboratory, Subjects: New Zealand White rabbits, Interventions: We established a rabbit model of Escherichia coli peritonitis and bacteremia, with high mortality rate, despite treatment with gentamicin and ceftriaxone. Twenty-five pairs of male New Zealand White rabbits were challenged intraperitoneally with E. coli O18ac K1 in 5% porcine mucin (mean 7 x 10(9) colony-forming units). All animals were treated with intravenous gentamicin (2.5 mg/kg) and ceftriaxone (100 mg/kg), and with either intra venous endotoxin neutralizing protein (50 mg/kg) or saline 1 hr after E. coli challenge, Measurements and Main Results: All animals were bacteremic 1 hr after challenge (mean 3.6 x 10(5) colony-forming units/mL), Animals in both groups developed tachycardia, hypotension, and acidosis (NS), Geometric mean serum endotoxin and tumor necrosis factor (TNF) concentrations were significantly (p < .001) higher 1 hr after challenge compared with baseline prechallenge concentrations in both groups, From 1 to 2 hrs after challenge, endotoxin concentrations increased 2.5-fold in control animals (95% confidence interval = 13.1 to 32.9 endotoxin units/mL, p = .024), whereas endotoxin concentrations increased only 1.5-fold in endotoxin neutralizing protein-treated animals (95% confidence interval = 20.4 to 23.8 endotoxin units/mL, NS), TNF concentrations increased significantly (p < .001) in both groups from 1 to 2 hrs after challenge, Eighteen (72%) of 25 endotoxin neutralizing protein treated animals vs, 11 (44%) of 25 controls survived 24 hrs (p = .032), Conclusions: Treatment with endotoxin neutralizing protein had the following effects: a) the increase in serum endotoxin was blunted, but not TNF concentrations measured 1 hr after antibiotic treatment; and b) survival in rabbits with E. coli sepsis was improved. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, INFECT DIS LAB, BOSTON, MA 02115 USA. ASSOCIATES CAPE COD INC, WOODS HOLE, MA USA. RP Saladino, RA (reprint author), CHILDRENS HOSP, DEPT MED, DIV EMERGENCY MED, 300 LONGWOOD AVE, BOSTON, MA 02115 USA. FU NIAID NIH HHS [AI18125] NR 15 TC 9 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 1996 VL 24 IS 7 BP 1203 EP 1207 DI 10.1097/00003246-199607000-00023 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA UX035 UT WOS:A1996UX03500023 PM 8674336 ER PT J AU Black, PM Alexander, E Tarbell, NJ Shrieve, DC Goumnerova, LC Loeffler, JS AF Black, PM Alexander, E Tarbell, NJ Shrieve, DC Goumnerova, LC Loeffler, JS TI Linear accelerator-based radiosurgery for malignant tumors of the central nervous system SO CRITICAL REVIEWS IN NEUROSURGERY LA English DT Article ID STEREOTAXIC RADIOSURGERY; RECURRENT C1 BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,BOSTON,MA. CHILDRENS HOSP,DEPT NEUROSURG,BOSTON,MA 02115. NR 4 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-0146 J9 CRIT REV NEUROSURG JI Crit. Rev. Neurosurg. PD JUL PY 1996 VL 6 IS 4 BP 225 EP 231 PG 7 WC Neurosciences; Surgery SC Neurosciences & Neurology; Surgery GA VH818 UT WOS:A1996VH81800005 ER PT J AU Sands, BE Podolsky, DK AF Sands, BE Podolsky, DK TI Toward new questions in inflammatory bowel disease in 1995 SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Review ID INTESTINAL EPITHELIUM; ULCERATIVE-COLITIS; MICE; CADHERIN; COLON; CELLS; GENE AB Advances during the past year have provided new perspectives on the pathogenesis and management of Crohn's disease and ulcerative colitis, Complex interactions of intestinal microflora, genetic predisposition, the epithelial barrier, and the mucosal immune system contribute to the onset and perpetuation of mucosal inflammation in inflammatory bowel disease. New insights into the pathogenesis of these diseases have been gained through clinical trials, studies of genetic animal models, and statistically based human genetics, A variety of research approaches continue to reframe the important questions in inflammatory bowel disease in novel, unanticipated ways. RP Sands, BE (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,32 FRUIT ST,GRJ-719,BOSTON,MA 02114, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JUL PY 1996 VL 12 IS 4 BP 319 EP 321 DI 10.1097/00001574-199607000-00001 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VB640 UT WOS:A1996VB64000001 ER PT J AU Trasler, JM Trasler, DG Bestor, TH Li, E Ghibu, F AF Trasler, JM Trasler, DG Bestor, TH Li, E Ghibu, F TI DNA methyltransferase in normal and Dnmt(n)/Dnmt(n) mouse embryos SO DEVELOPMENTAL DYNAMICS LA English DT Article DE DNA methylation; postimplantation development; mouse; decidua ID DECIDUAL CELLS; METHYLATION; UNDERMETHYLATION; LINEAGES; DOMAIN AB The mouse genome experiences a large decrease in net 5-methylcytosine between fertilization and implantation; de novo methylation brings 5-methylcytosine to adult somatic cell levels between implantation and gastrulation, Very little is known of the regulation of demethylation or de novo methylation, Levels of the one known form of DNA methyltransferase are very high in early embryos, but the enzyme is localized to the cytoplasm during most of preimplantation development. We show here that DNA methyltransferase is found exclusively in nuclei of the conceptus after implantation, and that nuclei of proximal decidual cells are free of detectable DNA methyltransferase, High levels of DNA methyltransferase were seen in all tissues, including the developing nervous system, of 9.5- to 12.5-day embryos. The large maternal stores of DNA methyltransferase become limiting prior to embryonic day 9.5, as shown by barely detectable immunostaining in 9.5-day embryos homozygous for a loss-of-function mutation (Dnmt(n)) in the DNA methyltransferase gene, These mutant embryos failed to develop past the 25-somite stage and showed evidence of developmental delay and some developmental asynchrony, Normal embryonic and extraembryonic tissues contained similar levels of DNA methyltransferase, even though severely reduced methylation levels and a loss of imprinting have previously been observed in extraembryonic tissues, These findings suggest that methylation patterns are not a simple function of the concentration of DNA methyltransferase, and that unidentified factors must be involved in the regulation of de novo methylation during early development of the mouse. (C) 1996 Wiley-Liss, Inc. C1 MCGILL UNIV,DEPT PEDIAT,MONTREAL,PQ H3H 1P3,CANADA. MCGILL UNIV,DEPT HUMAN GENET,MONTREAL,PQ H3H 1P3,CANADA. MCGILL UNIV,DEPT THERAPEUT & PHARMACOL,MONTREAL,PQ H3H 1P3,CANADA. MCGILL UNIV,DEPT BIOL,MONTREAL,PQ H3H 1P3,CANADA. COLUMBIA UNIV,DEPT GENET & DEV,NEW YORK,NY 10032. MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. RP Trasler, JM (reprint author), MCGILL UNIV,MONTREAL CHILDRENS HOSP,RES INST,2300 TUPPER ST,MONTREAL,PQ H3H 1P3,CANADA. FU NCI NIH HHS [CA60610]; NIGMS NIH HHS [GM00616] NR 28 TC 47 Z9 50 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUL PY 1996 VL 206 IS 3 BP 239 EP 247 DI 10.1002/(SICI)1097-0177(199607)206:3<239::AID-AJA2>3.0.CO;2-J PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA UU005 UT WOS:A1996UU00500002 PM 8896980 ER PT J AU Higashi, S King, GL AF Higashi, S King, GL TI Inhibitory effect of insulin on ET-1 production in retinal capillary pericytes and aortic smooth muscle cells SO DIABETES LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1996 VL 45 SU 3 BP 28 EP 28 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UV115 UT WOS:A1996UV11500063 ER PT J AU Mantzoros, CS Qu, DQ Frederich, RC Susulic, VS Lowell, BB MaratosFlier, E Flier, JS AF Mantzoros, CS Qu, DQ Frederich, RC Susulic, VS Lowell, BB MaratosFlier, E Flier, JS TI Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice SO DIABETES LA English DT Article ID NEUROPEPTIDE-Y; OBESITY; THERMOGENESIS; ADRENOCEPTOR; SEQUENCE; AGONIST AB To examine potential interactions between leptin and the beta(3) adrenergic system in the regulation of food intake, we determined the effects of treatment with a selective beta(3) adrenergic receptor (AR) agonist (CL 316,243 [1 mg/kg]) on body weight, food intake, and leptin expression. Studies were carried out in C57Bl/6J and FVB male control mice as well as in mice with targeted disruption of the beta(3) AR gene. These findings were correlated with measurement of the expression in hypothalamus of neuropeptide Y (NPY) and melanin concentrating hormone (MCH), two neuropeptides that may be involved in the central regulation of food intake. Treatment with CL 316,243 (1 mg/kg) for 12 or 24 h decreased leptin mRNA abundance and circulating levels to 20% of baseline in normal animals. No effect of the CL 316,243 compound was seen in mice with targeted disruption of the beta(3) AR gene. Despite the falling leptin levels, beta(3) agonist administration acutely suppressed food intake. Finally, the induced suppression of food intake and leptin levels occurred despite unchanged or increased hypothalamic expression of the orexigenic neuropeptides NPY and MCH. Thus, beta(3) AR agonists via beta(3) ARs suppress leptin levels acutely and simultaneously suppress food intake via a mechanism that operates downstream of leptin and two of its putative central targets. C1 BETH ISRAEL HOSP,DIV ENDOCRINOL,BOSTON,MA 02215. JOSLIN DIABET CTR,BOSTON,MA 02215. FU NHLBI NIH HHS [K08 HL-02564]; NIDDK NIH HHS [K08 DK-02119, P30DK462000] NR 31 TC 264 Z9 267 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1996 VL 45 IS 7 BP 909 EP 914 DI 10.2337/diabetes.45.7.909 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UU168 UT WOS:A1996UU16800011 PM 8666142 ER PT J AU Verge, CF Gianani, R Kawasaki, E Yu, LP Pietropaolo, M Jackson, RA Chase, HP Eisenbarth, GS AF Verge, CF Gianani, R Kawasaki, E Yu, LP Pietropaolo, M Jackson, RA Chase, HP Eisenbarth, GS TI Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies SO DIABETES LA English DT Article ID ISLET-CELL ANTIBODIES; HIGH-RISK; ASSAY; MELLITUS AB Islet cell antibodies (ICAs) are predictive of type I diabetes in first-degree relatives, but this immunohistochemical assay has proven difficult to standardize. As an alternative, we assessed the use of radioassays for antibodies against three molecularly characterized islet autoantigens, including ICA512bdc (amino acid residues 256-979 of the IA-2 molecule, incorporating the intracellular domain). We measured insulin autoantibodies (IAAs), GAD autoantibodies (GAAs), and ICA512bdc autoantibodies (ICA512bdcAAs) by radioassay, in addition to ICAs, in 882 first-degree relatives of patients with type I diabetes, 50 of whom later developed diabetes with a median follow-up of 2.0 years (maximum 11.3 years). The cutoff for each radioassay was determined by testing >200 control subjects. When autoantibody frequencies among the relatives were analyzed according to relationship to the proband, the offspring of diabetic fathers had a higher frequency of ICA512bdcAAs (P = 0.008), IAAs (P = 0.0001) and GAAs (P = 0.0001) than the offspring of diabetic mothers. ICA512bdcAAs and IAAs both showed a significant association with HLA-DR4-DQ8 (P = 0.0005). Among relatives developing diabetes, 98% had one or more of IAAs, GAAs, or ICA512bdcAAs, and 80% had two or more of these autoantibodies, compared with none of the control subjects. Using survival analysis to allow for different lengths of follow-up, there was a significant increase in the risk of diabetes with the number of these autoantibodies present, comparing zero, one, two, and three autoantibodies (P < 0.0001, log-rank test), and by Cox regression analysis, this was independent of ICAs and age. For relatives with two or more of these autoantibodies, the risk of diabetes within 3 years was 39% (95% CI, 27-52) and the risk within 5 years was 68% (95% CI, 52-84). Relatives with all three autoantibodies had a risk within 5 years estimated to be 100%. The presence of low first-phase insulin release further increased the risk for relatives with one or two autoantibodies. We conclude that the presence of two or more autoantibodies (out of IAAs, GAAs, and ICA512bdcAAs) is highly predictive of the development of type I diabetes among relatives. C1 UNIV COLORADO,HLTH SCI CTR,BARBARA DAVIS CTR CHILDHOOD DIABET,DENVER,CO 80262. JOSLIN DIABET CTR,BOSTON,MA 02215. FU NIDDK NIH HHS [DK-43279, DK-32083, DK-32493] NR 33 TC 620 Z9 642 U1 3 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1996 VL 45 IS 7 BP 926 EP 933 DI 10.2337/diabetes.45.7.926 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UU168 UT WOS:A1996UU16800013 PM 8666144 ER PT J AU King, GL Kunisaki, M Nishio, Y Inoguchi, T Shiba, T Xia, P AF King, GL Kunisaki, M Nishio, Y Inoguchi, T Shiba, T Xia, P TI Biochemical and molecular mechanisms in the development of diabetic vascular complications SO DIABETES LA English DT Article; Proceedings Paper CT 15th International-Diabetes-Federation Satellite Symposium on Diabetes and Macrovascular Complications CY NOV 12-13, 1994 CL OSAKA, JAPAN SP Int Diabet Federat, Multiclin Study Grp Diabet Macroangiopathy, Japan Cardiovasc Res Fdn, Japan Diabet Soc, Japan Atherosclerosis Soc ID PROTEIN-KINASE-C; ATPASE AB Hyperglycemia is the major causal factor in the development of diabetic vascular complications. The mechanism by which hyperglycemia causes the complications is not clear; however, it is very likely that hyperglycemia is mediating its adverse effects through multiple mechanisms. We have summarized some of these mechanisms in this review, with particular attention to the effect of hyperglycemia on the activation of diacylglycerol (DAG)-protein kinase C (PKC) pathway. We have reviewed existing information regarding various vascular tissues that show increased DAG and PKC levels. In addition, the mechanism by which hyperglycemia increases DAG as well as the cellular physiological consequences on the activation of PKC have been reviewed. C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP King, GL (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. RI Xia, Pu/G-3090-2010 OI Xia, Pu/0000-0003-4705-8878 FU NEI NIH HHS [EY05110] NR 27 TC 90 Z9 93 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1996 VL 45 SU 3 BP S105 EP S108 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UV115 UT WOS:A1996UV11500027 PM 8674872 ER PT J AU Kunisaki, M Fumio, U Nawata, H King, GL AF Kunisaki, M Fumio, U Nawata, H King, GL TI Vitamin E normalizes diacylglycerol-protein kinase C activation induced by hyperglycemia in rat vascular tissues SO DIABETES LA English DT Article; Proceedings Paper CT 15th International-Diabetes-Federation Satellite Symposium on Diabetes and Macrovascular Complications CY NOV 12-13, 1994 CL OSAKA, JAPAN SP Int Diabet Federat, Multiclin Study Grp Diabet Macroangiopathy, Japan Cardiovasc Res Fdn, Japan Diabet Soc, Japan Atherosclerosis Soc ID DIABETIC RATS; INHIBITION AB Hyperglycemia, a major cause of vascular complications in diabetes, has been shown to activate the diacylglycerol (DAG)-protein kinase C (PKC) pathway in vascular tissues, We have found that D-alpha-tocopherol (vitamin E) treatment reversed the adverse effects of hyperglycemia both in vitro and in vivo, In aortic smooth muscle cells (ASMCs), the PKC specific activity from the membranous fraction and total DAG were increased by 31 +/- 4% (P < 0.05) and 50 +/- 7% (P < 0.05), respectively, when the glucose levels were changed from 5.5 to 22 mmol/l, D-alpha-tocopherol prevented the glucose-stimulated increases in DAG level and PKC activity as well as the amount of PKC beta II isoform in ASMCs cultured with elevated glucose levels. Comparing streptozotocin-induced diabetic rats after 2 weeks of disease to controls, specific membranous PKC activities and total DAG levels were increased in aorta (162%, P < 0.05; 60%, P < 0.05), Intraperitoneal injection of D-alpha-tocopherol (40 mg/kg) every other day resulted in a significant decrease of the elevated membranous PKC specific activity and total DAG levels in parallel with a significant increase of D-alpha-tocopherol content in the aorta, These findings suggested that D-alpha-tocopherol can prevent the activation of PKC in the vascular cells and aorta induced by hyperglycemia by normalizing the elevated levels of DAG. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,JOSLIN DIABET CTR,RES DIV,BOSTON,MA 02215. KYUSHU UNIV,FAC MED,DEPT INTERNAL MED 3,FUKUOKA 812,JAPAN. FU NEI NIH HHS [EY-05110]; NIDDK NIH HHS [DK-36836] NR 12 TC 35 Z9 37 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1996 VL 45 SU 3 BP S117 EP S119 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UV115 UT WOS:A1996UV11500031 PM 8674876 ER PT J AU LopesVirella, MF Virella, G AF LopesVirella, MF Virella, G TI Cytokines, modified lipoproteins, and arteriosclerosis in diabetes SO DIABETES LA English DT Article; Proceedings Paper CT 15th International-Diabetes-Federation Satellite Symposium on Diabetes and Macrovascular Complications CY NOV 12-13, 1994 CL OSAKA, JAPAN SP Int Diabet Federat, Multiclin Study Grp Diabet Macroangiopathy, Japan Cardiovasc Res Fdn, Japan Diabet Soc, Japan Atherosclerosis Soc ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; NON-ENZYMATIC GLYCOSYLATION; CHOLESTERYL ESTER SYNTHESIS; VASCULAR ENDOTHELIAL-CELLS; SMOOTH-MUSCLE CELLS; IMMUNE-COMPLEXES; INTERLEUKIN-1; ANTIBODIES; ATHEROSCLEROSIS AB Modified Lipoproteins, particularly different forms of oxidized LDL (ox-LDL), have been reported to elicit humoral immune responses both in experimental animals, and humans. In diabetes, glycation and oxidation processes coexist and lead to the formation of glycoxidation products. Ox-LDL has been demonstrated in atheromatous lesions, anti-ox-LDL antibodies have been detected in circulation and in atheromatous plaques, and immune complexes (ICs) formed with LDL and anti-LDL (LDL-IC) have been isolated from the serum of patients with manifestations of atherosclerosis. In addition, in vitro formed LDL-ICs and ICs isolated from patients have been demonstrated to cause intracellular accumulation of cholesteryl esters (CEs) in human macrophages and fibroblasts. The accumulation of CEs in macrophages exposed to LDL-ICs is unique to this type of IC and is associated with paradoxical overexpression of LDL receptor and with increased synthesis and release of interleukin 1 beta and tumor necrosis factor (TNF) alpha. The overexpression of LDL receptors is higher in LDL-IC-stimulated macrophages that release markedly high amounts of TNF-alpha than in macrophages that release low amounts of TNF-alpha into the medium. The release of cytokines in the subendothelial space may have a significant role in promoting the interaction of endothelial cells with mononuclear cells, causing endothelial cell damage directly or indirectly, and also in inducing smooth muscle cell proliferation. Thus, in view of the above data, it can be concluded that humoral autoimmunity may play a significant role in the pathogenesis of atherosclerosis in diabetes. C1 MED UNIV S CAROLINA,DEPT MED,DIV METAB ENDOCRINOL & NUTR,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT MICROBIOL & IMMUNOL,CHARLESTON,SC 29425. RP LopesVirella, MF (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,109 BEE ST,CHARLESTON,SC 29403, USA. FU NHLBI NIH HHS [HL-46815] NR 49 TC 51 Z9 54 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1996 VL 45 SU 3 BP S40 EP S44 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UV115 UT WOS:A1996UV11500009 PM 8674888 ER PT J AU Mayfield, JA Reiber, GE Nelson, RG Greene, T AF Mayfield, JA Reiber, GE Nelson, RG Greene, T TI A foot risk classification system to predict diabetic amputation in Pima Indians SO DIABETES CARE LA English DT Article ID LOWER-EXTREMITY AMPUTATIONS; MANAGEMENT; MELLITUS; DISEASE AB OBJECTIVE - To quantify the contribution of various risk factors to the risk of amputation in diabetic patients and to develop a foot risk scoring system based on clinical data. RESEARCH DESIGN AND METHODS - A population-based case-control study was undertaken. Eligible subjects were 1) 25-85 years of age, 2) diabetic, 3) 50% or more Pima or Tohono O'odham Indian, 4) lived in the Gila River Indian Community, and 5) had had at least one National Institutes of Health research examination. Case patients had had an incident lower extremity amputation between 1983 and 1992; control subjects had no amputation by 1992. Medical records were reviewed to determine risk conditions and health status before the pivotal event that led to the amputation. RESULTS - Sixty-one people with amputations were identified and compared with 183 control subjects. Men were more likely to suffer amputation than women (odds ratio [OR] 6.5, 95% CI 2.6-15), and people with diabetic eye, renal, or cardiovascular disease were more likely to undergo amputation than those without (OR 4.6, 95% CI 1.7-12). The risk of amputation was almost equally associated with these foot risk factors. peripheral neuropathy, peripheral vascular disease, bony deformities, and a history of foot ulcers. After controlling for demographic differences and diabetes severity, the ORs for amputation with one loot risk factor was 2.1 (95% CI 1.4-3.3), with two risk factors, 4.5 (95% CI 2.9-6.9), and with three or four risk factors, 9.7 (95% CI 6.3-14.8). CONCLUSIONS - Male sex, end-organ complications of eye, heart, and kidney, and poor glucose control were associated with a higher amputation rate. Peripheral neuropathy, peripheral vascular disease, deformity, and a prior ulcer were similarly equally associated with an increased risk of lower extremity amputation. C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,HLTH SERV RES,SEATTLE,WA. NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. RP Mayfield, JA (reprint author), INDIANA UNIV,LONG HOSP,DEPT FAMILY PRACTICE,BOWEN RES CTR,1110 W MICHIGAN ST,ROOM 200,INDIANAPOLIS,IN 46202, USA. RI Nelson, Robert/B-1470-2012 FU AHRQ HHS [HS-07238] NR 28 TC 48 Z9 54 U1 2 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1996 VL 19 IS 7 BP 704 EP 709 DI 10.2337/diacare.19.7.704 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UT646 UT WOS:A1996UT64600003 PM 8799623 ER PT J AU Moore, BG Singaram, C Eckhoff, DE Gaumnitz, EA Starling, JR AF Moore, BG Singaram, C Eckhoff, DE Gaumnitz, EA Starling, JR TI Immunohistochemical evaluations of ultrashort-segment Hirschsprung's disease - Report of three cases SO DISEASES OF THE COLON & RECTUM LA English DT Article DE ultrashort-segment; Hirschsprung's disease; nitric oxide; myectomy; constipation; nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry ID PEPTIDERGIC INNERVATION; ANORECTAL MYECTOMY; ESOPHAGUS; ADULTS AB PURPOSE: Unlike classic Hirschsprung's disease, short-segment and ultrashort-segment varieties are usually found to be latent and milder. Ultrashort-segment Hirschsprung's disease may present as intractable chronic constipation in children over one year of age, adolescents, and adults. Anorectal myectomy has been shown in many instances to provide effective long-term treatment for certain patients with ultrashort-segment Hirschsprung's disease. Histologically, the affected segment in Hirschsprung's disease has been shown to have increased cholinergic nerves, lack of nitric oxide synthase-containing neuronal elements, and show moderate to severe loss of myenteric neurons. METHODS: Here, we report three cases that showed clinical and manometric evidence of ultrashort-segment Hirschsprung's disease. Two of the three patients responded well to myectomy. RESULTS: Detailed histologic and immunohistochemical evaluation of the internal anal sphincter and a comparison with three normal controls revealed absence of nitric oxide synthase-containing neurons in both cases that responded well to surgery and continued presence of these neurons in the patient who did not respond. A review of the current literature on various treatment modalities is included, CONCLUSIONS: Anorectal myectomy provides long-term relief of this chronic problem in a subgroup of patients with ultrashort-segment Hirschsprung's disease who lack nitrinergic neurons at the internal anal sphincter. C1 UNIV WISCONSIN,DEPT MED,DIV GASTROENTEROL,CLIN SCI CTR H6516,MADISON,WI 53792. UNIV WISCONSIN,DEPT SURG,DIV GASTROENTEROL,CLIN SCI CTR H6516,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,GRECC,SURG SERV,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,GRECC,MED SERV,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,GRECC,GERIATR SERV,MADISON,WI. NR 20 TC 10 Z9 10 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD JUL PY 1996 VL 39 IS 7 BP 817 EP 822 DI 10.1007/BF02054450 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA UX213 UT WOS:A1996UX21300017 PM 8674377 ER PT J AU Drinka, TJK AF Drinka, TJK TI Applying learning from self-directed work teams in business to curriculum development for interdisciplinary geriatric teams SO EDUCATIONAL GERONTOLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Association-for-Gerontology-in-Higher-Education CY MAR 10-13, 1994 CL CLEVELAND, OH SP Assoc Gerontol Higher Educ AB Business settings, which increasingly promote the value of teamwork and self-directed work teams (SDWTs), offer a popular model for team development training. SDWTs are formal, permanent organizational structures or units empowered to manage themselves and the work they do. SDWTs in business settings have many of the same features as, face similar issues and problems to, and have worked out solutions to many issues that also apply to interdisciplinary health care teams (IHTs). The literature on SDWTs in business settings has addressed team involvement in choosing team leadership, training team leaders, running team meetings, selecting new team members, disciplining team members, peer review by the team, and team compensation. Materials from organizational literature have been used to promote SDWTs in health settings. However application of SDWT curriculum to IHTs has not been examined. This paper compares the curriculum used by SDWTs in business settings with its potential application to interdisciplinary teams in, geriatrics. It addresses areas where application, may be valuable and others that are potentially problematic. It offers suggestions for using SDWT concepts to train for practice on IHTs and suggests IHT concepts that could be applied to SDWT curriculum when used in geriatric health care settings. RP Drinka, TJK (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR CLIN,MADISON,WI 53705, USA. NR 33 TC 9 Z9 9 U1 1 U2 5 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0360-1277 J9 EDUC GERONTOL JI Educ. Gerontol. PD JUL-AUG PY 1996 VL 22 IS 5 BP 433 EP 450 DI 10.1080/0360127960220504 PG 18 WC Education & Educational Research; Gerontology SC Education & Educational Research; Geriatrics & Gerontology GA UY263 UT WOS:A1996UY26300004 ER PT J AU Chow, JC Ling, PR Qu, ZS Laviola, L Ciccarone, A Bistrian, BR Smith, RJ AF Chow, JC Ling, PR Qu, ZS Laviola, L Ciccarone, A Bistrian, BR Smith, RJ TI Growth hormone stimulates tyrosine phosphorylation of JAK2 and STAT5, but not insulin receptor substrate-1 or SHC proteins in liver and skeletal muscle of normal rats in vivo SO ENDOCRINOLOGY LA English DT Article ID PROLACTIN RECEPTOR; GENE-EXPRESSION; IDENTIFICATION; SECRETION; GLUCOSE; CELLS AB GH has been shown to stimulate tyrosine phosphorylation of JAK2, several STAT proteins, insulin receptor substrate-1 (IRS-1), and SHC proteins in cultured cells. The goal of this study was to determine GH effects on protein tyrosine phosphorylation in liver and skeletal muscle of normal rats in vivo. Nonfasted male Sprague-Dawley rats (225-250 g) were injected with GH iv, and tissues were obtained after 5, 15, 30, or 60 min. At a maximally effective GH dose (1.5 mg/kg body weight), phosphotyrosine antibody immunoblots demonstrated marked stimulation of the tyrosine phosphorylation of JAK2 (maximal at 5 min) and a 95,000 M(r) protein (maximal at 15 min) in both liver and skeletal muscle. The 95,000 M(r) protein was recognized and immunodepleted by STAT5 antibody, but not by other STAT protein antibodies. Although basal tyrosine phosphorylation of IRS-1 and SHC was evident, GH did not stimulate tyrosine phosphorylation of either of these proteins in liver or skeletal muscle. In conclusion, GH stimulates the ty rosine phosphorylation of JAK2 and STAT5, but not IRS-1, SHC, or other STAT proteins in liver and skeletal muscle of normal rats. These results differ from findings in cultured cells and support the concept that selectivity for tyrosine kinase substrates is an important determinant of postreceptor signaling specificity in vivo. C1 BRIGHAM & WOMENS HOSP, JOSLIN DIABET CTR, BOSTON, MA 02215 USA. HARVARD UNIV, NEW ENGLAND DEACONESS HOSP, SCH MED, BOSTON, MA 02215 USA. OI Laviola, Luigi/0000-0001-8860-5845 FU NIDDK NIH HHS [DK-50411, DK-31933, DK-48503] NR 26 TC 68 Z9 68 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1996 VL 137 IS 7 BP 2880 EP 2886 DI 10.1210/en.137.7.2880 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UR955 UT WOS:A1996UR95500029 PM 8770909 ER PT J AU Lu, M Miller, CP Habener, JF AF Lu, M Miller, CP Habener, JF TI Functional regions of the homeodomain protein IDX-1 required for transactivation of the rat somatostatin genes SO ENDOCRINOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVATOR; BINDING-PROTEINS; DOMAINS; EXPRESSION; RECEPTOR; SEQUENCE; CELLS AB The insulin-, glucagon- and somatostatin-producing cells (beta, alpha and delta, respectively) in the pancreatic islets derive from a common precursor stem cell and differentiate sequentially during embryonic development. The homeodomain protein islet duodenum HOX (IDX)-1 [insulin promoter factor (IPF)-1/somatostatin transactivating factor (STF)-1)] is a transcription factor critically required for both the development of the pancreas and the transcriptional expression of the insulin gene. IDX-1 may also act to determine the differentiation of the common pancreatic precursor to beta, alpha and delta cells. Although IDX-1 is detected in most adult mouse islet beta-cells and regulates insulin gene transcription, it is also found in 158 of the delta-cells and transactivates the rat somatostatin gene. The roles of different domains of IDX-1 involved in the transactivation of the somatostatin gene are unclear. In this study, we have created a series of amino- and carboxy-terminal deletions, as well as point substitution mutations to delineate functional domains within the IDX-1 protein. We find that deletions amino-proximal to the homeodomain enhance DNA-binding to the TAAT-1 transcriptional control element within the somatostatin gene promoter. However, these amino-terminal deletions result in substantial decreases in transactivation of a transcriptional reporter containing the TAAT-1 element. Paradoxically, coexpression of the transcriptionally inactive, amino-terminally deleted IDX-1 mutant proteins, either with the wild-type IDX-1 or with themselves, results in a marked enhancement of transactivation of the transcriptional TAAT-1 element reporter. We provide evidence that this synergistic enhancement of transactivation is mediated by protein-protein interactions among the regions of IDX-1 located carboxyl-proximal to the homeodomain. Although successive deletions into the carboxyterminal region do not alter DNA-binding, these deletions result in a biphasic enhancement and diminution of transactivation. The IDX-1 homeodomain mediates sequence-specific DNA-binding because substitution mutations within this region abolish DNA-binding. All of the amino- and carboxy-terminal deletion proteins were present in nuclear extracts of transfected cells, suggesting that nuclear localization signals reside within the IDX-1 homeodomain. The mapping of the functional domains of IDX-1 may facilitate understanding of IDX-1-mediated gene regulation and islet cell development. C1 HARVARD UNIV, HOWARD HUGHES MED INST,MASSACHUSETTS GEN HOSP, SCH MED,MOLEC ENDOCRINOL LAB, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-30457] NR 36 TC 48 Z9 50 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1996 VL 137 IS 7 BP 2959 EP 2967 DI 10.1210/en.137.7.2959 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UR955 UT WOS:A1996UR95500040 PM 8770920 ER PT J AU Bullock, BP Heller, RS Habener, JF AF Bullock, BP Heller, RS Habener, JF TI Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor SO ENDOCRINOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION; INCRETIN HORMONE; GENE-EXPRESSION; ADIPOSE-TISSUE; GLUCOSE; INSULIN; MEMBRANES; AMIDE; BRAIN; SOMATOSTATIN AB The incretin hormone glucagon-like peptide-1 (GLP-1) is an important regulator of postprandial insulin secretion. In addition to its insulinotropic actions on pancreatic beta-cells, GLP-1 enhances glucose disposal by insulin-independent mechanisms, suggesting that GLP-1 receptors are located on extrapancreatic tissues. In this study, we examined the tissue distribution of GLP-1 receptor (GLP-1R) messenger RNA (mRNA) in rat by RNAse protection, RT-PCR, and in situ hybridization. We identified GLP-1R mRNA in the lung, pancreatic islets, stomach, and kidney by the RNAse protection assay. RT-PCR analysis also detected GLP-1R mRNA in the hypothalamus and heart. In situ hybridization experiments identified receptor mRNA in the gastric pits of the stomach, large nucleated cells in the lung, crypts of the duodenum, and pancreatic islets. No localized specific grains were found in kidney, skeletal muscle, heart, liver, or adipocytes. These results indicate that sequences corresponding to the cloned rat islet GLP-1 receptor are expressed in the pancreatic islets, lung, hypothalamus, stomach, heart, and kidney but not in adipose, liver, and skeletal muscle. Further, the GLP-1 receptor expressed in the kidney and heart may be structural variants of the known receptor. Therefore, the observed extrapancreatic actions of GLP-1 may not be strictly confined to interactions with the defined GLP-1 receptor. C1 HARVARD UNIV, HOWARD HUGHES MED INST,MASSACHUSETTS GEN HOSP, SCH MED,LAB MOL ENDOCRINOL, BOSTON, MA 02114 USA. RI Heller, R.Scott/A-7279-2008 NR 63 TC 359 Z9 377 U1 1 U2 23 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1996 VL 137 IS 7 BP 2968 EP 2978 DI 10.1210/en.137.7.2968 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UR955 UT WOS:A1996UR95500041 PM 8770921 ER PT J AU Treiman, DM AF Treiman, DM TI Neuron specific enolase and status epilepticus-induced neuronal injury SO EPILEPSIA LA English DT Editorial Material ID CONVULSIVE STATUS EPILEPTICUS; KAINIC ACID; BEHAVIORAL DEFICITS; SEIZURES; MORBIDITY; MORTALITY; CHILDREN; MODEL; EEG C1 W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. RP Treiman, DM (reprint author), UNIV CALIF LOS ANGELES,SCH MED,REED NEUROL RES CTR,DEPT NEUROL,RM C-128,710 WESTWOOD PLAZA,LOS ANGELES,CA 90095, USA. NR 32 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUL PY 1996 VL 37 IS 7 BP 595 EP 597 DI 10.1111/j.1528-1157.1996.tb00621.x PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA UY999 UT WOS:A1996UY99900001 PM 8681889 ER PT J AU Carmel, R Cairo, K Bondareff, W Gott, PS Cummings, JL Henderson, VW AF Carmel, R Cairo, K Bondareff, W Gott, PS Cummings, JL Henderson, VW TI Spouses of demented patients with low cobalamin levels: A new risk group for cobalamin deficiency SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE cobalamin deficiency; homocysteine; methylmalonic acid; dementia; relatives ID LOW SERUM COBALAMIN; DEOXYURIDINE SUPPRESSION TEST; MEGALOBLASTIC-ANEMIA; METHYLMALONIC ACID; ALZHEIMER-TYPE; SUBTLE; VITAMIN-B12; ABNORMALITIES; MALABSORPTION; FOLATE AB Low serum cobalamin levels are common in conditions such as dementia and often represent mild deficiency. We surveyed serum cobalamin levels prospectively in spouses and blood relatives of demented patients to determine if any familial predisposition exists for the low levels. Cobalamin status in most of the relatives found to have low levels was assessed further by means of blood counts, metabolic tests, neurologic evaluation, absorption studies and response to cobalamin therapy. Serum cobalamin levels in 36 spouses correlated with those of the 36 demented patients related to them (r=0.46, p=0.004). A significant association was not seen in 34 blood relatives of 34 demented patients (r=0.27). Most importantly, 67% of the spouses of demented patients with low serum cobalamin had low values themselves, compared with only 3% of the spouses of patients with normal levels (p=0.001). Detailed study of 4 of the 5 spouses (and 3 blood relatives) with low cobalamin levels showed no anemia in any case. Nevertheless, 4 of the subjects had metabolic evidence of deficiency and one had electrophysiological abnormalities; all these defects improved with cobalamin therapy. These observations identify a hitherto unsuspected group of people at high risk for cobalamin deficiency and suggest that spouses of demented patients with low cobalamin levels should also have their cobalamin levels measured. The increased frequency of low serum cobalamin levels in spouses of demented patients with low levels represents in most cases a true, mild cobalamin deficiency that responds to treatment. C1 UNIV SO CALIF,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90093. UNIV SO CALIF,SCH MED,DEPT PSYCHIAT,LOS ANGELES,CA 90093. UNIV SO CALIF,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90093. W LOS ANGELES VET AFFAIRS MED CTR,DEPT NEUROL,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,DEPT PSYCHIAT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,CTR HLTH SCI,LOS ANGELES,CA 90024. RP Carmel, R (reprint author), UNIV SO CALIF,SCH MED,DEPT MED,RMR 306,2025 ZONAL AVE,LOS ANGELES,CA 90093, USA. FU NCRR NIH HHS [MO1-RR-43]; NIA NIH HHS [AG-05142]; NIDDK NIH HHS [DK-32640] NR 28 TC 5 Z9 5 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JUL PY 1996 VL 57 IS 1 BP 62 EP 67 PG 6 WC Hematology SC Hematology GA UZ413 UT WOS:A1996UZ41300009 PM 8698133 ER PT J AU Kuikka, JT Belliveau, JW Hari, R AF Kuikka, JT Belliveau, JW Hari, R TI Future of functional brain imaging SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID CEREBRAL BLOOD-FLOW; TOMOGRAPHY; ACTIVATION C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,NMR CTR,DEPT RADIOL,CHARLESTOWN,MA 02129. HELSINKI UNIV TECHNOL,LOW TEMP LAB,SF-02150 ESPOO,FINLAND. RP Kuikka, JT (reprint author), KUOPIO UNIV HOSP,DEPT CLIN PHYSIOL,SF-70210 KUOPIO,FINLAND. RI Hari, Riitta/J-1880-2012 OI Hari, Riitta/0000-0002-3142-2703 NR 26 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD JUL PY 1996 VL 23 IS 7 BP 737 EP 740 DI 10.1007/BF00843700 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UX172 UT WOS:A1996UX17200001 PM 8662110 ER PT J AU Emery, DW Sachs, DH LeGuern, C AF Emery, DW Sachs, DH LeGuern, C TI Culture and characterization of hematopoietic progenitor cells from miniature swine SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE culture; bone marrow; progenitors; cytokines; swine ID BONE-MARROW TRANSPLANTATION; MAJOR HISTOCOMPATIBILITY COMPLEX; MEDIATED GENE-TRANSFER; LONG-TERM HEMATOPOIESIS; STEM-CELLS; MONOCLONAL-ANTIBODIES; INVITRO; EXPRESSION; RECONSTITUTION; INTERLEUKIN-3 AB Miniature swine are being used as a large animal model in which cultured and retrovirus-transduced hematopoietic stem cells (HSC) can be tested in a reproducible manner for their long-term in vivo repopulating ability. As part of these studies, long-term bone marrow culture (LTBMC) and progenitor colony assay systems were developed and used to characterize the in vitro growth potential and in vivo frequency of hematopoietic progenitors in this species. We found that LTBMCs initiated with a single marrow inoculum produced myeloid colony progenitors continuously for at least 7 weeks. The sites of myelopoietic activity in these cultures were uniquely restricted to isolated, morphologically diverse germinal centers rather than more disperse cobblestone patches. We also used the progenitor assay to screen several human and murine recombinant cytokines for cross-reactivity to swine bone marrow cells, including interleukin-3 (IL-3), IL-6, IL-11, granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF), c-kit ligand (also called mast cell growth factor [MGF]), and erythropoietin (Epo). With the exception of human and murine IL-3, each of the cytokines tested induced swine progenitor colony formation to varying degrees, with some combinations leading to the formation of primitive multilineage and high proliferative potential colonies. Finally, in an attempt to characterize alternative sources of HSC from swine, we compared the progenitor content of adult and juvenile swine bone marrow and fetal liver. The fetal liver samples were found to be highly enriched for both primitive and mature progenitors, while analysis of postnatal marrow samples revealed an approximately two-fold decline in overall progenitor frequency between the ages of 10 and 20 weeks. Taken together, these studies demonstrate the development and use of in vitro culture methods for characterizing hematopoietic elements from miniature swine and suggest a hierarchy of progenitor cell content in various hematopoietic tissues from this large animal model. C1 MASSACHUSETTS GEN HOSP EAST,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. FU NHLBI NIH HHS [HL46532] NR 43 TC 19 Z9 19 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1996 VL 24 IS 8 BP 927 EP 935 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA UY210 UT WOS:A1996UY21000011 PM 8690052 ER PT J AU Galpern, WR Burns, LH Deacon, TW Dinsmore, J Isacson, O AF Galpern, WR Burns, LH Deacon, TW Dinsmore, J Isacson, O TI Xenotransplantation of porcine fetal ventral mesencephalon in a rat model of Parkinson's disease: Functional recovery and graft morphology SO EXPERIMENTAL NEUROLOGY LA English DT Article ID PRODUCE L-DOPA; INTRACEREBRAL XENOGRAFTS; IMMUNOLOGICAL ASPECTS; DENERVATED STRIATUM; CULTURED INVITRO; ADULT-RATS; NEURONS; SURVIVAL; TRANSPLANTS; RELEASE AB Neurotransplantation of human fetal dopamine (DA) neurons is currently being investigated as a therapeutic modality for Parkinson's disease (PD). However, the practical limitations of human fetal transplantation indicate a need for alternative methodologies, Using the 6-hydroxydopamine rat model of PD, we transplanted dopaminergic neurons derived from Embryonic Day 27 porcine fetuses into the denervated striatum of cyclosporine A (CyA)-treated or non-CyA-treated rats. Functional recovery was assessed by amphetamine-induced rotation, and graft survival and morphology mere analyzed using neuronal and glial immunostaining as well as in situ hybridization with a porcine repeat element DNA probe, A significant, sustained reduction in amphetamine-induced rotational asymmetry was present in the CyA-treated rats whereas the non-CyA-treated rats showed a transient behavioral recovery. The degree of rotational recovery was highly correlated to the number of surviving transplanted porcine dopaminergic neurons, TH+ neuronal survival and graft volume were significantly greater in the CyA-treated group as compared to the non-CyA group. By donor-specific neuronal and glial immunostaining as well as donor-specific DNA labeling, we demonstrate that porcine fetal neuroblasts are able to survive in the adult brain of immunosuppressed rats, mediate functional recovery, and extensively reinnervate the host striatum. These findings suggest that porcine DA neurons may be a suitable alternative to the use of human fetal tissue in neurotransplantation for PD. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA 01655. BOSTON UNIV,BOSTON,MA 02215. DIACRIN INC,CHARLESTOWN,MA 02129. RP Galpern, WR (reprint author), HARVARD UNIV,MCLEAN HOSP,SCH MED,PROGRAM NEUROSCI,NEUROREGENERAT LAB,MRC-119,BELMONT,MA 02178, USA. FU NINDS NIH HHS [NS 29178, NS 30064] NR 61 TC 126 Z9 128 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 1996 VL 140 IS 1 BP 1 EP 13 DI 10.1006/exnr.1996.0109 PG 13 WC Neurosciences SC Neurosciences & Neurology GA UU458 UT WOS:A1996UU45800001 PM 8682173 ER PT J AU Brand, JG Feigin, AM AF Brand, JG Feigin, AM TI Biochemistry of sweet taste transduction SO FOOD CHEMISTRY LA English DT Article ID CANINE LINGUAL EPITHELIUM; RECEPTOR-CELLS; MECHANISMS; CONDUCTANCE; ACTIVATION; OLFACTION; MEMBRANES; SYSTEM AB Recent biochemical and biophysical studies point to mechanistic hypotheses for sweet taste transduction involving either second messengers or stimulus-gated ion channels. Biochemical studies have shown that sweet tasting stimuli enhance the production of the second messenger, cyclic AMP, in a GTP-dependent manner in taste tissue homogenates. The cyclic AMP thus produced apparently stimulates a protein kinase A which may phosphorylate ion channels, leading ultimately to depolarization, an increase in intracellular calcium ion activity, and release of neurotransmitter. Recent studies show that some sweeteners also induce the production of inositol 1,4,5-trisphosphate (IP3). Other sweet transduction processes not associated with second messenger production may exist. For example, evidence for a stimulus-gated type ion channel for sweet taste can be inferred from ion transport studies on lingual epithelia and from psychophysics. A recent study demonstrated that certain amphiphilic sweeteners are capable of directly stimulating purified G proteins in an in vitro assay. Perhaps these and other amphiphilic intense sweeteners cross the plasma membrane and directly stimulate the G protein, inducing production of second messenger and bypassing the receptor. A number of sweeteners are capable of forming ion channels or of simply perturbing the membrane, actions which could operate during stimulation of the sweet receptor cell. This type of action could explain the relatively longer response times and lingering taste intensity associated with many amphiphilic sweeteners. Copyright (C) 1996 Elsevier Science Ltd. C1 UNIV PENN, PHILADELPHIA, PA 19104 USA. VET AFFAIRS MED CTR, PHILADELPHIA, PA USA. RP Brand, JG (reprint author), MONELL CHEM SENSES CTR, 3500 MARKET ST, PHILADELPHIA, PA 19104 USA. NR 58 TC 13 Z9 13 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD JUL PY 1996 VL 56 IS 3 BP 199 EP 207 DI 10.1016/0308-8146(96)00015-5 PG 9 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA UW019 UT WOS:A1996UW01900002 ER PT J AU Moss, JB Price, AL Raz, E Driever, W Rosenthal, N AF Moss, JB Price, AL Raz, E Driever, W Rosenthal, N TI Green fluorescent protein marks skeletal muscle in murine cell lines and zebrafish SO GENE LA English DT Article; Proceedings Paper CT Conference on Fluorescent Proteins and Applications CY MAR 06-07, 1995 CL PALO ALTO, CA SP Palo Alto Inst Molec Med DE transfection; Danio rerio; embryo; myosin light chain; vital dye ID GENE-EXPRESSION; ENHANCER AB The green fluorescent protein (GFP) acts as a vital dye upon the absorption of blue light. When the gfp gene is expressed in bacteria, flies or nematodes, green fluorescence can be directly observed in the living organism. We inserted the cDNA encoding this 238-amino-acid (aa) jellyfish protein into an expression vector containing the rat myosin light-chain enhancer (MLC-GFP) to evaluate its ability to serve as a muscle-specific marker. Transiently, as well as stably, transfected C2C12 cell lines produced high levels of GFP distributed homogeneously throughout the cytoplasm and was not toxic through several cell passages. Expression of MLC-GFP was strictly muscle-specific, since Cos 7 fibroblasts transfected with MLC-GFP did not fluoresce, When GFP and beta Gal markers were compared, the GFP signal was visible in the cytoplasm of the living cell, whereas visualization of beta Gal required fixation and resulted in deformation of the cells, When the MLC-GFP construct was injected into zebrafish embryos, muscle-specific gfp expression was apparent within 24 h of development. gfp expression was never observed in non-muscle tissues using the MLC-GFP construct. Transgenic fish continued to express high levels of gfp in skeletal muscle at 1.5 months, demonstrating that GFP is an effective marker of muscle cells in vivo. RP Moss, JB (reprint author), MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,149 13TH ST,MAILCODE 1494201,CHARLESTOWN,MA 02129, USA. FU NIA NIH HHS [R01AG12316]; NIAMS NIH HHS [R01AR41926]; NICHD NIH HHS [F32HD07926] NR 16 TC 23 Z9 25 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 1 PY 1996 VL 173 IS 1 BP 89 EP 98 DI 10.1016/0378-1119(95)00729-6 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA UY073 UT WOS:A1996UY07300014 PM 8707062 ER PT J AU Dores, RM Rubin, DA Quinn, TW AF Dores, RM Rubin, DA Quinn, TW TI Is it possible to construct phylogenetic trees using polypeptide hormone sequences? SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Review ID GONADOTROPIN-RELEASING-HORMONE; ENDOPLASMIC-RETICULUM MEMBRANE; AMINO-ACID-SEQUENCE; GROWTH-HORMONE; LAMPREY BRAIN; INSULIN; EVOLUTION; GENE; PEPTIDE; BIOSYNTHESIS AB Because of the high degree of primary sequence conservation in neuropeptides and low molecular weight polypeptide hormones, these polypeptides are not useful for constructing phylogenetic trees based on maximum parsimony analysis. This review focuses on the organization of neuropeptide and polypeptide hormone precursors and discusses strategies for aligning polypeptide precursors for phylogenetic analysis. Examples are provided to support the hypothesis that some neuropeptide and polypeptide precursors and some high molecular weight polypeptide hormones can be used as data sets for resolving deep divergences among vertebrate taxa. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA 02114. RP Dores, RM (reprint author), UNIV DENVER,DEPT BIOL SCI,DENVER,CO 80208, USA. NR 72 TC 70 Z9 71 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD JUL PY 1996 VL 103 IS 1 BP 1 EP 12 DI 10.1006/gcen.1996.0088 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UW427 UT WOS:A1996UW42700001 PM 8812320 ER PT J AU Lee, MH Williams, BO Mulligan, G Mukai, S Bronson, RT Dyson, N Harlow, E Jacks, T AF Lee, MH Williams, BO Mulligan, G Mukai, S Bronson, RT Dyson, N Harlow, E Jacks, T TI Targeted disruption of p107: Functional overlap between p107 and Rb SO GENES & DEVELOPMENT LA English DT Article DE p107; Rb; gene targeting; apoptosis; retinal dysplasia; liver ID HUMAN RETINOBLASTOMA GENE; TRANSCRIPTION FACTOR E2F; MYOGENIC DIFFERENTIATION; CELL-PROLIFERATION; TRANSGENIC MICE; OSTEO-SARCOMA; CHIMERIC MICE; PROTEIN; EXPRESSION; FAMILY AB To explore the physiological role of p107, a member of retinoblastoma gene (Rb) family, we disrupted the mouse gene by homologous recombination in embryonic stem cells. p107 homozygous mutant mice were viable, fertile, and displayed no obvious abnormalities. To investigate possible functional overlap between p107 and Rb, mice with mutations at both loci were generated. Rb-+/-;p107(-/-) mice have a pronounced growth retardation and increased mortality rate during the first 3 weeks after birth. The Rb-+/-;p107(-/-) pups that survive to adulthood did not show any altered tumor predisposition when compared with Rb-+/- mice but developed multiple dysplastic lesions of the retina. Embryos homozygous for both Rb and p107 died at similar to 11.5 days of gestation, 2 days earlier than embryos homozygous for Rb alone. Histological examination revealed accelerated apoptosis in the liver and the central nervous system of Rb--/-;p107(-/-) embryos relative to Rb--/- embryos. These results provide the first in vivo evidence that p107 and Rb have overlapping functions in some tissues of the developing and adult mouse. C1 MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV,SCH VET MED,DEPT PATHOL,BOSTON,MA 02111. RI Williams, Bart/A-3539-2013 OI Williams, Bart/0000-0002-5261-5301 NR 48 TC 266 Z9 272 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 1 PY 1996 VL 10 IS 13 BP 1621 EP 1632 DI 10.1101/gad.10.13.1621 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UX663 UT WOS:A1996UX66300005 PM 8682293 ER PT J AU Cobrinik, D Lee, MH Hannon, G Mulligan, G Bronson, RT Dyson, N Harlow, E Beach, D Weinberg, RA Jacks, T AF Cobrinik, D Lee, MH Hannon, G Mulligan, G Bronson, RT Dyson, N Harlow, E Beach, D Weinberg, RA Jacks, T TI Shared role of the pRB-related p130 and p107 proteins in limb development SO GENES & DEVELOPMENT LA English DT Article DE p130; p107; RB family; chondrocyte; cartilage development; gene targeting ID RETINOBLASTOMA GENE-PRODUCT; LARGE T-ANTIGEN; CYCLIN-A; ADENOVIRUS E1A; CHIMERIC MICE; FAMILY; BINDING; MEMBER; CELLS; MOUSE AB The p130 protein shares extensive sequence similarity with pRB, the product of the retinoblastoma gene, and is a major E2F-associated protein in quiescent cells. To investigate its biological function, we have mutated p130 via gene targeting in the mouse. Homozygous mutation of p130 had little discernible effect on development or on the growth of mouse embryo fibroblasts in culture. Much of the E2F activity that normally associates with p130 in serum-starved mouse embryo fibroblasts associated instead with the highly related p107 protein. To determine whether p130 and p107 have overlapping biological roles, we produced mice having simultaneous inactivation of the p130 and p107 genes. Such mice exhibited deregulated chondrocyte growth, defective endochondral bone development, shortened limbs, and neonatal lethality. These findings indicate that p130 and p107 play an important role in limb development through their abilities to control chondrocyte proliferation. Thus, in certain settings p107 and p130 perform growth-regulatory functions that are not fulfilled by pRB. C1 MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02142. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. COLD SPRING HARBOR LAB,HOWARD HUGHES MED INST,COLD SPRING HARBOR,NY 11724. TUFTS UNIV,SCH MED,BOSTON,MA 02111. MIT,CTR CANC RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. NR 57 TC 334 Z9 339 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 1 PY 1996 VL 10 IS 13 BP 1633 EP 1644 DI 10.1101/gad.10.13.1633 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UX663 UT WOS:A1996UX66300006 PM 8682294 ER PT J AU Moffett, P Dayo, M Reece, M McCormick, MK Pelletier, J AF Moffett, P Dayo, M Reece, M McCormick, MK Pelletier, J TI Characterization of msim, a murine homologue of the Drosophila sim transcription factor SO GENOMICS LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MINDED GENE ENCODES; DNA-BINDING; AH-RECEPTOR; MESSENGER-RNA; C-JUN; PROTEIN; CLONING; REGULATOR; MIDLINE AB Mutations in the Drosophila single-minded (sim) gene result in loss of precursor cells that give rise to midline cells of the embryonic central nervous system. During the course of an exon-trapping strategy aimed at identifying transcripts that contribute to the etiology and pathophysiology of Down syndrome, we identified a human exon from the Down syndrome critical region showing significant homology to the Drosophila sim gene. Using a cross-hybridization approach, we have isolated a murine homolog of the Drosophila sim gene, which we designated msim. Nucleotide and predicted amino acid sequence analyses of msim cDNA clones indicate that this gene encodes a member of the basic-helix-loop-helix class of transcription factors. The murine and Drosophila proteins share 88% residues within the basic-hefix-loop-helix domain, with an overall homology of 92%. In addition, the N-terminal domain of MSIM contains two PAS dimerization motifs also featured in the Drosophila sim gene product, as well as a small number of other transcription factors. Northern blot analysis of adult murine tissues revealed that the msim gene produces a single mRNA species of similar to 4 kb expressed in a small number of tissues, with the highest levels in the kidneys and lower levels present in skeletal muscle, lung, testis, brain, and heart. lit situ hybridization experiments demonstrate that msim is also expressed in early fetal development in the central nervous system and in cartilage primordia. The characteristics of the msim gene are consistent with its putative function as a transcriptional regulator. (C) 1996 Academic Press, Inc. C1 MCGILL UNIV,DEPT BIOCHEM,MONTREAL,PQ H3G 1Y6,CANADA. MCGILL UNIV,MCGILL CANC CTR,MONTREAL,PQ H3G 1Y6,CANADA. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,CHARLESTOWN,MA 02129. OI Moffett, Peter/0000-0003-0678-4531 NR 51 TC 32 Z9 34 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 1 PY 1996 VL 35 IS 1 BP 144 EP 155 DI 10.1006/geno.1996.0333 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UV869 UT WOS:A1996UV86900019 PM 8661115 ER PT J AU Badaracco, MA Rosenbaum, J Goisman, R AF Badaracco, MA Rosenbaum, J Goisman, R TI The perils of treatment: Proceedings of the Harvard Residency Teaching Day SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID BORDERLINE PERSONALITY-DISORDER C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. RP Badaracco, MA (reprint author), DEACONESS HOSP,DEPT PSYCHIAT,1 DEACONESS RD,BOSTON,MA 02215, USA. OI Badaracco, Mary Anne/0000-0001-9645-0652 NR 14 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 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 1996 VL 4 IS 2 BP 90 EP 97 DI 10.3109/10673229609030528 PG 8 WC Psychiatry SC Psychiatry GA UY867 UT WOS:A1996UY86700004 PM 9384978 ER PT J AU Rosenbaum, JF Pollock, RA AF Rosenbaum, JF Pollock, RA TI Depressions of milder severity: Listening to data SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID PATTERN-ANALYSIS; FLUOXETINE; DESIPRAMINE; OUTPATIENTS; FLUVOXAMINE; TRIAL RP Rosenbaum, JF (reprint author), MASSACHUSETTS GEN HOSP,15 PARKMAN ST,WAC 815,BOSTON,MA 02114, USA. NR 18 TC 7 Z9 8 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 1996 VL 4 IS 2 BP 102 EP 104 DI 10.3109/10673229609030530 PG 3 WC Psychiatry SC Psychiatry GA UY867 UT WOS:A1996UY86700006 PM 9384980 ER PT J AU Tokushige, K Wakita, T Pachuk, C Moradpour, D Weiner, DB Zurawski, VR Wands, JR AF Tokushige, K Wakita, T Pachuk, C Moradpour, D Weiner, DB Zurawski, VR Wands, JR TI Expression and immune response to hepatitis C virus core DNA-based vaccine constructs SO HEPATOLOGY LA English DT Article ID HEPATOCELLULAR-CARCINOMA; PLASMID DNA; GENETIC IMMUNIZATION; INFECTION; REGIONS; RNA; IDENTIFICATION; SEQUENCE; GENOME; CELLS AB Hepatitis C virus (HCV) is a major worldwide cause of acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma, The development of vaccines against HCV have been complicated by the high variability of the envelope region, and it is Likely that the cellular immune responses to viral structural proteins may be important for eradicating persistent viral infection. Recently, it was reported that the injection into muscle cells of plasmids encoding viral genes resulted in the generation of strong cellular immune responses, We constructed vectors that express the highly conserved HCV core gene, hn this regard, the pHCV 2-2 construct contained the entire HCV core region and pHCV 4-2 contained both the 5' noncoding region and the core gene. Cellular expression of HCV core protein was assessed following transfection into human and murine cell lines, and higher intracellular levels of the 21-kd core protein were observed with pHCV 2-2, These HCV core DNA constructs were used to immunize BALB/c mice and produced low-level anti-HCV core humoral immune responses, To assess cytotoxic T-lymphocyte (CTL) activity generated in vivo a cloned syngeneic SP2/O myeloma cell line constitutively expressing HCV core protein was established and inoculated into BALB/c mice to produce growth of plasmacytomas. Strong CTL activity was generated because the tumor size and weight in pHCV 2-2-immunized mice were remarkably reduced compared with mice injected with mock DNA. Spontaneous CTL activity was also exhibited by splenocytes in an in vitro cytotoxicity assay. These investigations demonstrate that plasmid constructs expressing HCV core protein generate strong CTL activity, as assessed both in vivo and in vitro, and are promising candidates as antiviral agents. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,CHARLESTOWN,MA 02129. APOLLON INC,MALVERN,PA 19355. UNIV PENN,PHILADELPHIA,PA 19104. RI Weiner, David/H-8579-2014 FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 56 TC 74 Z9 83 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 1996 VL 24 IS 1 BP 14 EP 20 DI 10.1002/hep.510240104 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UW635 UT WOS:A1996UW63500004 PM 8707253 ER PT J AU Pal, L Toth, TL Leykin, L Isaacson, KB AF Pal, L Toth, TL Leykin, L Isaacson, KB TI High incidence of triploidy in in-vitro fertilized oocytes from a patient with a previous history of recurrent gestational trophoblastic disease SO HUMAN REPRODUCTION LA English DT Article DE fertilization; gestational trophoblastic disease; recurrent GTD; triploid ID HYDATIDIFORM MOLE; INVITRO FERTILIZATION; ORIGIN; POLYSPERMY; ZYGOTES; EMBRYOS; FETUS AB The patient described has a history of recurrent gestational trophoblastic disease following spontaneous conception, She subsequently underwent two cycles of in-vitro fertilization (IVF) for management of infertility related to tubal obstruction, IVF of the oocytes retrieved showed a significantly high incidence of abnormal fertilization resulting in the development of triploid embryos. This report explores the possible association of an oocyte defect predisposing to abnormal fertilization, resulting in a high incidence of triploid embryos, Since the development of partial hydatidiform moles is related to the origin of triploidy, this phenomenon is suggested to explain the occurrence of recurrent trophoblastic disease in this patient. We propose the use of intracytoplasmic sperm injection (ICSI) as a therapeutic option to minimize the incidence of triploidy in future IVF cycles; donor oocyte IVF would be another alternative. RP Pal, L (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT REPROD ENDOCRINOL & INFERTIL,IVF UNIT,BOSTON,MA 02114, USA. NR 21 TC 23 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUL PY 1996 VL 11 IS 7 BP 1529 EP 1532 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA VD880 UT WOS:A1996VD88000038 PM 8671499 ER PT J AU Verdrengh, M Springer, TA GutierrezRamos, JC Tarkowski, A AF Verdrengh, M Springer, TA GutierrezRamos, JC Tarkowski, A TI Role of intercellular adhesion molecule 1 in pathogenesis of staphylococcal arthritis and in host defense against staphylococcal bacteremia SO INFECTION AND IMMUNITY LA English DT Article ID INTERFERON; ICAM-1; MICE AB Intercellular adhesion molecule 1 (ICAM-1) is a member of the immunoglobulin superfamily that interacts with two integrins, LFA-1 and Mac-1. These interactions are critical for leukocyte extravasation into inflamed tissue. To assess the role of ICAM-1 expression in the pathogenesis of bacterial infection, homozygously mutant mice lacking the ICAM-1 gene were exposed to Staphylococcus aureus. Within 6 days after inoculation 50% of the animals in the ICAM-1(-/-) group, but none of the controls, had died. Despite the high level of mortality, ICAM-1(-/-) mice developed less frequent and less severe arthritis than their wild-type littermates. in agreement, normal mice inoculated with staphylococci and administered anti-ICAM-1 antibodies exhibited a higher frequency of mortality but less severe arthritis than the controls. Our results indicate that ICAM-1 on the one hand provides protection against systemic disease but on the other hand aggravates the local disease manifestation. C1 GOTHENBURG UNIV,DEPT RHEUMATOL,S-41346 GOTHENBURG,SWEDEN. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP Verdrengh, M (reprint author), GOTHENBURG UNIV,DEPT CLIN IMMUNOL,GULDHEDSGATAN 10,S-41346 GOTHENBURG,SWEDEN. NR 23 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1996 VL 64 IS 7 BP 2804 EP 2807 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UT657 UT WOS:A1996UT65700059 PM 8698512 ER PT J AU Pegues, CF Johnson, DC Pegues, DA Spencer, M Hopkins, CC AF Pegues, CF Johnson, DC Pegues, DA Spencer, M Hopkins, CC TI Implementation and evaluation of an algorithm for isolation of patients with suspected pulmonary tuberculosis SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLINICAL-FEATURES AB OBJECTIVE: To implement and evaluate an algorithm designed to assist in the consistent placement of patients with suspected pulmonary tuberculosis into negative-pressure isolation rooms (NPIRs). DESIGN: A standard algorithm was designed for the appropriate room placement of patients with suspected pulmonary tuberculosis using clinical, radiographic, and laboratory criteria and reported risk factors. A case-patient was defined as an inpatient who had at least one Mycobacterium tuberculosis culture-positive respiratory specimen from January 1, 1993, through December 31, 1994. Demographic, clinical, laboratory, case contact, and isolation and room placement data were collected prospectively on all case-patients. SETTING: A 900-bed university teaching and referral center. RESULTS: During 1993 and 1994, 69 patients were evaluated for possible pulmonary tuberculosis, and 31 case-patients were identified. Of the 31 case-patients, 26 (84%) were placed on respiratory isolation in NPIRs, including 19 (61%) who were isolated within 24 hours of admission (1993, 14 of 20 [70%]; 1994, 5 of 11 [45%]). Seven case-patients (23%) were isolated in NPIRs following delays that ranged from 2 to 31 days (median, 9 days), and five case-patients (16%) never were isolated during admissions of from 3 to 28 days (median, 4 days). These 12 case-patients contributed a total of 136 patient-exposure days during their hospitalizations. Misclassification of patient risk status by user error delayed isolation of five (42%) of the 12 improperly isolated case-patients. CONCLUSIONS: The use of an algorithm incorporating radiographic, laboratory, and clinical criteria and reported risk factors may assist in the rapid isolation of patients with suspected pulmonary tuberculosis (Infect Control Hosp Epidemiol 1996;17:412-418). C1 MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. RP Pegues, CF (reprint author), MASSACHUSETTS GEN HOSP,INFECT CONTROL UNIT,FRUIT ST,BOSTON,MA 02114, USA. NR 20 TC 18 Z9 19 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUL PY 1996 VL 17 IS 7 BP 412 EP 418 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA UZ263 UT WOS:A1996UZ26300002 PM 8839797 ER PT J AU Simpson, NS Goodman, LA Jupiter, JB AF Simpson, NS Goodman, LA Jupiter, JB TI Contoured LCDC plating of the proximal ulna SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article ID FRACTURES AB Comminuted fractures of the proximal ulna, particularly in combination with dislocation of the radial head, represent complex injuries which threaten both elbow and forearm motion. Thirty-seven complex proximal ulna fractures were treated with a dorsally applied, limited-contact titanium plate, contoured to lit the anatomy of the olecranon and proximal ulna. Twenty-four patients had Monteggia fracture/dislocations, and 13 had isolated but complex fractures of the proximal ulna. After an average follow tip of 24 months, good or excellent functional results were achieved in 27 patients. Copyright (C) 1996 Elsevier Science Ltd. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPED TRAUMA,BOSTON,MA 02114. NR 20 TC 38 Z9 41 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD JUL PY 1996 VL 27 IS 6 BP 411 EP 417 DI 10.1016/0020-1383(96)00031-9 PG 7 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA VD595 UT WOS:A1996VD59500008 PM 8881138 ER PT J AU Kobayashi, H Tanaka, N Winkler, M Zapol, WM AF Kobayashi, H Tanaka, N Winkler, M Zapol, WM TI Combined effects of NO inhalation and intravenous PGF(2 alpha) on pulmonary circulation and gas exchange in an ovine ARDS model SO INTENSIVE CARE MEDICINE LA English DT Article DE adult respiratory distress syndrome; nitric oxide; sheep; lung lavage; pulmonary circulation; pressure-flow relationship ID INHALED NITRIC-OXIDE; RESPIRATORY-DISTRESS-SYNDROME; CARDIAC-OUTPUT; ALMITRINE BISMESYLATE; PIG LUNGS; PROSTAGLANDIN-F2-ALPHA; VASOCONSTRICTION; HYPERTENSION; PRESSURE; SHUNT AB Objectives: Inhalation of nitric oxide (NO) selectively dilates pulmonary vessels in well-ventilated regions. Prostaglandin F-2 alpha (PGF(2 alpha) is a vasoconstrictor and is reported to enhance hypoxic pulmonary vasoconstriction. The objective of this study was to examine whether the combination of intravenous PGF(2 alpha) and inhaled NO in ARDS lungs has a beneficial effect on oxygenation. Design. We investigated the effect of intravenous PGF(2 alpha) infusion (0.05 - 10.0 mu g/kg per min) with and without NO inhalation (60 ppm) on the hemodynamics and gas exchange in an ovine ARDS model, examining the pulmonary artery pressure versus the flow plot by varying cardiac output. Measurements and results: After lung lavage, NO inhalation reduced the mean pulmonary arterial pressure (MPAP) by decreasing the zero-flow pressure intercept from 10.6+/-3.8 (mean+/-SD) to 8.5+/-3.8 mmHg (p<0.05) with no significant change in slope. NO inhalation improved PaO2 from 56+/-12 to 84+/-38 mmHg (p<0.005) and reduced pulmonary shunt from 65+/-5 to 53+/-8% (Qs/Qt) (p<0.001). The dose-dependent effects of PGF(2 alpha) infusion were: (1) increased MPAP attributed to an increased slope in pulmonary artery pressure-flow plot; (2) decreased cardiac index; (3) decreased Qs/Qt with unchanged PaO2. The dose-dependent decrease in Qs/Qt after PGF(2 alpha) infusion was attributed to the decreased cardiac output. Conclusions: It is suggested that inhalation of NO reduced the critical vascular pressure near alveoli without affecting upstream vessels, while infused PGF(2 alpha) constricted the larger upstream pulmonary artery vessels without appreciably affecting the critical pressure. Inhalation of NO into well-ventilated lung areas shifted perfusion to well-oxygenated areas, and there was no supplemental shift in blood flow by adding an infusion of PCF2 alpha. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. KITASATO UNIV,SCH MED,DEPT MED,KANAGAWA 228,JAPAN. FU NHLBI NIH HHS [HL 42391] NR 39 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JUL PY 1996 VL 22 IS 7 BP 656 EP 663 DI 10.1007/BF01709742 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA UZ452 UT WOS:A1996UZ45200008 PM 8844230 ER PT J AU Goisman, RM Zrebiec, JF AF Goisman, RM Zrebiec, JF TI Combined behavioral and psychodynamic supervision of social skills training groups SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA. JOSLIN DIABET CTR,MENTAL HLTH UNIT,BOSTON,MA 02215. RP Goisman, RM (reprint author), MASSACHUSETTS MENTAL HLTH CTR,74 FENWOOD RD,BOSTON,MA 02115, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JUL PY 1996 VL 46 IS 3 BP 417 EP 423 PG 7 WC Psychology, Clinical SC Psychology GA UV703 UT WOS:A1996UV70300011 PM 8753155 ER PT J AU Clement, PB Oliva, E Young, RH AF Clement, PB Oliva, E Young, RH TI Mullerian adenosarcoma of the uterine corpus associated with tamoxifen therapy: A report of six cases and a review of tamoxifen-associated endometrial lesions SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE uterus; tamoxifen; adenosarcoma; estrogen ID BREAST-CANCER PATIENTS; PATIENTS RECEIVING TAMOXIFEN; ADJUVANT TAMOXIFEN; POSTMENOPAUSAL WOMEN; ESTROGEN-RECEPTOR; CARCINOMA; SARCOMAS; UTERUS; STIMULATION; ADENOMYOMA AB Six consultation cases of mullerian adenosarcoma of the uterus were encountered in women who were receiving adjuvant tamoxifen therapy for carcinoma of the breast. To our knowledge, only one previous similar case has been reported. The women, who were 48-76 years of age, had received tamoxifen for periods of 6 months to 4 years (mean 2.7 years) in five of the cases; the duration of tamoxifen therapy in the sixth case is unknown. All of the tumors were polypoid endometrial masses that superficially invaded the myometrium in two cases. The microscopic appearance of the tumors was similar to that of previously described uterine mullerian adenosarcomas. These and other recent observations indicate that tamoxifen treatment may be complicated by uterine neoplasms other than endometrial adenocarcinoma. These findings also support previous observations that prolonged exogenous or endogenous hyperestrinism may lead to the development of mesenchymal and mixed epithelial-mesenchymal tumors of the uterus. C1 UNIV BRITISH COLUMBIA,DEPT PATHOL,VANCOUVER,BC,CANADA. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. RP Clement, PB (reprint author), VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,920 W 10TH,ROOM 1302,VANCOUVER,BC V5Z 4E3,CANADA. NR 59 TC 68 Z9 70 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 1996 VL 15 IS 3 BP 222 EP 229 DI 10.1097/00004347-199607000-00006 PG 8 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA UU924 UT WOS:A1996UU92400006 PM 8811383 ER PT J AU Eichhorn, JH Scully, RE AF Eichhorn, JH Scully, RE TI Endometrioid ciliated-cell tumors of the ovary: A report of five cases SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ovary; endometrioid; carcinoma; cilia; borderline tumor ID PAPILLARY SEROUS CARCINOMA; ADENOCARCINOMA AB Five patients with ovarian endometrioid tumors composed predominantly of ciliated cells are reported; two patients had bilateral neoplasms. Two unilateral, predominantly cystic ciliated-cell tumors from women in their 40s were associated with endometriosis: one was borderline and arose in an endometriotic cyst; the other was borderline with foci of carcinoma and was associated with ipsilateral ovarian and peritoneal endometriosis. Five predominantly adenofibromatous tumors in the three other women, all postmenopausal, were not associated with endometriosis. One woman with a borderline ciliated-cell adenofibroma had had a prior contralateral adnexectomy, another with a borderline ciliated-cell adenofibroma had a contralateral ciliated-cell adenofibroma, and the third woman had a ciliated-cell adenocarcinoma and a contralateral borderline ciliated-cell adenofibroma. In two of the latter three patients the fallopian tubes contained foci of ciliated-cell hyperplasia. All five ciliated-cell malignant tumors were stage I, were treated by operation alone, and had not recurred 21 to 64 (mean 39) months postoperatively. Ciliated-cell tumors of the ovary should be distinguished from serous and mixed serous and endometrioid cancers because of different pathological and possibly different clinical features. Criteria for separating endometrioid ciliated-cell tumors into benign, borderline, and malignant categories are presented; whether any of these neoplasms behaves in a clinically aggressive fashion has yet to be determined. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. RP Eichhorn, JH (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,WARREN 120,BOSTON,MA 02114, USA. NR 27 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 1996 VL 15 IS 3 BP 248 EP 256 DI 10.1097/00004347-199607000-00010 PG 9 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA UU924 UT WOS:A1996UU92400010 PM 8811387 ER PT J AU Harris, JR AF Harris, JR TI Breast-conserving therapy as a model for creating new knowledge in clinical oncology SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID PRIMARY RADIATION-THERAPY; CONSERVATIVE SURGERY; EARLY-STAGE; CANCER; RADIOTHERAPY; CHEMOTHERAPY; MASTECTOMY; RECURRENCE; CARCINOMA; PROGNOSIS C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT RADIAT ONCOL,BOSTON,MA 02115. RP Harris, JR (reprint author), HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 42 TC 19 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1996 VL 35 IS 4 BP 641 EP 648 DI 10.1016/0360-3016(96)00215-5 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA UY886 UT WOS:A1996UY88600001 PM 8690629 ER PT J AU Wallgren, A Bernier, J Gelber, RD Goldhirsch, A Roncadin, M Joseph, D CastiglioneGertsch, M AF Wallgren, A Bernier, J Gelber, RD Goldhirsch, A Roncadin, M Joseph, D CastiglioneGertsch, M TI Timing of radiotherapy and chemotherapy following breast-conserving surgery for patients with node-positive breast cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE breast cancer; breast-conserving surgery; radiation therapy ID EARLY-STAGE; RADIATION AB Purpose: A controversy exists regarding whether it is safe to delay radiation therapy until the completion of chemotherapy following breast-conserving surgery for patients with node-positive breast cancer, Within the context of two concurrent randomized clinical trials we had the opportunity to evaluate outcomes for patients who received breast irradiation after completing different durations of chemotherapy, Methods and Materials: From July 1986 to April 1993 the International Breast Cancer Study Group (IBCSG) Trial VI randomly assigned 1554 pre/perimenopausal node-positive breast cancer patients to receive cyclophosphamide, methotrexate, and fi-fluorouracil (CMF) for either three consecutive courses on months 1-3, or six consecutive courses on months 1-6, both with or without reintroduction CMF, IBCSG Trial VII randomly assigned 1266 postmenopausal node-positive breast cancer patients to receive tamoxifen for 5 years, or tamoxifen for 5 years with three early cycles of CMF, both with or without three courses of delayed CMF, Both trials allowed a choice of mastectomy, or breast-conserving surgery plus radiation therapy, and both were stratified by type of surgery, Radiotherapy was delayed until the initial block of CMF was completed; 4 or 7 months after surgery for pre/perimenopausal patients, and 2 or 4 months after surgery for postmenopausal patients, Over both trials, 718 eligible patients elected to receive breast-conserving surgery plus radiation therapy: 433 on Trial VI, and 285 on Trial VII. Four-year actuarial total failure rates (failure at any site), risks of developing distant metastases (DM at any time during observation), and overall survival (OS) were estimated using the Kaplan-Meier method, To avoid potential bias due to competing causes of failure, only patients who could be followed for at least 4 years (enrolled prior to July 1, 1990) were used to evaluate the patterns of first relapse site, Crude percents of local failure with or without other sites (LF), distant metastases including regional nodal failure (DM/RNF), or other first events (second primaries/death without recurrence) were estimated for each treatment group, For this report, an intent to treat analysis was performed at a median follow-up of 48 months, Results: No differences were found in the 4-year actuarial total failure rates, risks of developing distant metastases, and overall survival among the two radiotherapy groups of each study, The cumulative incidence of types of first failure and the 4-year crude rates showed no treatment differences in the patterns of site of first event, Estimates for the 4-year crude percent of local failures were 8 and 9% for pre/perimenopausal patients who had radiation therapy at 4 or 7 months after surgery, and 3 and 6% for postmenopausal patients who had radiation therapy at 2 months or 4 months after surgery, Conclusions: For node positive patients receiving breast-conserving surgery followed by radiation therapy, the incidence of breast recurrence in the conserved ipsilateral breast within 4 years was between 8 and 9% for pre/ perimenopausal patients and between 3 and 6% for postmenopausal patients, After 48 months of median follow-np, administering radiation therapy after three or six cycles of CMF for pre/perimenopausal women, or after no cycles or three cycles of CMF for postmenopausal women does not influence overall efficacy or local control in this series. C1 INT BREAST CANC STUDY GRP,CH-3007 BERN,SWITZERLAND. SAHLGRENS UNIV HOSP,DEPT GEN ONCOL,S-41345 GOTHENBURG,SWEDEN. OSPED CIVICO,DEPT RADIAT ONCOL,CH-6900 LUGANO,SWITZERLAND. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. OSPED CIVICO,DEPT MED ONCOL,CH-6900 LUGANO,SWITZERLAND. IST NAZL TUMORI CTR EUROPEO,CTR RIFERIMENTO ONCOL AVIANO,DIV ONCOL RADIOTERAP,AVIANO,ITALY. GEELONG HOSP,DEPT RADIAT ONCOL,GEELONG,VIC,AUSTRALIA. NR 12 TC 77 Z9 77 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1996 VL 35 IS 4 BP 649 EP 659 DI 10.1016/0360-3016(96)00186-1 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA UY886 UT WOS:A1996UY88600002 PM 8690630 ER PT J AU Martenson, JA Lipsitz, SR Wagner, H Kaplan, EH Otteman, LA Schuchter, LM Mansour, EG Talamonti, MS Benson, AB AF Martenson, JA Lipsitz, SR Wagner, H Kaplan, EH Otteman, LA Schuchter, LM Mansour, EG Talamonti, MS Benson, AB TI Initial results of a Phase II trial of high dose radiation therapy, 5-fluorouracil, and cisplatin for patients with anal cancer (E4292): An Eastern Cooperative Oncology Group Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE anal cancer; cisplatin; 5-fluorouracil; radiation therapy; sphincter preservation ID COMBINED MODALITY THERAPY; SQUAMOUS-CELL CARCINOMA; CHEMOTHERAPY; RADIOTHERAPY; IRRADIATION; MANAGEMENT AB Purpose: A prospective clinical trial was performed to assess the response and toxicity associated with the use of high dose radiation therapy, S-fluorouracil, and cisplatin in patients with anal cancer. Methods and Materials: Patients with anal cancer without distant metastasis were eligible for this study. Radiation therapy consisted of 59.4 Gy in 33 fractions; a 2 week break in treatment was taken after 36 Gy had been given. A treatment of 5-fluorouracil, 1,000 mg/m(2) per day intravenously, was given for the first 4 days of radiation therapy, and cisplatin, 75 mg/m(2) intravenously, was given on day 1 of radiation therapy. A second coarse of 5-fluorouracil and cisplatin was given after 36 Gy of radiation, when the radiation therapy was resumed. Results: Nineteen patients entered this study and received treatment. Thirteen (68%) had a complete response, 5 (26%) had a partial response, and 1 (5%) had stable disease. The patient with stable disease and one of the patients with a partial response had complete disappearance of tumor more than 8 weeks after completion of radiation therapy. Fifteen patients had toxicity of Grade 3 or higher: the worst toxicity was Grade 3 in eight patients, Grade 4 in six patients, and Grade 5 in one patient. The most common form of toxicity of Grade 3 or higher was hematologic. The one lethal toxicity was due to pseudomembranous colitis, which was a complication of antibiotic therapy for a urinary tract infection. Conclusion: Radiation therapy, cisplatin, and 5-fluorouracil resulted in an overall response rate of 95%. Significant toxicity occurred, an indication that this regimen is near the maximal tolerated dose. A Phase III clinical trial is planned in which radiation therapy, cisplatin, and 5-fluorouracil will be used as an experimental arm. C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV S FLORIDA,H LEE MOFFITT CANC CTR,TAMPA,FL 33682. N SHORE MED CTR,SKOKIE,IL. MCFARLAND CLIN,AMES,IA. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. CASE WESTERN METROHLTH MED CTR,CLEVELAND,OH. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. RP Martenson, JA (reprint author), MAYO CLIN & MAYO FDN,200 1ST ST SW,ROCHESTER,MN 55905, USA. FU NCI NIH HHS [CA13650, CA15488, CA23318] NR 20 TC 80 Z9 83 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1996 VL 35 IS 4 BP 745 EP 749 DI 10.1016/0360-3016(96)00146-0 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA UY886 UT WOS:A1996UY88600012 PM 8690640 ER PT J AU Hussey, DH Horton, JL Mendenhall, NP Munzenrider, JE Rose, CM Sunshine, JH AF Hussey, DH Horton, JL Mendenhall, NP Munzenrider, JE Rose, CM Sunshine, JH TI Manpower needs for radiation oncology: A preliminary report of the ASTRO Human Resources Committee SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID UNITED-STATES; RADIOLOGISTS C1 UNIV IOWA,COLL MED,DEPT RADIOL,DIV RADIAT ONCOL,IOWA CITY,IA. UNIV TEXAS,MD ANDERSON HOSP & TUMOR INST,DEPT RADIOTHERAPY,HOUSTON,TX 77030. UNIV FLORIDA,DEPT RADIAT ONCOL,GAINESVILLE,FL 32611. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CAMBRIDGE,MA 02138. ST JOSEPH MED CTR,DEPT RADIAT THERAPY,BURBANK,CA. AMER COLL RADIOL,PHILADELPHIA,PA. OI Mendenhall, Nancy/0000-0003-2893-7703 NR 14 TC 21 Z9 21 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1996 VL 35 IS 4 BP 809 EP 820 DI 10.1016/0360-3016(96)00209-X PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA UY886 UT WOS:A1996UY88600023 PM 8690651 ER PT J AU Hayman, J Weeks, J Mauch, P AF Hayman, J Weeks, J Mauch, P TI Economic analyses in health care: An introduction to the methodology with an emphasis on radiation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE economic analyses; cost effectiveness; cost benefit; radiation therapy; review ID CELL LUNG-CANCER; COST-EFFECTIVENESS; DECISION-ANALYSIS; RADIOTHERAPY TREATMENTS; LINEAR-ACCELERATOR; GLOTTIC CARCINOMA; NONMEDICAL COSTS; PROSTATE-CANCER; MANAGEMENT; GUIDE AB Payers are increasingly interested in knowing whether they are receiving value for the dollars they spend on health care, Because economic analyses will be used as a means of evaluating radiation therapy, it is important that radiation oncologists understand the basic methodology employed in such analyses, This review article describes the four basic types of economic analyses: cost minimization, cost effectiveness, cost utility, and cost benefit. Specification of alternative therapies, choice of perspective of the analysis, measurements of costs and benefits, and the role of discounting and sensitivity analyses are discussed. Published economic analyses that pertain directly to treatment with radiation therapy are reviewed, Finally, we close with a brief discussion of the potential areas for future economic outcomes research in radiation oncology. C1 HARVARD UNIV, SCH MED, JOINT CTR RADIAT THERAPY, BOSTON, MA 02115 USA. DANA FARBER CANC INST, DIV CANC EPIDEMIOL & CONTROL, CTR OUTCOMES & POLICY RES, BOSTON, MA 02115 USA. NR 62 TC 32 Z9 32 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1996 VL 35 IS 4 BP 827 EP 841 DI 10.1016/0360-3016(96)00172-1 PG 15 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA UY886 UT WOS:A1996UY88600025 PM 8690653 ER PT J AU Davies, RL Paster, BJ Dewhirst, FE AF Davies, RL Paster, BJ Dewhirst, FE TI Phylogenetic relationships and diversity within the Pasteurella haemolytica complex based on 16S rRNA sequence comparison and outer membrane protein and lipopolysaccharide analysis SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID POLYACRYLAMIDE GELS; STRAINS; ACTINOBACILLUS; BOVINE; CATTLE AB The outer membrane protein (OMP) and lipopolysaccharide (LPS) profiles of 30 untypeable isolates of Pasteurella haemolytica were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and compared with the profiles of typeable isolates. The phylogenetic relationships of 28 isolates representing each of the serotypes of P. haemolytica and Pasteurella trehalosi, as well as untypeable isolates of P. haemolytica, were determined by comparing 16S rRNA sequences. The analysis of the OMP and LPS profiles of the untypeable isolates revealed five groups, which were designated untypeable groups 1 (UG1) through UG5, The UG1 and UG2 isolates had OMP and LPS profiles identical to the profiles of certain serotype A1 and A2 isolates, respectively, Furthermore, UG1 isolates originating from cattle and sheep could he clearly differentiated on the basis of their OMP profiles, The OMP and LPS profiles of UG3 isolates were similar in appearance to the profiles of serotype All isolates, suggesting that these two groups are closely related, The OMP profiles of UG4 and UG5 isolates were unique and different from the OMP profiles of the UG1 through UG3 isolates, A comparison of 16S rRNA sequences revealed that typeable isolates of P. haemolytica could be divided into the following three groups: (i) serotype A1, A5 through A9, A12 through A14, and A16 isolates, (ii) serotype A2 isolates, and (iii) serotype All isolates, The isolates belonging to the first group all had identical sequences, whereas the sequences of isolates belonging to the second and third groups differed from the sequences of the isolates belonging to the first group at two and four base positions, respectively, The sequence data for the untypeable isolates confirmed the conclusions derived from the OMP and LPS analysis. Isolates belonging to UG1 and UG2 were identical to serotype Al and A2 isolates, respectively; isolates belonging to UG3 were related to serotype All isolates, although there was some sequence heterogeneity within this group; and isolates belonging to UG4 and UG5 were more distantly related to P, haemolytica than were isolates belonging to UG1 through UG3 and were clearly members of two different species, As expected, isolates of P, trehalosi were even more distantly related to P. haemolytica than were the untypeable isolates, but there was significantly more sequence variation among the four serotypes of this species than there was among the serotypes of P. haemolytica, The correlation of the OMP and LPS data with the 16S rRNA sequence data suggested that OMP and LPS analyses might be useful for preliminary screening and comparing large numbers of isolates in taxonomic and epidemiological studies of the Pasteurellaceae. C1 FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02115. RP Davies, RL (reprint author), UNIV GLASGOW,DIV INFECT & IMMUN,IBLS,JOSEPH BLACK BLDG,GLASGOW G12 8QQ,LANARK,SCOTLAND. FU Wellcome Trust NR 35 TC 28 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1996 VL 46 IS 3 BP 736 EP 744 PG 9 WC Microbiology SC Microbiology GA UW652 UT WOS:A1996UW65200019 PM 8782683 ER PT J AU Vandamme, P Vancanneyt, M VanBelkum, A Segers, P Quint, WGV Kersters, K Paster, BJ Dewhirst, FE AF Vandamme, P Vancanneyt, M VanBelkum, A Segers, P Quint, WGV Kersters, K Paster, BJ Dewhirst, FE TI Polyphasic analysis of strains of the genus Capnocytophaga and centers for disease control group DF-3 SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID CDC GROUP DF-3; POLYMERASE CHAIN-REACTION; FATTY-ACID COMPOSITION; SP-NOV; GLIDING BACTERIA; PROTEIN PROFILES; COMB-NOV; DNA; BACTEROIDES; IDENTIFICATION AB A polyphasic approach was used to determine the relationships between well-characterized reference strains representing all seven Capnocytophaga species. One Centers for Disease Control (CDC) group DF-3 strain, a presumed relative of the genus Capnocytophaga, and 15 field isolates were included as well. Fourteen isolates were assigned to named Capnocytophaga species, all of which could be differentiated by means of whole-organism protein electrophoresis, A separate position was occupied by the CDC group DF-3 strain and by one field isolate representing a novel Capnocytophaga species. The phylogenetic position of each taxon was determined by means of 16S rRNA sequence analysis. A considerable genotypic heterogeneity within the genus Capnocytophaga was detected in spite of the minimal phenotypic differences. Comparative 16S rRNA sequence analysis revealed that CDC group DF-3 is not a close relative of the capnocytophagas but constitutes a separate genus that clusters together with Bacteroides forsythus and Bacteroides distasonis, two generically misclassified Bacteroides species. The degree of protein similarity correlated with our and published DNA-DNA binding values. Percentage 16S rRNA similarity values of greater than 97% did not guarantee conspecificity. All Capnocytophaga strains had very similar fatty acid contents characterized by significant amounts of 14:0, 15:0 iso (greater than 55%), 16:0, 16:0 3OH, and 17:0 iso 3OH, PCR-mediated DNA fingerprinting allowed discrimination of most species, although some strains could not be classified efficiently because of DNA polymorphisms. C1 UNIV ANTWERP HOSP,DEPT MICROBIOL,ANTWERP,BELGIUM. UNIV ROTTERDAM HOSP,DEPT BACTERIOL,ROTTERDAM,NETHERLANDS. SSDZ,CTR DIAGNOST,DEPT MOLEC BIOL,DELFT,NETHERLANDS. FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02115. RP Vandamme, P (reprint author), STATE UNIV GHENT,MICROBIOL LAB,LEDEGANCKSTR 35,B-9000 GHENT,BELGIUM. RI Vandamme, Peter/B-7967-2009; OI Vandamme, Peter/0000-0002-5581-7937 FU NIDCR NIH HHS [I ROI DE08303, I ROI DE10374] NR 56 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1996 VL 46 IS 3 BP 782 EP 791 PG 10 WC Microbiology SC Microbiology GA UW652 UT WOS:A1996UW65200026 PM 8782690 ER PT J AU Grillo, HC AF Grillo, HC TI The education and qualification of thoracic surgeons in the USA SO INTERNATIONAL SURGERY LA English DT Article RP Grillo, HC (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. RI International Surgery, ICS/D-3993-2011 NR 0 TC 5 Z9 5 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0020-8868 J9 INT SURG JI Int. Surg. PD JUL-SEP PY 1996 VL 81 IS 3 BP 218 EP 223 PG 6 WC Surgery SC Surgery GA WF361 UT WOS:A1996WF36100002 PM 9028976 ER PT J AU Vorwerk, CK Lipton, SA Zurakowski, D Hyman, BT Sabel, BA Dreyer, EB AF Vorwerk, CK Lipton, SA Zurakowski, D Hyman, BT Sabel, BA Dreyer, EB TI Chronic low-dose glutamate is toxic to retinal ganglion cells - Toxicity blocked by memantine SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE chronic; glaucoma; glutamate; memantine; N-methyl-D-aspartate; retinal ganglion cells ID RECEPTOR-MEDIATED NEUROTOXICITY; ISCHEMIC NEURONAL DEGENERATION; NMDA RECEPTOR; PARKINSONS-DISEASE; ASPARTATE; MK-801; CULTURE; BRAIN; CHANNELS; CORTEX AB Purpose. It is well known that acute exposure to high concentrations of glutamate is toxic to central mammalian neurons. However, the effect of a chronic, minor elevation over endogenous glutamate levels has not been explored. The authors have suggested that such chronic exposure may play a role in glaucomatous neuronal loss. In the current study, they sought to explore whether a chronic, low-dose elevation in vitreal glutamate was toxic to retinal ganglion cells and whether this toxicity could be prevented with memantine, a glutamate antagonist. Methods. Rats were injected serially and intravitreally with glutamate to induce chronic elevations in glutamate concentration. A second group of rats was treated with intraperitoneal memantine and glutamate. Control groups received vehicle injection with or without concurrent memantine therapy. After 3 months, the animals were killed, and ganglion cell survival was evaluated, Results. Intravitreal injections raised the intravitreal glutamate levels from an endogenous range of 5 to 12 mu M glutamate to 26 to 34 mu M. This chronic glutamate elevation killed 42% of the retinal ganglion cells after 3 months. Memantine treatment alone had no effect on ganglion cell survival. However, when memantine was given concurrently with low-dose glutamate, memantine was partially protective against glutamate toxicity. Conclusions. These data suggest that minor elevations in glutamate concentration can be toxic to ganglion cells if this elevation is maintained for 3 months. Furthermore, memantine is efficacious at protecting ganglion cells from chronic low-dose glutamate toxicity. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. CHILDRENS HOSP,MOLEC & CELLULAR NEUROSCI LAB,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. OTTO VON GUERICKE UNIV,INST MED PSYCHOL,MAGDEBURG,GERMANY. RI Sabel, Bernhard/E-6579-2013; OI Sabel, Bernhard/0000-0002-4472-5543 FU NEI NIH HHS [R01-EY05477, R01-EY10009] NR 45 TC 213 Z9 226 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 1996 VL 37 IS 8 BP 1618 EP 1624 PG 7 WC Ophthalmology SC Ophthalmology GA UW831 UT WOS:A1996UW83100019 PM 8675405 ER PT J AU Sandberg, MA WeigelDiFranco, C Rosner, B Berson, EL AF Sandberg, MA WeigelDiFranco, C Rosner, B Berson, EL TI The relationship between visual field size and electroretinogram amplitude in retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE electroretinogram; gene; retinitis pigmentosa; rhodopsin; visual field ID VITAMIN-A; SUPPLEMENTATION; ROD AB Purpose. To determine to what degree visual field size is correlated with electroretinogram (ERG) amplitude among patients with the common forms of retinitis pigmentosa (RP). Methods. Visual field equivalent diameter to the V4e white test light of the Goldmann perimeter was correlated with log ERG amplitude elicited by 0.5 Hz or 30 Hz full-field flashes of white light. Primary analyses were conducted on data from 583 patients with the common forms of RP. Subset analyses were performed on data from patients with ERG responses with different ranges of amplitude to assess to what extent the correlation depends on ERG amplitude, as well as on data from patients of a given genetic type to determine whether the correlation depends on the mode of transmission. Data from patients with the rhodopsin, Pro23His mutation (n = 38) or with the rhodopsin, Pro347Leu mutation (n = 24) were analyzed to determine the correlation between visual field size and ERG amplitude for patients with the same mutation. Results, Visual field size was significantly correlated with ERG amplitude for every comparison (P less than or equal to 0.0003). Correlations generally were higher for ERGs elicited by 30 Hz flashes (r = 0.62 for the entire sample) than they were for those elicited by 0.5 Hz flashes (r = 0.53 for the entire sample). They were lower for truncated ranges of ERG amplitude, higher for patients with dominant or recessive disease than for patients with x-linked disease or for patients of all genetic types combined, and strong for patients with the same rhodopsin mutation (reaching a value of 0.87). Conclusions, Visual field size is significantly correlated with ERG amplitude for patients with RP. Correlation depends on the range of ERG amplitudes, the inheritance type, and, particularly, on whether the analysis is confined to a single gene mutation. RP Sandberg, MA (reprint author), HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, SCH MED, BERMAN GUND LAB STUDY RETINAL DEGENERAT, BOSTON, MA 02114 USA. FU NEI NIH HHS [EY00169, EY02014] NR 10 TC 41 Z9 44 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 1996 VL 37 IS 8 BP 1693 EP 1698 PG 6 WC Ophthalmology SC Ophthalmology GA UW831 UT WOS:A1996UW83100027 PM 8675413 ER PT J AU Teixeira, J Donahoe, PK AF Teixeira, J Donahoe, PK TI Molecular biology of MIS and its receptors SO JOURNAL OF ANDROLOGY LA English DT Review ID MULLERIAN-INHIBITING SUBSTANCE; TGF-BETA FAMILY; EXPRESSION; HORMONE; TESTIS; GENE C1 MASSACHUSETTS GEN HOSP,DEPT SURG,PEDIAT SURG RES LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 20 TC 28 Z9 29 U1 0 U2 1 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 SN 0196-3635 J9 J ANDROL JI J. Androl. PD JUL-AUG PY 1996 VL 17 IS 4 BP 336 EP 341 PG 6 WC Andrology SC Endocrinology & Metabolism GA VK243 UT WOS:A1996VK24300006 PM 8889695 ER PT J AU Chuang, LM Tai, TY Kahn, RC Wu, HP Lee, SC Lin, BJ AF Chuang, LM Tai, TY Kahn, RC Wu, HP Lee, SC Lin, BJ TI Signal transduction pathways for interleukin 4 and insulin in human hepatoma cells SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE hepatoma cells; insulin; interleukin 4; JAK kinases; signal transduction ID STIMULATES TYROSINE PHOSPHORYLATION; GROWTH-FACTOR-I; RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3'-KINASE; HEMATOPOIETIC-CELLS; XENOPUS-OOCYTES; KINASE-ACTIVITY; MYELOID CELLS; IRS-1; EXPRESSION AB IRS-1 has been found to relay the signals from the receptors for insulin, insulin-like growth factor-1, growth hormone, and many cytokines for the downstream effects in the various cell types tested, For interleukin 4 signaling, most studies were performed on hematopoietic cells and cell lines transfected with rat liver IRS-1 cDNA, In a liver cell lineage, IRS-1 expression has been found to be increased in hepatoma cells and hepatocytes in regenerating liver, To elucidate the possible function and the signal transduction pathway for interleukin 4, in comparison with insulin, in liver cells, we used the Hep 3B hepatoma cell line as a model system, Following insulin and interleukin 4 stimulation, rapid tyrosyl phosphorylation of IRS-1 occurred, Interleukin 4, but not insulin, stimulated the tyrosine phosphorylation of JAK1 and, to a lesser extent, JAK2, In contrast to the other cell types, the association of IRS-1 and Grb2 through the SH2 of Grb2 was demonstrated after IL-4 and insulin stimulation of the Hep3B hepatoma cells, Both insulin and interleukin 4 stimulated tyrosine phosphorylation and the enzyme activity of Erk1 kinase, Our results indicate that interleukin 4 and insulin might modulate hepatic cell growth and differentiation through many different or common pathways for the activation of JAK kinases and the usage of IRS-1 as a docking protein, The binding of IRS-1 with Grb2 after IL-4 as well as insulin stimulation may lead to MAP kinase activation, probably through the Grb2/sos/p21(ras) pathway. C1 NATL TAIWAN UNIV,COLL MED,GRAD INST MOLEC MED,TAIPEI 10764,TAIWAN. NATL TAIWAN UNIV,COLL MED,MED CLIN,TAIPEI 10764,TAIWAN. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DEPT MED,RES DIV,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MOLEC & CELLULAR PHYSIOL,BOSTON,MA 02215. RP Chuang, LM (reprint author), NATL TAIWAN UNIV,COLL MED,DEPT INTERNAL MED,TAIPEI 10764,TAIWAN. OI CHUANG, LEE-MING/0000-0003-0978-2662 NR 41 TC 15 Z9 15 U1 0 U2 0 PU JAPAN BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F 25-16 HONGO-5-CHOME, TOKYO TOKYO 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD JUL PY 1996 VL 120 IS 1 BP 111 EP 116 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY256 UT WOS:A1996UY25600018 PM 8864852 ER PT J AU Grimes, RY Hopmeyer, J Cape, EG Levine, RA Yoganathan, AP AF Grimes, RY Hopmeyer, J Cape, EG Levine, RA Yoganathan, AP TI How sensitive are jet centerline velocities to an opposing flow? Implications for using the centerline method to quantify regurgitant jet flow SO JOURNAL OF BIOMECHANICS LA English DT Article ID MITRAL REGURGITATION; PULSED DOPPLER; ECHOCARDIOGRAPHY AB A method for quantifying peak mitral and tricuspid regurgitant jet flow rate that utilizes a measure of jet orifice velocity (U-o, ms(-1)), a distal centerline velocity (U-m, ms(-1)), and the intervening distance (X, cm) was recently developed. This method, however, modeled the regurgitant jet as a free jet, whereas many atrial jets are counterflowing jets because of jet opposing intra-atrial flow fields (counterflows). This study evaluated the feasibility of using the free jet quantification equation in the atrium where ambient how fields may alter jet centerline velocities and therefore reduce the accuracy of jet flow rate calculations. A 4 cm wide chamber was used to pump counterflows of 0, 4, and 22 cm s(-1) against jets of 2.3, 4.8, and 6.4 m s(-1) originating from a 2 mm diameter orifice. For each counterflow-jet combination, jet centerline velocities were measured using laser Doppler anemometry. For free jets (no counterflow), how rate was calculated with 98% mean accuracy. For all jets in counterflow, the calculation was less accurate as (i) the ratio of jet orifice velocity to counterflow velocity decreased (U-o/U-c, where U(c)is counterflow velocity), i.e. the counterflow was relatively more intense, and (ii) centerline measurements were made further from the orifice. But although counterflow lowered jet centerline velocities beneath free jet values, it did so only significantly in the jet's distal portion, while the initial portion (X/D < 16, where D is jet orifice diameter) of a jet in counterflow behaved essentially as a free jet. Therefore, regurgitant jets, although not classically Free because of systolic atrial inflow, will decay in their initial portions as Free jets and hence are candidates for quantification with the centerline technique. Copyright (C) 1996 Elsevier Science Ltd. C1 GEORGIA INST TECHNOL,SCH MECH ENGN,CARDIOVASC FLUID MECH LAB,ATLANTA,GA 30332. UNIV PITTSBURGH,CHILDRENS HOSP PITTSBURGH,DIV PEDIAT CARDIOL,PITTSBURGH,PA 15213. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIAC ULTRASOUND LAB,BOSTON,MA. RP Grimes, RY (reprint author), GEORGIA INST TECHNOL,SCH CHEM ENGN,ATLANTA,GA 30332, USA. FU NHLBI NIH HHS [HL-45485] NR 14 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD JUL PY 1996 VL 29 IS 7 BP 967 EP 971 DI 10.1016/0021-9290(95)00150-6 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA UV350 UT WOS:A1996UV35000015 PM 8809628 ER PT J AU Lewandrowski, KU Venugopalan, V Tomford, WW Schomacker, KT Mankin, HJ Deutsch, TF AF Lewandrowski, KU Venugopalan, V Tomford, WW Schomacker, KT Mankin, HJ Deutsch, TF TI Kinetics of cortical bone demineralization: Controlled demineralization - A new method for modifying cortical bone allografts SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID DIFFERENTIATION; MATRIX AB We investigated the kinetics of hydrochloric acid demineralization of human cortical bone with the objective of developing a method of controlled demineralization for structural bone allografts. It is known that the demineralization of cortical bone is a diffusion rate limited process with a sharp advancing reaction front. The demineralization kinetics of human cortical bone, described as the advance of the reaction front versus immersion time, were determined by measuring extraction of bone mineral in both planar and cylindrical geometries. Mathematical models based on diffusional mass transfer were developed to predict this process. The experimental data fit well with the behavior predicted by the model. The model for planar geometry is applicable to controlled demineralization of cortical bone allografts of irregular shapes such as cortical struts. The model for cylindrical geometry is appropriate when curved surfaces are involved such as in diaphyseal bone allografts. This method of demineralization has direct application to clinical modification of cortical bone allografts to potentially enhance their osteoinductive properties. (C) 1996 John Wiley & Sons, Inc. C1 MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ORTHOPAED RES LAB,BOSTON,MA 02114. FU NIAMS NIH HHS [AR-21896] NR 25 TC 20 Z9 20 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD JUL PY 1996 VL 31 IS 3 BP 365 EP 372 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA UU786 UT WOS:A1996UU78600010 PM 8806062 ER PT J AU Magae, J Wu, CL Illenye, S Harlow, E Heintz, NH AF Magae, J Wu, CL Illenye, S Harlow, E Heintz, NH TI Nuclear localization of DP and E2F transcription factors by heterodimeric partners and retinoblastoma protein family members SO JOURNAL OF CELL SCIENCE LA English DT Article DE gene expression; cell cycle; protein trafficking ID CELL-CYCLE PROGRESSION; DNA-BINDING ACTIVITY; S-PHASE ENTRY; GENE-PRODUCT; COMPLEX-FORMATION; MOUSE E2F1; P107; RB; EXPRESSION; TRANSACTIVATION AB E2F is a family of transcription factors implicated in the regulation of genes required for progression through G(1) and entry into the S phase. The transcriptionally active forms of E2F are heterodimers composed of one polypeptide encoded by the E2F gene family and one polypeptide encoded by the DP gene family. The transcriptional activity of E2F/DP heterodimers is influenced by association with the members of the retinoblastoma tumor suppressor protein family (pRb, p107, and p130). Here the intracellular distribution of E2F and DP proteins was investigated in transiently transfected Chinese hamster and human cells. In transfected cells, DP-1 did not accumulate in the nucleus unless it was coexpressed with the heterodimeric partners E2F-1, E2F-2, or E2F-3. Domain mapping experiments showed that regions of E2F-1 and DP-1 that are required for stable association of the two proteins were also required for nuclear localization of DP-1. Unlike E2F-1, -2, and -3, E2F-4 did not accumulate in the nucleus unless it was coexpressed with DP-2. p107 and p130, but not pRb, stimulated nuclear localization of E2F-4, either alone or in combination with DP-2. These results indicate that DP proteins preferentially associate with specific E2F partners, and suggest that the ability of specific E2F/DP heterodimers to localize in the nucleus contributes to the regulation of E2F activity. C1 UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. NR 76 TC 109 Z9 112 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUL PY 1996 VL 109 BP 1717 EP 1726 PN 7 PG 10 WC Cell Biology SC Cell Biology GA UX930 UT WOS:A1996UX93000007 PM 8832394 ER PT J AU Panterne, B Hatzfeld, A Sansilvestri, P Cardoso, A Monier, MN Batard, P Hatzfeld, J AF Panterne, B Hatzfeld, A Sansilvestri, P Cardoso, A Monier, MN Batard, P Hatzfeld, J TI IL-3, GM-CSF and CSF-1 modulate c-fms mRNA more rapidly in human early monocytic progenitors than in mature or transformed monocytic cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE c-fms; down-modulation; cytokine; hematopoietic progenitor; monocyte ID COLONY-STIMULATING FACTOR; FACTOR-I RECEPTOR; HEMATOPOIETIC STEM-CELLS; BONE-MARROW PROGENITORS; GROWTH-FACTOR RECEPTORS; PROTO-ONCOGENE PRODUCT; GENE-EXPRESSION; INSITU HYBRIDIZATION; DOWN-MODULATION; DIFFERENTIATION AB We have previously shown that a low concentration of CSF-1 (1 U/ml) can trigger human immature monocytic progenitor proliferation in the presence of low concentrations of IL3 (1.7 U/ml). No c-fins down-regulation was observed during this early cell activation. In contrast, 20 U/ml of CSF-1, active on late monocytic cell growth, downregulated c-fms mRNA expression in immature progenitors and monocytes derived from bone marrow CD34(+) cells in culture, We have now extended this study to include the effects of various concentrations of GM-CSF, IL3 and G-CSF on c-fms expression, We observed that high doses of GM-CSF or IL3 down-modulated c-fms mRNA, whereas low doses of GM-CSF or IL3, which were active on early monocytic growth, had no such effect. Similar results were observed at the protein level, In contrast, whatever the concentration, G-CSF had no effect on c-fms mRNA or protein levels. We further observed that the more immature the c-fms expressing progenitors, the faster the down-medulation of this receptor, This was observed within less than 1 hour for immature bone marrow cells, 6 hours for peripheral blood monocytes and even longer far transformed monocytic cells. These results suggest that oncogene expression can be regulated much more rapidly in immature progenitors than was previously observed in mature cells or transformed cell lines. C1 CNRS,IFC1,UPR 9044,F-94801 VILLEJUIF,FRANCE. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. RI HATZFELD, Antoinette/I-2341-2013; HATZFELD, Jacques/I-2346-2013 OI HATZFELD, Antoinette/0000-0002-9147-533X; HATZFELD, Jacques/0000-0002-3468-6659 NR 37 TC 10 Z9 10 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUL PY 1996 VL 109 BP 1795 EP 1801 PN 7 PG 7 WC Cell Biology SC Cell Biology GA UX930 UT WOS:A1996UX93000015 PM 8832402 ER PT J AU Zuk, A Matlin, KS AF Zuk, A Matlin, KS TI Apical beta 1 integrin in polarized MDCK cells mediates tubulocyst formation in response to type I collagen overlay SO JOURNAL OF CELL SCIENCE LA English DT Article DE beta 1 integrin; epithelial polarity; tubulocyst; MDCK ID CANINE KIDNEY-CELLS; ACUTE-RENAL-FAILURE; EPITHELIAL-CELLS; EXTRACELLULAR-MATRIX; SURFACE POLARITY; ADHESION MOLECULES; ENDOTHELIAL-CELLS; MEMBRANE DOMAINS; TIGHT JUNCTIONS; RECEPTORS AB A number of epithelia form tubulocysts in vitro when overlaid with type I collagen gel. Because collagen receptors are generally believed to be expressed on the basolateral domain, the mechanism by which collagen elicits this morphogenetic response from the apical surface is unclear, To investigate the role of beta 1 integrins, the major receptor family for collagen, in this process, we overlaid polarized monolayers of MDCK II cells grown on permeable supports with type I collagen gel and correlated integrin polarity with the polarity of other apical and basolateral membrane markers during tubulocyst formation, Polarized monolayers of one clone of MDCK II cells, referred to as Heidelberg MDCK, initially respond to collagen overlay by stratifying; within 48 hours, lumena develop between the cell layers giving rise to tubulocysts, Tight junctions remain intact during tubulocyst formation because transepithelial electrical resistance does not significantly change, Major alterations are observed, however, in the expression and localization of apical and basolateral membrane markers. beta 1 integrins are necessary for tubulocyst morphogenesis because a function-blocking antibody administered to the apical pole of the cells completely inhibits the formation of these structures, To determine how apical-cell collagen interactions elicit tubulocyst formation, we examined whether beta 1 integrins are mobilized to apical plasma membranes in response to collagen overlay. We found that in the absence of collagen, polarized monolayers of Heidelberg MDCK cells endogenously express on apical plasma membranes a small pool of the beta 1 family, including alpha 2 beta 1 and alpha 3 beta 1. Collagen overlay does not mobilize additional beta 1 integrins to apical domains, If beta 1 integrins are not already apically expressed, as in the C6 MDCK cell line (Schoenenberger et al, (1994) J. Cell Biol. 107, 527-541), beta 1 integrins are not directed apically and tubulocysts do not develop in response to collagen, Thus, interaction of beta 1 integrins pre-existing on apical plasma membranes of polarized epithelia with type I collagen gel is the mechanism by which apical application of collagen elicits the formation of tubulocysts, Depolarized integrins on apical plasma membranes of polarized epithelia may be relevant to the pathogenesis of disease and injury. C1 HARVARD UNIV,SCH MED,DEPT MED,CHARLESTOWN,MA 02129. RP Zuk, A (reprint author), MASSACHUSETTS GEN HOSP,RENAL UNIT,149TH 13TH ST,CHARLESTOWN,MA 02129, USA. FU NIDDK NIH HHS [R01 DK46768, P01 DK38452, P30 DK43351] NR 71 TC 41 Z9 41 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUL PY 1996 VL 109 BP 1875 EP 1889 PN 7 PG 15 WC Cell Biology SC Cell Biology GA UX930 UT WOS:A1996UX93000023 PM 8832410 ER PT J AU Ayata, C Ma, JY Meng, W Huang, P Moskowitz, MA AF Ayata, C Ma, JY Meng, W Huang, P Moskowitz, MA TI L-NA-sensitive rCBF augmentation during vibrissal stimulation in type III nitric oxide synthase mutant mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE nitric oxide; cerebral blood flow; mice; knockout; coupling ID CEREBRAL BLOOD-FLOW AB Regional cerebral blood flow (rCBF) was studied in type III nitric oxide (NO) synthase (endothelial, eNOS) mutant and wild type mice during mechanical whisker stimulation before and after nitro-L-arginine (L-NA) superfusion using the closed cranial window technique. rCBF increased equally in cortical barrel fields in both strains during stimulation, as measured by laser Doppler-flowmetry, and was inhibited by L-NA superfusion (1 mM) in both groups. Hence, coupling of blood flow and metabolism appears neuronal NOS- (nNOS) but not eNOS-dependent in cortical barrel fields of the mouse. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROSURG & NEUROL,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT MED,CHARLESTOWN,MA 02129. RI Moskowitz, Michael/D-9916-2011 NR 10 TC 69 Z9 69 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 1996 VL 16 IS 4 BP 539 EP 541 PG 3 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA UU348 UT WOS:A1996UU34800002 PM 8964791 ER PT J AU Kawamata, T Alexis, NE Dietrich, WD Finklestein, SP AF Kawamata, T Alexis, NE Dietrich, WD Finklestein, SP TI Intracisternal basic fibroblast growth factor (bFGF) enhances behavioral recovery following focal cerebral infarction in the rat SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE basic fibroblast growth factor; cerebral infarction; behavior; recovery ID ARTERY OCCLUSION; CONSEQUENCES; BRAIN AB Basic fibroblast growth factor (bFGF) is a potent neurotrophic agent that promotes neuronal survival and outgrowth. Previous studies have shown that bFGF, administered intraventricularly or intravenously before or within hours after ischemia, reduces infarct size and neurological deficits in models of focal cerebral ischemia in rats. In the current study, we tested the hypothesis that bFGF, administered at later time points after ischemia, might improve behavioral recovery without affecting infarct size. Mature Sprague-Dawley rats received bFGF(I mu g/injection) or vehicle by biweekly intracisternal injection for 4 weeks, starting at 1 day following permanent proximal middle cerebral artery (MCA) occlusion. Animals were examined every other day using four different behavioral tests to assess sensorimotor and reflex function. At 4 weeks after ischemia, there was no difference in infarct volume between bFGF- and vehicle-treated animals. There was, however, an enhancement in the rate and degree of behavioral recovery among bFGF-treated animals, as measured by all four tests. There were no apparent side effects of bFGF treatment, except that bFGF-treated animals tended to recover body weight more slowly than did vehicle-treated animals following stroke. The mechanisms of enhancement of behavioral recovery by bFGF require further study, but may include protection against retrograde neuronal death and/or stimulation of neuronal sprouting. C1 MASSACHUSETTS GEN HOSP EAST, CNS, GROWTH FACTOR RES LAB, DEPT NEUROL, CHARLESTOWN, MA 02129 USA. MASSACHUSETTS GEN HOSP EAST, CNS, GROWTH FACTOR RES LAB, DEPT NEUROSURG, CHARLESTOWN, MA 02129 USA. UNIV MIAMI, SCH MED, DEPT NEUROL, CEREBRAL VASC DIS RES CTR, MIAMI, FL USA. FU NINDS NIH HHS [P01 NS10828] NR 19 TC 121 Z9 131 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 1996 VL 16 IS 4 BP 542 EP 547 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA UU348 UT WOS:A1996UU34800003 PM 8964792 ER PT J AU Hara, H Huang, PL Panahian, N Fishman, MC Moskowitz, MA AF Hara, H Huang, PL Panahian, N Fishman, MC Moskowitz, MA TI Reduced brain edema and infarction volume in mice lacking the neuronal isoform of nitric oxide synthase after transient MCA occlusion SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain edema; brain infarction; mutant mice; neuronal nitric oxide synthase; regional cerebral blood flow; transient focal ischemia ID FOCAL CEREBRAL-ISCHEMIA; SUPEROXIDE-DISMUTASE; RAT ISOCORTEX; MODEL; INHIBITION; INJURY; MESSENGER; INJECTION; RADICALS; MOUSE AB Infarct volume and edema were assessed after transient focal ischemia in mice lacking neuronal nitric oxide synthase (NOS) gene expression. With use of an 8-0 coated monofilament, the middle cerebral artery (MCA) of mutant (n = 32) and wild-type mice [SV-129 (n = 31), C57Black/6 (n = 18)] were occluded for 3 h and reperfused for up to 24 h, Regional CBF (rCBF), neurological deficits, water content, and infarct volume were examined in all three strains, rCBF, blood pressure, and heart rate did not differ between groups when measured for 1 h after reperfusion. Neurological deficits were less severe in mutant mice after MCA occlusion. Brain water content at 3 h after reperfusion and infarct volume at 24 h after reperfusion were greater in wild-type mice. These data indicate that genetic deletion of neuronal NOS confers resistance to focal ischemic injury in a reperfusion model. The findings agree with previous studies showing that tissue injury is less extensive after both permanent MCA occlusion and global ischemia in mice lacking neuronal NOS gene expression, Hence, NO may play a pivotal role in the pathogenesis of ischemic brain damage. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,NEUROL SERV,STROKE & NEUROVASC REGULAT LAB,DEPT SURG,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROL,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT MED,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828, NS2683, NS33335] NR 46 TC 319 Z9 331 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 1996 VL 16 IS 4 BP 605 EP 611 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA UU348 UT WOS:A1996UU34800010 PM 8964799 ER PT J AU Ohta, K Pang, XP Berg, L Hershman, JM AF Ohta, K Pang, XP Berg, L Hershman, JM TI Antitumor actions of cytokines on new human papillary thyroid carcinoma cell lines SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TUMOR-NECROSIS-FACTOR; PROGNOSTIC FACTORS; FACTOR-ALPHA; MOLECULAR-CLONING; MESSENGER-RNA; CANCER; GROWTH; THYROTROPIN; ACTIVATION; SURVIVAL AB To investigate the in vitro effects of cytokines on the growth of human papillary thyroid carcinoma (PTC) cells, we established six new PTC cell lines, designated BHP 5, 14, 15, 17, 18, and 19, from different patients. We studied the antiproliferative actions of cytokines by using BHP cells, NP cells (PTC cell. line), and ARO cells (anaplastic thyroid carcinoma cell line). These cells were treated with various concentrations of tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma), interleukin-1 beta (IL-1 beta), and transforming growth factor-beta 1 (TGF beta 1), alone and in combination. Cell proliferation was assessed by [H-3]thymidine incorporation and cell number measurement. In BHP cell lines, IFN gamma, IL-1 beta, and TGF beta 1 inhibited [H-3]thymidine incorporation and decreased cell number, but TNF alpha stimulated [H-3]thymidine incorporation. In NP cells, treatment with each cytokine decreased [H-3]thymidine incorporation and cell number. In contrast, the proliferation of ARO cells was either stimulated by or resistant to TNF alpha, IL-1 beta, and TGF beta 1. The effects of these cytokines on [H-3]thymidine incorporation were additive in these cell lines. The results suggest that IL-1 beta and TGF beta 1 play a pivotal role in growth inhibition of PTC cells, and the escape from negative control of IL-1 beta and TGF beta 1 may be a step toward anaplastic changes. The additive effects of these cytokines suggest that they act through different pathways. C1 UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, ENDOCRINE RES LAB, LOS ANGELES, CA 90073 USA. FU NCI NIH HHS [CA-61863] NR 26 TC 43 Z9 43 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1996 VL 81 IS 7 BP 2607 EP 2612 DI 10.1210/jc.81.7.2607 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UW842 UT WOS:A1996UW84200034 PM 8675585 ER PT J AU Pausova, Z Soliman, E Amizuka, N Janicic, N Konrad, EM Arnold, A Goltzman, D Hendy, GN AF Pausova, Z Soliman, E Amizuka, N Janicic, N Konrad, EM Arnold, A Goltzman, D Hendy, GN TI Role of the RET proto-oncogene in sporadic hyperparathyroidism and in hyperparathyroidism of multiple endocrine neoplasia type 2 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MEDULLARY-THYROID CARCINOMA; PARATHYROID CARCINOMA; MOLECULAR-CLONING; TYROSINE KINASE; II ONCOGENE; MEN 2A; PROTOONCOGENE; MUTATIONS; GENE; TUMORS AB Parathyroid tumors occur either sporadically or as part of inherited syndromes such as multiple endocrine neoplasia (MEN) types 2A and 2B. The development of both of these familial syndromes has been related to specific germline gain-of-function mutations predominantly in exons 10 and 11 (MEN 2A) and 16 (MEN 2B) of the RET proto-oncogene. The same mutations have also been implicated in the pathogenesis of sporadic medullary thyroid carcinoma and sporadic pheochromocytoma. The RET mutations are thought to have a transforming effect only in cells of neural crest origin such as thyroid parafollicular (C-cells) and adrenal chromaffin cells, which normally express the RET proto-oncogene. Expression of RET messenger RNA has not yet been studied in the parathyroid, however, we demonstrate in this study by a sensitive, semiquantitative RT-PCR technique and in situ hybridization, that RET is expressed in MEN 2A parathyroid tumors and in sporadic adenomas. Although DNA from a parathyroid tumor of a MEN 2A patient displayed an expected mutation, none of the previously described MEN 2A or 2B mutations were found in DNA of 34 sporadic adenomas. Our data suggest that parathyroid disease is an integral part of the MEN 2A syndrome, but that MEN 2 mutations in RET rarely play a part in the pathogenesis of sporadic parathyroid tumors. C1 ROYAL VICTORIA HOSP, CALCIUM RES LAB, MONTREAL, PQ H3A 1A1, CANADA. MCGILL UNIV, DEPT MED, MONTREAL, PQ H3A 2T5, CANADA. MCGILL UNIV, DEPT PHYSIOL, MONTREAL, PQ H3A 2T5, CANADA. MASSACHUSETTS GEN HOSP, LAB ENDOCRINE ONCOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NCI NIH HHS [CA-55909]; NIDDK NIH HHS [DK-11794] NR 55 TC 41 Z9 41 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1996 VL 81 IS 7 BP 2711 EP 2718 DI 10.1210/jc.81.7.2711 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UW842 UT WOS:A1996UW84200049 PM 8675600 ER PT J AU Mashimo, H He, XD Huang, PL Fishman, MC Goyal, RK AF Mashimo, H He, XD Huang, PL Fishman, MC Goyal, RK TI Neuronal constitutive nitric oxide synthase is involved in murine enteric inhibitory neurotransmission SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE VIP; ATP; inhibitory junction potential; smooth muscle; transgenic ID VASOACTIVE INTESTINAL POLYPEPTIDE; INTERNAL ANAL-SPHINCTER; GUINEA-PIG ILEUM; SMOOTH-MUSCLE; PEPTIDE-VIP; TAENIA-COLI; STIMULATION; MEDIATOR; RELAXATION; RELEASE AB Mice lacking neuronal nitric oxide synthase gene (ncNOS) were used to determine the enzymatic source of nitric oxide (NO) and its relationship with other putative inhibitory neurotransmitters. Inhibitory junction potentials (IJP) of circular smooth muscle of gastric fundus were studied, The IJP in the wild-type mise consists of overlapping components, the fast and slow IJPs. NOS inhibitor L-NA or VLP receptor antagonist VIP10-28, blocks the slow IJP but not the fast IJP, The fast IJP is blocked by alpha-beta methylene ATP tachyphylaxis, by reactive blue 2, and by apamin. The IJP in the ncNOS-deficient [ncNOS(-)] mutant is of short duration and is abolished by blockers of the fast IJP, but is unaffected by blockers of the slow IJP. Exogenous VIP produces membrane hyperpolarization in strips from wild-type bur not ncNOS(-) mice, The hyperpolarizing action of VIP is resistant to nifedipine but is sensitive to omega-conotoxin GVIA. In conclusion: (a) NO derived from ncNOS is an inhibitory neurotransmitter rather than a postjunctional mediator; (b) VLP is a prejunctional neurotransmitter that causes release of evanescent NO; and (c) ATP acts in parallel with the IP/NO pathway. (J. Clin. Invest. 1996. 98:8-13.). C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. VET ADM MED CTR W ROXBURY,CTR SWALLOWING & MOTIL DISORDERS,BOSTON,MA 02132. FU NIDDK NIH HHS [DK-07191-20]; NINDS NIH HHS [P01 NS 10828-19, R01-NS 33335] NR 35 TC 91 Z9 91 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 1 PY 1996 VL 98 IS 1 BP 8 EP 13 DI 10.1172/JCI118781 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UW362 UT WOS:A1996UW36200004 PM 8690808 ER PT J AU Weissmann, LB Corson, JM Neugut, AI Antman, KH AF Weissmann, LB Corson, JM Neugut, AI Antman, KH TI Malignant mesothelioma following treatment for Hodgkin's disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PERITONEAL MESOTHELIOMA; LUNG-CANCER; LEUKEMIA; RADIOTHERAPY; RISK; BONE AB Purpose: Asbestos exposure is the major known risk factor for mesothelioma, but several case reports have suggested ct link between radiation therapy and subsequent development of malignant mesothelioma, This report explores a possible association between radiation therapy for Hodgkin's disease and mesothelioma. Patients and Methods: Four cases of malignant mesothelioma were observed following Hodgkin's disease at the Mesothelioma Clinic of the Dana-Farber Cancer institute, A fifth such patient was found after a review of the literature. Results: In all five cases, the mesothelioma arose in the field of prior radiotherapy, No history of asbestos exposure wets elicited by careful questioning or by review of chest radiographs. Examination of lung tissue in one patient showed 250 ferruginous bodies per gram of lung tissue, consistent with no significant prior exposure, The mean interval between radiation treatment for Hodgkin's disease and development of mesothelioma was 15 years, which emphasizes the need for continued follow-up and evaluation of these patients and supports a causal relationship. Conclusion: Mesothelioma may need to be added to the list of second malignancies that arise following radiation therapy for Hodgkin's disease, Further support is given to a causal link between radiation exposure and mesothelioma. C1 DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA. COLUMBIA UNIV,COLL PHYS & SURG,DEPT MED,NEW YORK,NY. COLUMBIA UNIV,COLL PHYS & SURG,SCH PUBL HLTH,NEW YORK,NY. NR 18 TC 35 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 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1996 VL 14 IS 7 BP 2098 EP 2100 PG 3 WC Oncology SC Oncology GA UV715 UT WOS:A1996UV71500017 PM 8683242 ER PT J AU Luo, C Burgeon, E Rao, A AF Luo, C Burgeon, E Rao, A TI Mechanisms of transactivation by nuclear factor of activated T cells .1. SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYCLOSPORINE-A; COMPLEX; BINDING AB Nuclear factor of activated T cells-family proteins (NFAT1/NFATp, NFATc, NFAT3, and NFAT4/NFATx/NFATc3) play a key role in the transcription of cytokine genes and other genes during the immune response. We have defined the mechanisms of transactivation by NFAT1. NFAT1 possesses two transactivation domains whose sequences are riot conserved in the other NFAT-family proteins, and a conserved DNA-binding domain that mediates the recruitment of cooperating nuclear transcription factors even when it is expressed in the absence of other regions of the protein. The activity of the NH2-terminal transactivation domain is modulated by an adjacent regulatory region that contains several conserved sequence motifs represented only in the NFAT family. Our results emphasize the multiple levels at which NFAT-dependent transactivation is regulated, and predict significant differences in the architecture of cooperative transcription complexes containing different NFAT-family proteins. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-42471]; NIAID NIH HHS [P01 AI-35297]; NIGMS NIH HHS [GM-46227] NR 40 TC 79 Z9 79 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1996 VL 184 IS 1 BP 141 EP 147 DI 10.1084/jem.184.1.141 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UW677 UT WOS:A1996UW67700015 PM 8691127 ER PT J AU Decker, LL Shankar, P Khan, G Freeman, RB Dezube, BJ Lieberman, J ThorleyLawson, DA AF Decker, LL Shankar, P Khan, G Freeman, RB Dezube, BJ Lieberman, J ThorleyLawson, DA TI The Kaposi sarcoma-associated herpesvirus (KSHV) is present as an intact latent genome in KS tissue but replicates in the peripheral blood mononuclear cells of KS patients SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article AB Short DNA sequences have been identified, originally in association with Kaposi's sarcoma (KS) biopsies, that are highly homologous to oncogenic, lymphotropic herpesviruses. Recently a virus, Kaposi sarcoma associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8), bearing these sequences has been identified in a cell line derived from a body cavity-based lymphoma. In this report, we show that the same sequences are present ill KS biopsies as DNA molecules of a form and size characteristic of latent herpesviruses-large, covalently closed, circular episomes. The genomes migrate with an apparent size larger than the herpesvirus Epstein-Barr virus (172 kb). This form of the viral genome was found in four of four biopsies and three of five peripheral blood samples from KS patients. Linear forms of the viral genome, characteristic of viral replication, were not detected in the biopsies, but were present ill the peripheral blood of three out of five patients. The sequences for KSHV/HHV-8 were also detected ill the blood of four of five allograft patients and three of five healthy donors without KS suggesting that the virus is widespread throughout the human population. C1 TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. TUFTS UNIV NEW ENGLAND MED CTR,DEPT SURG,BOSTON,MA 02111. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02215. RI Lieberman, Judy/A-2717-2015 FU NCI NIH HHS [CA 31893, CA 65883]; NIAID NIH HHS [AI 18757] NR 19 TC 182 Z9 186 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1996 VL 184 IS 1 BP 283 EP 288 DI 10.1084/jem.184.1.283 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UW677 UT WOS:A1996UW67700031 PM 8691144 ER PT J AU Kuhlthau, K Mason, KO AF Kuhlthau, K Mason, KO TI Market child care versus care by relatives - Choices made by employed and nonemployed mothers SO JOURNAL OF FAMILY ISSUES LA English DT Article ID DETERMINANTS; FERTILITY; COSTS AB We study the determinants of whether mothers of preschool-aged children use market child care versus care by relatives to assess the importance of economics versus preferences. The evidence suggests that employed mothers turn to relatives for child care partly out of preference, not just because relatives are inexpensive. Public policies that encourage the use of relatives for child care might therefore increase parental satisfaction and quality of care. The analysis finds substantially similar results for African American and other women, but the results for employed mothers differ from those for nonemployed women, who appear to use child care primarily to enhance child development. C1 EAST WEST CTR,HONOLULU,HI 96848. RP Kuhlthau, K (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 15 TC 20 Z9 20 U1 0 U2 0 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0192-513X J9 J FAM ISSUES JI J. Fam. Issues PD JUL PY 1996 VL 17 IS 4 BP 561 EP 578 DI 10.1177/019251396017004007 PG 18 WC Family Studies SC Family Studies GA UX814 UT WOS:A1996UX81400007 ER PT J AU Silva, JA Harry, BE Leong, GB Weinstock, R AF Silva, JA Harry, BE Leong, GB Weinstock, R TI Dangerous delusional misidentification and homicide SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; aggression; violence; intermetamorphosis syndrome; delusions; delusional misidentification syndromes; homicide; psychiatry; forensic psychiatry ID CAPGRAS-SYNDROME AB A case involving a delusional misidentification syndrome associated with homicide is presented. The anglophonic literature concerning delusional misidentification and homicide is reviewed. Delusional misidentification may be a risk factor for potential violence toward others, including homicide of a delusionally misidentified person. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. HARRY S TRUMAN MEM VET HOSP,COLUMBIA,MO 65201. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV MISSOURI,SCH MED,COLUMBIA,MO. RP Silva, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PSYCHIAT SERV 116A,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 32 TC 9 Z9 9 U1 0 U2 2 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JUL PY 1996 VL 41 IS 4 BP 641 EP 644 PG 4 WC Medicine, Legal SC Legal Medicine GA UW195 UT WOS:A1996UW19500024 PM 8754574 ER PT J AU Perryman, KM Fitten, LJ AF Perryman, KM Fitten, LJ TI Effects of normal aging on the performance of motor-vehicle operational skills SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article ID OLDER DRIVERS; HUMAN-BRAIN; AGE; ATTENTION; VISION; LOCALIZATION; VISIBILITY; PERCEPTION; FIELD AB Operational skills involved in controlling a motor vehicle were measured in two groups of very healthy elderly drivers and a young control group to test the hypothesis that there are age-related declines in operational performance that may influence driver safety. An actual behind-the-wheel, standardized road test was employed using a motor vehicle equipped with sensors to record speed, braking activity, and lane position, as well as direction and magnitude ef front-wheel and eye-movement excursions. The data from these sensors were used as dependent measures of operational performance. Older drivers made fewer steering and eye-movement excursions and drifted across the center line more frequently than the young control group. Younger drivers drove significantly faster and executed more braking applications than did their older counterparts. The motor-vehicle operational performance of older healthy drivers was related to visual-spatial attentional declines and the useful field of vision associated with the normal aging process. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. VET ADM MED CTR,LOS ANGELES,CA. NR 46 TC 18 Z9 18 U1 1 U2 3 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD JUL PY 1996 VL 9 IS 3 BP 136 EP 141 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA VD974 UT WOS:A1996VD97400006 PM 8873878 ER PT J AU Jenike, MA AF Jenike, MA TI Continuous screaming responsive to electroconvulsive therapy SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 6 TC 0 Z9 0 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD JUL PY 1996 VL 9 IS 3 BP 154 EP 154 PG 1 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA VD974 UT WOS:A1996VD97400009 ER PT J AU Rosowsky, A Forsch, RA Moran, RG AF Rosowsky, A Forsch, RA Moran, RG TI Inhibition of folylpolyglutamate synthetase by substrate analogues with an ornithine side chain SO JOURNAL OF HETEROCYCLIC CHEMISTRY LA English DT Article ID GAMMA-GLUTAMATE SYNTHETASE; TAYLOR PTERIDINE SYNTHESIS; TERMINAL L-ORNITHINE; DIHYDROFOLATE-REDUCTASE; METHOTREXATE ANALOGS; AMINOPTERIN ANALOGS; 5,8-DIDEAZA ANALOGS; BIOLOGICAL-ACTIVITY; FOLATE ANALOGS; FOLIC-ACID AB N-alpha-[4-[[(4-Aminopteridin-6-yl)methyl]amino]benzoyl]-L- ormithine (dAPA-Orn) was synthesized, and its ability to inhibit folylpolyglutamate synthetase from mouse liver was compared with that of the corresponding 2,4-diamino analogue APA-Orn. Also compared were the inhibitory activities of the deaza analogues 5-deazaAPA-Orn, 8-deazaAPA-Orn, and 5,8-dideazaAPA-Orn, as well as those of N-alpha-pteroyl-L-ornithine (PteOrn) and its deaza analogues 5-deazaPteOrn and 5,8-dideazaPteOrn. The inhibition constant K-i of dAPA-Orn was 7-fold greater than that of APA-Orn, indicating that the 2-amino group plays a role in binding to the active site. The binding affinity of the 2,4-diamino compounds increased in the order 5-deazaAPA < APA-Orn < 5,8-dideazaAPA-Orn < 8-deazaAPA-Orn, and that of the 2-amino-4(3H)-oxo compounds increased in the order 5-deazaPteOrn < PteOrn < 5,8-dideazaPteOrn. The most potent inhibitor of both groups was 8-deazaAPA-Orn, with a K-i of 0.018 mu M, corresponding to an 8-fold and 15-fold increase in affinity relative to APA-Orn and 5-deazaAPA-Orn, respectively. The results suggest (a) that the binding of Orn-containing folylpolyglutamate synthetase inhibitors is affected to a greater degree by replacement of N-8 by a carbon atom than it is by the corresponding change at N-5, (b) that the effect of carbon for nitrogen replacement is greater in the 2,4-diamino derivatives than in the 2-amino-4(3H)-oxo compounds, and (c) that the 2,4-diamines are the better inhibitors. Comparison of the K-i values of the Orn-containing inhibitors with the K-m values of the corresponding glutamate-containing substrates revealed that K-m/K-i ratio can vary as much as 100-fold depending on the nature of the heterocyclic moiety, suggesting that caution should be exercised in using K-m values of known substrates to predict K-i values of putative inhibitors. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,MASSEY CANC CTR,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,DIV HEMATOL ONCOL,RICHMOND,VA 23298. RP Rosowsky, A (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 36 TC 2 Z9 2 U1 0 U2 2 PU HETERO CORPORATION PI TAMPA PA BOX 20285, TAMPA, FL 33622-0285 SN 0022-152X J9 J HETEROCYCLIC CHEM JI J. Heterocycl. Chem. PD JUL-AUG PY 1996 VL 33 IS 4 BP 1355 EP 1361 PG 7 WC Chemistry, Organic SC Chemistry GA VH864 UT WOS:A1996VH86400057 ER PT J AU Karras, JG Wang, ZH Coniglio, SJ Frank, DA Rothstein, TL AF Karras, JG Wang, ZH Coniglio, SJ Frank, DA Rothstein, TL TI Antigen-receptor engagement in B cells induces nuclear expression of STAT5 and STAT6 proteins that bind and transactivate an IFN-gamma activation site SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; TYROSINE PHOSPHORYLATION; KINASE-C; INTERFERON-GAMMA; LYMPHOCYTES-B; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; CROSS-LINKING; GROWTH-FACTOR; GENE AB The signal transducer and activator of transcription (STAT) family of transcription factors is triggered by cytokine and growth factor receptors in a number of cell types, and binds to a consensus sequence defined in part by the IFN-gamma activation site (GAS). It is not known whether these transcription factors respond to other kinds of growth stimuli, and, with particular relevance to lymphocytes, it is not known whether STAT proteins participate in Ag-specific responses. To determine the role of STAT proteins, coupling between Ag-receptor cross-linking and nuclear expression of DNA-binding protein complexes that recognize GAS sequences was evaluated. Ag-receptor triggering in primary B lymphocytes stimulated nuclear expression of a complex that specifically binds the IFN response factor-1 (IRF-1) GAS sequence, and is distinguished by electrophoretic mobility and GAS preference from IRF-1 GAS-binding complexes induced by IFN-gamma. Activation of nuclear IRF-1 GAS-binding activity by sig was inhibited by the tyrosine kinase inhibitor, herbimycin A, and binding activity was eliminated by tyrosine phosphatase treatment. Activation of IRF-1 GAS-binding activity was blocked by depletion of protein kinase C. The IRF-1 GAS-binding activity induced by sig engagement in B cells was transcriptionally active, and was found to consist of immunoreactive STAT5 and STAT6 proteins. This work demonstrates that the STAT signaling pathway previously associated with cytokine signaling is triggered in B lymphocytes through Ag-receptor engagement in a protein kinase C-dependent fashion. This heretofore described cytokine signaling pathway may play a role in bringing about Ag-specific proliferative and differentiative responses. C1 BOSTON UNIV,MED CTR,DEPT MED,BOSTON,MA 02118. BOSTON UNIV,MED CTR,DEPT MICROBIOL,BOSTON,MA 02118. BOSTON UNIV,MED CTR,EVANS MEM DEPT CLIN RES,BOSTON,MA 02118. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. FU NHLBI NIH HHS [T32-HL07501]; NIAID NIH HHS [T32-AI07309, AI29690] NR 61 TC 42 Z9 42 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1996 VL 157 IS 1 BP 39 EP 47 PG 9 WC Immunology SC Immunology GA UT109 UT WOS:A1996UT10900006 PM 8683142 ER PT J AU Sawasdikosol, S Chang, JH Pratt, JC Wolf, G Shoelson, SE Burakoff, SJ AF Sawasdikosol, S Chang, JH Pratt, JC Wolf, G Shoelson, SE Burakoff, SJ TI Tyrosine-phosphorylated Cbl binds to Crk after T cell activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIGNAL TRANSDUCTION; SH2 DOMAIN; V-CBL; PROTEIN; RECEPTOR AB Crk is a Src homology 2 (SH2)/Src homology 3 (SH3)-containing adapter protein that has been implicated in intracellular signaling in fibroblasts and PC12 pheochromocytoma cells. Crk has been shown to bind to a tyrosine-phosphorylated protein of 116 kDa after TCR-mediated T cell activation. Here we demonstrate that the Crk-associated p116 phosphoprotein is not the Crk-associated substrate (Cas) but, rather, is a protein product of the c-cbl proto-oncogene. Whereas Cas was not tyrosine-phosphorylated after T cell activation, Cbl became highly phosphorylated. Crk immunoprecipitates from activated T cell lysates contain tyrosine-phosphorylated Cbl. This association is mediated by the SH2 domain of Crk, as evidenced by the interaction between Cbl and the fusion protein product of a glutathione S-transferase (GST) expression construct encoding the Crk-SH2 domain in vitro. Furthermore, phosphopeptide-binding studies revealed that the GST-Crk SH2 domain binds to a tyrosine-phosphorylated peptide corresponding to amino acids 770-781 of Cbl with high affinity. Cbl is a protein tyrosine kinase (PTK) substrate that becomes phosphorylated after engagement of numerous cell surface receptors including the TCR. Data revealed by genetic studies in the nematode, Caenorhabditis elegans, implicates a Cbl-like molecule, Sli-1, as a negative regulator of the Let-23-signaling pathway. Because the signal from the Let-23 pathway affects the activation status of the Let-60 (Ras homologue in C. elegans) pathway, the activation-dependent association between Crk and Cbl may represent another TCR-generated signal leading to Ras-related pathways. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,RES DIV,BOSTON,MA 02115. FU NIAID NIH HHS [AI17258] NR 51 TC 58 Z9 58 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1996 VL 157 IS 1 BP 110 EP 116 PG 7 WC Immunology SC Immunology GA UT109 UT WOS:A1996UT10900014 PM 8683103 ER PT J AU Leaf, A Kang, JX AF Leaf, A Kang, JX TI Prevention of cardiac sudden death by N-3 fatty acids: A review of the evidence SO JOURNAL OF INTERNAL MEDICINE LA English DT Review DE polyunsaturated fatty acids; n-3 fatty acids; n-6 fatty acids; ventricular fibrillation; cardiac arrhythmias; prevention of arrhythmias ID VENTRICULAR-FIBRILLATION; ION CHANNELS; HEART-CELLS; ARRHYTHMIAS; MYOCYTES; MODULATION; THRESHOLD; ISCHEMIA; RATS AB The essential n-6 and n-3 polyunsaturated fatty acids can prevent ischaemia-induced ventricular fibrillation in rats, dogs and marmosets. In isolated neonatal rat cardiac myocytes, these have been shown to prevent tachyarrhythmias elevated calcium concentrations, toxic ouabain, a beta-adrenergic agent (isoproterenol), lysophosphatidylcholine and acylcarnitine. The antiarrhythmic effect is caused by a reduction in electrical excitability caused by partitioning of the free polyunsaturated fatty acids into the phospholipid cell membranes of the cardiac myocytes, which modulates membrane ion channels. Two clinical trials suggest they could prevent sudden cardiac death in humans. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. BROCKTON W ROXBURY VET AFFAIRS MED CTR,DEPT MED,W ROXBURY,MA. FU NIDDK NIH HHS [DK38165] NR 32 TC 54 Z9 60 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JUL PY 1996 VL 240 IS 1 BP 5 EP 12 DI 10.1046/j.1365-2796.1996.449803000.x PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VB321 UT WOS:A1996VB32100002 PM 8708597 ER PT J AU Eming, SA Snow, RG Yarmush, ML Morgan, JR AF Eming, SA Snow, RG Yarmush, ML Morgan, JR TI Targeted expression of insulin-like growth factor to human keratinocytes: Modification of the autocrine control of keratinocyte proliferation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE gene therapy; skin grafts ID HUMAN EPIDERMAL-CELLS; FACTOR-I IGF-1; GENE-EXPRESSION; SKIN FIBROBLASTS; SOMATOMEDIN-C; RECEPTOR; HORMONE; DIFFERENTIATION; PARACRINE; PROTEINS AB Somatomedin C/insulin-like growth factor-I (IGF-I) is required for the proliferation of keratinocytes in vitro. In skin, the cells known to synthesize IGF-I are melanocytes and fibroblasts of the dermis, To investigate the role of IGF-I as a mediator of keratinocyte proliferation, we have used retroviral-mediated gene transfer to introduce the gene encoding human IGF-I into diploid human keratinocytes, thus causing these cells to produce a growth factor they normally do not express, Modified cells synthesized and secreted significant levels of IGF-I (560 ng/10(7) cells/24 h) in vitro. Cells expressing IGF-I were no longer dependent on exogenously added EGF-I or insulin for their sustained growth in vitro under serum-free conditions. The growth of these cells did require added epidermal growth factor (EGF) and bovine pituitary extract. The addition of an antibody that neutralizes IGF-I inhibited cell growth, suggesting that IGF-I must be secreted by the cells to promote cell proliferation, To investigate the role of IGF-I in vivo, we grafted modified keratinocytes expressing IGF-I onto athymic mice. Grafts of epithelial sheets of modified cells formed a stratified epithelium comparable to control grafts of unmodified cells, When analyzed for keratin 16 expression and by quantitative staining for the nuclear proliferation antigen Ki-67, however, modified epithelia showed an increase in these markers of proliferation when compared with grafts of unmodified cells, This study demonstrates that genetic modification can be used to modify the autocrine control of keratinocyte proliferation, The de novo synthesis of IGF-I by keratinocytes could sustain keratinocytes growth in vitro and stimulate proliferation in vivo without significantly altering epidermal differentiation, These data further support the role of IGF-I as a paracrine mediator of epidermal proliferation and as a potential signal of mesenchymal-epithelial interactions. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURNS INST,BOSTON,MA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NIAMS NIH HHS [AR42012]; NICHD NIH HHS [HD28528] NR 38 TC 50 Z9 54 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1996 VL 107 IS 1 BP 113 EP 120 DI 10.1111/1523-1747.ep12298351 PG 8 WC Dermatology SC Dermatology GA UU897 UT WOS:A1996UU89700022 PM 8752849 ER PT J AU Medalie, DA Eming, SA Tompkins, RG Yarmush, ML Krueger, GG Morgan, JR AF Medalie, DA Eming, SA Tompkins, RG Yarmush, ML Krueger, GG Morgan, JR TI Evaluation of human skin reconstituted from composite grafts of cultured keratinocytes and human acellular dermis transplanted to athymic mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE epithelium; collagen; melanocyte ID BURN WOUND CLOSURE; EPIDERMAL-CELLS; FIBROBLASTS; GROWTH; DIFFERENTIATION; MELANOCYTES; COLLAGEN; AUTOGRAFTS; SUBSTITUTE; ALLOGRAFTS AB This study evaluates the use of composite grafts of cultured human keratinocytes and de-epidermalized, acellular human dermis to close full-thickness wounds in athymic mice, Grafts were transplanted onto athymic mice and studied up to 8 wk, Graft take was excellent, with no instances of infection or graft loss, By 1 wk, the human keratinocytes had formed a stratified epidermis that was fused with mouse epithelium, and by 8 wk the grafts resembled human skin and could be freely moved over the mouse dorsum, Immunostaining for keratins 10 and 16 and for involucrin revealed an initial pattern of epithelial immaturity, which by 8 wk had normalized to that of mature unwounded epithelium, Mouse fibroblasts began to infiltrate the acellular dermis as early as 1 wk, By 8 wk fibroblasts had completely repopulated the dermis, and blood vessels were evident in the most superficial papillary projections, Dermal elements, such as rete ridges and elastin fibers, which were present in the starting dermis, persisted for the duration of the experiment. Grafts using keratinocytes from dark-skinned donors as opposed to light-skin donors had foci of pigmentation as early as 1 wk that progressed to homogenous pigmentation of the graft by 6 wk, These results indicate that melanocytes that persist in vitro are able to resume normal function in vivo, Our study demonstrates that composite grafts of cultured keratinocytes combined with acellular dermis are a useful approach for the closure of full-thickness wounds. C1 MASSACHUSETTS GEN HOSP,TRAUMA SERV,BOSTON,MA 02114. SHRINERS BURNS INST,BOSTON,MA 02114. UNIV UTAH,HLTH SCI CTR,DEPT MED,DIV DERMATOL,SALT LAKE CITY,UT 84132. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NIAMS NIH HHS [AR42012-01A1]; NICHD NIH HHS [HD28528-01]; PHS HHS [G-M07035-21] NR 35 TC 84 Z9 92 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1996 VL 107 IS 1 BP 121 EP 127 DI 10.1111/1523-1747.ep12298363 PG 7 WC Dermatology SC Dermatology GA UU897 UT WOS:A1996UU89700023 PM 8752850 ER PT J AU Reue, K Doolittle, MH AF Reue, K Doolittle, MH TI Naturally occurring mutations in mice affecting lipid transport and metabolism SO JOURNAL OF LIPID RESEARCH LA English DT Review DE mouse mutations; lipoprotein lipase deficiency; lipase maturation; fatty liver; neuropathy ID COMBINED LIPASE DEFICIENCY; POLYCYSTIC KIDNEY-DISEASE; NIEMANN-PICK DISEASE; JUVENILE VISCERAL STEATOSIS; DYSTROPHY FLD MUTATION; SYSTEMIC CARNITINE DEFICIENCY; PROTEIN DISULFIDE ISOMERASE; CULTURED BROWN ADIPOCYTES; HUMAN LIPOPROTEIN-LIPASE; N-LINKED GLYCOSYLATION AB Naturally occurring mutations in the mouse provide a unique resource for identifying genes and characterizing proteins involved in lipid metabolism. Spontaneous mouse mutations have been described that affect various aspects of lipid metabolism, including cellular cholesterol homeostasis, fatty acid metabolism, serum lipoprotein levels, serum and tissue lipase activities, and lipid composition of tissues such as liver, nerve, kidney, and adrenal gland. Here we briefly describe the phenotypes and genetics of several mutants with blood and tissue lipid abnormalities, and then provide a more in-depth discussion of two mutations, fatty liver dystrophy (fld) and combined lipase deficiency (cld). Mice homozygous for the fld mutation exhibit fatty liver and hypertriglyceridemia during neonatal development, and a peripheral neuropathy that progresses throughout the lifetime of the animal. Combined lipase deficiency is characterized by a nearly complete absence of lipoprotein lipase and hepatic lipase activity resulting in neonatal lethality. Although the underlying genes for these two disorders have yet to be identified, candidates that have been implicated through the molecular and biochemical characterization of the mutants are discussed. C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90073. RP Reue, K (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,LIPID RES LAB,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. FU NHLBI NIH HHS [HL28482] NR 120 TC 40 Z9 45 U1 0 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 1996 VL 37 IS 7 BP 1387 EP 1405 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UZ048 UT WOS:A1996UZ04800001 PM 8827513 ER PT J AU Bird, DA Laposata, M Hamilton, JA AF Bird, DA Laposata, M Hamilton, JA TI Binding of ethyl oleate to low density lipoprotein, phospholipid vesicles, and albumin: A C-13 NMR study SO JOURNAL OF LIPID RESEARCH LA English DT Article DE plasma; bilayer; alcoholism; ethyl ester ID EGG PHOSPHATIDYLCHOLINE VESICLES; OLEIC-ACID; CHOLESTERYL OLEATE; SERUM-ALBUMIN; FATTY-ACIDS; SOLUBILIZATION; LOCALIZATION; BILAYERS; ETHANOL; ESTERS AB Fatty acid ethyl esters (FAEE), esterification products of ethanol and fatty acids, have been implicated as mediators of ethanol-induced organ damage. After ethanol ingestion in humans, FAEE circulate in blood, bound to lipoproteins and albumin. We have analyzed the binding of ethyl (1-C-13, 99%) oleate (EO) to small unilamellar phospholipid vesicles (SUV), human low density lipoprotein (LDL), and bovine serum albumin (BSA) by C-13-NMR spectroscopy. Binding of less than or equal to 25 mol% EO to SW yielded a single EO carbonyl peak (172.6-172.9 ppm) downfield from that of EO oil (171.9 ppm). Thus, the carbonyl forms hydrogen bonds with water in the SUV aqueous interface. At 30 mol% EO in SW, a second EO carbonyl peak appeared, indicating a limit in FAEE solubility in SUV. Addition of EO to isolated human LDL yielded a peak at 171.9 ppm, suggesting that the EO exists in an unhydrated environment, most likely the core of the lipoprotein. This binding was also observed using high levels of EO added to human serum. The addition of EO dissolved in ethanol or as an oil to a solution of BSA yielded no visible EO peak, whereas addition of (1-C-13, 99%) oleic acid resulted in several narrow peaks, demonstrating a much greater affinity of BSA for oleic acid than for EO. Bidirectional transfer of EO between LDL and SUV was observed and was 85% complete within 30 min. There was no measurable transfer of EO from LDL or SUV to albumin. The weak binding of EO to albumin will result in increased transport of EO by lipoproteins as plasma levels of EO increase. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV CLIN LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BOSTON UNIV,SCH MED,DEPT BIOPHYS,BOSTON,MA 02118. FU NHLBI NIH HHS [HL26335, HL41904]; NIDDK NIH HHS [DK37454] NR 28 TC 24 Z9 24 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 1996 VL 37 IS 7 BP 1449 EP 1458 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UZ048 UT WOS:A1996UZ04800005 PM 8827517 ER PT J AU Alterman, AI Snider, EC Cacciola, JS Brown, LS Zaballero, A Siddiqui, N AF Alterman, AI Snider, EC Cacciola, JS Brown, LS Zaballero, A Siddiqui, N TI Evidence for response set effects in structured research interviews SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID ADDICTION SEVERITY INDEX; DIAGNOSTIC INTERVIEW; VALIDITY; RELIABILITY; DISORDERS; SCHEDULE AB The Addiction Severity Index and NIMH Diagnostic Interview Schedule data of 20 methadone-maintained subjects with ''fake bad'' invalid profiles on the Personality Assessment Inventory, 15 methadone-maintained subjects with ''fake good'' invalid profiles, and 158 methadone-maintained subjects with valid profiles were compared. The findings revealed a number of significant group differences on both measures with the highest scores for the fake bad subjects and lowest scores for the fake good subjects. These findings suggest that the response sets exhibited in response to the Personality Assessment Inventory questionnaire extended to performance during the two semistructured interviews. There was no indication that interviewers were aware of misrepresentation. The limitations of the findings and alternative interpretations of the data are considered. C1 UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. ADDICT RES & TREATMENT CORP,BROOKLYN,NY. FU NIDA NIH HHS [DA05186, DA-05858, DA060142] NR 29 TC 9 Z9 9 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 1996 VL 184 IS 7 BP 403 EP 410 DI 10.1097/00005053-199607000-00002 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UY953 UT WOS:A1996UY95300002 PM 8691192 ER PT J AU Wenzel, SL Bakhtiar, L Caskey, NH Hardie, E Redford, C Sadler, N Gelberg, L AF Wenzel, SL Bakhtiar, L Caskey, NH Hardie, E Redford, C Sadler, N Gelberg, L TI Dually diagnosed homeless veterans in residential treatment: Service needs and service use SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID SUBSTANCE ABUSE; MENTALLY-ILL C1 RAND CORP,SANTA MONICA,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP Wenzel, SL (reprint author), UNIV CALIF LOS ANGELES,DIV FAMILY MED,50-071 CHS,BOX 951683,LOS ANGELES,CA 90095, USA. NR 16 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 1996 VL 184 IS 7 BP 441 EP 444 DI 10.1097/00005053-199607000-00010 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UY953 UT WOS:A1996UY95300010 PM 8691200 ER PT J AU Schulz, JB Huang, PL Matthews, RT Passov, D Fishman, MC Beal, MF AF Schulz, JB Huang, PL Matthews, RT Passov, D Fishman, MC Beal, MF TI Striatal malonate lesions are attenuated in neuronal nitric oxide synthase knockout mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE malonate; excitotoxicity; peroxynitrite; free radicals; nitric oxide; Huntington's disease ID SUPEROXIDE-DISMUTASE; PEROXYNITRITE; NEUROTOXICITY; NITRATION; CULTURES; ACID AB intrastriatal administration of the reversible succinate dehydrogenase inhibitor malonate produces both energy depletion and striatal lesions by a secondary excitotoxic mechanism. To investigate the role of nitric oxide (NO.) in the pathogenesis of the lesions we examined malonate toxicity in mice in which the genes for neuronal nitric oxide synthase (nNOS) or endothelial nitric oxide synthase (eNOS) were disrupted. Malonate striatal lesions were significantly attenuated in the eNOS mutant mice, and they were significantly increased in the eNOS mutant mice. Malonate-induced increases in levels of 2,3- and 2,5-dihydroxybenzoic acid/salicylate el markers of hydroxyl radical generation, were significantly attenuated in the nNOS knockout mice; Malonate-induced increases in 3-nitrotyrosine,a marker for peroxynitrite-mediated damage; were blocked in the nNOS mice, whereas a significant increase occurred in the eNOS mice. These findings show that NO. produced by nNOS results in generation of peroxynitrite, which plays a role in malonate neurotoxicity. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,DEPT MED,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 FU NINDS NIH HHS [NS 33335, NS 10828, NS 16367] NR 24 TC 79 Z9 79 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 1996 VL 67 IS 1 BP 430 EP 433 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UQ687 UT WOS:A1996UQ68700053 PM 8667023 ER PT J AU Tom, T Abedon, S Clark, RI Wong, W AF Tom, T Abedon, S Clark, RI Wong, W TI Neuroimaging characteristics in carbon monoxide toxicity SO JOURNAL OF NEUROIMAGING LA English DT Article ID INTOXICATION; BRAIN; ENCEPHALOPATHY; FEATURES AB Neuroimaging studies for 18 patients carrying carbon monoxide toxicity as a discharge diagnosis were reviewed. The most common positive findings were low-density lesions in the globus pallidus (7/18, 39%) and deep white matter changes (5/18, 28%). Six computed tomography head scans showed no acute changes. Advanced age, method of exposure (intentional vs accidental), and severity of carboxyhemoglobin level did not predict neuroradiological or clinical outcomes. Early neuroimaging could not be used to predict clinical courses (death or coma vs discharge to either an institution or a home) in the patient population studied. C1 W LOS ANGELES VET AFFAIRS MED CTR,NEUROBEHAB UNIT 691116AF,LOS ANGELES,CA 90073. UNIV CALIF SAN DIEGO,MED CTR,DEPT RADIOL,SAN DIEGO,CA 92103. UNIV CALIF SAN DIEGO,MED CTR,DEPT TOXICOL,SAN DIEGO,CA 92103. NR 12 TC 19 Z9 19 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD JUL PY 1996 VL 6 IS 3 BP 161 EP 166 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UY937 UT WOS:A1996UY93700005 PM 8704291 ER PT J AU Dyer, CA Kendler, A Philibotte, T Gardiner, P Cruz, J Levy, HL AF Dyer, CA Kendler, A Philibotte, T Gardiner, P Cruz, J Levy, HL TI Evidence for central nervous system glial cell plasticity in phenylketonuria SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE glial fibrillary acidic protein; gliosis; myelin; myelin basic protein; myelin/oligodendrocyte-specific protein; oligodendrocyte; Schwann cells ID FIBRILLARY ACIDIC PROTEIN; MONOCLONAL-ANTIBODIES O1; SCHWANN-CELLS; RAT-BRAIN; OLIGODENDROCYTES; ASTROCYTES; CULTURE; HYPERPHENYLALANINEMIA; PHENYLALANINE; EXPRESSION AB Phenylketonuria (PKU) is caused by mutation(s) in the phenylalanine hydroxylase (PAH) gene which lead to deficient PAH activity and an accumulation of phenylalanine in the blood. The primary pathologic finding is hypomyelination and gliosis of central nervous system white matter. Similar white matter pathology is observed in the Pah(enu2) mouse, a genetic model for PKU. We studied this mouse to examine the basis for these neuropathologic changes in PKU and to determine if hypomyelination and gliosis occur independently or are interrelated. Although white matter tracts within PKU brains are hypomyelinated, immunostaining and Western blot analyses revealed that these tracts contain abundant amounts of myelin markers, i.e. myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'phosphohydrolase, and myelin/oligodendrocyte-specific protein (MOSP). However, Western blot analyses also showed that MBP isoform expression was aberrant. Investigation of individual cells was performed by extraction of tissue sections with Triton X-100. Most of the MOSP was extracted, with the remaining MOSP clearly visible in dual labeled cells, i.e. MOSP was colocalized along glial fibrillary acidic protein (GFAP) filaments. Cells expressing both MBP and GFAP were also identified in optic tract. Double labeling with a riboprobe for MBP and antibodies specific for GFAP revealed that the majority of GFAP-positive cells expressed MBP mRNA. Our in vitro studies examined the response of cultured wild type oligodendrocytes to elevated phenylalanine for 4 weeks (wk). Under these conditions, about 50% of the oligodendrocytes expressed GFAP filaments and failed to elaborate membrane sheets. Proliferation of astrocytes appears not to be the source of gliosis, since the nuclei of GFAP-positive cells in the PKU brains did not immunostain for proliferating cell nuclear antigen. Dual-labeled cells were detected in normal mouse brain sections; however, PKU mouse white matter tracts were found to contain about twice the number of dual-labeled cells compared to normal tissue. Taken together, these data suggest that both myelinating and nonmyelinating oligodendrocytes are present in the normal adult brain, and that in response to a toxic factor such as elevated phenylalanine, myelinating oligodendrocytes adopt a nonmyelinating phenotype that expresses GFAP. Since myelinating Schwann cells and GFAP-positive nonmyelinating Schwann cells are normally present in adult peripheral nerve, and the myelinating Schwann cells react to pathologic situations by switching to GFAP-positive nonmyelinating cells, it may be that oligodendrocytes and Schwann cells are more similar than previously thought. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. NEW ENGLAND REG NEWBORN SCREENING PROGRAM,BOSTON,MA. CHILDRENS HOSP,GENET SERV,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP Dyer, CA (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,200 TRAPELO RD,WALTHAM,MA 02254, USA. FU NICHD NIH HHS [ND1-HD-2-3149]; NINDS NIH HHS [NS33198] NR 53 TC 51 Z9 56 U1 0 U2 3 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUL PY 1996 VL 55 IS 7 BP 795 EP 814 DI 10.1097/00005072-199607000-00005 PG 20 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UV317 UT WOS:A1996UV31700005 PM 8965095 ER PT J AU Davis, RL AF Davis, RL TI Differential distribution of potassium channels in acutely demyelinated, primary-auditory neurons in vitro SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MYELINATED AXONS; ION CHANNELS; PATCH-CLAMP; K-CHANNELS; MEMBRANE; FIBERS; NERVE; FROG; GOLDFISH; CELLS AB 1. Single-channel recordings of potassium channel activity were made from two populations of primary-auditory neurons maintained in tissue culture. The saccular nerve, which is the auditory component of the eighth cranial nerve in goldfish, was separated into two branches according to its peripheral innervation pattern. Neurons which innervated the rostral saccular macula corresponded to a class of cells that showed spike frequency adaptation; whereas, neurons which innervated the caudal macula were consistent with another type of cell that demonstrated bursting spontaneous firing patterns in vivo. Both somatic and internodal axonal membranes from each of these neuronal classes were studied after acute removal of the myelin sheath by microdissection. 2. Dye injections were used to discriminate neuronal from myelin membrane. After successful removal of the myelin, patch electrodes containing Lucifer yellow were used to fill a neuron and reveal its morphology within the myelin sheath. Patches on myelin led to filling of Schwann cells that surrounded the neuron. 3. Four kinds of potassium channels were observed and characterized according to unitary conductance, inactivation, and sensitivity to internal calcium. Three voltage-dependent K+ channel types were found on the somatic and axonal membrane of the two neuronal populations. Two channel types showed voltage-dependent inactivation and had average conductances of 32 and 19 pS, each with distinctive subconductance states. The third type of channel activity had an estimated conductance of 12 pS and was noninactivating. 4. The fourth type of channel was the Ca2+-activated K+ channel (k((Ca))), which was classified by the dependence of its activity on the calcium concentration at its cytoplasmic surface. Unlike the other three potassium channel types, this kind of channel was found exclusively on neurons that innervated the caudal sensory epithelium. As with the other kinds of potassium channels, it was found on both somatic and axonal internodal membranes. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,EATON PEABODY LAB,BOSTON,MA 02114. FU NIDCD NIH HHS [DC-00006, DC-00767, DC-00119] NR 28 TC 13 Z9 14 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 1996 VL 76 IS 1 BP 438 EP 447 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UY793 UT WOS:A1996UY79300032 PM 8836235 ER PT J AU Konradi, C Leveque, JC Hyman, SE AF Konradi, C Leveque, JC Hyman, SE TI Amphetamine and dopamine-induced immediate early gene expression in striatal neurons depends on postsynaptic NMDA receptors and calcium SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; amphetamine; NMDA; striatum; immediate early genes; Fos; CREB ID D-ASPARTATE RECEPTORS; C-FOS TRANSCRIPTION; PROTO-ONCOGENE FOS; RAT-BRAIN; CYCLIC-AMP; ANTICONVULSANT MK-801; SIGNALING PATHWAYS; SOMATOSTATIN GENE; RESPONSE ELEMENT; BINDING PROTEIN AB Amphetamine and cocaine induce the expression of both immediate early genes (IEGs) and neuropeptide genes in rat striatum. Despite the demonstrated dependence of these effects on D-1 dopamine receptors, which activate the cyclic AMP pathway, there are several reports that amphetamine and cocaine-induced IEG expression can be inhibited in striatum in vivo by NMDA receptor antagonists. We find that in vivo, the NMDA receptor antagonist MK-801 inhibits amphetamine induction of c-fos acutely and also prevents downregulation of IEG expression with chronic amphetamine administration. Such observations raise the question of whether dopamine/glutamate interactions occur al the level of corticostriatal and mesostriatal circuitry or within striatal neurons. Therefore, we studied dissociated striatal cultures in which midbrain and cortical presynaptic inputs are removed. In these cultures, we find that dopamine- or forskolin-mediated IEG induction requires Ca2+ entry via NMDA receptors but not via L-type Ca2+ channels. Moreover, blockade of NMDA receptors diminishes the ability of dopamine to induce phosphorylation of the cyclic AMP responsive element binding protein CREB. Although these results do not rule out a role for circuit-level dopamine/glutamate interactions, they demonstrate a requirement at the cellular level for interactions between the cyclic AMP and NMDA receptor pathways in dopamine-regulated gene expression in striatal neurons. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Konradi, C (reprint author), MASSACHUSETTS GEN HOSP,LAB MOLEC & DEV NEUROSCI,CNY 2,149 13TH ST,CHARLESTOWN,MA 02129, USA. OI Leveque, Jean-Christophe/0000-0003-2465-444X FU NIDA NIH HHS [R01 DA007134-14, DA00257, DA07134, R01 DA007134] NR 68 TC 237 Z9 241 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 1 PY 1996 VL 16 IS 13 BP 4231 EP 4239 PG 9 WC Neurosciences SC Neurosciences & Neurology GA UT323 UT WOS:A1996UT32300018 PM 8753884 ER PT J AU Baskaya, MK Hu, YG Donaldson, D Maley, M Rao, AM Prasad, MR Dempsey, RJ AF Baskaya, MK Hu, YG Donaldson, D Maley, M Rao, AM Prasad, MR Dempsey, RJ TI Protective effect of the 5-lipoxygenase inhibitor AA-861 on cerebral edema after transient ischemia SO JOURNAL OF NEUROSURGERY LA English DT Article DE cerebral blood flow; edema; ischemia; leukotriene; lipoxygenase; reperfusion; gerbil ID ARACHIDONIC-ACID METABOLISM; BRAIN-BARRIER PERMEABILITY; FREE FATTY-ACIDS; LEUKOTRIENE-C4; REPERFUSION; RATS; CYCLOOXYGENASE; PROSTAGLANDIN; LIBERATION; MEDIATORS AB This study examined the effect of AA-861, a specific 5-lipoxygenase inhibitor, on brain levels of leukotriene C-4 (LTC(4)) and correlated any changes with changes in edema formation and cerebral blood flow (CBF) after transient ischemia In gerbils. Brain levels of LTC(4) were observed to be increased at 1, 2, and 6 hours of reperfusion following 20 minutes of occlusion. At 2 hours of reperfusion, a pretreatment dose of 1000 mg/kg of AA-861 was required to inhibit more than 90% of the reperfusion-induced increases in brain LTC(4). At this dose, inhibition of LTC(4) production was observed at 2 and 6 hours of reperfusion. The specific gravity of both the cortex and subcortex was decreased at 6 hours of reperfusion after 20 minutes of occlusion. At 2 hours of reperfusion, no significant difference was observed in the specific gravity of the cortex and subcortex regions of gerbils pretreated with AA-861 or with vehicle, but at 6 hours of reperfusion significant positive differences were observed. Cerebral blood flow decreased to approximately 10% of preocclusion values during occlusion and returned to near-preocclusion values after 10 minutes of reperfusion. No significant differences were observed in regional CBF in the AA-861- and vehicle-pretreated gerbils during reperfusion. These findings indicate that LTC(4) production after transient cerebral ischemia may be an important contributor to the development of cerebral edema and that CBF does not mediate the LTC(4)-involved development of edema. C1 UNIV WISCONSIN,DEPT NEUROL SURG,CTR CLIN SCI,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. UNIV KENTUCKY,ALBERT B CHANDLER MED CTR,DEPT SURG,DIV NEUROSURG,LEXINGTON,KY 40536. NR 33 TC 50 Z9 55 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 1996 VL 85 IS 1 BP 112 EP 116 DI 10.3171/jns.1996.85.1.0112 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UT668 UT WOS:A1996UT66800016 PM 8683259 ER PT J AU Brownell, AL Elmaleh, DR Meltzer, PC Shoup, TM Brownell, GL Fischman, AJ Madras, BK AF Brownell, AL Elmaleh, DR Meltzer, PC Shoup, TM Brownell, GL Fischman, AJ Madras, BK TI Cocaine congeners as PET imaging probes for dopamine terminals SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE CFT (WIN 35,428); CCT (RTI-131); CDCT (dichloropane); positron emission tomography; Parkinson's disease ID POSITRON EMISSION TOMOGRAPHY; RECOGNITION SITES; PARKINSONS-DISEASE; BRAIN DOPAMINE; PRIMATE MODEL; I-125 RTI-55; RAT-BRAIN; BINDING; INVIVO; AUTORADIOGRAPHY AB PET imaging properties of three phenyltropane drugs with differing affinities and selectivities for the dopamine over serotonin transporter, were compared. Methods: Carbon-11-CFT (WIN 35,428, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropan), C-11-CCT (RTI-131, 2 beta-carbomethoxy-3 beta-(4-monochlorophenyl)tropane), and C-11-CDCT (dichloropane, 2 beta-carbomethoxy-3 beta-(3,4-dichlorophenyl)tropane) were evaluated as imaging probes for dopamine neurons in five normal and in two MPTP-treated cynomolgus monkeys (macaca fascicularis) using a high-resolution PET imaging system (PCR-I). Results: For C-11-CFT, the specific binding ratio (as defined by the ratio of radioactivity levels in striatum versus cerebellum) was 4.2 +/- 0.8 in caudate and 4.9 +/- 1.2 in putamen at 60 min and 4.9 +/- 1.2 and 5.5 +/- 1.1 at 90 min in control animals. In MPTP-treated monkeys the corresponding ratios were 1.4 +/- 0.1 in caudate and 1.5 +/- 0.1 in putamen at 60 min and 1.3 +/- 0.1 in caudate and 1.4 +/- 0.3 in putamen at 90 min. For the monochloro analog of CFT, C-11-CCT, the ratios in control caudate and putamen were 2.7 +/- 0.4 and 3.4 +/- 0.3, respectively, at 60 min and 3.7 +/- 0.5 and 4.4 +/- 0.6, respectively, at 90 min. In MPTP-treated animals, corresponding ratios were 1.4 +/- 0.4 and 1.5 +/- 0.3 at 60 min and 1.4 +/- 0.4 and 1.6 +/- 0.4 at 90 min. The dichloro analog of CFT, CDCT, which has the highest affinity for the dopamine transporter, generated the lowest ratios in control brains, 2.3 +/- 0.4 in caudate and 2.4 +/- 0.5 in putamen at 60 min. In one MPTP-treated monkey, the corresponding ratios were 1.6 +/- 0.4 and 1.8 +/- 0.3. In comparison with C-11-CFT, both C-11-CCT and C-11-CDCT were less selective and had high uptake in the thalamus. Conclusion: The present results clearly indicate that C-11-CFT is a useful ligand for monitoring dopamine neuronal degeneration. C1 ORGANIX INC,WOBURN,MA. HARVARD UNIV,SCH MED,SOUTHBOROUGH,MA 01772. NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA. RP Brownell, AL (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,PHYS RES LAB,EDWARDS BLDG,5TH FLOOR,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 32873-11]; NIDA NIH HHS [DA 06303]; NINDS NIH HHS [NS 30556] NR 39 TC 37 Z9 41 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1996 VL 37 IS 7 BP 1186 EP 1192 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UV693 UT WOS:A1996UV69300034 PM 8965196 ER PT J AU Elmaleh, DR Fischman, AJ Shoup, TM Byon, C Hanson, RN Liang, AY Meltzer, PC Madras, BK AF Elmaleh, DR Fischman, AJ Shoup, TM Byon, C Hanson, RN Liang, AY Meltzer, PC Madras, BK TI Preparation and biological evaluation of iodine-125-IACFT: A selective SPECT agent for imaging dopamine transporter sites SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID COCAINE RECOGNITION SITES; SEROTONIN UPTAKE SITES; NONHUMAN-PRIMATES; BINDING-SITES; MONKEY BRAIN; I-125 RTI-55; H-3 CFT; ANALOGS; ESTERS; RECEPTORS AB Parkinson's disease is a progressive neurodegenerative disorder that is associated with the loss of nerve terminals from specific brain areas, particularly in the caudate and putamen, which contains the highest concentrations of dopamine transporter sites. Previously, we synthesized and evaluated a series of C-11-labeled 2 beta-carbomethoxy-3 beta-aryltropane (WIN 35,428; CFT) derivatives as markers for the dopamine transporter system. These ligands have high affinity and specificity for dopamine transporter sites in vitro and in vivo in laboratory animals. The goal of this study was the preparation and preliminary biological characterization of two new ligands based on the structure of WIN 35,428, the E and Z isomers of N-iodoallyl-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (E and Z IACFT). Methods: E and Z IACFT were synthesized and radiolabeled with I-125. The ligands were characterized by in vitro assays of binding to dopamine and serotonin transporters and by autoradiography. Results: Iodine-125-IACFT was prepared in >60% radiochemical yield, and >98% radiochemical purity. Specific activity was 1500 Ci/mmole. In vitro, E-IACFT showed higher affinity for dopamine transporter sites than WIN 35,428 (6.6 versus 11 nM) and better selectivity than RTI-55. The Z isomer was found to have much lower affinity. One hour after an intravenous injection of I-125 IACFT in monkeys, ex vivo autoradiographs of the brain revealed high concentrations of tracer in dopamine rich regions such as the caudate-putamen. The striatum-to-cerebellum, striatum-to-cortex and striatum-to-thalamus ratios were 10.8, 7.2 and 8.3. Conclusion: These result suggest that radiolabeled E-IACFT may be a useful radioligand for SPECT imaging of dopamine transporter sites. IACFT could prove to be extremely useful for the noninvasive evaluation of patients with early Parkinson's disease. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. NORTHEASTERN UNIV,DEPT CHEM,BOSTON,MA 02115. ORGANIX INC,WOBURN,MA. RP Elmaleh, DR (reprint author), MASSACHUSETTS GEN HOSP,DIV NUCL MED,DEPT RADIOL,55 FRUUIT ST,BOSTON,MA 02114, USA. NR 31 TC 27 Z9 32 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1996 VL 37 IS 7 BP 1197 EP 1202 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UV693 UT WOS:A1996UV69300036 PM 8965198 ER PT J AU Li, KK Meara, JG Alexander, A AF Li, KK Meara, JG Alexander, A TI Location of the descending palatine artery in relation to the Le Fort I osteotomy SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MAJOR VASCULAR COMPLICATIONS; TOTAL MAXILLARY OSTEOTOMY; ORTHOGNATHIC SURGERY; BLOOD-LOSS AB Purpose: This study evaluated the positional relationship of the descending palatine artery to the Le Fort I osteotomy. Materials and Methods: Three separate examinations were performed. In the first, 30 human skulls were used, and measurements were made of the greater palatine canal and foramen in relation to maxillary landmarks pertaining to the Le Fort I osteotomy. In the second, 40 patients with normal or minimal sinus mucosal thickening were selected from a pool of patients who underwent computed tomography (CT) scanning for sinus evaluation. These patients were scanned on a Somatome Plus spiral CT scanner as part of a routine sinus protocol, with the addition of an axial image 3 mm above the nasal floor where the Le Fort I osteotomy is usually performed. The distance from the greater palatine canal to the piriform rim was measured, In the third, eight fresh cadavers were used, and the distance from the internal maxillary artery to the nasal floor was measured. Results: The internal maxillary artery enters the pterygopalatine fossa approximately 16.6 mm above the nasal floor and gives off the descending palatine artery, The descending palatine artery travels a short distance within the pterygopalatine fossa and then enters the greater palatine canal, It travels approximately 10 mm within the canal in an inferior, anterior, and slightly medial direction to exit the greater palatine foramen in the region of the second and third molars. Conclusion: Injury to the descending palatine artery during Le Fort I osteotomy can be minimized by not extending the osteotomy more than 30 mm posterior to the piriform rim in females, This distance can be extended to 35 mm in males. Pterygomaxillary separation should be made by closely adapting the cutting edge of a curved osteotome or right-angled saw to the pterygomaxillary fissure while avoiding excessive anterior angulation, Furthermore, the superior cutting edge of the osteotome or saw blade should be less than 10 mm above the nasal floor. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL HEAD & NECK SURG,BOSTON,MA 02114. LOUISIANA STATE UNIV,SCH MED,DEPT RADIOL,BATON ROUGE,LA 70803. RP Li, KK (reprint author), UNIV CALIF IRVINE,DEPT OTOLARYNGOL HEAD & NECK SURG,101 CITY DR S,BLDG 25,ORANGE,CA 92668, USA. NR 23 TC 34 Z9 41 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 1996 VL 54 IS 7 BP 822 EP 825 DI 10.1016/S0278-2391(96)90528-5 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UV705 UT WOS:A1996UV70500006 PM 8676226 ER PT J AU Perrott, DH AF Perrott, DH TI Treatment of mandibular angle fractures using one noncompression miniplate - Discussion SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material ID OSTEOSYNTHESIS; PLATES RP Perrott, DH (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 14 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 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 1996 VL 54 IS 7 BP 871 EP 872 DI 10.1016/S0278-2391(96)90539-X PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UV705 UT WOS:A1996UV70500017 ER PT J AU Dockray, GJ Varro, A Voronina, S Wang, T AF Dockray, GJ Varro, A Voronina, S Wang, T TI Regulation of post-translational processing of the gastrin precursor SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article; Proceedings Paper CT Scientific Meeting of the Physiological-Society CY APR 16-18, 1996 CL UNIV COLL LONDON, LONDON, ENGLAND SP Physiol Soc HO UNIV COLL LONDON C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. RP Dockray, GJ (reprint author), UNIV LIVERPOOL,PHYSIOL LAB,LIVERPOOL L69 3BX,MERSEYSIDE,ENGLAND. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL PY 1996 VL 494P BP S8 EP S8 PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VA341 UT WOS:A1996VA34100202 ER PT J AU Kern, RS Wallace, CJ Hellman, SG Womack, LM Green, MF AF Kern, RS Wallace, CJ Hellman, SG Womack, LM Green, MF TI A training procedure for remediating WCST deficits in chronic psychotic patients: An adaptation of errorless learning principles SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article ID CARD SORTING TEST; SCHIZOPHRENIA; PERFORMANCE AB Although a number of studies have demonstrated that psychiatric patients' performance deficits on the Wisconsin Card Sorting Test (WCST) can be modified through intervention, relatively little evidence exists to support the long-term durability of training effects. The present study tested the effectiveness and durability of a training procedure based on errorless learning principles, and in addition sought to determine the effect of previously committed errors on training and posttraining performance. Twenty-three chronic psychotic inpatients were randomly assigned to an Initial Error (n = 11) or No Initial Error (n = 12) group. The Initial Error group received two standard administrations of the WCST prior to training (where they were expected to commit many errors); the No Initial Error group had no prior exposure to the WCST. All subjects received training on the WCST which was followed by immediate, 1-, 2-, and 4-week post-tests. Results supported the effectiveness of training and the durability of effects, but previous error history showed no clear relationship to post-training performance. Copyright (C) 1996 Elsevier Science Ltd. C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. NR 19 TC 50 Z9 52 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JUL-AUG PY 1996 VL 30 IS 4 BP 283 EP 294 DI 10.1016/0022-3956(96)00028-3 PG 12 WC Psychiatry SC Psychiatry GA VP257 UT WOS:A1996VP25700005 PM 8905537 ER PT J AU VanLinthoudt, D Schumacher, HR Algeo, S Freundlich, B Schotland, DL Wood, MG AF VanLinthoudt, D Schumacher, HR Algeo, S Freundlich, B Schotland, DL Wood, MG TI Scleromyxedema with myopathy and hyperthyroidism SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE scleromyxedema; myopathy; mucinar papulosis; lichen myxedematosus; hyperthyroidism ID LICHEN MYXEDEMATOSUS; FIBROBLASTS AB We describe a 62-year-old woman who developed extensive papular skin eruption with dysphagia and proximal muscle weakness, Laboratory studies showed a progressive increase of muscle enzymes, lambda monoclonal gammopathy, and elevated serum thyroid hormones. Several skin and muscle biopsies were necessary, to reach the correct diagnosis of scleromyxedema in association with hyperthyroidism. Muscle biopsies contained rimmed vacuoles with some necrosis and regeneration, but no increased mucopolysaccharides, Hyperthyroidism was treated without appreciable improvement of the skin and muscle legions. Myopathy is an increasingly recognized feature of scleromyxedema; its pathogenesis is still unexplained. C1 VET AFFAIRS MED CTR,ARTHRITIS IMMUNOL CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT NEUROL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT DERMATOL LAB,PHILADELPHIA,PA 19104. NR 15 TC 8 Z9 8 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 1996 VL 23 IS 7 BP 1299 EP 1301 PG 3 WC Rheumatology SC Rheumatology GA UV681 UT WOS:A1996UV68100035 PM 8823713 ER PT J AU Herzog, DB Field, AE Keller, MB West, JC Robbins, WM Staley, J Colditz, GA AF Herzog, DB Field, AE Keller, MB West, JC Robbins, WM Staley, J Colditz, GA TI Subtyping eating disorders: Is it justified? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article; Proceedings Paper CT Society-for-Epidemiologic-Research Meeting CY JUN 24, 1995 CL SNOWBIRD, UT SP Soc Epidemiol Res DE anorexia nervosa; bulimia nervosa; recovery ID ANOREXIA-NERVOSA PATIENTS; LONG-TERM FOLLOW; BULIMIA-NERVOSA; CLINICAL-FEATURES; VALIDITY; HISTORY; CLASSIFICATIONS; DISTINCTION; COMORBIDITY; MORBIDITY AB Objective: DSM-IV subtypes anorexia nervosa by the presence or absence of bulimic symptoms. Assessing whether bulimic symptoms are related to the probability of recovery can provide justification for subtyping of anorexia. Method: Two hundred twenty-five treatment-seeking women with anorexia and/or bulimia nervosa were interviewed every 3 months for up to 4 years. Survival methods were used for analyses. Results: Less than half of the entire cohort recovered; however, the great majority of the women became less symptomatic over time. Contrary to findings from previous studies, bulimic anorexics had a higher rate of recovery than restricting anorexics. Conclusion: Differences in course provide some support for the subtyping of anorexia nervosa. Additional prospective studies are needed before subtyping can be warranted. C1 HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. BROWN UNIV,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02912. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. RP Herzog, DB (reprint author), MASSACHUSETTS GEN HOSP,EATING DISORDERS UNIT,15 PARKMAN ST,ACC 725,BOSTON,MA 02114, USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NIDDK NIH HHS [DK 42600]; NIMH NIH HHS [R01-MH38333] NR 59 TC 30 Z9 31 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 1996 VL 35 IS 7 BP 928 EP 936 DI 10.1097/00004583-199607000-00020 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UT650 UT WOS:A1996UT65000020 PM 8768354 ER PT J AU Lucchina, LC Kollias, N Gillies, R Phillips, SB Muccini, JA Stiller, MJ Trancik, RJ Drake, LA AF Lucchina, LC Kollias, N Gillies, R Phillips, SB Muccini, JA Stiller, MJ Trancik, RJ Drake, LA TI Fluorescence photography in the evaluation of acne SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID VULGARIS; MINOCYCLINE AB Background: Quantification of acne remains a challenge. It may be difficult to identify lesions by standard flash photography. Previous studies have shown that foci of light in fluorescence photographs correspond to high protoporphyrin IX production by Propionibacterium acnes in open comedones, follicles, and inflammatory lesions. Objective: Our purpose was to study the utility of fluorescence photography for evaluation of acne. Methods: Forty subjects with mild to moderate acne vulgaris were randomly selected to apply either clindamycin 1% topical solution or vehicle twice daily, Counts of acne lesions and flash and fluorescence photographs were obtained at baseline, and at 4, 8, and 12, weeks. Results: At 12 weeks, the treatment group had a larger percentage change in open comedones, less fluorescence in all areas assessed, and a larger percent decrease in fluorescence than the vehicle group. Conclusion: Fluorescence photography appears to be a useful tool to chart the course of acne treatment. C1 HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, DEPT DERMATOL, BOSTON, MA 02114 USA. UPJOHN CO, KALAMAZOO, MI 49001 USA. NR 29 TC 48 Z9 49 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 1996 VL 35 IS 1 BP 58 EP 63 DI 10.1016/S0190-9622(96)90497-1 PG 6 WC Dermatology SC Dermatology GA UV430 UT WOS:A1996UV43000010 PM 8682965 ER PT J AU Frame, LH Rhee, EK Bernstein, RC Fei, HL AF Frame, LH Rhee, EK Bernstein, RC Fei, HL TI Reversal of reentry and acceleration due to double-wave reentry: Two mechanisms for failure to terminate tachycardias by rapid pacing SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RECURRENT VENTRICULAR-TACHYCARDIA; CYCLE LENGTH; CIRCUS MOVEMENT; ATRIAL-FLUTTER; MODEL; INTERRUPTION; ENTRAINMENT; PATHWAY; HEART; REFRACTORINESS AB Objectives. We sought to demonstrate mechanisms by which rapid pacing can cause conduction block without terminating reentry. Background. Rapid pacing can fail to terminate or can accelerate tachycardias in patients. Mechanisms for these responses are poorly understood. Methods. We studied reentry in the canine atrial tricuspid ring and a left ventricular ring in vitro in 12 preparations. Activations were recorded from 10 sites around the ring, and monophasic action potentials were recorded from critical sites of block. Rapid pacing at cycle lengths that intermittently caused conduction block was performed at multiple sites. Results. Action potential alternans contributed to block of an orthodromic impulse during rapid pacing. When pacing continued for two stimuli after orthodromic block, a second episode of block could reverse the direction of tachycardia. Continued pacing at this site was likely to produce block of an antidromic impulse, which may initiate double-wave reentry. Double-wave reentry could be sustained or nonsustained. Its cycle length was 56% to 77% of the single-wave cycle length. The ratio of double-wave cycle length to single-wave cycle length was inversely correlated with the relative excitable gap (p < 0.01). Double-wave reentry can be a mechanism for persistent cycle length alternation during tachycardia. Conclusions. Successful termination of reentry by rapid pacing required block of an orthodromic impulse and stopping pacing within one stimulus after orthodromic block Reversal of reentry makes the circuit resistant to termination from this site of pacing, Antidromic block can cause acceleration due to double-wave reentry when there is a substantial excitable gap. C1 UNIV PENN,DEPT MED,DIV CARDIOVASC,PHILADELPHIA,PA 19104. RP Frame, LH (reprint author), VET AFFAIRS MED CTR,CARDIOL SECT 111C,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. FU NHLBI NIH HHS [HL 38386] NR 29 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1996 VL 28 IS 1 BP 137 EP 145 DI 10.1016/0735-1097(96)00096-4 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UU650 UT WOS:A1996UU65000021 PM 8752806 ER PT J AU Schwammenthal, E Levine, RA AF Schwammenthal, E Levine, RA TI Dynamic subaortic obstruction: A disease of the mitral valve suitable for surgical repair? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID SYSTOLIC ANTERIOR MOTION; VENTRICULAR OUTFLOW OBSTRUCTION; TERM FOLLOW-UP; HYPERTROPHIC CARDIOMYOPATHY; ECHOCARDIOGRAPHIC ASSESSMENT; TRACT OBSTRUCTION; SEPTAL MYOTOMY; LEAFLET; MECHANISM; COAPTATION C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,BOSTON,MA. RP Schwammenthal, E (reprint author), TEL AVIV UNIV,CARDIAC ULTRASOUND LAB,CHAIM SHEBA MED CTR,IL-52621 TEL HASHOMER,ISRAEL. NR 39 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1996 VL 28 IS 1 BP 203 EP 206 DI 10.1016/0735-1097(96)00213-6 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UU650 UT WOS:A1996UU65000030 PM 8752815 ER PT J AU Haverstock, BD Chen, F Jacobs, AM AF Haverstock, BD Chen, F Jacobs, AM TI Considerations of prescription medications for the pregnant pediatric patient SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Review ID ANTIFUNGAL AGENTS; IMIPENEM-CILASTATIN; DRUG-THERAPY; MATERNAL USE; FETAL; ACETAMINOPHEN; ERYTHROMYCIN; INFANT; CLINDAMYCIN; ARTHROPATHY AB Prescription medications are thought to cause less than 1% of all congenital abnormalities. However, prescribing a medication to treat the foot disorder of a pregnant patient can be a source of anxiety for the physician. The authors review some of the medications commonly prescribed in pediatric medical practice and evaluate their use and safety during pregnancy. RP Haverstock, BD (reprint author), DEACONESS MED CTR,DEPT PODIATR MED & SURG,ST LOUIS,MO 63139, USA. NR 107 TC 0 Z9 0 U1 0 U2 0 PU AMER PODIATRIC MED ASSN PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 SN 0003-0538 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD JUL PY 1996 VL 86 IS 7 BP 334 EP 346 PG 13 WC Orthopedics SC Orthopedics GA UY670 UT WOS:A1996UY67000009 PM 8757486 ER PT J AU Budisavljevic, MN Cheek, D Ploth, DW AF Budisavljevic, MN Cheek, D Ploth, DW TI Calciphylaxis in chronic renal failure SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID VASCULAR CALCIFICATION; SKIN NECROSIS; TISSUE NECROSIS; HYPERPARATHYROIDISM; PATIENT AB Calciphylaxis is a rare and life-threatening complication that is estimated to occur in 1% of patients with ESRD each year. Typically, extensive microvascular calcification and occlusion/thrombosis leads to violaceous skin lesions, which progress to nonhealing ulcers and sepsis. Secondary infection of skin lesions is common, often leading to sepsis and death, The lower extremities are predominantly involved (roughly 90% of patients). Patients with skin involvement over She trunk or proximal extremities have a poorer prognosis. Although most calciphylaxis patients have abnormalities of the calcium:phosphate axis or elevated levels of parathyroid hormone, these abnormalities do not appear io be fundamental to the pathophysiology of the disorder, and the etiology of calciphylaxis remains unclear, Recently, functional protein C deficiency has been hypothesized to cause a hypercoagulable state that could induce thrombosis in small vessels, with resulting skin ischemia, necrosis, and gangrene. The lack of understanding of the pathophysiology of the disease results in treatments that are equally unsatisfactory, Patients who undergo parathyroidectomy have a tendency to improve, but the prognosis for the disease is poor and mortality remains high. C1 MED UNIV S CAROLINA,DIV NEPHROL,DEPT MED,CHARLESTON,SC 29425. RALPH H JOHNSON VET ADM MED CTR,CHARLESTON,SC. NR 18 TC 159 Z9 162 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 1996 VL 7 IS 7 BP 978 EP 982 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA UY441 UT WOS:A1996UY44100002 PM 8829111 ER PT J AU Barnes, JL Woodruff, KA Levine, SP Abboud, HE AF Barnes, JL Woodruff, KA Levine, SP Abboud, HE TI Inhibition of mesangial cell proliferation by platelet factor 4 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE mesangial cells; platelet factor 4; proliferation; platelet-derived growth factor ID HUMAN MEGAKARYOCYTOPOIESIS INVITRO; VASCULAR ENDOTHELIAL-CELLS; FIBROBLAST GROWTH-FACTOR; FACTOR-IV; GLOMERULAR LOCALIZATION; BETA-THROMBOGLOBULIN; BINDING; PROTEINS; EXPRESSION; MIGRATION AB Platelet factor 4 (PF4), an abundant platelet secretory product, is a strong candidate for modulating glomerular pathology, Because PF4 might be released from platelets and influence intrinsic cell growth during glomerular injury, the effect of PF4 on fetal calf serum- and platelet-derived growth factor (PDGF)-induced mesangial cell mitogenesis was examined, Mitogenesis was measured as the amount of H-3-thymidine incorporated into acid-precipitable material as well as by autoradiography, The effect of PF4 on mesangial cell expression of mRNA for PDGF A chain and transforming growth factor-beta (TGF-beta(1)) was also examined, Fetal calf serum (10%)- and PDGF (10 ng/mL)-stimulated increases in mesangial cell H-3-thymidine incorporation were inhibited by incremental concentrations of PF4 (1 to 25 mu g/mL) showing a maximum reduction of approximately 80% at 25 mu g/mL of PF4, PF4 was effective when added 24 h before and 1, 4, and 8 h, but not 16 h after the addition of PDGF, indicating that inhibition occurred at delayed events in cell-cycle regulation. PF4 inhibited PDGF-induced increments in mRNA encoding PDGF A chain and TGF-beta(1). Also, PF4 did not interfere with PDGF receptor binding. The results of this study show that PF4 is a negative regulator of mesangial cell proliferation and suggest an interference in cell growth by pathways associated with modulation of the autocrine growth factors PDGF and TGF-beta(1). C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT MED,DIV HEMATOL,BRONX,NY 10467. RP Barnes, JL (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV NEPHROL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDDK NIH HHS [DK 43988, DK 38758] NR 48 TC 10 Z9 11 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 1996 VL 7 IS 7 BP 991 EP 998 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA UY441 UT WOS:A1996UY44100004 PM 8829113 ER PT J AU Norling, LL Thornhill, BA Chevalier, RL AF Norling, LL Thornhill, BA Chevalier, RL TI Abnormal glomerular response to atrial natriuretic peptide in rats with aortocaval fistulas SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE cGMP; phosphodiesterase; sodium retention; heart failure ID CONGESTIVE-HEART-FAILURE; GUANYLATE-CYCLASE; RENAL HEMODYNAMICS; FACTOR RECEPTORS; ANP RECEPTORS; CYCLIC-GMP; CGMP; CAPTOPRIL; CLEARANCE; DOGS AB Heart failure is characterized by a blunted natriuretic and diuretic response to atrial natriuretic peptide (ANP). To investigate this, a rat model of compensated high-output heart failure was used to determine whether glomerular response to ANP differs in animals with high cardiac output compared with control animals. An aortocaval (AC) fistula was made below the level of the renal arteries in male Sprague-Dawley rats. At 6 wk, one group of AC fistula (N = 6) and control rats (N = 6) was injected with radiolabeled microspheres for determination of hemodynamic parameters, including cardiac output, renal blood flow, and vascular resistance, Rats with AC fistulas had significant changes in cardiac output (218 +/- 17 versus 57 +/- 11 mL/min, P less than or equal to 0.0001), renal blood flow (3.4 +/- 0.7 versus 8.4 +/- 1.9 mL/min left, P less than or equal to 0.05; 3.0 +/- 0.4 versus 7.2 +/- 1.9 mL/min Right, P less than or equal to 0.05), and fetal vascular resistance (0.6 +/- 0.1 versus 2.7 +/- 0.4 mm Hg/mL per min, P < 0.001) compared with control animals, respectively, In another group of animals, after 6 wk, glomeruli were isolated from kidneys. Extracellular (EC) and intracellular (IC) cGMP was measured as an indication of glomerular response to ANP. Early glomerular response to ANP (10(-8) mol/L) showed a similar acute 13- to 18-fold rise in IC cGMP after 30 sec exposure to ANP (P less than or equal to 0.0001 versus no ANP; N = 4 AC fistula rats and N = 4 control rats). During 1-h incubations with ANP, glomerular response was characterized by a five- to sevenfold increase in EC cGMP. However, glomeruli of AC fistula rats produced significantly less EC cGMP than did those of control animals (21.3 +/- 2.5 Versus 44 +/- 4.9 fMol cGMP/2000 glomeruli, P less than or equal to 0.005; N = 5 AC fistula rats and N = 5 control rats, respectively). Probenecid sensitive transport of EC cGMP between AC fistula and control rats (86% decrease versus 82% decrease) was similar. However, glomeruli from AC fistula animals had significantly less phosphodiesterase activity compared with control animals (3.6 +/- 0.4 versus 5.4 +/- 0.7 nMol cGMP/mg protein per min, P less than or equal to 0.01; N = 4 AC fistula rats and N = 5 control rats, respectively), It is speculated that reduced glomerular generation of cGMP in response to ANP contributes to sodium retention in heart failure, but may be compensated for in part by decreased phosphodiesterase-mediated hydrolysis of cGMP. RP Norling, LL (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT NEPHROL UNIT,ACC 709,15 PARKMAN ST,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK 45179] NR 37 TC 3 Z9 3 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 1996 VL 7 IS 7 BP 1038 EP 1044 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA UY441 UT WOS:A1996UY44100010 PM 8829119 ER PT J AU Onuma, T Laffel, LMB Angelico, MC Krolewski, AS AF Onuma, T Laffel, LMB Angelico, MC Krolewski, AS TI Apolipoprotein E genotypes and risk of diabetic nephropathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE IDDM; diabetic nephropathy; apolipoprotein E ID INSULIN-DEPENDENT DIABETICS; CORONARY-HEART-DISEASE; E POLYMORPHISM; RENAL-FAILURE; E PHENOTYPE; E ISOFORMS; MELLITUS; LIPOPROTEIN; ATHEROSCLEROSIS; HYPERTENSION AB Genetic susceptibility contributes to the development of diabetic nephropathy. In considering potentially important genetic factors, this study examined the association between genetic polymorphisms in apolipoprotein (apo) E and diabetic nephropathy in 146 patients with insulin-dependent diabetes mellitus (IDDM) of 15 to 21 years' duration. Using a casecontrol study design, patients with proteinuria (N = 41) (albumin excretion rate (AER) greater than or equal to 250 mu g/min) and patients with microalbuminuria (N = 31) (AER 20 to 250 mu g/min) were compared with patients who had normoalbuminuria (N = 74) (AER <20 mu g/min). Genetic polymorphisms at the apo E locus were identified by the method of denaturing gradient-gel electrophoresis. There was no significant difference in allele frequencies in the proteinuric, microalbuminuric, or normoalbuminuric groups (e2 7.3%, 9.7%, 9.5%; e3 78.1%, 72.6%, 68.2%; e4 14.6%, 17.7%, 22.3%; respectively), The distribution of the apo E genotypes among the three groups of patients was also similar. These results suggest that apo E genotypes are not associated with the development of early or advanced diabetic nephropathy in patients with IDDM. C1 JOSLIN DIABET CTR,EPIDEMIOL & GENET SECT,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [R01-DK41526] NR 35 TC 54 Z9 56 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 1996 VL 7 IS 7 BP 1075 EP 1078 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA UY441 UT WOS:A1996UY44100015 PM 8829124 ER PT J AU Clyde, AT Hemenway, D Nagurney, JT AF Clyde, AT Hemenway, D Nagurney, JT TI Seat belt use, insurance status, and hospital bad debt SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE motor vehicle; seat belts; safety belts; insurance; bad debt; hospitalizations; injury ID FIREARM INJURIES; COST; TRAUMA; SAFETY AB Objectives: Previous studies have shown that not wearing a seat belt is associated with both increased injury severity and higher hospital charges, In this article, we examine whether unrestrained motorists are also more likely (a) to be medically uninsured, and (6) to leave their hospital bills unpaid, Methods: We reviewed the hospital clinical and billing records for all occupants in motor vehicle collisions admitted to the Massachusetts General Hospital Emergency Department during a 2-month period (n = 265), Using data on seat belt use, insurance status, bad debt, admission to the hospital, driver or passenger status, age and sex, we performed simple correlation and multiple regression analyses to determine the association between (a) seat belt use and insurance status and (b) seat belt use and hospital bad debt. Results: Unrestrained patients were more likely both to be uninsured and, holding insurance status and other factors constant, to generate bad debt for the hospital, Conclusions: Our findings are similar to previous studies that show that the public pays a significant share of the medical care charges associated with risk-taking behavior, Propitious selection, an economic theory, may explain such findings, It asserts that risk-taking individuals are least likely to buy insurance voluntarily and will also he the ones most likely to deliberately place themselves in dangerous situations, Our findings show that people who do not use seat belts are more likely to have outstanding hospital bills; the public effectively pays for these bills in higher taxes or insurance premiums. C1 HARVARD UNIV, SCH PUBL HLTH, DEPT HLTH POLICY & MANAGEMENT, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEPT EMERGENCY SERV, BOSTON, MA 02114 USA. NR 20 TC 6 Z9 6 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 EI 1529-8809 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JUL PY 1996 VL 41 IS 1 BP 100 EP 104 DI 10.1097/00005373-199607000-00015 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA UX857 UT WOS:A1996UX85700020 PM 8676399 ER PT J AU Sparr, LF AF Sparr, LF TI Mental defenses and posttraumatic stress disorder: Assessment of criminal intent SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE posttraumatic stress disorder; criminal defense; forensic assessment; mens rea ID TRAUMA SYNDROME EVIDENCE; INSANITY DEFENSE; EXPERT WITNESS; PSYCHIATRY; COURT; SCALE; MMPI AB Since its formal introduction into psychiatric nomenclature more than a decade ago, the diagnosis of posttraumatic stress disorder (PTSD) has become firmly entrenched in the legal landscape. In part, this is because PTSD seems easy to understand. It is one of only a few mental disorders for which the psychiatric Diagnostic and Statistical Manual (DSM) describes a known cause. Since the diagnosis is usually based on patients' self-report, however, it creates the possibility of distortion aimed at avoidance of criminal punishment, and, as a result, has achieved mired success as a criminal defense. When providing expert testimony mental health witnesses must take care to distinguish between mere PTSD and a causal connection between PTSD and the criminal act in question. PTSD has not only been used to abrogate or diminish responsibility, but also to arrange pre-trial plea bargaining agreements or play a role in sentencing determinations The author explores various uses and potential abuses of PTSD in criminal jurisprudence and offers suggestions regarding retrospective PTSD assessment. C1 OREGON HLTH SCI UNIV,SCH MED,PORTLAND,OR 97207. RP Sparr, LF (reprint author), PORTLAND VA MED CTR,PORTLAND,OR 97207, USA. NR 72 TC 14 Z9 14 U1 2 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUL PY 1996 VL 9 IS 3 BP 405 EP 425 DI 10.1007/BF02103655 PG 21 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA UW921 UT WOS:A1996UW92100001 PM 8827646 ER PT J AU Frueh, BC Smith, DW Barker, SE AF Frueh, BC Smith, DW Barker, SE TI Compensation seeking status and psychometric assessment of combat veterans seeking treatment for PTSD SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE PTSD; compensation seeking ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; VALIDITY; SYMPTOMS; SCALE; RELIABILITY AB Examined differences between compensation seeking (CS) veterans and noncompensation seeking (NCS) veterans on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and other psychological measures in 142 combat veterans evaluated for posttraumatic stress disorder (PTSD) at an outpatient Veterans Affairs (VA) hospital PTSD clinic. Patients were grouped on the basis of their compensation seeking status, with 69% classified as CS for PTSD. The CS veterans achieved significantly more pathological scores across a wide range of psychological inventories and MMPI-2 validity indices, although they did not differ in frequency of PTSD diagnoses from NCS veterans. Implications of these findings are discussed, and clinicians are advised to be aware of the compensation seeking status of combat-veterans being evaluated for PTSD. C1 MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29401. UNIV ARKANSAS,FAYETTEVILLE,AR 72701. RP Frueh, BC (reprint author), RALPH H JOHNSON VET AFFAIRS MED CTR,PSYCHOL SERV 116B,109 BEE ST,CHARLESTON,SC 29401, USA. NR 39 TC 49 Z9 49 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUL PY 1996 VL 9 IS 3 BP 427 EP 439 DI 10.1007/BF02103656 PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA UW921 UT WOS:A1996UW92100002 PM 8827647 ER PT J AU Little, SE AF Little, SE TI Handbook of post-traumatic therapy - Williams,MB, Sommer,JF SO JOURNAL OF TRAUMATIC STRESS LA English DT Book Review RP Little, SE (reprint author), US DEPT VET AFFAIRS,VET OUTREACH & RESOURCE CTR,SPRINGFIELD,VA, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUL PY 1996 VL 9 IS 3 BP 661 EP 662 DI 10.1002/jts.2490090324 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA UW921 UT WOS:A1996UW92100023 ER PT J AU Shipp, TD Genest, D Benacerraf, BR AF Shipp, TD Genest, D Benacerraf, BR TI A case of fetal decapitation SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID AMNIOTIC BAND SYNDROME; DIAGNOSIS C1 MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUL PY 1996 VL 15 IS 7 BP 535 EP 537 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA UV428 UT WOS:A1996UV42800009 PM 8803870 ER PT J AU Barry, MJ AF Barry, MJ TI The impact of co-morbidity on life expectancy among men with localized prostate cancer - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material RP Barry, MJ (reprint author), MASSACHUSETTS GEN HOSP,MED PRACTICES EVALUAT CTR,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 1996 VL 156 IS 1 BP 132 EP 132 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA UQ317 UT WOS:A1996UQ31700042 ER PT J AU Zannetti, S LItalien, GJ Cambria, RP AF Zannetti, S LItalien, GJ Cambria, RP TI Functional outcome after surgical treatment for intermittent claudication SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 28-29, 1995 CL MONTREAL, CANADA SP New England Soc Vasc Surg ID PERIPHERAL ARTERIAL-DISEASE; QUALITY-OF-LIFE; OCCLUSIVE DISEASE; INFRAINGUINAL BYPASS; VASCULAR-SURGERY; MORBIDITY; IMPACT; RISK; REVASCULARIZATION; RECONSTRUCTION AB Purpose: Although patency data for lower extremity bypass grafts are readily available, few reports have focused on patients' satisfaction after surgical reconstruction for claudication. We reviewed our experience with surgical treatment for claudication, focusing on late outcome from the patients' perspective to further refine surgical decision making in patients with intermittent claudication. Patients and Methods: From February 1987 through April 1994, 114 consecutive patients underwent surgical bypass for intermittent claudication. Nine patients were lost to follow-up, leaving the study cohort composed of 105 patients with a mean age of 63 years (range 42 to 82 years). Sixty-two percent of the procedures were inflow reconstructions, and the remainder were infrainguinal bypasses. Clinical and demographic data were gathered from record review, and late follow-up was obtained by return visit or telephone interview. Patient satisfaction and level of function were assessed by a simple five-point questionnaire administered by a research nurse. Actuarial methods were used to calculate late graft patency and survival. Cox regression analysis was used to identify clinical and anatomic factors predictive of late survival and favorable outcome. Results: Cardiac risk assessment revealed that 75% of patients either had no clinical markers for cardiac disease or had been treated with. previous coronary artery bypass grafting or percutaneous transluminal angioplasty; despite this 61% of patients underwent specific preoperative cardiac testing. Most (68%) inflow procedures were aortobifemoral bypass grafts, and 93% of outflow procedures were femoropopliteal bypass grafts. Two thirds of infrainguinal grafts were performed with autogenous conduits, with prosthetic femoropopliteal bypass grafts performed only to the above-knee popliteal artery Early graft failure with successful immediate revision occurred in 5% of patients. No operative deaths or early or late amputations occurred. At a mean follow-up of 4.5 years 96% of surviving patients had a patent graft. However, primary unassisted patency at 4 years was superior for inflow (92% +/- 4%) versus outflow (81% +/- 6%) procedures (p = 0.009). Late readmission for cardiac-related events occurred in 12%, and late cardiac-related death occurred in 5%. Actuarial. survival at 5 years was 80% +/- 5%, with diabetes being the only negative survival predictor (risk ratio 2.6, 95% confidence interval 1 to 7, p = 0.049); 60% of late deaths were cancer-related. Satisfactory late results were reported by 82% of patients, with age less than or equal to 70 years (odds ratio 4.01, 95% confidence interval 1.2 to 13.7, p = 0.026) and normalization (greater than or equal to 0.85) of ankle/brachial index (odds ratio 5.7, 95% confidence interval 1.6 to 20, p = 0.008) being powerful independent predictors of patient satisfaction. Conclusions: After considering cardiac-related short- and long-term prognosis, we conclude that lower extremity bypass grafting for intermittent claudication will produce optimal results when restricted to younger (<70 years) nondiabetic patients in whom near normalization of the postoperative ankle/brachial index can be anticipated. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV VASC SURG,BOSTON,MA 02114. RI van Doorn, Louk/G-5326-2010 OI van Doorn, Louk/0000-0003-1493-0973 NR 29 TC 33 Z9 35 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 1996 VL 24 IS 1 BP 65 EP 73 DI 10.1016/S0741-5214(96)70146-5 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA VA170 UT WOS:A1996VA17000009 PM 8691530 ER PT J AU Stern, Y Liu, XH Albert, M Brandt, J Jacobs, DM DelCastilloCastaneda, C Marder, K Bell, K Sano, M Bylsma, F Lafleche, G Tsai, WY AF Stern, Y Liu, XH Albert, M Brandt, J Jacobs, DM DelCastilloCastaneda, C Marder, K Bell, K Sano, M Bylsma, F Lafleche, G Tsai, WY TI Application of a growth curve approach to modeling the progression of Alzheimer's disease SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID MINI-MENTAL STATE; COGNITIVE DYSFUNCTION; IMPAIRMENT; DEMENTIA; PREDICTION; PATTERN; DECLINE; RATES AB Background. Studies using clinical measures to track AD progression often assume linear declines over the entire course of the disease. which may not be justified. The objective of this study was to model change in measures of the clinical severity of Alzheimer's disease (AD) over time. Methods. We developed a method to apply growth curve models to prospective data and characterize AD patients' functional change over time. Data from the modified Mini-Mental State Examination (mMMSE) and measures of basic and instrumental ADL. administered semiannually for up to 5 years to 236 patients with probable AD, were modeled. Results. The rate of decline in mMMS scores per 6-month interval gradually increased as scores dropped from the maximum of 57 to 20. The rate of decline then decreased as scores approached 0, resulting in an inverse ''S'' curve. The rate of increase in instrumental ADL scores per interval attenuated as the scores increased. while that for basic ADL scores across intervals was constant. Conclusions. Differences in the pattern of progression of the three measures is in pan a function of their psychometric properties. The progression curves may also reflect content-specific features of the instruments. Superimposition oi. the modeled decline in these three content areas suggests a hypothetical model of the relative timing of cognitive and and functional changes in AD. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT NEUROL,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,SCH PUBL HLTH,NEW YORK,NY 10032. JOHNS HOPKINS UNIV,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21218. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROL,CAMBRIDGE,MA 02138. RP Stern, Y (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,GERTRUDE H SERGIEVSKY CTR,630 W 168TH ST,NEW YORK,NY 10032, USA. FU NCRR NIH HHS [RR-00645]; NIA NIH HHS [AG-07370] NR 23 TC 43 Z9 43 U1 2 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 1996 VL 51 IS 4 BP M179 EP M184 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VN556 UT WOS:A1996VN55600015 PM 8681001 ER PT J AU Plotkin, MD Kaplan, MR Verlander, JW Lee, WS Brown, D Poch, E Gullans, SR Hebert, SC AF Plotkin, MD Kaplan, MR Verlander, JW Lee, WS Brown, D Poch, E Gullans, SR Hebert, SC TI Localization of the thiazide sensitive Na-Cl cotransporter, rTSCl, in the rat kidney SO KIDNEY INTERNATIONAL LA English DT Article ID CALCIUM-BINDING PROTEIN; DISTAL NEPHRON; RENAL-CORTEX; TRANSPORT; TUBULE; CELLS AB A thiazide sensitive Na-Cl cotransporter, rTSC1, has recently been cloned from a rat kidney cortex cDNA library. The molecular regulation and nephron localization of this protein is unknown. The purpose of this study was to examine the nephron distribution and subcellular localization of the rTSC1 protein in the rat kidney. In situ hybridization showed rTSC1 transcripts were localized to short, convoluted tubule segments in the kidney cortex. Polyclonal antibodies raised against a 110 amino acid segment from the amino terminus of rTSC1 recognized three major bands of 135, 140 and 155 kDa on Western blotting of membrane protein from cortex but not outer medulla of the rat kidney. Immunofluorescence studies using the antibody alone and in double labeling experiments with antibodies against the H(+)ATPase and calbindin D28, showed intense labeling of apical membranes in the distal nephron beginning in the initial distal convoluted tubule and terminating within the connecting tubule. The intensity of labeling diminished from proximal to distal sites along the distal tubule. Ultrastructural studies by immunoelectron microscopy showed the cotransporter protein to be localized predominately on apical microvilli of the distal convoluted tubule cells. These results are consistent with rTSC1 encoding the apical thiazide sensitive Na-Cl cotransporter in the distal tubule. C1 BRIGHAM & WOMENS HOSP,DIV RENAL,DEPT MED,BOSTON,MA 02115. UNIV FLORIDA,COLL MED,DIV NEPHROL HYPERTENS & TRANSPLANTAT,GAINESVILLE,FL. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. RI Verlander, Jill/I-5991-2015 FU NIDDK NIH HHS [DK08887, DK08898, DK45792] NR 20 TC 146 Z9 149 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 1996 VL 50 IS 1 BP 174 EP 183 DI 10.1038/ki.1996.300 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA UT645 UT WOS:A1996UT64500022 PM 8807586 ER PT J AU Piza, JE Northrop, CC Eavey, RD AF Piza, JE Northrop, CC Eavey, RD TI Neonatal mesenchyme temporal bone study: Typical receding pattern versus increase in Potter's sequence SO LARYNGOSCOPE LA English DT Article ID MIDDLE-EAR; AMNIOTIC-FLUID; CONTAMINATION AB The fate of mesenchyme, which lines the fetal and newborn bony middle ear, is not well understood, The authors wished to test previous observations that a greater amount of mesenchyme was found in Potter's sequence (renal anomalies, pulmonary hypoplasia, and oligohydramnios). Using celloidin-embedded neonatal temporal bones (68 cases, 123 ears), with clinical and autopsy information, middle ear volumes were compared among diagnostic groups using analysis of variance. In 16 ears of Potter's sequence cases the volume of mesenchyme increased in proportion to the size of the middle ear. Conversely, in all other cases the volume of mesenchyme remained constant compared to increasing middle ear size. Both the volume of the bony middle ear and the volume of the air cavity increased at 15 mm(3)/500 g of body weight (gbw). Mesenchyme percentage decreased by 2%/500 gbw. Middle ear mesenchyme appears to recede rather than reabsorb. However, in Potter's sequence cases the volume of mesenchyme increases, raising issues of a missing renal signal that inhibits mesenchymal growth under normal circumstances. C1 UNIV COSTA RICA,SAN JOSE,COSTA RICA. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP Piza, JE (reprint author), HOSP NACL NINOS DR CARLOS SAENZ HERRERA,DEPT PATHOL,APARTADO 1654-1000,SAN JOSE,COSTA RICA. NR 26 TC 9 Z9 9 U1 0 U2 2 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 1996 VL 106 IS 7 BP 856 EP 864 DI 10.1097/00005537-199607000-00014 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA UW659 UT WOS:A1996UW65900014 PM 8667983 ER PT J AU Li, KK Cheney, ML Teknos, TN AF Li, KK Cheney, ML Teknos, TN TI The importance of mandibular position in microvascular mandibular reconstruction SO LARYNGOSCOPE LA English DT Article ID FIXATION; FLAP AB The challenge of mandibular reconstruction rests in the difficulty of re-creating the intricate three-dimensional relationship of the oral cavity, thereby ensuring occlusal relationships, oral competence, and facial contour. Recent advances in microvascular surgery have made reliable transfer of autologous tissue possible, but successful reconstruction depends on accurate insetting of the bone flap. The authors reviewed their five years of experience with mandibular reconstruction and found six patients with a poor reconstructive result secondary to improper insetting of the bone flap. Anteromedially rotated and free-floating proximal mandibular segments appeared to be the most significant contributor to incorrect placement of the bone flap. Based on their findings, the authors devised a simple technique for stabilizing proximal mandibular segments. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL HEAD & NECK SURG,BOSTON,MA 02114. NR 21 TC 12 Z9 12 U1 0 U2 0 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 1996 VL 106 IS 7 BP 903 EP 907 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA UW659 UT WOS:A1996UW65900022 PM 8667991 ER PT J AU Fishman, SM Prince, JB Herman, JB Cassem, NH AF Fishman, SM Prince, JB Herman, JB Cassem, NH TI Pocket-sized electronic clinical referencing SO M D COMPUTING LA English DT Article RP Fishman, SM (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114, USA. NR 7 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0724-6811 J9 M D COMPUT JI M D Comput. PD JUL-AUG PY 1996 VL 13 IS 4 BP 310 EP 313 PG 4 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA UV361 UT WOS:A1996UV36100005 PM 8754237 ER PT J AU Niemi, P Poncelet, BP Kwong, KK Weisskoff, RM Rosen, BR Brady, TJ Kantor, HL AF Niemi, P Poncelet, BP Kwong, KK Weisskoff, RM Rosen, BR Brady, TJ Kantor, HL TI Myocardial intensity changes associated with flow stimulation in blood oxygenation sensitive magnetic resonance imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE echo planar imaging; dipyridamole; deoxyhemoglobin; coronary blood flow ID INTRAVENOUS DIPYRIDAMOLE; SENSORY STIMULATION; CORONARY FLOW; PERFUSION; CONTRAST; BRAIN; HEMODYNAMICS; EXERCISE; MRI AB Functional magnetic resonance imaging exploits deoxygenated blood as an endogeneous source for contrast in assessing local changes in tissue perfusion, intrinsic changes in myocardial signal intensity were measured during dipyridamole induced coronary vasodilatation with T-2(*)-weighted echo planar MRI in healthy volunteers. Concurrently, changes in flow velocity in the left anterior descending coronary artery were measured using a time-of-flight method, Dipyridamole infusion produced 14 +/- 6% increase in myocardial signal intensity (n = 7). Temporal profile of the myocardial signal intensity changes correlated well with the augmentation of coronary flow velocity. The data are consistent with the concept that changes in myocardial deoxyhemoglobin content due to altered flow result in changes in magnetic susceptibility that can be detected on T-2(*)-weighted MR images. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,NMR CTR,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CHARLESTOWN,MA. FU NHLBI NIH HHS [HL 39810]; PHS HHS [P01 #48729] NR 21 TC 51 Z9 51 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUL PY 1996 VL 36 IS 1 BP 78 EP 82 DI 10.1002/mrm.1910360114 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UT368 UT WOS:A1996UT36800013 PM 8795024 ER PT J AU Christensen, JD Barrere, BJ Boada, FE Vevea, JM Thulborn, KR AF Christensen, JD Barrere, BJ Boada, FE Vevea, JM Thulborn, KR TI Quantitative tissue sodium concentration mapping of normal rat brain SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE sodium; MRI; quantitation; brain ID MAGNETIC-RESONANCE; 1.5 T; INVIVO; NMR; NA-23; WATER; SPECTROSCOPY; RELAXATION; RECEIVER; ECHO AB A quantitative in vivo method for obtaining maps of tissue sodium concentration (TSC) by MRI is compared to the invasive, global Na-22 radionuclide dilutional technique in the normal rat brain, The NIR method uses a three-dimensional projectional acquisition scheme to minimize signal losses from transverse relaxation, Internal calibration standards are used to convert the signal intensity into TSC after correction for B-1 inhomogeneities by using the ratio of Na-23 and H-1 images obtained with identical B-1 distributions and sensitivities at the two frequencies, Over the biological range of concentrations, the TSC, measured as the ratio of MR signals of Na-23 and H-1, gives a linear response with concentration, In the normal rat brain, the mean TSC measured using the MRI method (TSC = 45 +/- 4 mM, animals = 5) is not significantly different from the global Na-22 radionuclide method (TSC = 49 +/- 6 mM, animals = 7). C1 MASSACHUSETTS GEN HOSP,NMR CTR,DEPT RADIOL,CHARLESTOWN,MA. UNIV PITTSBURGH,MED CTR,DEPT RADIOL,MR RES CTR,PITTSBURGH,PA. RI Thulborn, Keith/D-9183-2015 OI Thulborn, Keith/0000-0001-6197-4296 FU NCI NIH HHS [R01 CA63661]; NHLBI NIH HHS [R01 HL45176] NR 31 TC 56 Z9 57 U1 1 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUL PY 1996 VL 36 IS 1 BP 83 EP 89 DI 10.1002/mrm.1910360115 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UT368 UT WOS:A1996UT36800014 PM 8795025 ER PT J AU Cohen, RD Welch, C Xia, YR Lusis, AJ Reue, K AF Cohen, RD Welch, C Xia, YR Lusis, AJ Reue, K TI Localization of mouse peroxisome proliferator-activated receptor delta (Ppard) on Chromosome 17 near colipase (Clps) SO MAMMALIAN GENOME LA English DT Article ID FATTY-ACIDS C1 W LOS ANGELES VET AFFAIRS MED CTR,LIPID RES LAB,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT PATHOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,INST MOL BIOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,DEPT MICROBIOL & MOLEC GENET,LOS ANGELES,CA 90095. FU NHLBI NIH HHS [HL28481] NR 7 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 1996 VL 7 IS 7 BP 557 EP 558 DI 10.1007/s003359900167 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UZ385 UT WOS:A1996UZ38500023 PM 8672143 ER PT J AU Amstalden, EMI Xavier, R Kattapuram, SV Bertolo, MB Swartz, MN Rosenberg, AE AF Amstalden, EMI Xavier, R Kattapuram, SV Bertolo, MB Swartz, MN Rosenberg, AE TI Paracoccidioidomycosis of bones and joints - A clinical, radiologic, and pathologic study of 9 cases SO MEDICINE LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; PATIENT; BRASILIENSIS; ESTROGENS C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. STATE UNIV CAMPINAS,DEPT PATHOL,SCH MED,SAO PAULO,BRAZIL. STATE UNIV CAMPINAS,DEPT RHEUMATOL,SCH MED,SAO PAULO,BRAZIL. NR 41 TC 1 Z9 3 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JUL PY 1996 VL 75 IS 4 BP 212 EP 225 DI 10.1097/00005792-199607000-00004 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA VB200 UT WOS:A1996VB20000004 ER PT J AU Netti, PA Roberge, S Boucher, Y Baxter, LT Jain, RK AF Netti, PA Roberge, S Boucher, Y Baxter, LT Jain, RK TI Effect of transvascular fluid exchange on pressure-flow relationship in tumors: A proposed mechanism for tumor blood flow heterogeneity SO MICROVASCULAR RESEARCH LA English DT Article ID HUMAN ADENOCARCINOMA LS174T; INTERSTITIAL PRESSURE; MICROVASCULAR PERMEABILITY; SOLID TUMORS; SCID MICE; MACROMOLECULES; TRANSPORT; GROWTH; ANGIOGENESIS; XENOGRAFT AB Tumor blood flow (TBF) is characterized by spatial and temporal heterogeneities. Despite the crucial role of TBF in tumor growth, metastasis, and therapy, the mechanisms underlying these heterogeneities are not fully understood. Tumor vessels are, in general, more leaky than normal vessels and this may enhance the efficiency of fluid exchange between the vascular and the interstitial space. The coupling between transvascular fluid exchange and hemodynamics in tumors has not been explored previously. To investigate the role of transvascular fluid exchange on afferent and efferent blood flow, we modeled the tumor vasculature as an equivalent single vessel which is permeable and deformable and embedded in a fluid medium with uniform pressure. Simulations were carried out to examine the effects of vessel leakiness, vessel compliance, and interstitial fluid pressure on (a) pressure-flow relationship, (b) arterial-venous pressure relationship, and (c) pressure profile along the vessel. Experiments suggested by model simulations required an independent control of arterial and venous pressure and tumor blood flow. To this end, we perfused tissue-isolated tumors ex vivo and obtained data on perfusate flow rate vs arterial and venous pressures. The simulations predicted the following trends as a result of an enhanced fluid filtration across the vessel wall: (a) for a fixed arterial-venous pressure difference, efferent flow decreases with increasing venous pressure, (b) changes in venous pressure are not completely transmitted to the arterial side, and (c) the pressure profile along the vessel becomes less steep. The experimental results confirmed these trends and indicated that vascular and interstitial flow are coupled in isolated tumors. The implications of this coupling for the spatial and temporal heterogeneity in TBF are discussed. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Netti, PA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. OI NETTI, PAOLO/0000-0002-2435-7181 FU NCI NIH HHS [R35-CA-56591] NR 39 TC 132 Z9 137 U1 0 U2 11 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD JUL PY 1996 VL 52 IS 1 BP 27 EP 46 DI 10.1006/mvre.1996.0041 PG 20 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UW560 UT WOS:A1996UW56000003 PM 8812751 ER PT J AU Jones, R Kirton, OC AF Jones, R Kirton, OC TI Lung microvessel injury from peritoneal abscesses and gram-negative bacteremia SO MICROVASCULAR RESEARCH LA English DT Article ID EXPERIMENTAL INTRAABDOMINAL ABSCESSES; RESPIRATORY-DISTRESS SYNDROME; ESCHERICHIA-COLI ENDOTOXIN; TUMOR NECROSIS FACTOR; PULMONARY-HYPERTENSION; EXPERIMENTAL-MODEL; INTERLEUKIN-1; INFECTION; SEPSIS; RATS AB To analyze the effect of an extrathoracic focus of infection on lung vessel wall structure, we produced peritoneal abscesses in the rat, over a period of 3 to 7 weeks, by implanting capsules containing live gram-negative bacteria (3.0 x 10(7) Escherichia coli and 5.0 x 10(7) Bactercides fragilis) with an adjutant. We document here by arteriography, morphometric analysis, and high resolution microscopy, microvessel cell injury, and wall remodeling. In the sepsis-injured lung, both dilated and thick-walled microvessels are present. The walls of dilated vessels are disrupted by extensive endothelial and precursor smooth muscle cell injury. In thick-walled vessels these cells are hypertrophied, and the precursor smooth muscle cells express filaments, demonstrating a shift toward a contractile phenotype. Infiltrating monocytic cells focally consolidate alveolar regions. Ln the residual nonconsolidated regions, alveolar-capillary membrane cells are attenuated and the capillaries dilated. Vessel changes after 7 weeks are similar to those after 3 weeks but alveolar-capillary membrane injury is more extensive. These structural changes, including the development of precursor smooth muscle cells, may contribute to the known increase in reactivity of these lung vessels to challenge by vasoactive agents. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,BOSTON,MA. UNIV MIAMI,SCH MED,DEPT SURG,DIV TRAUMA,MIAMI,FL 33101. RP Jones, R (reprint author), MASSACHUSETTS GEN HOSP EAST,DEPT ANESTHESIA,MOLEC & CELL BIOL LAB,149 13TH ST,CHARLESTOWN,MA 02129, USA. FU NHLBI NIH HHS [NHLB123591] NR 34 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD JUL PY 1996 VL 52 IS 1 BP 84 EP 100 DI 10.1006/mvre.1996.0046 PG 17 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UW560 UT WOS:A1996UW56000008 PM 8812762 ER PT J AU Frierson, HF Gaffey, MJ Zukerberg, LR Arnold, A Williams, ME AF Frierson, HF Gaffey, MJ Zukerberg, LR Arnold, A Williams, ME TI Immunohistochemical detection and gene amplification of cyclin D1 in mammary infiltrating ductal carcinoma SO MODERN PATHOLOGY LA English DT Article DE BCL-1; breast cancer; chromosome 11q13; cyclin D1; histologic grade ID HUMAN BREAST-CANCER; CHROMOSOME-11 TRANSLOCATION BREAKPOINTS; CENTROCYTIC LYMPHOMA; PROTEIN EXPRESSION; PUTATIVE ONCOGENE; PRAD1/CYCLIN D1; POOR PROGNOSIS; CELL; BCL-1; OVEREXPRESSION AB The deregulation of cyclin D1 (BCL-1, PRAD1, CCND1) protein, normally synthesized in the G(1) phase of the cell cycle, has been implicated in the pathogenesis of some malignant neoplasms, including invasive mammary carcinomas, We used rabbit polyclonal antibody 19 to detect cyclin D1 in 55 infiltrating ductal carcinomas and compared the findings to six important clinicopathologic parameters and cyclin D1 gene amplification. Nuclear immunoreactivity of variable intensity for cyclin D1 was present in 35% of the neoplasms, whereas immunoreactivity of normal mammary epithelial nuclei was absent, No significant correlations were observed between immunoreactivity and patient age, axillary lymph node status, estrogen receptors, progesterone receptors, histologic grade, or any of its three components, There was a correlation between cyclin D1 immunostaining and tumor size (P = 0.013), Fourteen of 15 tumors 2 cm or less were negative, whereas 7 of 12 neoplasms larger than 4 cm were immunopositive, Fifteen percent of the invasive carcinomas had cyclin D1 gene amplification, Of these eight tumors, six showed cyclin D1 immunoreactivity (P = 0.017), In this study, cyclin D1 was detected immunohistochemically in approximately one-third of infiltrating ductal carcinomas; approximately one-third of these had detectable cyclin D1 gene amplification, These results further implicate cyclin D1 in breast tumorigenesis and are additional evidence for the role of cell cycle regulatory proteins in invasive mammary carcinoma. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL UNIT,BOSTON,MA 02114. RP Frierson, HF (reprint author), UNIV VIRGINIA,HLTH SCI CTR,DEPT PATHOL,BOX 214,CHARLOTTESVILLE,VA 22908, USA. FU NCI NIH HHS [P30 CA 44579, CA55909] NR 38 TC 29 Z9 30 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUL PY 1996 VL 9 IS 7 BP 725 EP 730 PG 6 WC Pathology SC Pathology GA UX184 UT WOS:A1996UX18400002 PM 8832554 ER PT J AU Young, RH Clement, PB AF Young, RH Clement, PB TI Mullerianosis of the urinary bladder SO MODERN PATHOLOGY LA English DT Article DE endocervicosis; endometriosis; endosalpingiosis; mullerianosis; urinary bladder ID ADENOCARCINOMA AB Three women, 37, 44, and 46 years of age, had masses up to 4 cm in maximal size, which involved the posterior wall of the urinary bladder, treated by transurethral resection, Microscopic examination showed prominent involvement of the lamina propria and muscularis propria by tubules and cysts lined by mullerian-type epithelium; in two cases, the latter also focally replaced the urothelium and formed polypoid projections into the bladder lumen, The tubules and cysts were usually round to oval but occasionally exhibited prominent branching, In all three cases, the glands were predominantly lined by tubal-type epithelium (including ciliated cells, intercalated, and peg cells), that represented endosalpingiosis. Each case also contained a minor component of glands lined by columnar mucinous cells (endocervicosis), In one case, there was a minor component of typical endometriosis, and, in another, endometrioid epithelium was associated with prominent pseudoxanthoma cells in the adjacent stroma, On the basis of these three cases, striking endosalpingiosis of the urinary bladder, which has not been previously documented, is usually associated with endocervicosis, endometriosis, or both, and, in such cases, the designation ''mullerianosis'' is appropriate, Mullerianosis can be distinguished from adenocarcinoma and various non-neoplastic glandular lesions of the urinary bladder on the basis of a variety of architectural and cytologic features. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA. UNIV BRITISH COLUMBIA,VANCOUVER HOSP,DEPT PATHOL,VANCOUVER,BC V5Z 1M9,CANADA. UNIV BRITISH COLUMBIA,CTR HLTH SCI,VANCOUVER,BC V5Z 1M9,CANADA. NR 20 TC 75 Z9 77 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUL PY 1996 VL 9 IS 7 BP 731 EP 737 PG 7 WC Pathology SC Pathology GA UX184 UT WOS:A1996UX18400003 PM 8832555 ER PT J AU Nielsen, GP OConnell, JX Dickersin, GR Rosenberg, AE AF Nielsen, GP OConnell, JX Dickersin, GR Rosenberg, AE TI Collagenous fibroma (desmoplastic fibroblastoma): A report of seven cases SO MODERN PATHOLOGY LA English DT Article DE collagenous fibroma; desmoplastic fibroblastoma; fibroblastoma; fibroma; soft tissue ID TENDON SHEATH; NEOPLASMS; SARCOMA; TUMOR AB We report the clinical features, light microscopic and ultrastructural appearance, and the immunohistochemical profile of seven benign fibrous tumors recently designated as desmoplastic fibroblastoma. The tumors occurred in four women and three men, who ranged in age from 41 to 76 years (mean, 53 yr). The tumors were located in the left thigh, right shoulder, right upper arm, left forearm, right neck, posterior neck, and foot and measured from 1.5 to 8 cm (mean, 4.6 cm) in greatest diameter. Four tumors were located in the subcutaneous tissue, two tumors were intramuscular, and one tumor involved the subcutaneous tissue and adjacent skeletal muscle, Six patients underwent a simple excision; one patient underwent a wide excision of the tumor. Grossly, the tumors were well circumscribed with a white to tan-white, bulging cut surface, Microscopically, they all displayed similar features and were composed of widely separated stellate- or spindle-shaped cells embedded in a hypovascular fibrous or fibromyxoid stroma. No mitotic figures, calcifications, or necrosis were identified, Five tumors were well demarcated, and two tumors had focally infiltrating margins, Ultrastructural examination performed on two cases showed that the tumor cells had features of fibroblasts and myofibroblasts. Immunohistochemical examinations performed on six cases showed that all of the tumors were diffusely positive for vimentin. One tumor showed diffuse staining for smooth muscle actin, and two tumors were focally positive for that antibody, One tumor showed diffuse staining for muscle actin, and another one was focally positive, Two tumors demonstrated diffuse faint staining for S100 protein, There was no staining for desmin, keratin, or CD34, Follow-up information was available in four cases and ranged from 1 to 60 months (average, 24 mo), No tumor recurred, Although the term desmoplastic fibroblastoma has been applied to this neoplasm, we think that the name collagenous fibroma is more appropriate for these tumors. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. VANCOUVER HOSP,DEPT PATHOL,VANCOUVER,BC,CANADA. HLTH SCI CTR,VANCOUVER,BC,CANADA. NR 16 TC 45 Z9 49 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUL PY 1996 VL 9 IS 7 BP 781 EP 785 PG 5 WC Pathology SC Pathology GA UX184 UT WOS:A1996UX18400010 PM 8832562 ER PT J AU Eckner, R Ludlow, JW Lill, NL Oldread, E Arany, Z Modjtahedi, N DeCaprio, JA Livingston, DM Morgan, JA AF Eckner, R Ludlow, JW Lill, NL Oldread, E Arany, Z Modjtahedi, N DeCaprio, JA Livingston, DM Morgan, JA TI Association of p300 and CBP with simian virus 40 large T antigen SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SV40 LARGE-T; LARGE TUMOR-ANTIGEN; RETINOBLASTOMA SUSCEPTIBILITY GENE; TRANSFORMATION-GOVERNING SEQUENCE; HUMAN ADENOVIRUS TYPE-5; REGION 1A PROTEINS; CELLULAR PROTEINS; BINDING; DIFFERENTIATION; PRODUCTS AB p300 and the CREB-binding protein CBP are two large nuclear phosphoproteins that are structurally highly related. Both function, in part, as transcriptional adapters and are targeted by the adenovirus E1A oncoprotein. We show here that p300 and CBP interact with another transforming protein, the simian virus 40 large T antigen (T). This interaction depends on the integrity of a region of T which is critical for its transforming and mitogenic properties and includes its LXCXE Rb-binding motif. T interferes with normal p300 and CBP function on at least two different levels. The presence of T alters the phosphorylation states of both proteins and inhibits their transcriptional activities on certain promoters. Although E1A and T show little sequence similarity, they interact with the same domain of p300 and CBP, suggesting that this region exhibits considerable flexibility in accommodating diverse protein ligands. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 62 TC 211 Z9 212 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1996 VL 16 IS 7 BP 3454 EP 3464 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UT086 UT WOS:A1996UT08600024 PM 8668161 ER PT J AU Henry, MF Silver, PA AF Henry, MF Silver, PA TI A novel methyltransferase (Hmt1p) modifies poly(A)(+)-RNA-binding proteins SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; RNA-BINDING-PROTEINS; MYELIN-BASIC-PROTEIN; SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; ESCHERICHIA-COLI; NUCLEAR-PROTEIN; SHUTTLE VECTORS; YEAST; GLYCINE AB RNA-binding proteins play many essential roles in the metabolism of nuclear pre-mRNA. As such, they demonstrate a myriad of dynamic behaviors and modifications. In particular, heterogeneous nuclear ribo-nucleoproteins (hnRNPs) contain the bulk of methylated arginine residues in eukaryotic cells. We have identified the first eukaryotic hnRNP-specific methyltransferase via a genetic screen for proteins that interact with an abundant poly(A) (+)-RNA-binding protein termed Npl3p. We have previously shown that npl3-I mutants are temperature sensitive for growth and defective for export of mRNA from the nucleus. New mutants in interacting genes were isolated by their failure to survive in the presence of the npl3-I allele. Four alleles of the same gene were identified in this manner. Cloning of the cognate gene revealed an encoded protein with similarity to methyltransferases that was termed HMTI for hnRNP methyltransferase. HMT1 is not required for normal cell viability except when NPL3 is also defective. The Hmt1 protein is located in the nucleus. We demonstrate that Npl3p is methylated by Hmt1p both in vivo and in vitro. These findings now allow further exploration of the function of this previously uncharacterized class of enzymes. C1 DANA FARBER CANC INST, DIV CELLULAR & MOLEC BIOL, BOSTON, MA 02115 USA. HARVARD UNIV, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. NR 73 TC 129 Z9 131 U1 0 U2 3 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 JUL PY 1996 VL 16 IS 7 BP 3668 EP 3678 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UT086 UT WOS:A1996UT08600046 PM 8668183 ER PT J AU Chen, HE Chang, S Trub, T Neel, BG AF Chen, HE Chang, S Trub, T Neel, BG TI Regulation of colony-stimulating factor 1 receptor signaling by the SH2 domain-containing tyrosine phosphatase SHPTP1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MACROPHAGE CELL-LINE; CSF-1 RECEPTOR; GROWTH-FACTOR; KINASE INSERT; FACTOR-I; BINDING-SITE; MOTH-EATEN; PROTEIN; ACTIVATION; GENE AB SHPTP1 (PTP1C, HCP, SHP) is an SH2 domain-containing tyrosine phosphatase expressed predominantly in hematopoietic cells. A frameshift mutation in the SHPTP1 gene causes the motheaten (me/me) mouse. These mice are essentially SHPTP1 null and display multiple hematopoietic abnormalities, most prominently hyperproliferation and inappropriate activation of granulocytes and macrophages. The me/me phenotype suggests that SHPTP1 negatively regulates macrophage proliferative pathways. Using primary bone marrow-derived macrophages from me/me mice and normal littermates, we examined the role of SHPTP1 in regulating signaling by the major macrophage mitogen colony-stimulating factor 1 (CSF-1) (also known as macrophage colony-stimulating factor). Macrophages from me/me mice hyperproliferate in response to CSF-1. In the absence of SHPTP1, the CSF-1 receptor (CSF-1R) is hyperphosphorylated upon CSF-1 stimulation, suggesting that SHPTP1 dephosphorylates the CSF-1R At least some CSF-1R-associated proteins also are hyperactivated. SHPTP1 is associated constitutively, via its SH2 domains, with an unidentified 130-kDa phosphotyrosyl protein (P130). P130 and SHPTP1 are further tyrosyl phosphorylated upon CSF-1 stimulation. Tyrosylphosphorylated SHPTP1 binds to Grb2 via the Grb2 SH2 domain. Moreover, in me/me macrophages, Grb2 is associated, via its SH3 domains, with several tyrosyl phosphoproteins. These proteins are hyperphosphorylated on tyrosyl residues in me/me macrophages, suggesting that Grb2 may recruit substrates for SHPTP1. Our results indicate that SHPTP1 is a critical negative regulator of CSF-1 signaling in vivo and suggest a potential new function for Grb2. C1 HARVARD UNIV,SCH MED,PROGRAM BIOL & BIOMED SCI,BOSTON,MA 02215. JOSLIN DIABET CTR,BOSTON,MA 02215. RP Chen, HE (reprint author), BETH ISRAEL HOSP,MOLEC MED UNIT,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NCI NIH HHS [R01CA49152] NR 60 TC 171 Z9 173 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1996 VL 16 IS 7 BP 3685 EP 3697 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UT086 UT WOS:A1996UT08600048 PM 8668185 ER PT J AU Wu, CL Classon, M Dyson, N Harlow, E AF Wu, CL Classon, M Dyson, N Harlow, E TI Expression of dominant-negative mutant DP-1 blocks cell cycle progression in G(1) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; E2F TRANSCRIPTION FACTOR; ADENOVIRUS-E1A PREVENTS; COMPLEX-FORMATION; BINDING PROTEIN; TRANSACTIVATION; IDENTIFICATION; INHIBITION; CLONING; DNA AB Unregulated expression of the transcription factor E2F promotes the G(1)-to-S phase transition in cultured mammalian cells. However, there has been no direct evidence for an E2F requirement in this process. To demonstrate that E2F is obligatory for cell cycle progression, we attempted to inactivate E2F by overexpressing dominant-negative forms of one of its heterodimeric partners, DP-1. We dissected the functional domains of DP-1 and separated the region that facilitate heterodimer DNA binding from the E2F dimerization domain. Various DP-1 mutants were introduced into cells via transfection, and the cell cycle profile of the transfected cells was analyzed by flow cytometry. Expression of wild-type DP-1 or DP-1 mutants that bind to both DNA and E2F drove cells into S phase. In contrast, DP-1 mutants that retained E2F binding but lost DNA binding arrested cells in the G(1) phase of the cell cycle. The DP-1 mutants that were unable to bind DNA resulted in transcriptionally inactive E2F complexes, suggesting that the G(1) arrest is caused by formation of defective E2F heterodimers. Furthermore, the G(1) arrest instigated by these DP-1 mutants could be rescued by coexpression of wild-type E2F or DP protein. These experiments define functional domains of DP and demonstrate a requirement for active E2F complexes in cell cycle progression. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC ONCOL LAB,SCH MED,CHARLESTOWN,MA 02129. FU NCI NIH HHS [R01-CA55339, R01-CA60636] NR 73 TC 114 Z9 118 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1996 VL 16 IS 7 BP 3698 EP 3706 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UT086 UT WOS:A1996UT08600049 PM 8668186 ER PT J AU Huang, J Blackwell, TK Kedes, L Weintraub, H AF Huang, J Blackwell, TK Kedes, L Weintraub, H TI Differences between MyoD DNA binding and activation site requirements revealed by functional random sequence selection SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HELIX-LOOP-HELIX; MUSCLE-SPECIFIC EXPRESSION; ESCHERICHIA-COLI; TRANSCRIPTIONAL ACTIVATION; MYOGENIN GENE; CYCLIC AMPLIFICATION; MOUSE EMBRYOGENESIS; REGULATORY FACTORS; ENHANCER-BINDING; MAMMALIAN-CELLS AB A method has been developed for selecting functional enhancer/promoter sites from random DNA sequences in higher eukaryotic cells. Of sequences that were thus selected for transcriptional activation by the muscle-specific basic helix-loop-helix protein MyoD, only a subset are similar to the preferred in vitro binding consensus, and in the same promoter context an optimal in vitro binding site was inactive. Other sequences with full transcriptional activity instead exhibit sequence preferences that, remarkably, are generally either identical or very similar to those found in naturally occurring muscle-specific promoters. This first systematic examination of the relation between DNA binding and transcriptional activation by basic helix-loop-helix proteins indicates that binding per se is necessary but not sufficient for transcriptional activation by MyoD and implies a requirement for other DNA sequence-dependent interactions or conformations at its binding site. C1 UNIV SO CALIF, SCH MED, DEPT BIOCHEM & MOLEC BIOL, LOS ANGELES, CA 90033 USA. FRED HUTCHINSON CANC RES CTR, HOWARD HUGHES MED INST, SEATTLE, WA 98104 USA. UNIV SO CALIF, SCH MED, INST MED GENET, LOS ANGELES, CA 90033 USA. CTR BLOOD RES, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. NR 80 TC 37 Z9 37 U1 0 U2 0 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 JUL PY 1996 VL 16 IS 7 BP 3893 EP 3900 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UT086 UT WOS:A1996UT08600070 PM 8668207 ER PT J AU Loh, C Carew, JA Kim, J Hogan, PG Rao, A AF Loh, C Carew, JA Kim, J Hogan, PG Rao, A TI T-cell receptor stimulation elicits an early phase of activation and a later phase of deactivation of the transcription factor NFAT1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN KINASE-C; CYCLOSPORINE-A; LYMPHOCYTES-T; IDENTIFICATION; BINDING; COMPLEX; FK506; INTERLEUKIN-2; MECHANISMS; PROMOTER AB We show here that NFAT1 is rapidly activated, then slowly deactivated, by stimulation of T cells through their antigen receptor. Within minutes of T-cell receptor stimulation, NFAT1 is dephosphorylated, translocates from the cytoplasm into the nucleus, and shows an increase in its ability to bind to DNA. These changes are dependent on calcium mobilization and calcineurin activation, since they are also elicited by ionomycin and are blocked by the immunosuppressive drug cyclosporin A. After several hours of T-cell receptor stimulation, the majority of the NFAT1 in the cell reverts to its original phosphorylated form, reappears in the cytoplasm, and again displays a low affinity for DNA. Deactivation of NFAT1 is facilitated by phorbol 12-myristate 13-acetate and inhibitors of capacitative calcium entry and most likely reflects the slow return of intracellular free calcium concentrations towards resting levels. Our results suggest that calcineurin-dependent signalling pathways mediate the early activation of NFAT1, while phorbol 12-myristate W-acetate-dependent feedback pathways contribute to the late deactivation. Persistent NFAT-dependent cytokine gene transcription in activated T cells may be mediated by other NFAT family proteins in addition to NFAT1 during the immune response. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI35297]; NIGMS NIH HHS [GM42667] NR 64 TC 95 Z9 98 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1996 VL 16 IS 7 BP 3945 EP 3954 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UT086 UT WOS:A1996UT08600075 PM 8668212 ER PT J AU Luo, C Burgeon, E Carew, JA McCaffrey, PG Badalian, TM Lane, WS Hogan, PG Rao, A AF Luo, C Burgeon, E Carew, JA McCaffrey, PG Badalian, TM Lane, WS Hogan, PG Rao, A TI Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEAR FACTOR; CYCLOSPORINE-A; INTERLEUKIN-4 GENE; ACTIVATION GENES; PROMOTER; IDENTIFICATION; ELEMENTS; BINDING; COMPLEX; LYMPHOCYTE AB Transcription factors of the NFAT family play a key role in the transcription of cytokine genes and other genes during the immune response. We have identified two new isoforms of the transcription factor NFAT1 (previously termed NFATp) that are the predominant isoforms expressed in murine and human T cells. When expressed in Jurkat T cells, recombinant NFAT1 is regulated, as expected, by the calmodulin-dependent phosphatase calcineurin, and its function is inhibited by the immunosuppressive agent cyclosporin A (CsA). Transactivation by recombinant NFAT1 in Jurkat T cells requires dual stimulation with ionomycin and phorbol 12-myristate 13-acetate; this activity is potentiated by coexpression of constitutively active calcineurin and is inhibited by CsA. Immunocytochemical analysis indicates that recombinant NFAT1 localizes in the cytoplasm of transiently transfected T cells and translocates into the nucleus in a CsA-sensitive manner following ionomycin stimulation. When expressed in COS cells, however, NFAT1 is capable df transactivation, but it is not regulated correctly: its subcellular localization and transcriptional function are not affected by stimulation of the COS cells with ionomycin and phorbol 12-myristate 13-acetate. Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. HARVARD UNIV,MICROCHEM FACIL,CAMBRIDGE,MA 02138. FU NCI NIH HHS [CA42471]; NIGMS NIH HHS [GM46227] NR 71 TC 164 Z9 167 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1996 VL 16 IS 7 BP 3955 EP 3966 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UT086 UT WOS:A1996UT08600076 PM 8668213 ER PT J AU Speliotes, EK Caday, CG Do, T Weise, J Kowall, NW Finklestein, SP AF Speliotes, EK Caday, CG Do, T Weise, J Kowall, NW Finklestein, SP TI Increased expression of basic fibroblast growth factor (bFGF) following focal cerebral infarction in the rat SO MOLECULAR BRAIN RESEARCH LA English DT Article DE basic fibroblast growth factor; cerebral ischemia; cerebral infarction; rat; northern blot; in situ hybridization; immunohistochemistry ID MESSENGER-RNA; FACTOR IMMUNOREACTIVITY; FOREBRAIN ISCHEMIA; TIME-COURSE; BRAIN; NEURONS; FGF; PROTEIN; PROLIFERATION; ANGIOGENESIS AB Basic fibroblast growth factor (bFGF) is a polypeptide with potent trophic effects on brain neurons, glia, and endothelial cells. In the current study, we used Northern blotting, in situ hybridization, and immunohistochemical techniques to examine bFGF expression in brain following focal infarction due to permanent occlusion of the proximal middle cerebral artery in mature Sprague-Dawley rats. We found a four-fold increase in bFGF mRNA in tissue surrounding focal infarcts at 1 day after ischemia. In situ hybridization showed that this increase was found throughout several structures in the ipsilateral hemisphere, including frontoparietal, temporal, and cingulate cortex, as well as in caudoputamen, globus pallidus, septal nuclei, nucleus accumbens, and olfactory tubercle. Increased bFGF mRNA expression was associated with cells having the distinct morphological appearance of astroglia in these structures. Immunohistochemistry showed an increase in the size and number of bFGF-immunoreactive (IR) nuclei in these same structures, as well as a shift from nuclear to nuclear plus cytoplasmic localization of immunoreactivity, beginning at 1 day, and peaking at 3 days after ischemia. Double immunostaining identified bFGF-IR cells as astroglia in these structures. (An exception was the piriform cortex, in which both increased bFGF mRNA levels and increased bFGF-IR was found in neurons at 1 day after ischemia.) Overall, the peak of increased bFGF expression preceded the peak in expression of the astroglial marker GFAP within the ipsilateral hemisphere. Increased bFGF expression may play an important role in the glial, neuronal, and vascular changes occurring after focal infarction. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROL, CNS, GROWTH FACTOR RES LAB, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. VET ADM MED CTR, DEPT NEUROL & PATHOL, BEDFORD, MA USA. BOSTON UNIV, SCH MED, BOSTON, MA 02118 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 57 TC 71 Z9 73 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUL PY 1996 VL 39 IS 1-2 BP 31 EP 42 DI 10.1016/0169-328X(95)00351-R PG 12 WC Neurosciences SC Neurosciences & Neurology GA UU373 UT WOS:A1996UU37300004 ER PT J AU Girardet, C Walker, WH Habener, JF AF Girardet, C Walker, WH Habener, JF TI An alternatively spliced polycistronic mRNA encoding cyclic adenosine 3',5'-monophosphate (cAMP)-responsive transcription factor CREB (cAMP response element-binding protein) in human testis extinguishes expression of an internally translated inhibitor CREB isoform SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GENE-TRANSCRIPTION; EXON; ADENOSINE-3',5'-MONOPHOSPHATE; ACTIVATION; CONTAINS; PROMOTER; ENHANCER; SUBUNIT; SITE; RNAS AB Cyclic AMP response element-binding protein (CREB) regulates the expression of cAMP-responsive genes, In the rat testis, several isoforms of CREB arise from alternative exon splicing that occurs cyclically during the 12-day cell association cycles of spermatogenesis. Insertion of alternatively spliced exon W into CREB mRNA during spermatogenesis results in a polycistronic RNA that encodes two novel internally translated CREB repressor isoforms called I-CREBs, consisting of the carboxy-terminal DNA-binding domain devoid of the transactivation domains, Here we report the alternative splicing of an additional novel exon Z in CREB mRNA expressed in human but not in mouse or rat testis, Insertion of exon Z abolishes the synthesis of one of the two inhibitor CREBs due to the introduction of an inframe stop codon within exon Z. We show that exon Z is not spliced into mRNAs in mouse and rat testes due to the evolution of mutations in the splice signals flanking exon Z. These findings suggest that the splicing in of exon Z may be part of a human-specific mechanism to regulate cAMP-dependent regulatory pathways in spermatogenesis by extinguishing the expression of a CREB repressor. C1 MOLEC ENDOCRINOL LAB, BOSTON, MA 02114 USA. HOWARD HUGHES MED INST, MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-25532] NR 31 TC 21 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 1996 VL 10 IS 7 BP 879 EP 891 DI 10.1210/me.10.7.879 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UV734 UT WOS:A1996UV73400010 PM 8813728 ER PT J AU Parkos, CA Colgan, SP Diamond, MS Nusrat, A Liang, TW Springer, TA Madara, JL AF Parkos, CA Colgan, SP Diamond, MS Nusrat, A Liang, TW Springer, TA Madara, JL TI Expression and polarization of intercellular adhesion molecule-1 on human intestinal epithelia: Consequences for CD11b/CD18-mediated interactions with neutrophils SO MOLECULAR MEDICINE LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-3; INFLAMMATORY BOWEL-DISEASE; INTEGRIN MAC-1 CD11B/CD18; INTERFERON-GAMMA; MONOCLONAL-ANTIBODIES; ICAM-1 EXPRESSION; TRANSENDOTHELIAL MIGRATION; LEUKOCYTE TRANSMIGRATION; ELECTROLYTE TRANSPORT; COUNTER-RECEPTOR AB Background: Epithelial dysfunction and patient symptoms in inflammatory intestinal diseases such as ulcerative colitis and Crohn's disease correlate with migration of neutrophils (PMN) across the intestinal epithelium. Ln vitro modeling of PMN transepithelial migration has revealed distinct differences from transendothelial migration. By using polarized monolayers of human intestinal epithelia (T84), PMN transepithelial migration has been shown to be dependent on the leukocyte integrin CD11b/CD18 (Mac-1), but not on CD11a/CD18 (LFA-1). Since intercellular adhesion molecule-1 (ICAM-1) is an important endothelial counterreceptor for these intergrins, its expression in intestinal epithelia and role in PMN-intestinal epithelial interactions was investigated. Materials and Methods: A panel of antibodies against different domains of ICAM-1, polarized monolayers of human intestinal epithelia (T84), and natural human colonic epithelia were used to examine the polarity of epithelial ICAM-1 surface expression and the functional role of ICAM-1 in neutrophil-intestinal epithelial adhesive interactions. Results: While no surface expression of ICAM-1 was detected on unstimulated T84 cells, interferon-gamma (IFN gamma) elicited a marked expression of ICAM-1 that selectively polarized to the apical epithelial membrane. Similarly, apically restricted surface expression of ICAM-1 was detected in natural human colonic epithelium only in association with active inflammation. With or without IFN gamma pre-exposure, physiologically directed (basolateral-to-apical) transepithelial migration of PMN was unaffected by blocking monoclonal antibodies (mAbs) to ICAM-1. In contrast, PMN migration across IFN-gamma-stimulated monolayers in the reverse (apical-to-basolateral) direction was inhibited by anti-ICAM-1 antibodies. Adhesion studies revealed that T84 cells adhered selectively to purified CD11b/CD18 and such adherence, with or without IFN gamma pre-exposure, was unaffected by ICAM-1 mAb. Similarly, freshly isolated epithelial cells from inflamed human intestine bound to CD11b/CD18 in an ICAM-1-independent fashion. Conclusions: These data indicate that ICAM-1 is strictly polarized in intestinal epithelia and does not represent a counterreceptor for neutrophil CD11b/CD18 during physiologically directed transmigration, but may facilitate apical membrane-PMN interactions after the arrival of PMN in the intestinal lumen. C1 BRIGHAM & WOMENS HOSP,DEPT ANESTHESIA,DIV GASTROINTESTINAL PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR DIGEST DIS,BOSTON,MA 02115. RP Parkos, CA (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. RI Nusrat, Asma/B-3887-2009; Parkos, Charles/B-3896-2009; Colgan, Sean/B-4573-2009 FU NCI NIH HHS [CA31799, CA31798]; NHLBI NIH HHS [HL54229] NR 74 TC 136 Z9 137 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD JUL PY 1996 VL 2 IS 4 BP 489 EP 505 PG 17 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UY023 UT WOS:A1996UY02300011 PM 8827719 ER PT J AU Yagnik, PM Chong, PST AF Yagnik, PM Chong, PST TI Spinal accessory nerve injury: A complication of carotid endarterectomy SO MUSCLE & NERVE LA English DT Article DE spinal accessory nerve; carotid endarterectomy ID STENOSIS RP Yagnik, PM (reprint author), MED COLL PENN & HAHNEMANN UNIV,PHILADELPHIA VA MED CTR,DEPT NEUROL,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 18 TC 13 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JUL PY 1996 VL 19 IS 7 BP 907 EP 909 DI 10.1002/(SICI)1097-4598(199607)19:7<907::AID-MUS16>3.0.CO;2-F PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UQ394 UT WOS:A1996UQ39400017 PM 8965848 ER PT J AU Reddy, S Smith, DBJ Rich, MM Leferovich, JM Reilly, P Davis, BM Tran, K Rayburn, H Bronson, R Cros, D BaliceGordon, RJ Housman, D AF Reddy, S Smith, DBJ Rich, MM Leferovich, JM Reilly, P Davis, BM Tran, K Rayburn, H Bronson, R Cros, D BaliceGordon, RJ Housman, D TI Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy SO NATURE GENETICS LA English DT Article ID UNSTABLE CTG REPEAT; MYOSIN HEAVY-CHAIN; FRAGILE-X SYNDROME; MUSCULAR-DYSTROPHY; SKELETAL-MUSCLE; MDX MOUSE; MESSENGER-RNA; CONTRACTILE PROPERTIES; TRIPLET REPEAT; GENE AB Myotonic dystrophy (DM) is an autosomal dominant disorder resulting from the expansion of a CTG repeat in the 3' untranslated region of a putative protein kinase (DMPK). To elucidate the role of DMPK in DM pathogenesis we have developed Dmpk deficient (Dmpk-/-) mice. Dmpk-/- mice develop a late-onset, progressive skeletal myopathy that shares some pathological features with DM. Muscles from mature mice show variation in fibre size, increased fibre degeneration and fibrosis. Adult Dmpk-/- mice show ultrastructural changes in muscle and a 50% decrease in force generation compared to young mice. Our results indicate that DMPK may be necessary for the maintenance of skeletal muscle structure and function and suggest that a decrease in DMPK levels may contribute to DM pathology. C1 MIT,CTR CANC RES,CAMBRIDGE,MA 02138. UNIV PENN,SCH MED,DEPT NEUROSCI,PHILADELPHIA,PA 19104. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02214. FU NIA NIH HHS [P0IAG 1332901] NR 78 TC 224 Z9 230 U1 0 U2 6 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 1996 VL 13 IS 3 BP 325 EP 335 DI 10.1038/ng0796-325 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA UU283 UT WOS:A1996UU28300021 PM 8673132 ER PT J AU Duffy, FH McAnulty, GB Albert, MS AF Duffy, FH McAnulty, GB Albert, MS TI Effects of age upon interhemispheric EEG coherence in normal adults SO NEUROBIOLOGY OF AGING LA English DT Article DE quantitative EEG; interhemispheric coherence; healthy adults; age; gender; handedness; corpus callosum; principal components analysis; analysis of variance; canonical correlation ID HUMAN CORPUS-CALLOSUM; BRAIN ELECTRICAL-ACTIVITY; ALZHEIMERS-DISEASE; SEXUAL DIMORPHISM; FREQUENCY-ANALYSIS; HEALTHY-SUBJECTS; SENILE DEMENTIA; VISUAL-CORTEX; ELECTROENCEPHALOGRAM; DENSITY AB Age-related differences in quantified electrophysiological measures of interhemispheric EEG coherence were studied in 371 subjects (171 males and 200 females), ages 20-80, all of whom were judged to be optimally healthy. Principal components analysis (PCA) was performed on interhemispheric coherence of Laplacian referenced data from eight homologous left-right electrode pairs, from 0.5 to 32 Hz. Regression procedures, using signals from artifact monitoring channels, were used to minimize effects of eye movement and muscle artifact. Forty-six factors described 80% of the total variance, with electrode location the primary source of communality in factor formation. Within 350 right-handed subjects, results indicated a broad trend for decreased interhemispheric coherence with advancing age. Using canonical correlation, the coherence-based factors also successfully predicted spectral variables, previously found to maximally illustrate age-related EEG desynchronization. We speculate that age-related reduction of interhemispheric coherence may in part explain age-related EEG desynchrony and stems from age-related reduction of cortical connectivity. Gender differences of interhemispheric coherence were also evident. Females demonstrated higher interhemispheric coherence than males. Within a smaller subpopulation of 63 subjects (21 left and 32 right handed), there was a gender-by-handedness interaction, with higher interhemispheric coherence in right-handed females than right-handed males and the reverse in left-handed male and female subjects. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP Duffy, FH (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIA NIH HHS [P01AG04953]; NICHD NIH HHS [P30HD18655] NR 78 TC 36 Z9 40 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 1996 VL 17 IS 4 BP 587 EP 599 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA UZ206 UT WOS:A1996UZ20600013 PM 8832634 ER PT J AU Wright, MT Cummings, JL AF Wright, MT Cummings, JL TI Neuropsychiatric disturbances Alzheimer's disease and other dementias: Recognition and management SO NEUROLOGIST LA English DT Article DE dementia; neuropsychiatric disturbances; differential diagnosis; psychotherapy; pharmacotherapy ID PSYCHIATRIC-SYMPTOMS; BEHAVIORAL SYMPTOMS; SENILE DEMENTIA; L-DEPRENYL; NEUROLEPTIC TREATMENT; ELDERLY MEN; PSYCHOSIS; DELUSIONS; DEPRESSION; AGITATION AB BACKGROUND- Dementia is a syndrome with many possible causes. It is most commonly seen in the elderly but can also occur in younger people. Conditions that cause dementia produce memory and other cognitive difficulties as well as a variety of neuropsychiatric disturbances. The neuropsychiatric problems associated with dementias diminish the quality of life for both patients and their caregivers and contribute to the decision to institutionalize patients. REVIEW SUMMARY- Psychomotor activity disturbances, agitation, aggression, personality alterations, anxiety, depression, psychosis, eating disturbances, alterations in libido and sexual activity, and sleep changes are commonly noted in demented patients. Neuropsychiatric disturbances in demented patients can stem directly from illnesses causing dementia or they can be secondary to other factors (e.g., primary psychiatric illnesses, medical illnesses, medication side effects, environmental factors). Nonpharmacologic and pharmacologic treatments can ameliorate many of the neuropsychiatric problems associated with dementias. CONCLUSIONS- Many of the neuropsychiatric concomitants of dementia can be ameliorated if they are accurately characterized and appropriate treatments are applied. Environmental manipulations, psychotherapeutic interventions, and psychotropic medications can decrease patient and caregiver distress and may delay institutionalization of patients. A better understanding of the neuropsychiatric symptoms associated with dementias may lead to new insights into similar symptoms that accompany other neurobiological processes. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,BEHAV NEUROSCI SECT,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA 90073. NR 89 TC 1 Z9 1 U1 5 U2 11 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD JUL PY 1996 VL 2 IS 4 BP 207 EP 218 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA VZ502 UT WOS:A1996VZ50200003 ER PT J AU Mendez, MF Cherrier, MM Perryman, KM AF Mendez, MF Cherrier, MM Perryman, KM TI Epileptic forced thinking from left frontal lesions SO NEUROLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; TEMPORAL-LOBE EPILEPSY; PARTIAL SEIZURES AB Forced thinking is an incompletely understood and rarely described epileptic aura. We studied three patients with forced thinking from left frontal lesions, two neoplastic and one vascular. All thr ee experienced repetitive, intrusive thoughts at the onset of seizures. Their forced thinking was associated with the desire to vocalize, orobuccal movements, and speech arrest. The episodes occurred with other ictal manifestations and responded to antiseizure therapy. These patients suggest that epileptic forced thinking is a heterogeneous phenomenon; forced thinking from left frontal lesions is a manifestation of expressive language and is distinct from experiential thoughts arising from temporal limbic foci. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP Mendez, MF (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEUROBEHAV UNIT 691 116AF,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 29 TC 11 Z9 11 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1996 VL 47 IS 1 BP 79 EP 83 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA UX188 UT WOS:A1996UX18800015 PM 8710129 ER PT J AU Mui, S Briggs, M Chung, H Wallace, RB GomezIsla, T Rebeck, GW Hyman, BT AF Mui, S Briggs, M Chung, H Wallace, RB GomezIsla, T Rebeck, GW Hyman, BT TI A newly identified polymorphism in the apolipoprotein E enhancer gene region is associated with Alzheimer's disease and strongly with the epsilon 4 allele SO NEUROLOGY LA English DT Article ID HUMAN-FIBROBLASTS; BINDING-ACTIVITY; TYPE-4 ALLELE; RISK FACTOR; FREQUENCY; RECEPTORS; VARIANT; MUTANT AB Apolipoprotein E allele 4 (apoE epsilon 4) is a major risk factor for late-onset AD. Inheritance of this allele is associated with an earlier age of onset of dementia in individuals with AD. It is unknown whether other polymorphisms in the apoE gene may influence the effect of apoE epsilon 4 on AD. We screened portions of the promoter enhancer element and of the apoE receptor binding domain for other polymorphisms that could affect risk of AD. In particular, a C/G polymorphism at position +113 of the apoE mRNA in the apoE intron 1 enhancer element (IE1) has been recently identified. We found no other polymorphisms. We studied the relationship of the two alleles of the IE1 polymorphism with AD and found an apparent association between IE1 G; and AD (n = 94; p = 0.0515). However, the IE1 G allele is also closely associated with apoE epsilon 4 (p < 0.0001). When the presence of apoE epsilon 4 is covaried, the association between the IE1 G allele and AD is no longer statistically significant (odds ratio = 1.29, 95% confidence interval: 0.44, 3.78). In contrast, epsilon 4 is still highly associated with AD when IE1 G is controlled for (odds ratio = 5.91, 95% confidence interval: 3.29, 10.63). Furthermore, there is no significant association between the age of onset of dementia and the inheritance of the G allele. We believe that the apparent association between IE1 G and AD is a consequence of the association between the 4 and IE1 G alleles. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. UNIV IOWA,COLL MED,DEPT PREVENT MED & BIOSTAT,IOWA CITY,IA. FU NIA NIH HHS [AG05134, AG01206, AG12406] NR 33 TC 58 Z9 65 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1996 VL 47 IS 1 BP 196 EP 201 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA UX188 UT WOS:A1996UX18800035 PM 8710077 ER PT J AU Kim, E Cho, KO Rothschild, A Sheng, M AF Kim, E Cho, KO Rothschild, A Sheng, M TI Heteromultimerization and NMDA receptor-clustering activity of chapsyn-110, a member of the PSD-95 family of proteins SO NEURON LA English DT Article ID TUMOR-SUPPRESSOR GENE; MOLECULAR CHARACTERIZATION; SUBCELLULAR-LOCALIZATION; CHANNEL PROTEINS; K+ CHANNELS; RAT-BRAIN; SUBUNIT; HOMOLOG; NEURONS; CLONING AB Chapsyn-110, a novel membrane-associated putative guanylate kinase (MAGUK) that binds directly to N-methyl-D-aspartate (NMDA) receptor and Shaker K+ channel subunits, is 70%-80% identical to, and shares an identical domain organization with, PSD-95/SAP90 and SAP97. In rat brain, chapsyn-110 protein shows a somatodendritic expression pattern that overlaps partly with PSD-95 but that contrasts with the axonal distribution of SAP97. Chapsyn-110 associates tightly with the postsynaptic density in brain, and mediates the clustering of both NMDA receptors and K+ channels in heterologous cells. Indeed, chapsyn-110 and PSD-95 can heteromultimerize with each other and are recruited into the same NMDA receptor and K, channel clusters. Thus, chapsyn-110 and PSD-95 may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signalling proteins. C1 BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. RP Kim, E (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROBIOL,HOWARD HUGHES MED INST,BOSTON,MA 02114, USA. RI Kim, Eunjoon/C-1566-2011; Cho, Kyung-Ok/C-1705-2011 NR 36 TC 433 Z9 442 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1996 VL 17 IS 1 BP 103 EP 113 DI 10.1016/S0896-6273(00)80284-6 PG 11 WC Neurosciences SC Neurosciences & Neurology GA UY981 UT WOS:A1996UY98100011 PM 8755482 ER PT J AU Moratalla, R Elibol, B Vallejo, M Graybiel, AM AF Moratalla, R Elibol, B Vallejo, M Graybiel, AM TI Network-level changes in expression of inducible Fos-Jun proteins in the striatum during chronic cocaine treatment and withdrawal SO NEURON LA English DT Article ID C-FOS; DOPAMINE-RECEPTORS; RAT STRIATUM; INDUCTION; DYNORPHIN; IMMUNOREACTIVITY; SENSITIZATION; AMPHETAMINE; ACTIVATION; SYSTEMS AB Repeated exposures to psychomotor stimulants produce long-term changes in behavior ranging from addiction to behavioral sensitization. Many of these behaviors depend on the nigrostriatal system of the basal ganglia. We show here that chronic cocaine exposure not only leads to time-varying alterations in the inducibility of bZIP transcription factors in individual striatal neurons, but also to long-lasting network changes in which ensembles of striatal neurons express these proteins. These network-level adaptations suggest that the behavioral sensitization induced by repeated psychomotor stimulant exposure may reflect an enduring functional reorganization of basal ganglia circuits. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,REPROD ENDOCRINE UNIT,BOSTON,MA 02114. RP Moratalla, R (reprint author), MIT,DEPT BRAIN & COGNIT SCI,E25-618,CAMBRIDGE,MA 02139, USA. RI Moratalla, Rosario/H-9280-2015 OI Moratalla, Rosario/0000-0002-7623-8010 FU NIDA NIH HHS [DA08037] NR 41 TC 217 Z9 220 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1996 VL 17 IS 1 BP 147 EP 156 DI 10.1016/S0896-6273(00)80288-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA UY981 UT WOS:A1996UY98100015 PM 8755486 ER PT J AU Holmgren, M Liu, Y Xu, Y Yellen, G AF Holmgren, M Liu, Y Xu, Y Yellen, G TI On the use of thiol-modifying agents to determine channel topology SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 4th Annual Neuropharmacology Conference CY NOV 14-16, 1996 CL WASHINGTON, DC DE site-directed mutagenesis; chemical modification; thiol reagents; methane thiosulfonate; membrane protein topology; potassium channels ID ACETYLCHOLINE-RECEPTOR; SULFHYDRYL; CYSTEINES; BINDING; INNER AB A powerful tool in the study of cloned ion channels is the combined use of site-directed mutagenesis and chemical modification. Site-directed mutagenesis is used to introduce new cysteine residues at specific positions in a channel protein, and chemical modification by thiol-specific reagents is then used to assess the exposure of the introduced cysteines. This method has been used to assess secondary structure, membrane topology and conformational changes. We report that one commonly used, charged reagent (MTSEA; aminoethyl methanethiosulfonate) can cross the membrane quite readily. We also find that other reagents that are quite membrane-impermeant can cross the membrane when patches are electrically leaky. Both of these undesired effects can be controlled by the use of a thiol scavenger. These findings argue for caution in the use of modifying reagents to determine the membrane topology of channels and Other membrane proteins. Copyright (C) 1996 Elsevier Science Ltd C1 MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BRANDEIS UNIV,GRAD DEPT BIOCHEM,WALTHAM,MA 02254. OI Yellen, Gary/0000-0003-4228-7866 FU NINDS NIH HHS [NS29693, R01 NS029693, NS09774] NR 15 TC 175 Z9 177 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUL PY 1996 VL 35 IS 7 BP 797 EP 804 DI 10.1016/0028-3908(96)00129-3 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA VU959 UT WOS:A1996VU95900005 PM 8938712 ER PT J AU Kim, E Sheng, M AF Kim, E Sheng, M TI Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 4th Annual Neuropharmacology Conference CY NOV 14-16, 1996 CL WASHINGTON, DC DE potassium channel; PSD-95; SAP97; PDZ domain; subcellular targeting; membrane cytoskeleton ID TUMOR-SUPPRESSOR GENE; GLYCINE RECEPTOR; RAT-BRAIN; 2-HYBRID SYSTEM; BETA-SUBUNIT; DROSOPHILA; NEURONS; PROTEIN; LOCALIZATION; HOMOLOG AB The molecular mechanisms underlying the clustering and localization of K+ channels in specific microdomains on the neuronal surface are largely unknown. The Shaker subclass of voltage-gated K+ channel alpha-subunits interact through their cytoplasmic C-terminus with a family of membrane-associated putative guanylate kinases, including PSD-95 and SAP97. We show here that heterologous coexpression of either SAP97 or PSD-95 with various Shaker-type subunits results in the coclustering of these proteins with the K+ channels. Mutation of the C-terminal sequence (-ETDV) of the Shaker subunit Kv1.4 abolishes its binding to, and prevents its clustering with, SAP97 and PSD-95. Whereas PSD-95 induces plaque-like clusters of K+ channels at the cell surface; however, SAP97 coexpression results in the formation of large round intracellular aggregates into which both SAP97 and the K+ channel proteins are colocalized. The efficiency of surface clustering by PSD-95 varies with different Shaker subunits: striking Kv1.4 clustering occurs in >60% of cotransfected cells, whereas Kv1.1 and Kv1.2 form convincing clusters with PSD-95 only in approximately 10% of cells. Copyright (C) 1996 Elsevier Science Ltd C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Kim, Eunjoon/C-1566-2011 NR 29 TC 120 Z9 122 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUL PY 1996 VL 35 IS 7 BP 993 EP 1000 DI 10.1016/0028-3908(96)00093-7 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA VU959 UT WOS:A1996VU95900022 PM 8938729 ER PT J AU Willingham, DB Koroshetz, WJ Peterson, EW AF Willingham, DB Koroshetz, WJ Peterson, EW TI Motor skills have diverse neural bases: Spared and impaired skill acquisition in Huntington's disease SO NEUROPSYCHOLOGY LA English DT Article ID SEQUENTIAL ARM MOVEMENTS; PARKINSONS-DISEASE; PROCEDURAL MEMORY; BASAL GANGLIA AB The striatum contributes to the learning of some, but not all, motor skills. The researchers suggest that the striatum plays a role when participants learn a repeating sequence of movements, but it does not contribute when they learn a new mapping between perceptual cues and the appropriate motor response. The researchers tested patients with striatal damage due to Huntington's disease (HD) on 2 versions of a tracking task. In 1 task, the target moved randomly, allowing participants to learn the relationship between the joystick and cursor. Patients showed normal learning. In the other task, the target moved in a repeating pattern, and participants could improve performance by learning the repeating sequence of movements necessary to track the pattern. Patients were impaired on this task. Learning sequences is impaired in HD, whereas learning new mappings between perceptual cues and responses is not. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Willingham, DB (reprint author), UNIV VIRGINIA,DEPT PSYCHOL,102 GILMER HALL,CHARLOTTESVILLE,VA 22903, USA. NR 36 TC 50 Z9 50 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JUL PY 1996 VL 10 IS 3 BP 315 EP 321 DI 10.1037/0894-4105.10.3.315 PG 7 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA UY062 UT WOS:A1996UY06200001 ER PT J AU Rudolf, GD Cronin, CA Landwehrmeyer, GB Standaert, DG Penney, JB Young, AB AF Rudolf, GD Cronin, CA Landwehrmeyer, GB Standaert, DG Penney, JB Young, AB TI Expression of N-methyl-D-aspartate glutamate receptor subunits in the prefrontal cortex of the rat SO NEUROSCIENCE LA English DT Article DE excitatory amino acid receptors; mRNA; in situ hybridization histochemistry; motor control; cognitive processing; excitotoxicity ID AMINO-ACID RECEPTORS; PROTEIN-KINASE-C; ALZHEIMERS-DISEASE; NMDA RECEPTORS; VISUAL-CORTEX; NORMAL INDIVIDUALS; SPLICE VARIANTS; NERVOUS-SYSTEM; BINDING; POLYAMINES AB The laminar distribution and cellular levels of expression of mRNAs encoding N-methyl-D-aspartate receptor subunits (NMDAR1, NMDAR2A-D and the alternatively spliced isoforms of NMDAR1) were examined in prefrontal cortex of rat by in situ hybridization using film and emulsion autoradiography. Film autoradiograms demonstrated a distinctive laminar distribution of hybridization signals for each of the probes recognizing NMDAR1, NMDAR2A and NMDAR2B messenger RNA; hybridization with probes for NMDAR2C and NMDAR2D resulted in scattered signals without laminar organization. Grain counting disclosed that neurons in layer V displayed the highest and neurons in layer IV the lowest absolute number of grains for all probes examined. Correction for cell size demonstrated statistically significant differences in cellular labelling density of up to 50% across neurons in different cortical layers. The cellular density profiles across cortical laminae differed between probes. Hybridization with a probe recognizing all isoforms of NMDAR1 resulted in significantly lower densities of cellular labelling in neurons of layer IV than of layers II/III, V and VI. Cellular labelling densities following hybridization with probes recognizing alternatively spliced segments of NMDAR1 were examined. Densities were low in neurons of the upper cortical layers II/III and IV using probes for the messenger RNA encoding the amino terminal insert, NMDAR1(1XX) and the second carboxy terminal deletion, NMDAR1(XX1); hybridization with a probe for the messenger RNA encoding the first carboxy terminal deletion, NMDAR1(X1X) resulted in low cellular signal densities in neurons of layers IV and VIb. NMDAR2A messenger RNA expression was of relatively uniform intensity in neurons of layers II-V but significantly lower in neurons of the inner part of layer VI. NMDAR2B expression was most dense in layer II neurons. These data indicate that neurons in different cortical laminae express distinct N-methyl-D-aspartate receptor subunit messenger RNA phenotypes. In addition, the observed differences in density of N-methyl-D-aspartate receptor subunit messenger RNA expression suggest that cortical laminae differ in the relative contribution of N-methyl-D-aspartate receptors to their excitatory responses. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG11337] NR 40 TC 37 Z9 37 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JUL PY 1996 VL 73 IS 2 BP 417 EP 427 DI 10.1016/0306-4522(96)00048-6 PG 11 WC Neurosciences SC Neurosciences & Neurology GA UQ403 UT WOS:A1996UQ40300009 PM 8783259 ER PT J AU Sobel, EL Gilles, FH Leviton, A Tavare, CJ HedleyWhyte, ET Rorke, LB Adelman, LS Blank, WF Fulling, KH Blair, JD DeMello, D Sotrel, A Orsini, EN Isaacs, H Hashida, Y Price, RA Yunis, EJ Zaias, BW Becker, LE Davis, RL deLeon, GA Huff, D Mestre, G Shamszadeh, M AF Sobel, EL Gilles, FH Leviton, A Tavare, CJ HedleyWhyte, ET Rorke, LB Adelman, LS Blank, WF Fulling, KH Blair, JD DeMello, D Sotrel, A Orsini, EN Isaacs, H Hashida, Y Price, RA Yunis, EJ Zaias, BW Becker, LE Davis, RL deLeon, GA Huff, D Mestre, G Shamszadeh, M TI Survival of children with infratentorial neuroglial tumors SO NEUROSURGERY LA English DT Article DE brain; child; factor scores; neuroglial; survival probability; tumor ID BRAIN-TUMORS; ASTROCYTOMAS; GLIOMAS; AGE AB OBJECTIVE: The goal of this study is the improvement of the prognostic information associated with conventional diagnoses. Our previous factor analysis of 26 reliably identified histological features in infratentorial childhood neuroglial tumors yielded five interpretable, uncorrelated, quantitative histological factors that we named spongy, fibrillary, proliferative, nuclear, and ring. Five quantitative scores, one for each of the five factors, provide an objective method for quantifying the histological heterogeneity of a tumor. The scores, alone or in conjunction with conventional diagnoses, identify groups of histologically homogeneous tumors. METHODS: Multivariate Cox proportional hazards models were developed to assess the contribution of each factor to survival prognosis, after allowing patient-specific demographic and clinical data in the models as covariates. Hazard ratios, estimated for each statistically significant factor and covariate in the multivariate model, provide the basis for the determination of the prognosis. The hazard ratio is the ratio of the hazard function for subjects with an attribute, e.g., an age of 10 years, to the hazard function for subjects who have some chosen baseline attribute, e.g., an age of 1 year. The important criterion of this ratio is beta, a statistic estimated from the survival data in the Childhood Brain Tumor Consortium database of infratentorial neuroglial tumors. Kaplan-Meier survival curves were used to investigate differences in the survival of factor-determined subgroups of patients with various diagnoses. RESULTS: An increased likelihood of survival is associated with older age, more tumor removal, more recent decade of surgical intervention, and high spongy and fibrillary factor scores. A decreased likelihood of survival is associated with high nuclear, proliferative, and ring factor scores. Gender, location within the infratentorial compartment, and subsequent treatment did not add prognostic information. For certain subgroups of astrocytoma and for ependymoma and medulloblastoma, factors are important in predicting survival with greater accuracy. CONCLUSION: Factor scores provide clinically useful quantitative estimates of survival probability that are more specific and accurate than the general estimates based on the conventional diagnosis alone. C1 UNIV SO CALIF,SCH MED,DEPT PREVENT MED BIOSTAT,LOS ANGELES,CA. CHILDRENS HOSP,DEPT NEUROEPIDEMIOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. CHILDRENS HOSP PHILADELPHIA,DEPT NEUROPATHOL,PHILADELPHIA,PA 19104. UNIV PENN,PHILADELPHIA,PA 19104. TUFTS UNIV,NEW ENGLAND MED CTR HOSP,NEUROPATHOL LAB,BOSTON,MA 02111. BARNES & ST LOUIS CHILDRENS HOSP,ST LOUIS,MO. CARDINAL GLENNON MEM HOSP,ST LOUIS,MO. HARVARD UNIV,CHILDRENS HOSP,BOSTON,MA 02115. CHILDRENS HOSP DENVER,DENVER,CO. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA. CHILDRENS HOSP PITTSBURGH,PITTSBURGH,PA 15213. HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA. UNIV SO CALIF,LOS ANGELES CTY MED CTR,LOS ANGELES,CA 90033. ST CHRISTOPHERS HOSP CHILDREN,PHILADELPHIA,PA 19133. RP Sobel, EL (reprint author), CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED NEUROPATHOL,MS 43,4650 SUNSET BLVD,LOS ANGELES,CA 90027, USA. FU NCI NIH HHS [R01 CA20462, R01 CA49532] NR 40 TC 16 Z9 16 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUL PY 1996 VL 39 IS 1 BP 45 EP 54 DI 10.1097/00006123-199607000-00010 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UU672 UT WOS:A1996UU67200023 PM 8805139 ER PT J AU Das, A Hochberg, FH AF Das, A Hochberg, FH TI Clinical presentation of intracranial metastases SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID CENTRAL NERVOUS-SYSTEM; SUBDURAL-HEMATOMA; CEREBROVASCULAR COMPLICATIONS; CEREBRAL METASTASES; DIABETES-INSIPIDUS; BRAIN METASTASIS; CANCER-PATIENTS; BREAST-CANCER; MANAGEMENT; TUMORS AB Intracranial metastases are the single most costly neurologic ailment. This article provides the clinician with detailed statements of the patterns of their appearance and tumors of origin, Most common causative cancers are of lung, breast, or melanoma origin. Aggressive therapies carry with them the risk of nervous system dissemination of rare tumors, remote complications of these cancers and the morbidity of therapy. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. NR 65 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1996 VL 7 IS 3 BP 377 EP & PG 16 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UX610 UT WOS:A1996UX61000005 PM 8823770 ER PT J AU Schaefer, PW Budzik, RF Gonzalez, RG AF Schaefer, PW Budzik, RF Gonzalez, RG TI Imaging of cerebral metastases SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Review ID CONTRAST-ENHANCED MR; DOSE GADOPENTETATE DIMEGLUMINE; POSITRON EMISSION TOMOGRAPHY; WHITE MATTER LESIONS; HUMAN BRAIN-TUMORS; MENINGEAL CARCINOMATOSIS; COMPUTED-TOMOGRAPHY; GD-DTPA; MAGNETIZATION-TRANSFER; LEPTOMENINGEAL METASTASIS AB MR imaging with intravenous gadolinium has greatly enhanced our ability to detect and delineate intracranial metastases as well as to differentiate them from other disease processes. Techniques such as magnetization transfer and triple dose gadolinium imaging have further improved lesion detection. Consideration of these radiologic techniques, including the issues and controversies of screening and cost effectiveness, suggests a reasonable approach to imaging patients with possible intracranial metastases. Newer modalities such as echo planar imaging, spectroscopy PET, and SPECT, may in the future, prove to be very useful in the evaluation of patients with intracranial metastases. Proper imaging is also critical to appropriate diagnosis and management of meningeal metastases, calvarial metastases, and paraneoplastic disease. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEURORADIOL,BOSTON,MA 02114. NR 132 TC 18 Z9 18 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1996 VL 7 IS 3 BP 393 EP & PG 32 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UX610 UT WOS:A1996UX61000006 PM 8823771 ER PT J AU Carter, BS Harsh, GR AF Carter, BS Harsh, GR TI Diagnosis of suspected intracranial metastases - Role of direct tissue examination SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID STEREOTACTIC BIOPSY; BRAIN METASTASES; LESIONS; EXPERIENCE; TUMORS AB Accurate histologic diagnosis is often critical to the appropriate choice of treatment of patients suspected of harboring brain metastases. In most cases, frame based stereotactic biopsy can provide an accurate histologic diagnosis with minimal risk of morbidity. In addition, newer modalities allow for efficient coupling of stereotactic biopsy with, treatment in a single session. These include frameless stereotactic systems that facilitate the combination of open biopsy and resection as well as biopsy procedures that are combined with focal interstitial or external beam irradiation. These techniques provide increasingly convenient and effective means of achieving both diagnosis and treatment of cerebral metastases. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BRAIN TUMOR CTR,BOSTON,MA 02114. NR 23 TC 8 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1996 VL 7 IS 3 BP 425 EP & PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UX610 UT WOS:A1996UX61000007 PM 8823772 ER PT J AU Batchelor, T DeAngelis, LM AF Batchelor, T DeAngelis, LM TI Medical management of cerebral metastases SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Review ID VASOGENIC BRAIN EDEMA; VASCULAR-PERMEABILITY FACTOR; SPINAL-CORD COMPRESSION; DEEP-VEIN THROMBOSIS; POSTOPERATIVE VENOUS THROMBOEMBOLISM; PNEUMOCYSTIS-CARINII PNEUMONIA; VENA-CAVA FILTER; NEUROSURGICAL PATIENTS; INTRACRANIAL-PRESSURE; PERITUMORAL EDEMA AB Brain edema, seizures, and venous thromboembolism are frequently encountered complications of cerebral metastases that result In increased morbidity and mortality. Effective medical management of these complications with steroids, anticonvulsants, and anticoagulants can result in symptomatic improvement and a better quality of life for these patients. However, these medical therapies should be administered only when indicated as each is associated with potentially serious toxicity. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,NEW YORK,NY. MEM SLOAN KETTERING CANC CTR,NEUROL SERV,NEW YORK,NY 10021. RP Batchelor, T (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,32 FRUIT ST,BOSTON,MA 02114, USA. NR 117 TC 27 Z9 28 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1996 VL 7 IS 3 BP 435 EP & PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UX610 UT WOS:A1996UX61000008 PM 8823773 ER PT J AU McDermott, MW Cosgrove, GR Larson, DA Sneed, PK Gutin, PH AF McDermott, MW Cosgrove, GR Larson, DA Sneed, PK Gutin, PH TI Interstitial brachytherapy for intracranial metastases SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID BRAIN METASTASES; RADIATION-THERAPY; TUMORS; IRRADIATION; IMPLANTS AB In large medical centers, the availability of radiosurgery has relegated brachytherapy to a lesser role in the treatment of newly diagnosed solitary brain metastases. However, the treatment planning in radiosurgery is complex, and in some case the hardware is prohibitively expensive; low or high dose rate brachytherapy requires only a stereotactic frame, commercially available software, and encapsulated radionuclides or newer tiny linear accelerators. Interstitial brachytherapy also remains an option for the treatment of recurrent solitary metastases when other forms of treatment have failed. This article reviews the radiobiology of low and high dose rate interstitial brachytherapy, the University of California San Francisco (UCSF) results using iodine-125 implants, and early experience with the photon radiosurgery system (PRS) at Massachusetts General Hospital for the treatment of brain metastases. C1 UNIV CALIF SAN FRANCISCO,DEPT NEUROSURG,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT RADIAT ONCOL,SAN FRANCISCO,CA 94143. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. NR 20 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1996 VL 7 IS 3 BP 485 EP & PG 12 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UX610 UT WOS:A1996UX61000011 PM 8823776 ER PT J AU Alexander, E Loeffler, JS AF Alexander, E Loeffler, JS TI Recurrent brain metastases SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID CONTRAST-ENHANCED MR; SURGICAL-TREATMENT; INTRACRANIAL NEOPLASMS; SYSTEMIC CHEMOTHERAPY; CEREBRAL METASTASES; MAPPING TECHNIQUES; TUMORS; CANCER; RADIOSURGERY; MANAGEMENT AB Metastases of the brain are the most frequent metastatic neurologic complication of systemic cancer and are second only to metabolic encephalopathies as a cause of central nervous system dysfunction in cancer patients. Despite recent significant advances in the diagnosis and treatment of metastases to the brain, many patients will suffer from recurrence. Future advances in the use of chemotherapy, radiosurgery, and newer cancer therapy techniques may lead to further increases in the efficacy of treatment for recurrent brain metastases. C1 BRIGHAM & WOMENS HOSP,BRAIN TUMOR CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROSURG,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. JOINT CTR RADIAT THERAPY,DANA FARBER CANC INST,BOSTON,MA 02115. RP Alexander, E (reprint author), BRIGHAM & WOMENS HOSP,DEPT NEUROSURG,FUNCT NEUROSURG PROGRAM,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 54 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1996 VL 7 IS 3 BP 517 EP & PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UX610 UT WOS:A1996UX61000014 PM 8823779 ER PT J AU Thornton, AF Harsh, GR AF Thornton, AF Harsh, GR TI Recommendations for treatment of brain metastases SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID RADIOTHERAPY AB As treatment options for cerebral metastases have increased, so has controversy regarding relative indications for their use. The therapeutic options, criteria for choice, and recommendations for treatment require careful consideration of available data. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BRAIN TUMOR CTR,BOSTON,MA 02114. RP Thornton, AF (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BRAIN TUMOR CTR,32 FRUIT ST,BOSTON,MA 02114, USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1996 VL 7 IS 3 BP 559 EP & PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UX610 UT WOS:A1996UX61000018 PM 8823783 ER PT J AU Harsh, GR AF Harsh, GR TI Management of cerebral metastases - Preface SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Editorial Material RP Harsh, GR (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,N 15 PARKMAN ST,SUITE 331,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 1996 VL 7 IS 3 BP R13 EP R14 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UX610 UT WOS:A1996UX61000001 ER PT J AU Siegner, SW Netland, PA AF Siegner, SW Netland, PA TI Optic disc hemorrhages and progression of glaucoma SO OPHTHALMOLOGY LA English DT Article ID LOW-TENSION GLAUCOMA; OPEN-ANGLE GLAUCOMA; VISUAL-FIELD DEFECTS; OCULAR HYPERTENSION; NERVE DAMAGE; PRESSURE AB Purpose: To assess progressive changes of the optic nerve head and visual fields in patients with glaucoma and ocular hypertension after optic disc hemorrhage. Methods: The authors reviewed the charts of 91 patients with 121 disc hemorrhages who had a mean follow-up of 41.9 +/- 3.6 months. The frequency of visual field and optic nerve head changes in these patients was studied. Results: The mean intraocular pressure at the examination when the disc hemorrhage was noted was 18.9 +/- 0.5 mmHg. Overall, 64 (63%) of 101 eyes showed progressive changes of visual fields after disc hemorrhage, compared with 24 (24%) of 101 control eyes (P < 0.0005). Similarly, 56 (79%) of 71 eyes showed progressive changes of optic nerve head contour by masked evaluation of stereophotographs, compared with 16 (22%) of 71 control eyes (P < 0.0005). Eyes with disc hemorrhage showed significantly greater progression of visual field defects in patients with open-angle glaucoma (P < 0.001), low-tension glaucoma (P < 0.05), and ocular hypertension (P = 0.0067) compared with control eyes matched by age, follow-up time, and diagnosis. Similarly, progressive changes of optic nerve head contour were observed more often in eyes after disc hemorrhage in patients with open-angle glaucoma (P < 0.0005), low-tension glaucoma (P < 0.025), and ocular hypertension (P < 0.005), compared with controls. The mean time interval to progression after disc hemorrhage was observed was 16.8 +/- 2.0 months for visual field changes and 23.8 +/- 2.9 months for optic nerve head changes. In eyes with disc hemorrhage, 27 (22%) of 121 had recurrent hemorrhages at a mean interval of 21.5 +/- 2.9 months after previous hemorrhage. The most common site of disc hemorrhage was the inferotemporal quadrant. Eyes with disc hemorrhage that occurred on the temporal side of the optic nerve head had a significantly lower intraocular pressure (P < 0.02) and greater progressive changes of the optic discs (P < 0.001) compared with eyes with hemorrhage on the nasal side. Conclusion: The authors' results indicate that disc hemorrhages in eyes with glaucoma or ocular hypertension often are associated with progressive changes of the optic nerve head and visual fields. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. NR 52 TC 92 Z9 93 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1996 VL 103 IS 7 BP 1014 EP 1024 PG 11 WC Ophthalmology SC Ophthalmology GA UY313 UT WOS:A1996UY31300013 PM 8684789 ER PT J AU Gebhardt, MC AF Gebhardt, MC TI Molecular biology of sarcomas SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID SOFT-TISSUE SARCOMAS; P53 GENE; MULTIDRUG-RESISTANCE; GERMLINE MUTATIONS; AMPLIFICATION; CANCER; RETINOBLASTOMA; OSTEOSARCOMAS; PROTEIN; SPECTRUM AB There has been an explosion of information relating to the molecular biology of sarcomas that will soon impact the diagnosis and treatment of patients with this type of cancer. Some of these sarcoma-related findings are reviewed for the orthopedist with an interest in oncology. C1 HARVARD UNIV,SCH MED,DEPT ORTHOPAED SURG,ORTHOPAED ONCOL SERV,MASSACHUSETTS GEN HOSP,BOSTON,MA. RP Gebhardt, MC (reprint author), HARVARD UNIV,ORTHOPAED ONCOL SERV,MASSACHUSETTS GEN HOSP,SCH MED,CONNECT TISSUE ONCOL CTR,BOSTON,MA 02114, USA. NR 58 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 SN 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD JUL PY 1996 VL 27 IS 3 BP 421 EP & PG 10 WC Orthopedics SC Orthopedics GA UQ402 UT WOS:A1996UQ40200002 PM 8649726 ER PT J AU Meara, JG Brown, MT Caradonna, D Varvares, MA AF Meara, JG Brown, MT Caradonna, D Varvares, MA TI Massive, destructive, dentigerous cyst: A case report SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID TUMORS; SINUS C1 ST LOUIS UNIV,HLTH SCI CTR,DEPT OTOLARYNGOL,ST LOUIS,MO 63110. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. NR 12 TC 1 Z9 2 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUL PY 1996 VL 115 IS 1 BP 141 EP 144 DI 10.1016/S0194-5998(96)70151-1 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA VA141 UT WOS:A1996VA14100023 PM 8758645 ER PT J AU Kradin, RL Xia, WJ Pike, M Byers, HR Pinto, C AF Kradin, RL Xia, WJ Pike, M Byers, HR Pinto, C TI Interleukin-2 promotes the motility of dendritic cells and their accumulation in lung and skin SO PATHOBIOLOGY LA English DT Article DE dendritic cells; interleukin-2; motility ID INTERFERON-GAMMA; ACCESSORY CELLS; LYMPHOCYTES; MECHANISM; INDUCTION; ALPHA; IL-2; RAT AB Dendritic cells (DC) play a critical role as antigen-presenting cells in vivo. It has previously been shown that DC accumulate in the lung in response to parenteral injections of IFN-gamma. In the current paper, we report that rat DC express the interleukin-2 receptor (IL-2R) alpha-chain (OX-39) and display enhanced motility in response to IL-2 in Boyden chamber and video time-lapse microscopy assays. Increased motility was specifically inhibited by pretreating DC with OX-39 (anti-IL-2R) but not OX-22 (anti-CD45RC), an isotype-matched murine monoclonal antibody. The intratracheal injection of IL-2 increased the number of OX-6+ dendritic cells located around pulmonary venules and in the lung interstitium. When IL-2 was injected into the footpad of the rat. DC were increased around dermal venules at 24 h. This effect was blocked by the parenteral injection of anti-OX-39. We conclude that IL-2 is a potent enhancer of DC motility and may cooperate with other T helper(h)-1 proinflammatory cytokines in attracting DC to sites of inflammation. C1 MASSACHUSETTS GEN HOSP, PULMONARY & CRIT CARE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, ARTHRITIS UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DERMATOPATHOL UNIT, BOSTON, MA 02114 USA. RP Kradin, RL (reprint author), MASSACHUSETTS GEN HOSP, IMMUNOPATHOL UNIT, COX 5, BOSTON, MA 02114 USA. FU PHS HHS [R0148385] NR 21 TC 25 Z9 25 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD JUL-AUG PY 1996 VL 64 IS 4 BP 180 EP 186 DI 10.1159/000164033 PG 7 WC Cell Biology; Pathology SC Cell Biology; Pathology GA WF931 UT WOS:A1996WF93100002 PM 9031326 ER PT J AU Homer, CJ Szilagyi, P Rodewald, L Bloom, SR Greenspan, P Yazdgerdi, S Leventhal, JM Finkelstein, D Perrin, JM AF Homer, CJ Szilagyi, P Rodewald, L Bloom, SR Greenspan, P Yazdgerdi, S Leventhal, JM Finkelstein, D Perrin, JM TI Does quality of care affect rates of hospitalization for childhood asthma? SO PEDIATRICS LA English DT Article DE asthma; children; quality of care ID PULSE OXIMETRY; CHILDREN; MANAGEMENT; SEVERITY; THERAPY AB Background. Hospitalization rates for childhood asthma are three times as high in Boston, Massachusetts, as in Rochester, New York; New Haven, Connecticut, rates are intermediate. We undertook this study to determine how care for children admitted for asthma varies across these communities. Methods. We performed a community-wide retrospective chart review. We reviewed a random sample of all asthma hospitalizations, from 1988 to 1990, of children 2 to 12 years old living in these communities (n = 614). Abstracted data included demographics, illness severity, and treatment before admission. Results. Compared with Rochester children, Boston children were less likely to have received maintenance preventive therapy (inhaled corticosteroids or cromolyn [odds ratio (OR), 0.4 (0.2, 0.9)]), acute ''rescue'' therapy (oral corticosteroids [OR, 0.2 (0.1, 0.4)]), or inhaled beta-agonist therapy [OR, 0.5 (0.3, 1.0)]. A larger proportion of admitted asthmatic patients in Boston (34%) were in the least severely ill group-oxygen saturation 95% or above-compared with patients in Rochester (20%). Conclusions. The quality of ambulatory care, including choice of preventive therapies and thresholds for admission, likely plays a key role in determining community hospitalization rates for chronic conditions such as childhood asthma. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. UNIV ROCHESTER,STRONG MEM HOSP,DEPT PEDIAT,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED,ROCHESTER,NY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06510. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RP Homer, CJ (reprint author), CHILDRENS HOSP,CLIN EFFECTIVENESS PROGRAM,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU AHRQ HHS [HS-06060] NR 22 TC 145 Z9 149 U1 1 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1996 VL 98 IS 1 BP 18 EP 23 PG 6 WC Pediatrics SC Pediatrics GA UU137 UT WOS:A1996UU13700003 PM 8668406 ER PT J AU Rohrich, RJ Handren, J Kersh, R Hergrueter, CA May, JW AF Rohrich, RJ Handren, J Kersh, R Hergrueter, CA May, JW TI Prevention of microvascular thrombosis with short-term infusion of human tissue-type plasminogen activator SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID DEEP VENOUS THROMBOSIS; CORONARY THROMBOLYSIS; MYOCARDIAL-INFARCTION; PLATELET RECEPTOR; UROKINASE; BINDING; TRIAL; REVASCULARIZATION; IDENTIFICATION; ANTIBODIES AB A locally active thrombolytic agent, human tissue-type plasminogen activator (t-PA), given over a finite time period (24 hours) by local infusion, maintains long-term microvascular patency (7 days) in a proven thrombosis model using an arterial inversion graft in the rabbit model. Thirteen rabbits in the control group and 16 rabbits in the experimental group underwent an arterial inversion graft followed by continuous infusion (24 hours) with human tissue-type plasminogen activator (experimental) or normal saline (control). No significant clinical bleeding or alteration of coagulation parameters was noted in hematologic studies in both experimental and control groups. Scanning electron microscopy of the postoperative human tissue-type plasminogen activator-perfused arteries suggests an interaction of the human tissue-type plasminogen activator with specific platelet receptors in reversing microvascular thrombosis by decreasing or preventing further platelet aggregation and adhesion. Human tissue-type plasminogen activator infused locally for a finite period (24 hours) allows adequate time for platelet metamorphosis to occur in converting a thrombogenic to a nonthrombogenic vessel surface. The clinical ramifications in preventing or reversing microvascular thrombosis in free-tissue transfers and replantation surgery are apparent. Further study in this area will enhance our understanding of the pathogenesis and prevention of microvascular thrombosis. C1 MASSACHUSETTS GEN HOSP,DIV PLAST & RECONSTRUCT SURG,BOSTON,MA 02114. RP Rohrich, RJ (reprint author), UNIV TEXAS,DIV PLAST & RECONSTRUCT SURG,SW MED CTR,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. NR 35 TC 24 Z9 25 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUL PY 1996 VL 98 IS 1 BP 118 EP 128 DI 10.1097/00006534-199607000-00019 PG 11 WC Surgery SC Surgery GA UU776 UT WOS:A1996UU77600019 PM 8657763 ER PT J AU Misraji, J Nguyen, PL AF Misraji, J Nguyen, PL TI Urinalysis - When and when not to order SO POSTGRADUATE MEDICINE LA English DT Article ID MICROSCOPIC HEMATURIA; URINARY SEDIMENT; YOUNG-ADULTS; PROTEINURIA; MICROHEMATURIA; DISEASE AB Although routine urinalysis is common, the results are important in management of only certain diseases. Screening urinalysis to detect asymptomatic bacteriuria is recommended in adults 60 years of age or older, diabetic patients of any age, pregnant women, and adolescents. A positive result for protein on dipstick urinalysis should be evaluated in conjunction with other clinical and laboratory data (eg, the patient's age, physical findings, renal function, results of microscopic urinalysis). Evaluation of hematuria should always include dipstick analysis and microscopic examination of urine. Diabetes screening is best done with measurement of plasma glucose levels. Other available urinalysis tests include measurement of pH, specific gravity, ketones, bilirubin, and urobilinogen. In patients with renal or urinary tract disease, microscopic examination of urinary sediment is important. C1 MASSACHUSETTS GEN HOSP, DEPT PATHOL, SERV HEMATOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, HEMATOL LAB, BOSTON, MA 02114 USA. RP Misraji, J (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL, WARREN BLDG,2ND FLOOR, FRUIT ST, BOSTON, MA 02114 USA. NR 22 TC 0 Z9 0 U1 1 U2 1 PU JTE MULTIMEDIA PI BERWYN PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD JUL PY 1996 VL 100 IS 1 BP 173 EP + PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA UX226 UT WOS:A1996UX22600018 ER PT J AU Levy, HL Lobbregt, D Platt, LD Benacerraf, BR AF Levy, HL Lobbregt, D Platt, LD Benacerraf, BR TI Fetal ultrasonography in maternal PKU SO PRENATAL DIAGNOSIS LA English DT Article DE maternal phenylketonuria; pregnancy; fetal ultrasonography ID CROWN-RUMP LENGTH; INTERNATIONAL SURVEY; TREATED PREGNANCIES; GESTATIONAL-AGE; PHENYLKETONURIA; HYPERPHENYLALANINEMIA; DIAGNOSIS; SIZE AB Maternal phenylketonuria (PKU) is teratogenic and results in birth defects that include microcephaly, mental retardation, congenital heart disease, and intrauterine growth retardation. Treatment with a low phenylalanine diet can prevent or reduce the severity of the complications. Optimal benefit, however, requires frequent monitoring with fetal ultrasonography as a critical element. We have studied ultrasonography in 39 pregnancies enrolled in the Maternal PKU Collaborative Study and followed at our centre. First-trimester examinations in 24 pregnancies resulted in the discovery of non-viability in five. In each, this led to discontinuation of the difficult and expensive diet. Among the 33 pregnancies with second-trimester evaluation, congenital heart disease was identified in five. Two of these pregnancies were terminated. Microcephaly as determined by biparietal diameter (BPD) was identified in the second trimester in only one of nine fetuses who had microcephaly at birth. Among 20 pregnancies with third-trimester ultrasound, fetal microcephaly was identified by BPD in three of seven who had birth microcephaly. We conclude that fetal ultrasonography in maternal PKU is valuable during the first trimester in identifying non-viable pregnancies and determining gestational age and is also valuable during the second trimester in identifying congenital heart disease and perhaps other major anomalies, but not in identifying fetal microcephaly. Third-trimester ultrasound seems to be of limited usefulness. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT OBSTET,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT OBSTET,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,DEPT OBSTET & GYNECOL,LOS ANGELES,CA. FU NICHD NIH HHS [N01 HD-2-3149] NR 15 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD JUL PY 1996 VL 16 IS 7 BP 599 EP 604 DI 10.1002/(SICI)1097-0223(199607)16:7<599::AID-PD915>3.0.CO;2-5 PG 6 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA UZ654 UT WOS:A1996UZ65400002 PM 8843468 ER PT J AU Bonifacino, JS Marks, MS Ohno, H Kirchhausen, T AF Bonifacino, JS Marks, MS Ohno, H Kirchhausen, T TI Mechanisms of signal-mediated protein sorting in the endocytic and secretory pathways SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article ID TRANS-GOLGI NETWORK; MANNOSE 6-PHOSPHATE RECEPTOR; FACTOR-II RECEPTOR; DI-LEUCINE MOTIF; LYSOSOMAL MEMBRANE-GLYCOPROTEINS; GROWTH-FACTOR RECEPTOR; CYTOPLASMIC DOMAIN; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; COATED PITS AB The ability to sort proteins to different intracellular compartments is an essential property of all cells. Many diseases are caused by a failure of certain proteins to be sorted properly in the endocytic and secretory pathways. In addition, various intracellular pathogens use their hosts' protein-sorting machinery at different stages of their life cycles. These facts underscore the importance of understanding the mechanisms of protein sorting at a molecular level. In this article, we review recent advances in the identification of signals that direct proteins to their correct intracellular locations and of the recognition molecules that bind to the signals. The implications of these findings for the trafficking of various proteins are discussed. C1 UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA. RP Bonifacino, JS (reprint author), NICHHD,CELL BIOL & METAB BRANCH,NATL INST HLTH,BLDG 18T,ROOM 101,BETHESDA,MD 20892, USA. RI Ohno, Hiroshi/L-7899-2014; OI Ohno, Hiroshi/0000-0001-8776-9661; Marks, Michael/0000-0001-7435-7262; Bonifacino, Juan S./0000-0002-5673-6370 NR 76 TC 39 Z9 40 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD JUL PY 1996 VL 108 IS 4 BP 285 EP 295 PG 11 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VD968 UT WOS:A1996VD96800001 PM 8863342 ER PT J AU Biancone, L Andres, G Stamenkovic, I AF Biancone, L Andres, G Stamenkovic, I TI Autoimmune diseases of the kidney: An update SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review ID TUBULAR BASEMENT-MEMBRANE; RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS; ANTINEUTROPHIL-CYTOPLASMIC ANTIBODIES; SYSTEMIC LUPUS-ERYTHEMATOSUS; MURINE INTERSTITIAL NEPHRITIS; GLOMERULAR EPITHELIAL-CELLS; PASSIVE HEYMANN NEPHRITIS; RECEPTOR-RELATED PROTEIN; WEGENERS GRANULOMATOSIS; IMMUNE DEPOSITS C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02129. FU NCI NIH HHS [CA-55735]; NIDDK NIH HHS [DK-36807] NR 175 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUL PY 1996 VL 212 IS 3 BP 225 EP 238 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UT648 UT WOS:A1996UT64800004 PM 8677267 ER PT J AU Sachs, G AF Sachs, G TI Is divalproex sodium an appropriate initial treatment for bipolar depression? SO PSYCHIATRIC ANNALS LA English DT Article ID DOUBLE-BLIND TRIAL; AFFECTIVE DISORDERS; PROPHYLACTIC LITHIUM; AFFECTIVE-ILLNESS; IMIPRAMINE; CARBAMAZEPINE; MANIA; BUPROPION; UNIPOLAR RP Sachs, G (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,15 PARKMAN ST,SUITE 815,BOSTON,MA 02114, USA. NR 35 TC 7 Z9 7 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUL PY 1996 VL 26 IS 7 SU S BP S454 EP S459 PG 6 WC Psychiatry SC Psychiatry GA UY628 UT WOS:A1996UY62800007 ER PT J AU Mueser, KT Glynn, SM Corrigan, PW Baber, W AF Mueser, KT Glynn, SM Corrigan, PW Baber, W TI A survey of preferred terms for users of mental health services SO PSYCHIATRIC SERVICES LA English DT Article AB To determine how users of mental health services would like to be addressed by professionals, a survey of 302 persons participating in a variety of inpatient and outpatient psychiatric programs was conducted. Forty-five percent of the sample preferred the term ''client,'' 20 percent preferred the term ''patient,'' 8 percent preferred the term ''consumer,'' and 27 percent either expressed no clear preference for one term or provided another term. The results suggest that no one term is favored by users of mental health services. Professionals and persons receiving mental health services are encouraged to talk over individual preferences to help establish a working alliance. C1 DARTMOUTH COLL SCH MED,DEPT PSYCHIAT,HANOVER,NH. DARTMOUTH COLL SCH MED,DEPT COMMUNITY & FAMILY MED,HANOVER,NH. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV MED,LOS ANGELES,CA 90024. UNIV CHICAGO,CTR PSYCHOSOCIAL REHABIL,CHICAGO,IL 60637. UNIV CHICAGO,SCH MED,DEPT PSYCHIAT,CHICAGO,IL 60637. NR 3 TC 22 Z9 22 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD JUL PY 1996 VL 47 IS 7 BP 760 EP 761 PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA UV458 UT WOS:A1996UV45800016 PM 8807693 ER PT J AU Demopulos, C Fava, M McLean, NE Alpert, JE Nierenberg, AA Rosenbaum, JF AF Demopulos, C Fava, M McLean, NE Alpert, JE Nierenberg, AA Rosenbaum, JF TI Hypochondriacal concerns in depressed outpatients SO PSYCHOSOMATIC MEDICINE LA English DT Article DE functional somatic symptoms; hypochondriacal concerns; depression ID BELIEFS; FEARS; SOMATIZATION; ATTITUDES; SYMPTOMS; DISORDER; ANXIETY AB The relationship between hypochondriacal concerns, as assessed by the Illness Attitude Scales, and depressive symptoms was examined in a sample of 100 drug-free outpatients with major depressive disorder. These patients were treated with fluoxetine for 8 weeks, and the effect of treatment on hypochondriacal symptoms was examined. All patients were administered the Structured Clinical Interview for DSM-III-R, the Hamilton Depression Rating Scale, the Symptom Questionnaire, and the Personality Disorders Questionnaire-Revised. We found little relationship bet ch een severity of depressive symptoms and hypochondriacal concerns. Measures of anxiety, somatic symptoms, and psychological distress were more consistently related to these concerns. Similarly, patients with either histrionic personality disorder or a lifetime history of panic disorder had greater hypochondriacal concerns than patients without these diagnoses. After open treatment with fluoxetine, the degree of hypochondriacal concern showed statistically significant decreases, which were only partly related to the degree of change in depression and anxiety severity. Our findings suggest that the presence of hypochondriacal concerns among depressed outpatients is more closely related to the presence of anxiety than depressive symptoms. The relatively small impact of an acute course of antidepressant treatment on hypochondriacal concerns in our sample suggests that these concerns may be enduring characteristics modulated only to a limited extent by short term pharmacological alterations of affective state. C1 MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. RP Demopulos, C (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,WAC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R0-1 MH48483-03] NR 33 TC 25 Z9 25 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 1996 VL 58 IS 4 BP 314 EP 320 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA UY248 UT WOS:A1996UY24800003 PM 8827793 ER PT J AU Rosenthal, DI Thrall, JH AF Rosenthal, DI Thrall, JH TI The future is separating us: Disenrollment from professional societies as the result of financial pressure SO RADIOLOGY LA English DT Editorial Material DE economics, medical; opinions; radiology and radiologists; radiology and radiologists, socioeconomic issues RP Rosenthal, DI (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,WHITE 289,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1996 VL 200 IS 1 BP 44 EP 44 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UT115 UT WOS:A1996UT11500012 PM 8657941 ER PT J AU Hoffer, FA Chung, T Diller, L Kozakewich, H Fletcher, JA Shamberger, RC AF Hoffer, FA Chung, T Diller, L Kozakewich, H Fletcher, JA Shamberger, RC TI Percutaneous biopsy for prognostic testing of neuroblastoma SO RADIOLOGY LA English DT Article DE biopsies, technology; neoplasms, in infants and children; neuroblastoma ID MYC GENE AMPLIFICATION; NEURO-BLASTOMA; STAGE NEUROBLASTOMAS; DIAGNOSIS; TUMORS; CHEMOTHERAPY; CHILDHOOD; RELEVANCE; PATTERNS; SURGERY AB PURPOSE: To determine whether percutaneous biopsy can provide the diagnostic and prognostic information necessary to treat children with advanced neuroblastoma. MATERIALS AND METHODS: From 1991 through 1995, 21 percutaneous biopsies were performed in 20 children with advanced neuroblastoma by using 15- or 16-gauge core biopsy needles. An average of six samples were obtained. Since September 1994, fresh tissue was sent to the reference laboratory, where touch preparations were prepared for N-myc evaluation. RESULTS: Histologic confirmation and prognostic information (Shimada classification) were obtained in all cases. Genetic prognostic information was obtained in 19 patients (95%), DNA index (ploidy) in 18 (90%), N-myc gene expression in 14 (70%), and cytogenetic analysis in 10 (50%). N-myc and ploidy determinations were successful in all five biopsy specimens obtained since September 1994. CONCLUSION: Percutaneous biopsy of advanced neuroblastoma is a feasible alternative to open biopsy. C1 CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. RP Hoffer, FA (reprint author), CHILDRENS HOSP,DEPT RADIOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 27 TC 22 Z9 22 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1996 VL 200 IS 1 BP 213 EP 216 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UT115 UT WOS:A1996UT11500038 PM 8657913 ER PT J AU Mazoyer, B Belliveau, JW AF Mazoyer, B Belliveau, JW TI New progress in brain imaging SO RECHERCHE LA French DT Article C1 UNIV PARIS 07,FAC MED XAVIER BICHAT,F-75221 PARIS,FRANCE. GIP CYCERON,CEA,DEPT RECH MED,GRP IMAGERIE NEUROFONCTIONNELLE,CAEN,FRANCE. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,NMR CTR,CHARLESTOWN,MA. RI mazoyer, bernard/A-5369-2009; Mazoyer, Bernard/B-6303-2012 OI mazoyer, bernard/0000-0003-0970-2837; Mazoyer, Bernard/0000-0003-0970-2837 NR 5 TC 0 Z9 0 U1 0 U2 0 PU SOC ED SCIENTIFIQUES PI PARIS 06 PA 57 RUE DE SEINE, 75280 PARIS 06, FRANCE SN 0029-5671 J9 RECHERCHE JI Recherche PD JUL-AUG PY 1996 IS 289 BP 26 EP 33 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UV094 UT WOS:A1996UV09400021 ER PT J AU Reppas, JB Dale, AM Sereno, MI Tootell, RBH AF Reppas, JB Dale, AM Sereno, MI Tootell, RBH TI Vision as subjective perception SO RECHERCHE LA French DT Article ID CORTEX C1 MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA. UNIV CALIF SAN DIEGO,DEPT SCI COGNIT,SAN DIEGO,CA. RP Reppas, JB (reprint author), HARVARD UNIV,CAMBRIDGE,MA 02138, USA. RI Sereno, Martin/F-7657-2012 OI Sereno, Martin/0000-0002-7598-7829 NR 11 TC 0 Z9 0 U1 0 U2 0 PU SOC ED SCIENTIFIQUES PI PARIS 06 PA 57 RUE DE SEINE, 75280 PARIS 06, FRANCE SN 0029-5671 J9 RECHERCHE JI Recherche PD JUL-AUG PY 1996 IS 289 BP 52 EP 56 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UV094 UT WOS:A1996UV09400027 ER PT J AU Felsenfeld, AJ Rodriguez, M AF Felsenfeld, AJ Rodriguez, M TI Parathyroid gland function in the hemodialysis patient SO SEMINARS IN DIALYSIS LA English DT Article ID CHRONIC-RENAL-FAILURE; SECONDARY HYPERPARATHYROIDISM; HORMONE SECRETION; SET-POINT; INTRAVENOUS CALCITRIOL; NORMAL HUMANS; CALCIUM; RELEASE; TISSUE; OSTEODYSTROPHY AB The focus of this review is to provide a perspective on the applications and advantages of dynamic testing of parathyroid gland function in the dialysis patient. This review will: 1) consider the clinical utility of dynamic testing of the parathyroid gland and how the application of the information obtained with this testing can provide a better understanding of the physiology of parathyroid gland secretion in uremia; and 2) attempt to reconcile some of the different methodologies which have been used to evaluate the set point of calcium and the slope of the PTH-calcium curve. It will offer our interpretation of the meaning of the set point of calcium, a term which, in our opinion, has generated considerable confusion with respect to dynamic testing of the parathyroid gland. RP Felsenfeld, AJ (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEPHROL SECT W111L,DEPT MED,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. RI Rodriguez, teresa/H-5452-2011 NR 24 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JUL-AUG PY 1996 VL 9 IS 4 BP 303 EP 309 DI 10.1111/j.1525-139X.1996.tb00683.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA VA663 UT WOS:A1996VA66300003 ER PT J AU Coburn, JW Frazao, J AF Coburn, JW Frazao, J TI Calcitriol in the management of renal osteodystrophy SO SEMINARS IN DIALYSIS LA English DT Article ID SEVERE SECONDARY HYPERPARATHYROIDISM; DOSE INTRAVENOUS CALCITRIOL; AMBULATORY PERITONEAL-DIALYSIS; CHRONIC UREMIC PATIENTS; PULSE ORAL CALCITRIOL; LOW CALCIUM DIALYSATE; DOUBLE-BLIND TRIAL; HEMODIALYSIS-PATIENTS; PARATHYROID-HORMONE; BONE-DISEASE RP Coburn, JW (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEPHROL SECT W111L,WADSWORTH DIV,MED SERV,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. RI Frazao, Joao/J-9811-2013 OI Frazao, Joao/0000-0002-8081-5474 NR 77 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JUL-AUG PY 1996 VL 9 IS 4 BP 316 EP 326 DI 10.1111/j.1525-139X.1996.tb00687.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA VA663 UT WOS:A1996VA66300005 ER PT J AU Bumpous, JM Curtin, HD Prokopakis, EP Janecka, IP AF Bumpous, JM Curtin, HD Prokopakis, EP Janecka, IP TI Applications of image-guided navigation in the middle cranial fossa: An anatomic study SO SKULL BASE SURGERY LA English DT Article ID SURGERY AB Determining the location of pertinent anatomic structures (ie, the internal auditory canal [IAC]) in middle cranial fossa surgery is commonly based on indirect inferences from bony landmarks. Several methods have been proposed for identification of the IAC, each using bony landmarks coupled with geometric formulation. Identification of the IAC based on bony architecture and geometry may be severely limited when a mass lesion is present, Image-guided surgery has the advantage of rapid localization and may be helpful in navigating a complex surgical field which has been distorted by tumor. This study evaluates the feasibility and accuracy of the ISG viewing wand in determining pertinent anatomic landmarks in the middle fossa of the human cadaver. High-resolution (1 mm) computed tomography was performed on a preserved human cadaver head in which fixed fiducial markers had been placed. Subsequently, the cadaver had was registered in a simulated operative field, and middle fossa craniotomy was performed. The foramen spinosum, foramen ovale, greater superficial petrosal nerve, internal carotid artery, arcuate eminence; and IAC were identified visually, and three independent localizations of each structure were performed with the viewing wand. Accurate localizations were consistently performed within 1 mm for each anatomic landmark, Image-guided navigation is both feasible and accurate in determining intraoperative landmarks in the middle fossa. Image-guidance may enhance surgical accuracy and efficiency. Further clinical studies evaluating image-guided techniques in the middle fossa are warranted. C1 UNIV LOUISVILLE,SCH MED,DEPT SURG,DIV OTOLARYNGOL HNS,LOUISVILLE,KY 40292. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02115. UNIV PITTSBURGH,SCH MED,DEPT OTOLARYNGOL,PITTSBURGH,PA. HARVARD UNIV,SCH MED,DEPT PLAST SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROSURG,BOSTON,MA 02115. RI Bumpous, Jeffrey/B-8127-2013 NR 6 TC 3 Z9 3 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 1052-1453 J9 SKULL BASE SURG JI Skull Base Surg. PD JUL PY 1996 VL 6 IS 3 BP 187 EP 190 DI 10.1055/s-2008-1058644 PG 4 WC Clinical Neurology; Otorhinolaryngology; Surgery SC Neurosciences & Neurology; Otorhinolaryngology; Surgery GA VC938 UT WOS:A1996VC93800010 PM 17170977 ER PT J AU Hirayama, F Ogawa, M AF Hirayama, F Ogawa, M TI Cytokine regulation of early lymphohematopoietic development SO STEM CELLS LA English DT Review DE lymphohematopoietic progenitors; early lymphopoiesis; cytokine regulation ID MULTIPOTENTIAL HEMATOPOIETIC PROGENITORS; COLONY-STIMULATING FACTOR; T-CELL DEVELOPMENT; PRECURSOR CELLS; B-LYMPHOPOIESIS; INTERLEUKIN-3-DEPENDENT PROLIFERATION; NEGATIVE REGULATION; POSITIVE SELECTION; FETAL LIVER; BONE-MARROW AB A two-step methylcellulose culture provided a method to study the differentiation of murine lymphohematopoietic progenitors, In the presence of two cytokines, one from a group consisting of Steel factor (SF) and flt3/flk2 ligand (FL) and the other from a group consisting of interleukin 6 (IL-6), G-CSF, IL-11 and IL-12, murine lymphohematopoietic progenitors proliferated and generated not only myeloid lineage cells but also committed B cell progenitors, Although somewhat less effectively than SF and FL, IL-4 also synergized with IL-6 or IL-11 in support of B lymphopoiesis, This early process of B lymphopoiesis appears to proceed through three stages: lymphohematopoietic proliferative stage, commitment stage and early B lymphoid proliferative stage, Surprisingly, IL-3 could neither replace nor act synergistically with SF, IL-4 or FL in maintaining the B lymphoid potential of the cells in the primary culture, although IL-3 was very effective in support of multilineage myeloid colony formation, In addition, when added to permissive cytokine combinations, IL-3 inhibited development of the B cell lineage. After screening available lymphohematopoietic cytokines, it was found that IL-1 (both alpha and beta) also has similar inhibitory effects on early B lymphopoiesis. Studies using in vivo transfer of primary colonies suggested that cytokine regulation of commitment to T cell lineage may also be similar to that of B cell lineage. C1 VET ADM MED CTR,RALPH H JOHNSON DEPT,CHARLESTON,SC 29401. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. FU NIDDK NIH HHS [DK 32294, DK 48714] NR 41 TC 10 Z9 11 U1 0 U2 1 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JUL PY 1996 VL 14 IS 4 BP 369 EP 375 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA UZ877 UT WOS:A1996UZ87700001 PM 8843538 ER PT J AU Juppner, H AF Juppner, H TI Jansen's metaphyseal chondrodysplasia - A disorder due to a PTH/PTHrP receptor gene mutation SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID MESSENGER RIBONUCLEIC-ACIDS; PARATHYROID-HORMONE PTH; PEPTIDE RECEPTOR; CHONDROCYTES; CARTILAGE; RHODOPSIN; DYSPLASIA; TISSUES AB Jansen's metaphyseal chondrodysplasia (JMC) is a rare genetic disorder that is characterized by short-limbed dwarfism and severe, agonist-independent hypercalcemia. An activating PTH/PTHrP receptor mutation that results in constitutive cAMP accumulation was recently identified in the genomic DNA of a patient with this disorder. These findings provide a plausible explanation for the abnormal regulation of growth-plate chondrocytes and mineral ion homeostasis in JMC, and may have significant implications for understanding the broader biological role of PTHrP and its receptor. C1 MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Juppner, H (reprint author), MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,DEPT MED,BOSTON,MA 02114, USA. NR 48 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD JUL PY 1996 VL 7 IS 5 BP 157 EP 162 DI 10.1016/1043-2760(96)00063-X PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UX355 UT WOS:A1996UX35500001 PM 18406742 ER PT J AU Compton, CC AF Compton, CC TI Cultured epithelial autografts for burn wound resurfacing: Review of observations from an 11-year biopsy study SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Article ID EPIDERMAL-CELL CULTURES; SURFACE-AREA WOUNDS; AUTOLOGOUS KERATINOCYTES; MOUSE SKIN; GROWTH; EXPERIENCE; THRESHOLDS; COVERAGE; MICE AB In an 11-year study of 35 patients treated with cultured epithelial autografts (CEA) grafted to full-thickness burn wounds excised to muscle fascia, biopsies of successfully engrafted CEA were analyzed by light microscopic, immunohistochemical, morphometric, electron microscopic and ultrastructural immunolabeling techniques in order to study skin regeneration and wound healing. Controls consisted of both healed meshed split-thickness autograft (MSTA) interstices on the same patient biopsied at comparable postgrafting time points and body site- and age-matched normal skin. On long-term follow-up, all biopsies were derived from sun-protected body sites to eliminate the possibility of pathologic changes due to actinic injury. The long-term results indicate that CEA regenerate a stable epidermis that is histologically normal and are capable of inducing dermal regeneration from immature wound bed connective tissue. More recent studies on 10 patients in which CEA were transplanted to engrafted, cryopreserved homograft dermis instead of granulation tissue showed increased take rates of CEA (average 85 to 90 percent) and acceleration of rete ridge formation and normalization of keratin programs within the differentiated epidermis on histologic examination. RP Compton, CC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,WARREN 2,BOSTON,MA 02114, USA. NR 36 TC 10 Z9 10 U1 1 U2 3 PU HEALTH MANAGEMENT PUBLICATIONSINC PI WAYNE PA 950 WEST VALLEY RD, STE 2800, WAYNE, PA 19087 SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD JUL-AUG PY 1996 VL 8 IS 4 BP 125 EP 133 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA VD691 UT WOS:A1996VD69100004 ER PT J AU Richards, S Gray, R Peto, R Gaynon, P Masera, G Pession, A Rondelli, R Valsecchi, MG Reiter, A Riehm, H Schrappe, M McIntyre, OR Bleyer, A Cairo, M Reaman, G Sather, H Trigg, M Auclerc, MF Bancillon, A Lepage, E Schaison, G Clavell, L Datton, V Donnelly, M Gelber, R Sallan, SE SackmanMuriel, F Santarelli, MT Perez, C Solidoro, A Bailey, C Burnett, A Chessells, J Eden, OB GordonSmith, EC Lilleyman, J Land, VJ Mahoney, D Murphy, S Steuber, CP Vietti, T Crist, W Hancock, M Pui, CH Simone, J Mittra, I Shetty, PA Allison, R Baigent, C Clarke, M Duong, H Durrant, J Godwin, J Greaves, E Harwood, C Peto, J Sinclair, D Wheatley, K AF Richards, S Gray, R Peto, R Gaynon, P Masera, G Pession, A Rondelli, R Valsecchi, MG Reiter, A Riehm, H Schrappe, M McIntyre, OR Bleyer, A Cairo, M Reaman, G Sather, H Trigg, M Auclerc, MF Bancillon, A Lepage, E Schaison, G Clavell, L Datton, V Donnelly, M Gelber, R Sallan, SE SackmanMuriel, F Santarelli, MT Perez, C Solidoro, A Bailey, C Burnett, A Chessells, J Eden, OB GordonSmith, EC Lilleyman, J Land, VJ Mahoney, D Murphy, S Steuber, CP Vietti, T Crist, W Hancock, M Pui, CH Simone, J Mittra, I Shetty, PA Allison, R Baigent, C Clarke, M Duong, H Durrant, J Godwin, J Greaves, E Harwood, C Peto, J Sinclair, D Wheatley, K TI Duration and intensity of maintenance chemotherapy in acute lymphoblastic leukaemia: Overview of 42 trials involving 12,000 randomised children SO LANCET LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; MEDICAL-RESEARCH-COUNCIL; CANCER-STUDY-GROUP; CHILDHOOD; THERAPY; INTENSIFICATION; RISK; REMISSION; RELAPSE; DOSAGE AB Background The effects on long-term outcome in childhood acute lymphoblastic leukaemia (ALL) of the duration and the intensity of maintenance chemotherapy need to be assessed reliably. With this objective the Childhood ALL Collaborative Group coordinated a worldwide overview of all randomised trials that began before 1987. Methods. Individual patient data were sought for about 3900 children in trials of longer vs shorter maintenance leg, 3 vs 2 years), 3700 in trials of intensive ''reinduction'' chemotherapy during maintenance, and 4400 in trials of various other questions, including 1300 in trials of pulses of vincristine and prednisone (VP) during maintenance. Analyses were of survival in first remission, overall survival, and cause-specific mortality. Findings Deaths during remission were increased by longer maintenance (2.7% vs 1.2%), VP pulses (4.0 vs 3.2%), and intensive reinduction (4.8% vs 3.3%), but these increases were counterbalanced by reductions in relapses. Total events (relapse or death) were significantly reduced by longer maintenance (23.3% vs 27.6%), VP pulses (31.2% vs 40.4%) and intensive reinduction (27.8% vs 35.8%) (each 2p<0.001). Many of those who relapsed were successfully re-treated, however, and only for intensive reinduction was overall survival significantly improved (18.5% vs 22.3%; 2p=0.01). Interpretation Intensive reinduction chemotherapy in these trials produced an absolute improvement of about 4% in long-term survival; if the extra deaths in remission had been avoided, this would have been a 5% benefit. Further improvements in survival seem more likely to be obtained with intensive treatment than with longer low-level maintenance. C1 DANA FARBER CANC INST, BOSTON, MA USA. INEN, LIMA, PERU. MRC, LONDON W1N 4AL, ENGLAND. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN USA. TATA MEM HOSP, BOMBAY, MAHARASHTRA, INDIA. RP Richards, S (reprint author), RADCLIFFE INFIRM, CTSU, CHILDHOOD ALL SECRETARIAT, OXFORD OX2 6HE, ENGLAND. RI Schrappe, Martin/A-8109-2010 NR 36 TC 52 Z9 53 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUN 29 PY 1996 VL 347 IS 9018 BP 1783 EP 1788 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UU469 UT WOS:A1996UU46900008 ER PT J AU Emanuel, EJ Fairclough, DL Daniels, ER Clarridge, BR AF Emanuel, EJ Fairclough, DL Daniels, ER Clarridge, BR TI Euthanasia and physician-assisted suicide: Attitudes and experiences of oncology patients, oncologists, and the public SO LANCET LA English DT Article ID DEPRESSION; LIFE; CARE; END AB Background Euthanasia and physician-assisted suicide are pressing public issues. We aimed to collect empirical data on these controversial interventions, particularly on the attitudes and experiences of oncology patients. Methods We interviewed, by telephone with vignette-style questions, 155 oncology patients, 355 oncologists, and 193 members of the public to assess their attitudes and experiences in relation to euthanasia and physician-assisted suicide. Findings About two thirds of oncology patients and the public found euthanasia and physician-assisted suicide acceptable for patients with unremitting pain. Oncology patients and the public found euthanasia and physician-assisted suicide least acceptable in vignettes involving ''burden on the family'' and ''life viewed as meaningless''. In no vignette-even for patients with unremitting pain-did a majority of oncologists find euthanasia or physician-assisted suicide ethically acceptable. Patients actually experiencing pain were more likely to find euthanasia or physician-assisted suicide unacceptable. More than quarter of oncology patients had seriously thought about euthanasia or physician-assisted suicide and nearly 12% had seriously discussed these interventions with physicians or others. Patients with depression and psychological distress were significantly more likely to have seriously discussed euthanasia, hoarded drugs, or read Final Exit. More than half of oncologists had received requests for euthanasia or physician-assisted suicide. Nearly one in seven oncologists had carried out euthanasia or physician-assisted suicide. Interpretation Euthanasia and physician-assisted suicide are important issues in the care of terminally ill patients and while oncology patients experiencing pain are unlikely to desire these interventions patients with depression are more likely to request assistance in committing suicide. Patients who request such an intervention should be evaluated and, where appropriate, treated for depression before euthanasia can be discussed seriously. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. UNIV MASSACHUSETTS,SURVEY RES CTR,BOSTON,MA 02125. RP Emanuel, EJ (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,CTR OUTCOMES & POLICY RES,BOSTON,MA 02115, USA. NR 29 TC 249 Z9 250 U1 9 U2 47 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 29 PY 1996 VL 347 IS 9018 BP 1805 EP 1810 DI 10.1016/S0140-6736(96)91621-9 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UU469 UT WOS:A1996UU46900014 PM 8667927 ER PT J AU Doyle, DA Lee, A Lewis, J Kim, E Sheng, M MacKinnon, R AF Doyle, DA Lee, A Lewis, J Kim, E Sheng, M MacKinnon, R TI Crystal structures of a complexed and peptide-free membrane protein-binding domain: Molecular basis of peptide recognition by PDZ SO CELL LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; SEPTATE JUNCTIONS; HOMOLOG AB Modular PDZ domains, found in many cell junction-associated proteins, mediate the clustering of membrane ion channels by binding to their C-terminus. The X-ray crystallographic structures of the third PDZ domain from the synaptic protein PSD-95 in complex with and in the absence of its peptide ligand have been determined at 1.8 Angstrom and 2.3 Angstrom resolution, respectively. The structures reveal that a four-residue C-terminal stretch (X-Thr/Ser-X-Val-COO-) engages the PDZ domain through antiparallel main chain interactions with a beta sheet of the domain. Recognition of the terminal carboxylate group of the peptide is conferred by a cradle of main chain amides provided by a Gly-Leu-Gly-Phe loop as well as by an arginine side chain. Specific side chain interactions and a prominent hydrophobic pocket explain the selective recognition of the C-terminal consensus sequence. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. RP Doyle, DA (reprint author), ROCKEFELLER UNIV,LAB MOL NEUROBIOL & BIOPHYS,NEW YORK,NY 10021, USA. RI Kim, Eunjoon/C-1566-2011 NR 39 TC 824 Z9 838 U1 0 U2 29 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 28 PY 1996 VL 85 IS 7 BP 1067 EP 1076 DI 10.1016/S0092-8674(00)81307-0 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV484 UT WOS:A1996UV48400013 PM 8674113 ER PT J AU Edelmann, W Cohen, PE Kane, M Lau, K Morrow, B Bennett, S Umar, A Kunkel, T Cattoretti, G Chaganti, R Pollard, JW Kolodner, RD Kucherlapati, R AF Edelmann, W Cohen, PE Kane, M Lau, K Morrow, B Bennett, S Umar, A Kunkel, T Cattoretti, G Chaganti, R Pollard, JW Kolodner, RD Kucherlapati, R TI Meiotic pachytene arrest in MLH1-deficient mice SO CELL LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; SACCHAROMYCES-CEREVISIAE; MISMATCH REPAIR; SYNAPTONEMAL COMPLEX; COLON-CANCER; GENES; MUTATIONS; LOCUS; IDENTIFICATION; HOMOLOG AB Germ line mutations in DNA mismatch repair genes including MLH1 cause hereditary nonpolyposis colon cancer. To understand the role of MLH1 in normal growth and development, we generated mice that have a null mutation of this gene. Mice homozygous for this mutation show a replication error phenotype, and extracts of these cells are deficient in mismatch repair activity. Homozygous mutant males show normal mating behavior but have no detectable mature sperm. Examination of meiosis in these males reveals that the cells enter meiotic prophase and arrest at pachytene. Homozygous mutant females have normal estrous cycles and reproductive and mating behavior but are infertile. The phenotypes of the mlh1 mutant mice are distinct from those deficient in msh2 and pms2. The different phenotypes of the three types of mutant mice suggest that these three genes may have independent functions in mammalian meiosis. C1 ALBERT EINSTEIN COLL MED,DEPT DEV & MOL BIOL,BRONX,NY 10467. DANA FARBER CANC INST,BOSTON,MA 02115. NIEHS,RES TRIANGLE PK,NC 27709. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY. MEM SLOAN KETTERING CANC CTR,DEPT GENET,NEW YORK,NY 10021. RP Edelmann, W (reprint author), ALBERT EINSTEIN COLL MED,DEPT MOLEC GENET,BRONX,NY 10467, USA. OI Cattoretti, Giorgio/0000-0003-3799-3221 FU NCI NIH HHS [CA 67944]; NICHD NIH HHS [HD/AI 30280]; NIGMS NIH HHS [GM 50006] NR 58 TC 412 Z9 423 U1 3 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 28 PY 1996 VL 85 IS 7 BP 1125 EP 1134 DI 10.1016/S0092-8674(00)81312-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV484 UT WOS:A1996UV48400018 PM 8674118 ER PT J AU Choe, H Farzan, M Sun, Y Sullivan, N Rollins, B Ponath, PD Wu, LJ Mackay, CR LaRosa, G Newman, W Gerard, N Gerard, C Sodroski, J AF Choe, H Farzan, M Sun, Y Sullivan, N Rollins, B Ponath, PD Wu, LJ Mackay, CR LaRosa, G Newman, W Gerard, N Gerard, C Sodroski, J TI The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates SO CELL LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HAMSTER OVARY CELLS; ENVELOPE GLYCOPROTEIN; T-CELL; HTLV-III/LAV; MONONUCLEAR PHAGOCYTES; CD4-MEDIATED FUSION; MACROPHAGE TROPISM; MOLECULAR-CLONING; MEMBRANE-FUSION AB We examined the ability of chemokine receptors and related G protein-coupled receptors to facilitate infection by primary, clinical HIV-1 isolates. CCR5, when expressed along with CD4, the HIV-1 receptor, allowed cell lines resistant to most primary HIV-1 isolates to be infected. CCR3 facilitated infection by a more restricted subset of primary viruses, and binding of the CCR3 ligand, eotaxin, inhibited infection by these isolates. Utilization of CCR3 and CCR5 on the target cell depended upon the sequence of the third variable (V3) region of the HIV-1 gp120 exterior envelope glycoprotein. The ability of various members of the chemokine receptor family to support the early stages of HIV-1 infection helps to explain viral tropism and beta-chemokine inhibition of primary HIV-1 isolates. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. LEUKOSITE INC,CAMBRIDGE,MA 02142. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,PERLMUTTER LAB,DEPT PEDIAT,DEPT MED,CHILDRENS HOSP,BOSTON,MA 02115. RP Choe, H (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI24755, AI28691] NR 108 TC 1911 Z9 1938 U1 12 U2 89 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 28 PY 1996 VL 85 IS 7 BP 1135 EP 1148 DI 10.1016/S0092-8674(00)81313-6 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV484 UT WOS:A1996UV48400019 PM 8674119 ER PT J AU Kinane, TB Mark, EJ Connolly, SA Shannon, DC AF Kinane, TB Mark, EJ Connolly, SA Shannon, DC TI A newborn triplet with episodes of respiratory distress and a pulmonary mass - Congenital cystic adenomatoid malformation of the lung SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SEQUESTRATION; MANAGEMENT; PATHOLOGY; DIAGNOSIS; CHILDREN C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Kinane, TB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 29 TC 3 Z9 3 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 27 PY 1996 VL 334 IS 26 BP 1726 EP 1732 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA UT400 UT WOS:A1996UT40000008 ER PT J AU Falagas, ME Snydman, DR George, MJ Werner, B Ruthazer, R Griffith, J Rohrer, RH Freeman, R George, MG Fawaz, K Hoffman, MA Kaplan, M Gill, M Rubin, RH Dienstag, JL Dorna, M ORourke, E Vacanti, J Jenkins, R Lewis, WD Hammer, S Martin, M Fairchild, R Werner, BG Grady, GF Leszczynski, J Dougherty, N Katz, A Fausett, G Platt, R Cheeseman, SH Pasternack, M Gorbach, SL AF Falagas, ME Snydman, DR George, MJ Werner, B Ruthazer, R Griffith, J Rohrer, RH Freeman, R George, MG Fawaz, K Hoffman, MA Kaplan, M Gill, M Rubin, RH Dienstag, JL Dorna, M ORourke, E Vacanti, J Jenkins, R Lewis, WD Hammer, S Martin, M Fairchild, R Werner, BG Grady, GF Leszczynski, J Dougherty, N Katz, A Fausett, G Platt, R Cheeseman, SH Pasternack, M Gorbach, SL TI Incidence and predictors of cytomegalovirus pneumonia in orthotopic liver transplant recipients SO TRANSPLANTATION LA English DT Article ID IMMUNE GLOBULIN; INFECTION; GANCICLOVIR; DISEASE; PROPHYLAXIS; IMPACT; HEART AB The incidence, predictors, and outcome of cytomegalovirus pneumonia in OLT recipients have not been well defined. We conducted an analysis of prospectively collected data from 141 OLT recipients who mere included as part of a randomized, placebo-controlled trial of CMV immune globulin prophylaxis. Cytomegalovirus pneumonia was diagnosed in 13 of 141 (9.2%) OLT recipients during the first year posttransplant and was associated with a higher 1-year mortality compared with those recipients without CMV pneumonia (84.6 vs. 11.2%, P=0.0001), Univariate analysis demonstrated that CMV viremia (P=0.001), invasive fungal disease (P=0.0001), donor(+)/pretransplant recipient(-) CMV serologic status (P=0.013), abdominal operation (excluding retransplantation) after liver transplantation (P=0.0027), bacteremia (P=0.0105), and advanced United Network of Organ Sharing status (P=0.023) mere associated with CMV pneumonia. Cytomegalovirus viremia was diagnosed in 11 of 18 patients with CMV pneumonia at a median of 11 days (range 1-66 days) before diagnosis of CMV pneumonia. In a multivariate analysis using a time-dependent, Cox proportional hazards model, CMV viremia (RR=8.6, 95% CI 1.8-39.7, P=0.0012), invasive fungal disease (RR=6.5, 95% CI 2.1-20.3, P=0.0001), and abdominal reoperation (RR=4.4, 95% CI 1.4-13.1, P=0.0043) were found to be independent predictors of CMV pneumonia. The attributable mortality associated with CMV pneumonia within the first year after liver transplantation for the patients with CR;IV pneumonia was 67.4%. Intensified measures for prevention of CMV should be considered for patients at high risk. of developing CMV pneumonia. C1 TUFTS UNIV NEW ENGLAND MED CTR, DEPT MED, BOSTON, MA 02111 USA. TUFTS UNIV NEW ENGLAND MED CTR, DEPT PATHOL & SURG, BOSTON, MA 02111 USA. TUFTS UNIV, SCH MED, MEDFORD, MA 02155 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. CHILDRENS HOSP, BOSTON, MA USA. NEW ENGLAND DEACONESS HOSP, BOSTON, MA 02215 USA. MASSACHUSETTS STATE LAB INST, BOSTON, MA USA. CLIN DATA ANAL COMM, BOSTON, MA USA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 FU NIDDK NIH HHS [R10 DK31389] NR 31 TC 24 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 1996 VL 61 IS 12 BP 1716 EP 1720 DI 10.1097/00007890-199606270-00009 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UU564 UT WOS:A1996UU56400009 PM 8685949 ER PT J AU Mentzer, SJ Longtine, J Fingeroth, J Reilly, JJ DeCamp, MM ODonnell, W Swanson, SJ Faller, DV Sugarbaker, DJ AF Mentzer, SJ Longtine, J Fingeroth, J Reilly, JJ DeCamp, MM ODonnell, W Swanson, SJ Faller, DV Sugarbaker, DJ TI Immunoblastic lymphoma of donor origin in the allograft after lung transplantation SO TRANSPLANTATION LA English DT Article ID LYMPHOPROLIFERATIVE DISEASE; RENAL-TRANSPLANTATION; RECIPIENT; IMMUNOSUPPRESSION; CANCER AB Posttransplant lymphoproliferative disorders (PTLD) are EBV-associated lymphoid neoplasms that are caused by the uncontrolled growth of EBV-infected B lymphocytes. The clinical presentation of PTLD can range from benign polyclonal lymphoproliferative disorders to aggressive monoclonal immunoblastic lymphomas. In this report, we describe a seronegative lung transplant recipient who developed an immunoblastic lymphoma 4 months after lung transplantation from a seropositive donor. The neoplastic cells expressed B lymphocyte markers (CD19(+), CD20(+), sIgM(+), kappa(+)) as well as the EBV antigen EBNA-2. A cell line with similar cytologic features spontaneously grew hom in vitro cultures of the patient's peripheral blood mononuclear cells, The cell Line and the lymphoma were EBV(+), expressed a similar spectrum of B cell surface proteins, and had the donor's HLA haplotype. Analysis of immunoglobulin gene rearrangements and viral terminal repeat sequences revealed that the cell line and the tumor represented distinct B cell clones. Cultured peripheral blood mononuclear cells were restimulated in vitro with the EBV transformed cell Line and tested for cytolytic activity. The host T cells demonstrated high levels of cytolytic activity against the tumor cell line that was abrogated by the addition of a anti-monomorphic HLA class I monoclonal antibody (mAb) (W6/32). These studies indicate that cells of donor origin can persist in the transplanted organ and may lead to an EBV-associated posttransplant lymphoma. C1 BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED & PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. BOSTON UNIV,SCH MED,CTR CANC RES,BOSTON,MA 02118. FU NHLBI NIH HHS [HL47078] NR 28 TC 19 Z9 19 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 1996 VL 61 IS 12 BP 1720 EP 1725 DI 10.1097/00007890-199606270-00010 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UU564 UT WOS:A1996UU56400010 PM 8685950 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI Cost savings at the end of life - What do the data show? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ADVANCE DIRECTIVES; NATIONAL HOSPICE; CANCER-PATIENTS; CARE; DEATH; HOME; EXPENDITURES; SERVICES; TRIAL AB Medical care at the end of life consumes 10% to 12% of the total health care budget and 27% of the Medicare budget. Many people claim that increased use of hospice and advance directives and lower use of high-technology interventions for terminally ill patients will produce significant cost savings. However, the studies on cost savings from hospice and advance directives are not definitive, The 3 randomized trials show no savings from these interventions, but either they are too small for confidence in their negative results or their intervention and cost accounting are flawed, The nonrandomized trials of hospice and advance directives show a wide range of savings, from 68% to none. Five methodological issues obscure the assessment of these studies: (1) selection bias in those patients who use hospice and advance directives, (2) the different time frames of assessing the costs, (3) the limited types of medical costs evaluated, (4) the variability of reporting the savings, and (5) the lack of generalizability of the findings to other patient populations, A more definitive study that assessed patients' end-of-life care preferences, use of hospice and advance directives, and direct and indirect costs would be desirable, In the absence of such a study, the existing data suggest that hospice and advance directives can save between 25% and 40% of health care costs during the last month of life, with savings decreasing to 10% to 17% over the last 6 months of life and decreasing further to 0% to 10% over the last 12 months of life. These savings are less than most people anticipate. Nevertheless, they do indicate that hospice and advance directives should be encouraged because they certainly do not cost more and they provide a means for patients to exercise their autonomy over end-of-life decisions. C1 HARVARD UNIV,SCH MED,DIV MED ETH,BOSTON,MA 02115. RP Emanuel, EJ (reprint author), DANA FARBER CANC INST,CTR OUTCOMES & POLICY RES,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 43 TC 168 Z9 169 U1 3 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 26 PY 1996 VL 275 IS 24 BP 1907 EP 1914 DI 10.1001/jama.275.24.1907 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA UR975 UT WOS:A1996UR97500037 PM 8648872 ER PT J AU Garber, JE Schrag, D AF Garber, JE Schrag, D TI Testing for inherited cancer susceptibility SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP Garber, JE (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,MAYER 3A31,BOSTON,MA 02115, USA. NR 10 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 26 PY 1996 VL 275 IS 24 BP 1928 EP 1929 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UR975 UT WOS:A1996UR97500040 PM 8648875 ER PT J AU Heller, RS Kieffer, TJ Habener, JF AF Heller, RS Kieffer, TJ Habener, JF TI Point mutations in the first and third intracellular loops of the glucagon-like peptide-1 receptor alter intracellular signaling SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; CELLS; EXPRESSION; TRANSDUCTION; GENE AB The glucagon-like peptide-1 receptor (GLP-1R) is a member of the glucagon family of seven transmembrane spanning receptors. To investigate how different portions of the GLP-1R may be important in cAMP and intracellular calcium signaling, single amino acid substitutions in the receptor were made by site directed mutagenesis. Receptor binding, cAMP, and intracellular calcium measurements were made in transfected COS-7 cells. The change of amino acid H180R (His to Arg) in the first intracellular loop caused a decrease in the affinity of binding of GLP-1 from 7 nM in the wild type receptor to 150 nM and resulted in a 50% decrease in GLP-1 stimulated cAMP production In response to 10 nM GLP-1, the receptor's ability to stimulate intracellular calcium was altered from a prolonged to a transient response of the same magnitude. Mutation in the 3rd intracellular loop at position R348G (Arg to Gly) decreased receptor affinity from 7 to 83 nM and nearly abolished cAMP production at all concentrations of GLP-1 tested. The GLP-1 stimulated rise in free intracellular calcium was also diminished and this was reversed when cells were treated with forskolin. These results also indicate that GLP-1R signaling via intracellular calcium is dependent on the receptor's ability to also generate cAMP. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,MASSACHUSETTS GEN HOSP,LAB MOLEC ENDOCRINOL,BOSTON,MA 02114. RI Heller, R.Scott/A-7279-2008 FU NIDDK NIH HHS [DK30834] NR 30 TC 44 Z9 44 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 25 PY 1996 VL 223 IS 3 BP 624 EP 632 DI 10.1006/bbrc.1996.0945 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UV152 UT WOS:A1996UV15200026 PM 8687446 ER PT J AU Gao, JL Sen, AI Kitaura, M Yoshie, O Rothenberg, ME Murphy, PM Luster, AD AF Gao, JL Sen, AI Kitaura, M Yoshie, O Rothenberg, ME Murphy, PM Luster, AD TI Identification of a mouse eosinophil receptor for the CC chemokine eotaxin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article AB The CC chemokine eotaxin is a selective chemoattractant for eosinophils in vitro and induces eosinophil migration in vivo. Here we show that the mouse orphan receptor previously named macrophage inflammatory protein-1 alpha receptor-like 2 is a functional eotaxin receptor. For consistency with other nomenclature, we have renamed the receptor mouse CC chemokine receptor 3. Human and mouse eotaxin, but not other chemokines, induced transient increases in [Ca2+](i) in human embryonic kidney 293 cells expressing the receptor. RNA for the receptor was abundant in primary eosinophils, but at low levels in neutrophils and macrophages. These properties make this receptor the best known candidate to mediate mouse eosinophil responses to eotaxin. (C) 1996 Academic Press, Inc. C1 SHIONOGI INST MED SCI,OSAKA 566,JAPAN. HARVARD UNIV,SCH MED,DEPT GENET,HOWARD HUGHES MED INST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,CHARLESTOWN,MA 02129. RP Gao, JL (reprint author), NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892, USA. NR 14 TC 66 Z9 66 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 25 PY 1996 VL 223 IS 3 BP 679 EP 684 DI 10.1006/bbrc.1996.0955 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UV152 UT WOS:A1996UV15200036 PM 8687456 ER PT J AU Song, KS Scherer, PE Tang, ZL Okamoto, T Li, SW Chafel, M Chu, C Kohtz, DS Lisanti, MP AF Song, KS Scherer, PE Tang, ZL Okamoto, T Li, SW Chafel, M Chu, C Kohtz, DS Lisanti, MP TI Expression of caveolin-3 in skeletal, cardiac, and smooth muscle cells - Caveolin-3 is a component of the sarcolemma and co-fractionates with dystrophin and dystrophin-associated glycoproteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROUS-SARCOMA VIRUS; PLASMA-MEMBRANE; MUSCULAR-DYSTROPHY; PROTEIN-COMPONENT; COMPLEX; PHOSPHORYLATION; DIFFERENTIATION; VESICLES; TYROSINE; SEQUENCE AB Caveolae are microdomains of the plasma membrane that have been implicated in signal transduction, Caveolin, a 21-24-kDa integral membrane protein, is a principal component of the caveolae membrane, Recently, we and others have identified a family of caveolin-related proteins; caveolin has been retermed caveolin-1. Caveolin-3 is most closely related to caveolin-1, but caveolin-3 mRNA is expressed only in muscle tissue types, Here, we examine (i) the expression of caveolin-3 protein in muscle tissue types and (ii) its localization within skeletal muscle fibers by immunofluorescence microscopy and subcellular fractionation, For this purpose, we generated a novel monoclonal antibody (mAb) probe that recognizes the unique N-terminal region of caveolin-3, but not other members of the caveolin gene family, A survey of tissues and muscle cell types by Western blot analysis reveals that the caveolin 3 protein is selectively expressed only in heart and skeletal muscle tissues, cardiac myocytes, and smooth muscle cells, Immunolocalization of caveolin-3 in skeletal muscle fibers demonstrates that caveolin-3 is localized to the sarcolemma (muscle cell plasma membrane) and coincides with the distribution of another muscle-specific plasma membrane marker protein, dystrophin, In addition, caveolin-3 protein expression is dramatically induced during the differentiation of C2C12 skeletal myoblasts in culture, Using differentiated C2C12 skeletal myoblasts as a model system, we observe that caveolin-3 co-fractionates with cytoplasmic signaling molecules (G-proteins and Src-like kinases) and members of the dystrophin complex (dystrophin, alpha-sarcoglycan, and beta-dystroglycan), but is clearly separated from the bulk of cellular proteins. Caveolin-3 co-immunoprecipitates with antibodies directed against dystrophin, suggesting that they are physically associated as a discrete complex. These results are consistent with previous immunoelectron microscopic studies demonstrating that dystrophin is localized to plasma membrane caveolae in smooth muscle cells. C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SHRINERS HOSP CRIPPLED CHILDREN,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. MT SINAI SCH MED,DEPT PATHOL,NEW YORK,NY 10029. RI Lisanti, Michael/C-6866-2013 FU NCI NIH HHS [CA071326]; NIGMS NIH HHS [GM-50443] NR 45 TC 507 Z9 512 U1 0 U2 13 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 21 PY 1996 VL 271 IS 25 BP 15160 EP 15165 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UT106 UT WOS:A1996UT10600076 PM 8663016 ER PT J AU Anderson, AC Earp, BE Frederick, CA AF Anderson, AC Earp, BE Frederick, CA TI Sequence variation as a strategy for crystallizing RNA motifs SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE X-ray crystallography; RNA structure; hairpin; pseudoknot; oligonucleotide synthesis ID RECOGNITION; RESOLUTION; HELIX AB The determination of RNA structures by X-ray crystallography is an exciting and developing field. At present, the crystallographic characterization of RNA is limited by the difficulty in obtaining large, high quality crystals. This paper outlines several techniques for improving the likelihood of obtaining RNA crystals, for improving the size of those crystals, and for extending the limit of the diffraction maxima. Sequence variations have proven to be more effective in changing the quality of the crystals than variations in crystallization conditions, often making the difference between obtaining true single crystals and multiply twinned crystalline material. (C) 1996 Academic Press Limited C1 HARVARD UNIV,COMM HIGHER DEGREES BIOPHYS,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. NR 26 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 21 PY 1996 VL 259 IS 4 BP 696 EP 703 DI 10.1006/jmbi.1996.0351 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UT105 UT WOS:A1996UT10500012 PM 8683576 ER PT J AU Gould, RA Ball, S Kaspi, SP Otto, MW Pollack, MH Shekhar, A Fava, M AF Gould, RA Ball, S Kaspi, SP Otto, MW Pollack, MH Shekhar, A Fava, M TI Prevalence and correlates of anger attacks: A two site study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE anger attack; anger; depression; panic disorder ID PANIC DISORDER; BEHAVIOR; IRRITABILITY; FLUOXETINE; DEPRESSION; SCALE AB Although anger attacks have been described in depressed outpatients, they have not been well studied in other disorders. In Study 1, we examined the prevalence of anger attacks in 50 outpatients with panic disorder. In Study 2, we replicated the initial findings at an independent site and examined the specificity of anger attacks by comparing their occurrence in patients with panic disorder, patients with other non-panic anxiety disorders and patients with a depressive disorder. At both sites, we also explored the relationship between anger attacks and demographic and clinical characteristics, such as gender, presence and severity of depression, and social anxiety measures. In both sites, the prevalence of anger attacks in patients with panic disorder was approximately one-third. However, anger attacks were not unique to panic disorder, with similar rates emerging for patients with other anxiety disorders. Furthermore, patients with depressive diagnoses had twice the prevalence of anger attacks than did anxiety patients. At both sites, those with anger attacks were significantly more depressed and were likely to have either current or past history of major depression. Anger attacks were not associated with social anxiety measures, but were related to cluster B, cluster C and self-defeating personality disorder traits. Our findings support the notion that anger attacks are best conceptualized as an associated feature of depression. C1 INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. RP Gould, RA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BEHAV THERAPY UNIT,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH 19600] NR 25 TC 51 Z9 53 U1 2 U2 2 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 JUN 20 PY 1996 VL 39 IS 1 BP 31 EP 38 DI 10.1016/0165-0327(96)00017-1 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UX171 UT WOS:A1996UX17100005 PM 8835651 ER PT J AU Waytes, AT Rosen, FS Frank, MM AF Waytes, AT Rosen, FS Frank, MM TI Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANGIONEUROTIC-EDEMA; ESTERASE INHIBITOR; ACID THERAPY; C1-INHIBITOR; MANAGEMENT AB Background. Hereditary angioedema results from a congenital deficiency of functional C1 inhibitor and is characterized by episodic bouts of edema, which may be life-threatening when they involve the larynx. We evaluated the effectiveness of a C1 inhibitor concentrate in the prevention and treatment of attacks of hereditary angioedema. The concentrate was vapor-heated to inactivate hepatitis and hunan immunodeficiency viruses. Methods. We conducted two double-blind, placebo-controlled studies. The first was a crossover study consisting of two 17-day trials in which prophylactic infusions of either C1 inhibitor (25 plasma units per kilogram of body weight) or placebo were given intravenously every third day to six patients with hereditary angioedema. The second study was conducted in patients with acute attacks of hereditary angioedema and assessed the length of time to a clinical response after infusions of either 25 plasma units of C1 inhibitor per kilogram (55 infusions in 11 patients). Results. The infusions of C1 inhibitor concentrate resulted in close to normal functional levels of C1 inhibitor and C4. As compared with placebo, prophylactic infusions of C1 inhibitor resulted in significantly lower daily symptom scores for the severity of edema of the extremities (P < 0.01), larynx (P < 0.05), abdomen (P < 0.05), and genitourinary tract (P < 0.05). Likewise, during the treatment study the time from the start of an infusion to the beginning of improvement in symptoms was shorter for the C1 inhibitor infusions than the placebo infusions (55 vs. 563 minutes, P < 0.001). There was no evidence of toxicity. Conclusions. Infusions of a vapor-heated C1 inhibitor concentrate are safe and effective means of both preventing attacks of hereditary angioedema and treating acute attacks. (C) 1996, Massachusetts Medical Society. C1 CHILDRENS HOSP,CTR BLOOD RES,DIV IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. FU NCRR NIH HHS [GCRC RR-02172] NR 27 TC 222 Z9 224 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 20 PY 1996 VL 334 IS 25 BP 1630 EP 1634 DI 10.1056/NEJM199606203342503 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA UQ706 UT WOS:A1996UQ70600003 PM 8628358 ER PT J AU Goodfriend, TL Elliott, ME Catt, KJ AF Goodfriend, TL Elliott, ME Catt, KJ TI Drug therapy - Angiotensin receptors and their antagonists SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SMOOTH-MUSCLE CELLS; II RECEPTOR; GLOMERULOSA CELLS; NORMAL VOLUNTEERS; HEALTHY-SUBJECTS; CALCIUM SIGNAL; HYPERTROPHY; INHIBITION; RESPONSES; HYPERPLASIA C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,DEPT PHARMACOL,MADISON,WI 53706. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP Goodfriend, TL (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 82 TC 418 Z9 448 U1 0 U2 7 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 20 PY 1996 VL 334 IS 25 BP 1649 EP 1654 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UQ706 UT WOS:A1996UQ70600007 PM 8628362 ER PT J AU Williams, MJA Lee, MY DiSalvo, TG Dec, GW Picard, MH Palacios, IF Semigran, MJ AF Williams, MJA Lee, MY DiSalvo, TG Dec, GW Picard, MH Palacios, IF Semigran, MJ TI Biopsy-induced flail tricuspid leaflet and tricuspid regurgitation following orthotopic cardiac transplantation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ENDOMYOCARDIAL BIOPSY; VALVULAR REGURGITATION; HEART-TRANSPLANTATION; DOPPLER; ECHOCARDIOGRAPHY; PRESSURES; EXERCISE AB Damage to the tricuspid valve apparatus has been described after endomyocardial biopsy and may be associated with hemodynamically significant tricuspid regurgitation (TR). This study was performed to determine the prevalence of TR and flail tricuspid leaflet in cardiac transplant recipients and to evaluate the use of a 45 cm sheath placed directly in the right ventricle during endomyocardial biopsy to reduce the incidence of these complications. Echocardiograms and right heart catheterization dan of 72 orthotopic cardiac transplant recipients were assessed for the presence of flail tricuspid leaflet, TR, and right-sided cardiac dysfunction 29 +/- 20 months (mean +/- SD) after transplantation. Moderate or severe TR was present in 23 patients (32%). Ten patients (14%) had flail tricuspid leaflet, with 7 of these having severe TR. Right atrial pressure (10 +/- 5 vs 6 +/- 5 mm Hg, p < 0.05) was higher, cardiac index (2.0 +/- 0.2 vs 2.5 +/- 0.7 L/min/m(2), p < 0.05) was lower, and right-sided cardiac dimensions were greater in patients with gall leaflets than in those without flail leaflets. Both the prevalence of flail tricuspid leaflet (41% to 6%, p < 0.0001) and mean grade of TR (2 to 1, p < 0.0001) were reduced after the use of a 45 cm sheath. We conclude that TR secondary to biopsy-induced damage to the valve apparatus occurs in cardiac transplant recipients and is associated with signs of early right-sided heart failure. Use of a 45 cm sheath during endomyocardial biopsy reduces the prevalence of flail tricuspid leaflet and the severity of TR. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Michael, Williams/C-1759-2008; OI Michael, Williams/0000-0003-4822-4962; Picard, Michael/0000-0002-9264-3243 NR 26 TC 53 Z9 54 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 1996 VL 77 IS 15 BP 1339 EP 1344 DI 10.1016/S0002-9149(96)00202-0 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UT061 UT WOS:A1996UT06100013 PM 8677876 ER PT J AU DAquila, RT Hughes, MD Johnson, VA Fischl, MA Sommadossi, JP Liou, SH Timpone, J Myers, M Basgoz, N Niu, M Hirsch, MS Costanzo, L Ruben, S Berzins, B Martinez, A Fishman, I Kazial, K Cort, SN Robinson, P Hall, D Macy, H McLaren, C Rooney, J Warwick, J CavailleColl, M Valentine, F Booth, D Soeiro, R Stein, D Zingman, B Schliosberg, J Polsky, B Sepkowitz, K Sharpe, V Giordano, M Wanke, C Gulick, R Craven, D Grodman, C Fife, K Black, J Todd, K Nixon, H Sperber, K Gerits, P Mildvan, D Nicholas, P Murphy, RL Kessler, H Pulvirenti, J Squires, K Saag, M Weingarten, J Gnann, J Havlir, D Fegan, C Spector, S Richman, D Jacobson, M Dybeck, K Joseph, P Clanon, K McKenzie, S Daniel, P Dayton, D Leonard, J Schooley, R Kuritzkes, D Ray, G Putnam, B Jayaweera, D PatroneReese, J Tanner, T Moebus, J Reed, N StJacque, R Henry, K Swindells, S Eron, J Ragan, D Horton, J Lane, T Frank, I Norris, A Pomerantz, R Hauptman, S Geiseler, J Leedom, J Canchola, F Olson, C Deyton, L Pettinelli, C AF DAquila, RT Hughes, MD Johnson, VA Fischl, MA Sommadossi, JP Liou, SH Timpone, J Myers, M Basgoz, N Niu, M Hirsch, MS Costanzo, L Ruben, S Berzins, B Martinez, A Fishman, I Kazial, K Cort, SN Robinson, P Hall, D Macy, H McLaren, C Rooney, J Warwick, J CavailleColl, M Valentine, F Booth, D Soeiro, R Stein, D Zingman, B Schliosberg, J Polsky, B Sepkowitz, K Sharpe, V Giordano, M Wanke, C Gulick, R Craven, D Grodman, C Fife, K Black, J Todd, K Nixon, H Sperber, K Gerits, P Mildvan, D Nicholas, P Murphy, RL Kessler, H Pulvirenti, J Squires, K Saag, M Weingarten, J Gnann, J Havlir, D Fegan, C Spector, S Richman, D Jacobson, M Dybeck, K Joseph, P Clanon, K McKenzie, S Daniel, P Dayton, D Leonard, J Schooley, R Kuritzkes, D Ray, G Putnam, B Jayaweera, D PatroneReese, J Tanner, T Moebus, J Reed, N StJacque, R Henry, K Swindells, S Eron, J Ragan, D Horton, J Lane, T Frank, I Norris, A Pomerantz, R Hauptman, S Geiseler, J Leedom, J Canchola, F Olson, C Deyton, L Pettinelli, C TI Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection - A randomized, double-blind, placebo-controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; COMBINATION THERAPY; MULTIDRUG-RESISTANCE; REPLICATION; INHIBITION; INTERFERON AB Objective: To study the addition of a third human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, nevirapine, to the combination of zidovudine and didanosine. Design: A 48-week, randomized, double-blind, placebo-controlled trial at 16 AIDS (acquired immunodeficiency syndrome) Clinical Trials Units. Patients: 398 adults who had HIV-1 infection, had 350 or fewer CD4(+) T lymphocytes/mm(3), and had had more than 6 months of previous nucleoside therapy. Intervention: 1) Either nevirapine or placebo (200 mg/d for 2 weeks, then 400 mg/d thereafter) and 2) open-label zidovudine (600 mg/d) and didanosine (400 mg/d for patients weighing greater than or equal to 60 kg). Measurements: CD4(+) T lymphocyte counts, time to first HIV-1 disease progression event or death, adverse events, and nevirapine levels in plasma samples taken at random were measured in all patients. Plasma levels of HIV-1 RNA; HIV-1 infectivity titer in peripheral blood mononuclear cells; serum p24 antigen levels; and plasma levels of zidovudine and didanosine were measured in patients enrolled at half the study sites. Results: After 48 weeks of study treatment, the patients assigned to the triple-combination regimen (nevirapine, zidovudine, and didanosine) had an 18% higher mean absolute CD4 cell count (95% CI, 7% to 29%; P = 0.001), a 0.32 log(10) lower mean infectious HIV-1 titer in peripheral blood mononuclear cells (CI, 0.05 to 0.59 log(10) infectious units per million cells; P = 0.023), and a 0.25 log(10) lower mean plasma HIV-1 RNA level (CI, 0.03 to 0.48 log(10) RNA copies/mL; P = 0.028) than did patients assigned to the double-combination regimen (zidovudine and didanosine). Severe rashes were more common among patients assigned to receive the triple combination (9% compared with 2%; P = 0.002). Risk for disease progression did not differ between the two groups (relative hazard of the triple-combination group, 1.24 [CI, 0.75 to 2.06]; P > 0.2), although the study had only moderate power to detect a major difference. Conclusions: Adding nevirapine to zidovudine and didanosine improved the long-term immunologic and virologic effects of therapy and was associated with severe rash among the patients studied, who had had extensive previous therapy. These results support 1) the continuing development of combinations of more than two antiretroviral drugs to increase and prolong HIV-1 suppression and 2) the potential utility of nevirapine in combination regimens. C1 AIDS CLIN TRIALS GRP OPERAT OFF,ROCKVILLE,MD. NORTHWESTERN UNIV,CHICAGO,IL 60611. NIAID,PHARMACEUT & REGULATORY AFFAIRS BRANCH,BETHESDA,MD 20892. FRONTIER SCI & TECHNOL RES FDN INC,STAT & DATA MANAGEMENT CTR,AMHERST,MA. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. BRISTOL MYERS SQUIBB CO,WALLINGFORD,CT 06492. GLAXO WELLCOME CO,RES TRIANGLE PK,NC. US FDA,BETHESDA,MD 20014. NYU,MED CTR,NEW YORK,NY. CLIN SITE MONITORING GRP,DURHAM,NC. ALBERT EINSTEIN COLL MED,NEW YORK,NY. CORNELL UNIV,NEW YORK,NY. BOSTON CITY HOSP,BOSTON,MA 02118. INDIANA UNIV,INDIANAPOLIS,IN 46204. MT SINAI MED CTR,NEW YORK,NY 10029. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV CINCINNATI,CINCINNATI,OH. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. UNIV MIAMI,MIAMI,FL 33152. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV N CAROLINA,CHAPEL HILL,NC. UNIV PENN,PHILADELPHIA,PA 19104. UNIV SO CALIF,LOS ANGELES,CA. NIAID,DIV AIDS,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,AIDS CLIN TRIALS GRP STAT DATA & ANAL CTR,BOSTON,MA 02115. UNIV ALABAMA,SCH MED,DEPT MED,DIV INFECT DIS,BIRMINGHAM,AL 35294. VET AFFAIRS MED CTR,BIRMINGHAM,AL 35294. UNIV MIAMI,SCH MED,DEPT MED,MIAMI,FL 33101. UNIV ALABAMA,DEPT PHARMACOL,DIV CLIN PHARMACOL,SCH MED,BIRMINGHAM,AL 35294. GENENTECH INC,DEPT BIOSTAT,S SAN FRANCISCO,CA 94080. GEORGETOWN UNIV,MED CTR,DEPT MED,DIV INFECT DIS,WASHINGTON,DC 20007. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. US FDA,DIV BIOSTAT & EPIDEMIOL,ROCKVILLE,MD 20852. OI Murphy, Robert/0000-0003-3936-2052 NR 46 TC 234 Z9 237 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 15 PY 1996 VL 124 IS 12 BP 1019 EP 1030 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA UQ658 UT WOS:A1996UQ65800001 PM 8633815 ER PT J AU Vecsei, L Beal, MF AF Vecsei, L Beal, MF TI Huntington's disease, behavioral disturbances, and kynurenines: Preclinical findings and therapeutic perspectives SO BIOLOGICAL PSYCHIATRY LA English DT Article DE behavior; Huntington's disease; kynurenine; quinolinic acid ID QUINOLINIC ACID; AFFECTIVE-DISORDER; RAT-BRAIN; LESIONS; MODEL; CHOREA C1 HARVARD UNIV,SCH MED,NEUROL SERV,MASSACHUSETTS GEN HOSP,BOSTON,MA. RP Vecsei, L (reprint author), SZENT GYORGYI UNIV,SCH MED,DEPT NEUROL,POB 397,H-6701 SZEGED,HUNGARY. RI Vecsei, Laszlo/B-2066-2010 OI Vecsei, Laszlo/0000-0001-8037-3672 NR 29 TC 14 Z9 15 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 1996 VL 39 IS 12 BP 1061 EP 1063 DI 10.1016/0006-3223(95)00377-0 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UP701 UT WOS:A1996UP70100014 PM 8780845 ER PT J AU Ho, CY Otterud, B Legare, RD Varvil, T Saxena, R DeHart, DB Kohler, SE Aster, JC Dowton, SB Li, FP Leppert, M Gilliland, DG AF Ho, CY Otterud, B Legare, RD Varvil, T Saxena, R DeHart, DB Kohler, SE Aster, JC Dowton, SB Li, FP Leppert, M Gilliland, DG TI Linkage of a familial platelet disorder with a propensity to develop myeloid malignancies to human chromosome 21q22.1-22.2 SO BLOOD LA English DT Article ID FUSION TRANSCRIPT; RECEPTOR GENE; AML1 GENE; LEUKEMIA; TRANSLOCATION; PROTEIN; IDENTIFICATION; HOMOLOGY; REGION; IFNAR AB Linkage analysis was performed on a large pedigree with an autosomal dominant platelet disorder and a striking propensity in affected family members to develop hematologic malignancy, predominantly acute myelogenous leukemia. We report the linkage of the autosomal dominant platelet disorder to markers on chromosome 21q22. Four genetic markers completely cosegregate with the trait and yield maximum logarithm of difference scores ranging from 4.9 to 10.5 (theta = .001). Two flanking markers, D21S1265 and D21S167, define a critical region for the disease locus of 15.2 centimorgan. Further analysis of this locus may identify a gene product that affects platelet production and function and contributes to the molecular evolution of hematologic malignancy. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,SCH PUBL HLTH,BOSTON,MA 02115. UNIV WASHINGTON,SCH MED,DEPT GENET,ST LOUIS,MO. UNIV UTAH,GENOME CTR,TECHNOL ACCESS SECT,SALT LAKE CITY,UT. NR 37 TC 69 Z9 71 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1996 VL 87 IS 12 BP 5218 EP 5224 PG 7 WC Hematology SC Hematology GA UQ709 UT WOS:A1996UQ70900033 PM 8652836 ER PT J AU Dignass, AU Podolsky, DK AF Dignass, AU Podolsky, DK TI Interleukin 2 modulates intestinal epithelial cell function in vitro SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; GENE-EXPRESSION; FACTOR-ALPHA; RESTITUTION; LOCALIZATION; RECEPTOR; MODEL; LINE; MONOLAYERS; SECRETION AB Although interleukin 2 (IL-2) has been presumed to have a highly circumscribed range of target cells limited largely to classic immune cell populations, the presence of functional IL-2 receptors in rat epithelial cell lines has recently been demonstrated. Limited information is available about the functional effects of IL-2 on intestinal epithelial cells. The effect of recombinant IL-2 on intestinal epithelial cell migration was assessed using a previously described in vitro model of epithelial restitution by quantitation of cells migrating into standard wounds established in confluent IEC-B cell monolayers, Transforming growth factor beta content was assessed by Northern blot and bioassay. Exogenous IL-2 enhanced epithelial cell restitution in vitro on average 3.8-fold; this effect was independent of cell proliferation. Enhancement of restitution through IL-2 could be completely blocked through antibodies directed against TGF beta(1) and interleukin-2 receptor, indicating that stimulation of epithelial cell restitution is specifically enhanced by interleukin-2 and mediated through a TGF beta-dependent pathway. In addition, increased expression of TGF beta(1) mRNA and increased levels of bioactive TGF beta peptide in wounded monolayers treated with IL-2 compared to unwounded monolayers cultured in serum-deprived medium alone support the notion that enhancement of epithelial cell restitution in vitro is mediated through a TGF beta-dependent pathway. These studies suggest that IL-2, a potent cytokine whose biological origin and targets have been presumed to be largely limited to lymphocyte and macrophage populations, may play a role in preserving the integrity of the intestinal epithelium following various forms of injuries. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,GASTROENTEROL UNIT,DEPT MED,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [DK41557, DK43351] NR 44 TC 57 Z9 58 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUN 15 PY 1996 VL 225 IS 2 BP 422 EP 429 DI 10.1006/excr.1996.0193 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA UU965 UT WOS:A1996UU96500022 PM 8660931 ER PT J AU Kolodner, R AF Kolodner, R TI Biochemistry and genetics of eukaryotic mismatch repair SO GENES & DEVELOPMENT LA English DT Review ID HETERODUPLEX PLASMID DNA; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; TRANSFORMATION; CONVERSION; HOMOLOGS; MUTANTS; SYSTEM; GENES; YEAST C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP Kolodner, R (reprint author), DANA FARBER CANC INST,CHARLES A DANA DIV HUMAN CANC GENET,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA67151]; NIGMS NIH HHS [GM50006] NR 87 TC 504 Z9 512 U1 2 U2 16 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 15 PY 1996 VL 10 IS 12 BP 1433 EP 1442 DI 10.1101/gad.10.12.1433 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UU117 UT WOS:A1996UU11700001 PM 8666228 ER PT J AU Brown, SA Imbalzano, AN Kingston, RE AF Brown, SA Imbalzano, AN Kingston, RE TI Activator-dependent regulation of transcriptional pausing on nucleosomal templates SO GENES & DEVELOPMENT LA English DT Article DE transcriptional pausing; nucleosomes; hsp70; heat shock factor 1; hSW1/SNF complex; transcriptional activators ID RNA POLYMERASE-II; HEAT-SHOCK GENES; DROSOPHILA-MELANOGASTER; HSP70 GENE; ELONGATION; PROMOTER; INVITRO; INITIATION; INVIVO; COMPLEXES AB Promoter-proximal pausing during transcriptional elongation is an important way of regulating many diverse genes, including human c-myc and c-fos, some HIV genes, and the Drosophila heat shock loci. To characterize the mechanisms that regulate pausing, we have established an in vitro system using the human hsp70 gene. We demonstrate that nucleosome formation increases by >100-fold the duration of a transcriptional pause on the human hsp70 gene in vitro at the same location as pausing is observed in vivo. Readthrough of this pause is increased by an activator that contains the human heat shock factor 1 (HSF1) transcriptional activation domains. Maximal effect of the activator requires that the system be supplemented with fractions that have hSWI/SNF activity, which has been shown previously to alter nucleosome structure. No significant readthrough is observed in the absence of activator, and neither the activator nor the hSWI/SNF fraction affected elongation on naked DNA; therefore, these results suggest that an activator can cause increased readthrough of promoter-proximal pausing by decreasing the inhibitory effect of nucleosomes on transcriptional elongation. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 53 TC 161 Z9 162 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 15 PY 1996 VL 10 IS 12 BP 1479 EP 1490 DI 10.1101/gad.10.12.1479 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UU117 UT WOS:A1996UU11700005 PM 8666232 ER PT J AU White, RA Hughes, RT Adkison, LR Bruns, G Zon, LI AF White, RA Hughes, RT Adkison, LR Bruns, G Zon, LI TI The gene encoding protein kinase SEK1 maps to mouse chromosome 11 and human chromosome 17 SO GENOMICS LA English DT Article ID MEK AB We report the mapping of the human and mouse genes encoding SEK1 (SAPK/ERK kinase-1), a newly identified protein kinase that is a potent physiological activator of the stress-activated protein kinases. The human SERK1 gene was assigned to human chromosome 17 using genomic DNAs from human-rodent somatic cell hybrid lines. A specific human PCR product was observed solely in the somatic cell line containing human chromosome 17. The mouse Serk1 gene was mapped to chromosome 11, closely linked to D11Mit4, using genomic DNAs from a (C57BL/6J x Mus spretus) F-1 x M. spretus backcross. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV GENET,BOSTON,MA 02115. MERCER UNIV,SCH MED,DIV BIOMED SCI,MACON,GA 31207. RP White, RA (reprint author), UNIV MISSOURI,BIOMOLEC LAB,CHILDRENS MERCY HOSP,SCH MED,SECT GENET,2801 WYANDOTTE AVE,KANSAS CITY,MO 64108, USA. FU NHLBI NIH HHS [HL32262] NR 17 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 15 PY 1996 VL 34 IS 3 BP 430 EP 432 DI 10.1006/geno.1996.0309 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UU191 UT WOS:A1996UU19100021 PM 8786147 ER PT J AU Liang, TJ Reid, AE Xavier, R Cardiff, RD Wang, TC AF Liang, TJ Reid, AE Xavier, R Cardiff, RD Wang, TC TI Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE c-met; hepatocyte growth factor; receptor tyrosine kinase; carcinogenesis; sarcoma ID HEPATOCYTE GROWTH-FACTOR; FMS PROTO-ONCOGENE; TYROSINE KINASE; LEUCINE-ZIPPER; POINT MUTATION; SCATTER FACTOR; RECEPTOR; DOMAIN; IDENTIFICATION; ACTIVATION AB Receptor tyrosine kinases are important in cell signal transduction and proliferation, Abnormal expression of tyrosine kinases often leads to malignant transformation, C-met is a tyrosine kinase receptor and its ligand is hepatocyte growth factor (HGF), HGF/c-met plays diverse roles in regulation of cell growth, shape and movement. Constitutively activated met, such as tpr-met, is a potent oncogene in vitro, but its carcinogenic role in vivo remains unclear, Our study demonstrates that expression of tpr-met leads to development of mammary tumors and other malignancies in transgenic mice, and suggests that deregulated met expression may be involved in mammary carcinogenesis. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV CALIF DAVIS,SCH MED,DEPT PATHOL,DAVIS,CA 95616. NR 26 TC 82 Z9 83 U1 4 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 15 PY 1996 VL 97 IS 12 BP 2872 EP 2877 DI 10.1172/JCI118744 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UT429 UT WOS:A1996UT42900026 PM 8675700 ER PT J AU Sen, J Kapeller, R Fragoso, R Sen, R Zon, LI Burakoff, SJ AF Sen, J Kapeller, R Fragoso, R Sen, R Zon, LI Burakoff, SJ TI Intrathymic signals in thymocytes are mediated by p38 mitogen-activated protein kinase SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MICE AB Thymocytes develop into mature functional T cells in the inductive environment of the thymus where thymocyte-stromal cell interactions and cytokines provide survival and differentiation signals as cues for thymocyte maturation. Disruption of the thymic microenvironment results in attenuation of T cell maturation, suggesting that intrathymic signals are essential for differentiation and repertoire selection. We have previously shown that several inducible nuclear factors such as AP-1, NF-AT, and NF-kappa B are activated in response to intrathymic signals. Here we demonstrate that in thymocytes p38 mitogen-activated protein (MAP) kinase, a member of the MAP kinase family of proteins that include the extracellular-signal regulated kinases and Jun aminoterminal kinases, is highly activated in response to intrathymic signals in vivo. These studies suggest a role for p38 MAP kinase in T cell survival and differentiation. C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,WALTHAM,MA 02254. RP Sen, J (reprint author), DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,ROOM D1840,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 39542]; NIGMS NIH HHS [GM 43874] NR 29 TC 58 Z9 60 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1996 VL 156 IS 12 BP 4535 EP 4538 PG 4 WC Immunology SC Immunology GA UP662 UT WOS:A1996UP66200002 PM 8648093 ER PT J AU Xu, H Bickford, JK Luther, E Carpenito, C Takei, F Springer, TA AF Xu, H Bickford, JK Luther, E Carpenito, C Takei, F Springer, TA TI Characterization of murine intercellular adhesion molecule-2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; T-CELL ACTIVATION; MONOCLONAL-ANTIBODY; COUNTER-RECEPTOR; IMMUNE-SYSTEM; CLONING; LFA-1; ICAM-1; EXPRESSION; MOUSE AB Rat mAbs were raised against murine intercellular adhesion molecule-2 (ICAM-2). Immune precipitation and purification reveal that the murine ICAM-2 glycoprotein is 55 kDa and is similar in size to human ICAM-2. ICAM-2 is expressed on a variety of leukocyte cell lines, including T and B lymphoma, mastocytoma, and macrophage lines. ICAM-2 is well expressed on endothelioma cell lines, and in contrast to ICAM-1, expression is not increased by inflammatory cytokines. One of the mAb to ICAM-2 partially or completely inhibits binding of cells expressing LFA-1 to purified ICAM-2, and binding of cells expressing ICAM-2 to purified LFA-1. The findings in the mouse are congruent with those in the human, suggesting functional conservation of ICAM-2 across species. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT PATHOL,BOSTON,MA 02215. PFIZER INC,DEPT MOL GENET & PROT CHEM,GROTON,CT 06340. COMPUCYTE CORP,CAMBRIDGE,MA 02142. TERRY FOX LAB HEMATOL ONCOL,VANCOUVER,BC,CANADA. FU NCI NIH HHS [CA31798] NR 42 TC 43 Z9 43 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1996 VL 156 IS 12 BP 4909 EP 4914 PG 6 WC Immunology SC Immunology GA UP662 UT WOS:A1996UP66200051 PM 8648141 ER PT J AU Perkins, DL Listman, JA MarshakRothstein, A Kozlow, W Kelley, VR Finn, PW Rimm, IJ AF Perkins, DL Listman, JA MarshakRothstein, A Kozlow, W Kelley, VR Finn, PW Rimm, IJ TI Restriction of the TCR repertoire inhibits the development of memory T cells and prevents autoimmunity in lpr mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LPR/LPR MICE; SYSTEMIC AUTOIMMUNITY; TRANSGENIC MICE; RECEPTOR; GENE; DEFECT; MOUSE; GLD; LYMPHOCYTES; GAMMA AB The lpr mutation, a disruption of the fas gene, induces spontaneous autoimmunity characterized by high titers of autoantibodies, lymphadenopathy, autoreactive T cells, and early mortality. The mechanism of autoimmunity, however, remains unknown. The driving force for disease could result from the T cell recognition of autoantigen or, alternatively, an intrinsic T cell defect that promotes autoreactivity, We investigated the role of antigen-TCR interaction in the pathogenesis of lpr autoimmunity by transferring the DO-11.10 TCR beta-chain transgene (V beta 8.2-D beta 1.1-J beta 1.1) to the MRL-lpr/lpr background producing the MRL-lpr beta strain. Our results show that the MRL-lpr beta transgenic strain has increased survival, lower titers of autoantibodies, and decreased lymphadenopathy compared with nontransgenic littermates. These beneficial effects were associated with decreased expansion of CD4(+) T cells expressing memory phenotypes (CD44(+), CD45RB(-), and LECAM(-)) in the transgenic compared with nontransgenic strains. A role for impaired recognition of autoantigen by T cells expressing the TCR transgene was suggested by comparing the phenotypes of V beta 8.2(+) (transgene(+)) vs V beta 8.2(-) (transgene(-)) CD4(+) T cells within the transgenic mice. These experiments show that V beta 8.2(-) T cells, which express endogenously rearranged TCR, are the major contributors to the expansion of memory T cells in the transgenic mice. In contrast, T cells with memory phenotypes expand similarly in both the V beta.2(+) and V beta 8.2(-) subsets of nontransgenic mice. Based on these results, we hypothesize that TCR recognition of autoantigen is a major contributor to autoimmunity in lpr mice and that T cells expressing a memory phenotype are perpetrators of this process. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV PULM,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV PULM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. BOSTON UNIV,MED CTR,DEPT MICROBIOL,BOSTON,MA 02115. RP Perkins, DL (reprint author), BRIGHAM & WOMENS HOSP,LAB IMMUNOGENET & TRANSPLANTAT,BOSTON,MA 02115, USA. FU NIAID NIH HHS [R01 AI33100, R29 AI-31517]; NICHD NIH HHS [T32 HD 07268] NR 49 TC 25 Z9 26 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1996 VL 156 IS 12 BP 4961 EP 4968 PG 8 WC Immunology SC Immunology GA UP662 UT WOS:A1996UP66200058 PM 8648148 ER PT J AU Juang, JH BonnerWeir, S Ogawa, Y Vacanti, JP Weir, GC AF Juang, JH BonnerWeir, S Ogawa, Y Vacanti, JP Weir, GC TI Outcome of subcutaneous islet transplantation improved by polymer device SO TRANSPLANTATION LA English DT Article ID STREPTOZOTOCIN-DIABETIC RATS; STRUCTURES INVIVO; CELL MASS; GROWTH; LIVER; SITE; NORMOGLYCEMIA; MORPHOLOGY; MICE AB Syngeneic transplantation of rat islets into subcutaneous tissue failed to cure streptozocin diabetes, The reason is unknown, but poor vascularization may play a role, We hypothesize that if a well-vascularized subcutaneous site could be created, islet grafts would do well, Four hundred freshly isolated mouse islets were transplanted syngeneically under the renal capsule or into the intraperitoneal cavity and compared with 800 islets in subcutaneous tissue of streptozocin-diabetic mice, Four weeks after transplantation, 14 of 14 under the renal capsule, 4 of 8 in the intraperitoneal site, and 0 of 7 in the subcutaneous tissue site achieved normoglycemia, To create vascularized organoids, we transplanted 800 mouse islets into polyvinyl alcohol (PVA) or polyglycolic acid (PGA) polymers in subcutaneous tissue of streptozocin-diabetic mice either immediately (four in PVA and six in PGA) or 7 days (four in PVA and four in PGA) after implantation, Four weeks after transplantation, the mean blood glucose level and body weight had no change with PVA, However, the mean body weight increased significantly with PGA and 3/10 became normoglycemic. When transplanting 400 islets with PGA polymers intraperitoneally, all animals (n=5) remained hyperglycemic 3 months later. In contrast, four of five recipients transplanted with 800 islets with PGA polymers subcutaneously became normoglycemic, The grafts from successful animals contained numerous revascularized islets containing a substantial amount of insulin. These preliminary results indicate that subcutaneous islet transplantation using PGA polymers can improve the metabolic status and, in some cases, even cure diabetes in streptozocin-diabetic mice. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02215. CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. RI Juang, Jyuhn-Huarng /C-2465-2011 FU NIDDK NIH HHS [DK 35449, DK 36836] NR 28 TC 97 Z9 99 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 15 PY 1996 VL 61 IS 11 BP 1557 EP 1561 DI 10.1097/00007890-199606150-00001 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UR023 UT WOS:A1996UR02300001 PM 8669096 ER PT J AU Chandrasekar, B Melby, PC Troyer, DA Freeman, GL AF Chandrasekar, B Melby, PC Troyer, DA Freeman, GL TI Induction of proinflammatory cytokine expression in experimental acute chagasic cardiomyopathy SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TUMOR-NECROSIS-FACTOR; TRYPANOSOMA-CRUZI; DYSFUNCTION; INFECTION; ENDOTOXIN AB One of the hallmarks of Chagas' disease (caused by Trypanosoma cruzi) is progressive cardiomyopathy. The disease is associated with increased serum TNF-alpha levels, and TNF-alpha is known to depress cardiac function. It is, however, not known whether the cytokines are produced within the infected myocardium. One-month-old male Lewis rats were injected with cell culture-derived T. cruzi trypomastigotes and killed 15 days post-infection. As compared to normal animals, histologic analysis of infected animals revealed dense infection with amastigotes within myocytes and a minimal inflammatory infiltrate in the myocardium. Northern blot analysis of total RNA revealed no signal for IL-1 beta or TNF-alpha, and a weak signal for IL-6 in the control rat hearts, and high levels of expression for the three genes in the infected rats. Western blots revealed results similar to that of mRNA levels, suggesting that, in addition to mechanical damage, infection by T. cruzi induces proinflammatory cytokine production in the myocardium itself, which may further exacerbate the pathology, and affect adversely myocardial function. (C) 1996 Academic Press, Inc. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 19 TC 32 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 14 PY 1996 VL 223 IS 2 BP 365 EP 371 DI 10.1006/bbrc.1996.0900 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UR696 UT WOS:A1996UR69600029 PM 8670288 ER PT J AU Taylor, DS Laubach, JP Nathan, DG MatheyPrevot, B AF Taylor, DS Laubach, JP Nathan, DG MatheyPrevot, B TI Cooperation between core binding factor and adjacent promoter elements contributes to the tissue-specific expression of interleukin-3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; GENE-EXPRESSION; MAMMALIAN-CELLS; LYMPHOCYTES-T; ENHANCER; PROTEIN; FUSION; CHAIN; SITES; AML1 AB Tissue specific expression of interleukin-3 (IL-3) is mediated via cis-acting elements located within 315 base pairs of the transcription start. This is achieved in part through the positive activities of the AP-1 and Elf-1 sites in the IL-3 promoter. The contribution to T cell-specific expression by other promoter sites was assessed in a transient expression assay with IL-3 promoter constructs linked to a luciferase gene, focusing initially on the core binding factor (CBF) site, which is footprinted in vivo upon T cell activation, Activity of the CBF site is shown to be critically dependent on the adjacent activator site Act-1. Together the Act-1 and CBF sites form a functional unit (AC unit) with dual activity. The AC unit is demonstrated to enhance basal activity of promoters both in fibroblasts and T cells. This activity is further inducible in activated T cells, but not in fibroblasts, In addition to the already identified NIP repressor site, evidence is presented for a second repressor region that restricts promoter activity in fibroblasts, Finally, a novel positive regulatory element has been mapped in the IL-3 promoter between nucleotide -180 and -210 that leads to increased expression in T cells. Together these results demonstrate that T cell expression of IL-3 is not specified by the activity of a single tissue-specific element, but instead involves multiple interacting elements that provide both specific positive regulation in T cells and specific negative regulation in fibroblasts. C1 DANA FARBER CANC INST,DEPT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP Taylor, DS (reprint author), DANA FARBER CANC INST,DIV PEDIAT HEAMTOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [T32CA09172-20]; NIDDK NIH HHS [R01 DK41758] NR 36 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 14 PY 1996 VL 271 IS 24 BP 14020 EP 14027 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ660 UT WOS:A1996UQ66000016 PM 8662845 ER PT J AU Zhang, ZS Hocker, M Koh, TJ Wang, TC AF Zhang, ZS Hocker, M Koh, TJ Wang, TC TI The human histidine decarboxylase promoter is regulated by gastrin and phorbol 12-myristate 13-acetate through a downstream cis-acting element SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYRISTATE ACETATE; ENHANCER ELEMENT; GENE; HISTAMINE; IDENTIFICATION; CELLS; INDUCTION; RECEPTOR; MOUSE; FOS AB Transcriptional regulation of the human histidine decarboxylase (HDC) gene by gastrin and the phorbol ester phorbol 12-myristate 13 acetate (PMA) was studied using transient transfection of human HDC promoter-luciferase constructs in a human gastric carcinoma cell line (AGS-B) that expresses the human cholecystokinin-B/gastrin receptor, The transcriptional activity of the human HDC promoter was stimulated 3-4-fold by gastrin and 13-fold by PMA, effects that could be blocked by down-regulation or antagonism of protein kinase C. 5'- and 3'-deletion analysis demonstrated that the sequence responsible for gastrin- and PMA-stimulated transactivation (gastrin response element (GAS-RE)) was located in a region (+2 to +24) downstream of the transcriptional start site (+1) in the human HDC promoter and contained a palindrome (5'-CCCTTTAAATAAAGGG-3'). When ligated upstream of the herpes simplex virus 1 thymidine kinase promoter, a single copy of the GAS-RE was sufficient to confer responsiveness to gastrin and PMA, Electrophoretic mobility shift assays with specific competitors and factor-specific antibody supershifts showed that the labeled GAS-RE bound a novel nuclear factor(s). In addition, both gastrin and PMA increased binding of this factor to the GAS-RE, Hence, the palindromic GAS-RE site is sufficient to explain the gastrin/PMA responsiveness of the human HDC promoter and appears to bind a novel transcription factor. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. FU NIDDK NIH HHS [R01 DK 48077] NR 46 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 14 PY 1996 VL 271 IS 24 BP 14188 EP 14197 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ660 UT WOS:A1996UQ66000040 PM 8662934 ER PT J AU Tanaka, S Ito, T Wands, JR AF Tanaka, S Ito, T Wands, JR TI Neoplastic transformation induced by insulin receptor substrate-1 overexpression requires an interaction with both Grb2 and Syp signaling molecules SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3'-KINASE; NCK PROTEIN; SH2 DOMAIN; IRS-1; EXPRESSION; PHOSPHORYLATION; CELLS AB The insulin receptor substrate-1 (IRS-1) is the major intracellular substrate of insulin and insulin-like growth factor-I (IGF-I) receptor tyrosine kinase activity, and this protein has been found to be overexpressed in human hepatocellular carcinomas. IRS-1 contains several src homology 2 (SH2) binding motifs that interact following tyrosyl phosphorylation with SH2-containing proteins, and this interaction may be essential for transmitting the growth signal from the cell surface to the nucleus, We have previously reported that overexpression of IRS-1 may induce neoplastic transformation of NIH 3T3 cells. This study examines the role of two SH2-containing molecules, namely the Grb2 adapter and Syp tyrosine phosphatase proteins as important components of the cellular transforming activity of IRS-1. Mutations of tyrosine 897 in the YVNI motif (Y897F) and of tyrosine 1180 in the YIDL motif (Y1180F) reduced the intracellular interaction of IRS-1 with Grb2 and Syp proteins, respectively. Furthermore, a single mutation at either Phe-897 or Phe-1180 substantially but not completely reduced IGF-I-dependent transforming activity of IRS-1, whereas creation of a double mutation of both tyrosine residues (Y897F/Y1180F) strikingly attenuated the transforming activity of IRS-1. Stable expression of the IRS-1 mutant constructs in MH 3T3 cells was associated with a lower level of activation of the mitogen-activated protein kinase kinase (MAPKK)/MAPK cascade following IGF-I stimulation compared with cells stably transfected with the ''wild-type'' IRS-1 gene, These results suggest that IRS-1-induced cellular transformation requires an interaction with both Grb2 and Syp signal transduction molecules since neither interaction alone appears to be required, and this event subsequently leads to activation of the MAPKK/MAPK cascade. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-08169, AA-02666] NR 46 TC 79 Z9 80 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 14 PY 1996 VL 271 IS 24 BP 14610 EP 14616 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UQ660 UT WOS:A1996UQ66000099 PM 8662827 ER PT J AU Lerner, LH Bailey, EM Connolly, SA Threlkeld, SC AF Lerner, LH Bailey, EM Connolly, SA Threlkeld, SC TI A newborn boy with multiple hemorrhagic vesicles, lymphadenopathy, and respiratory distress - Langerhans'-cell histiocytosis, Letterer-Siwe subtype. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CONGENITAL CYTOMEGALOVIRUS-INFECTION; SCALDED-SKIN SYNDROME; CUTANEOUS MASTOCYTOSIS; PROGNOSTIC FACTORS; NEONATAL SEPSIS; DERMATOSIS; EXPERIENCE; DIAGNOSIS; LEUKEMIA; LESIONS C1 FALMOUTH HOSP,FALMOUTH,MA. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Lerner, LH (reprint author), MASSACHUSETTS GEN HOSP,DIV DERMATOPATHOL,BOSTON,MA 02114, USA. NR 53 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 13 PY 1996 VL 334 IS 24 BP 1591 EP 1597 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA UP663 UT WOS:A1996UP66300008 ER PT J AU Corbley, MJ Cherington, V Traxler, PM Lydon, NB Roberts, TM AF Corbley, MJ Cherington, V Traxler, PM Lydon, NB Roberts, TM TI A strategy for screening anti-tumor drugs utilizing oncogenes encoded in retroviral vectors SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID PROTEIN-KINASE-C; VIRUS PHOSPHORYLATES TYROSINE; FACTOR SIGNAL-TRANSDUCTION; OKADAIC ACID; TRANSFORMING GENES; MAMMALIAN-CELLS; LAVENDUSTIN-A; GROWTH; INHIBITION; ERBSTATIN AB A novel strategy for isolating potential anti-tumor drugs is presented. It is predicated on the idea that future anti-tumor drugs will be specific inhibitors of the signal-transduction pathways responsible for cell proliferation. Briefly, retroviral vectors are used to introduce focus-forming oncogenes into a test population of target cells, which ave grown to confluence and treated with signal-transduction inhibitors. The inhibitors are screened for the ability to suppress the development of transformed foci without killing the confluent monolayer of nontransformed quiescent cells. For this work, a panel of inhibitors was first screened against the oncogene res. The protein kinase C (PKC) inhibitor CGP 41251 and the protein tyrosine kinase (PTK) inhibitor CGP 45047 suppressed ras-induced focus formation and left a viable monolayer of quiescent cells. Focus inhibition was reversible; conversely, drug addition to developing foci retarded further expansion. CGP 41251 generally blocked proliferation of ras or control cells, suggesting that oncogenes cannot substitute for PKC. PTK inhibitors erbstatin and CGP 520 and phosphatase inhibitor okadaic acid failed to inhibit focus formation at concentrations toxic to the monolayer. Lavendustin A and CGP 47778A showed neither focus inhibition nor toxicity. In the complementary screen, a single inhibitor (CGP 41251) was tested against several oncogenes, including src, raf and polyomavirus middle T antigen. Focus formation by all oncogenes was suppressed. The strategy has several advantages over current drug-screening assays, and it can be adapted to large-scale screening with many drugs and many oncogenes. (C) 1996 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. CIBA GEIGY LTD,DIV PHARMACEUT,RES DEPT,BASEL,SWITZERLAND. RP Corbley, MJ (reprint author), DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 35 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 11 PY 1996 VL 66 IS 6 BP 753 EP 759 PG 7 WC Oncology SC Oncology GA UP063 UT WOS:A1996UP06300008 PM 8647645 ER PT J AU Yan, RQ Luo, H Darnell, JE Dearolf, CR AF Yan, RQ Luo, H Darnell, JE Dearolf, CR TI A JAK-STAT pathway regulates wing vein formation in Drosophila SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE stat mutation; pattern formation ID HEMATOPOIETIC ONCOGENE; MELANOGASTER; MUTATION; LETHAL; LOCUS; GENES AB We present evidence that the JAK-STAT signal transduction pathway regulates multiple developmental processes in Drosophila, We screened for second-site mutations that suppress the phenotype of the hyperactive hop(Tum-l) Jak kinase, and recovered a mutation that meiotically maps to the known chromosomal position of D-Stat, a Drosophila stat gene, This hypomorphic mutation, termed stat(HJ), contains a nucleotide substitution in the first D-Stat intron, resulting in a reduction in the number of correctly processed transcripts, Further, the abnormally processed mRNA encodes a truncated protein that has a dominant negative effect on transcriptional activation by the wild-type cDNA in cell culture, stat(HJ) mutants exhibit patterning defects that include the formation of ectopic wing veins, similar to those seen in mutants of the epidermal growth factor/receptor pathway, Abnormalities in embryonic and adult segmentation and in tracheal development were also observed, The hop(Tum-l) and stat(HJ) mutations can partially compensate for each other genetically, and flop overexpression can increase D-Stat transcriptional activity in vitro, indicating that the gene products interact in a common regulatory pathway. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEV GENET GRP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,CANC BIOL SECT,BOSTON,MA 02115. RP Yan, RQ (reprint author), ROCKEFELLER UNIV,MOLEC CELL BIOL LAB,NEW YORK,NY 10021, USA. FU NHLBI NIH HHS [HL48823]; NIAID NIH HHS [AI34420, AI32489] NR 27 TC 52 Z9 52 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 11 PY 1996 VL 93 IS 12 BP 5842 EP 5847 DI 10.1073/pnas.93.12.5842 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500032 PM 8650180 ER PT J AU Joung, I Strominger, JL Shin, J AF Joung, I Strominger, JL Shin, J TI Molecular cloning of a phosphotyrosine-independent ligand of the p56(lck) SH2 domain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE p62; Ser; Thr kinase; Ref(2)P; cdc24; PEST ID RNA AB A novel human cDNA encoding a cytosolic 62-kDa protein (p62) that binds to the Src homology 2 (SH2) domain of p56(lck) in a phosphotyrosine-independent manner has been cloned. The cDNA is composed of 2074 nucleotides with an open reading frame encoding 440 amino acids. Northern analysis suggests that p62 is expressed ubiquitously in ail tissues examined. p62 is not homolgous to any known protein in the data base. However, it contains a cysteine-rich region resembling a zinc finger motif, a potential G-protein-binding region, a PEST motif, and several potential phosphorylation sites, Using T7-epitope tagged p62 expression in HeLa cells, the expressed protein was shown to bind to the lck SH2 domain, Deletion of the N-terminal 50 amino acids abolished binding, but mutagenesis of the single tyrosine residue in this region had no effect on binding, Thus, the cloned cDNA indeed encodes the p62 protein, which is a phosphotyrosine-independent ligand for the lck SH2 domain, Its binding mechanism is unique with respect to binding modes of other known ligands for SH2 domains. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. FU NCI NIH HHS [CA47554]; NIGMS NIH HHS [GM48961] NR 24 TC 123 Z9 125 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 11 PY 1996 VL 93 IS 12 BP 5991 EP 5995 DI 10.1073/pnas.93.12.5991 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500059 PM 8650207 ER PT J AU Solomon, KR Rudd, CE Finberg, RW AF Solomon, KR Rudd, CE Finberg, RW TI The association between glycosylphosphatidylinositol-anchored proteins and heterotrimeric G protein alpha subunits in lymphocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL-TRANSDUCING MOLECULE; KIDNEY MICROVILLAR MEMBRANE; TYROSINE KINASES P56(LCK); DECAY-ACCELERATING FACTOR; T-CELL ACTIVATION; BINDING PROTEIN; ECTO-ENZYMES; RECEPTOR; ANTIBODIES; TRANSPORT AB Glycosylphosphatidylinositol (GPI)-anchored proteins are nonmembrane spanning cell surface proteins that have been demonstrated to be signal transduction molecules. Because these proteins do not extend into the cytoplasm, the mechanism by which cross-linking of these molecules leads to intracellular signal transduction events is obscure, Previous analysis has indicated that these proteins are associated with src family member tyrosine kinases; however, the role this interaction plays in the generation of intracellular signals is not clear. Here we show that GPI-anchored proteins are associated with alpha subunits of heterotrimeric GTP binding proteins (G proteins) in both human and murine lymphocytes, When the GPI-anchored proteins CD59, CD48, and Thy-1 were immunoprecipitated from various cell lines or freshly isolated lymphocytes, all were found to be associated with a 41-kDa phosphoprotein that we have identified, by using specific antisera, as a mixture of tyrosine phosphorylated G protein alpha subunits: a small amount of G(i alpha 1), and substantial amounts of G(i alpha 2) and G(i alpha 3) GTP binding assays performed with immunoprecipitations of CD59 indicated that there was GTP-binding activity associated with this molecule. Thus, we have shown by both immunochemical and functional criteria that GPI-anchored proteins are physically associated with G proteins. These experiments suggest a potential role of G proteins in the transduction of signals generated by GPI-anchored molecules expressed on lymphocytes of both mouse and human. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP Solomon, KR (reprint author), DANA FARBER CANC INST,INFECT DIS LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [2 R01-AI31628-04] NR 53 TC 96 Z9 97 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 11 PY 1996 VL 93 IS 12 BP 6053 EP 6058 DI 10.1073/pnas.93.12.6053 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UQ455 UT WOS:A1996UQ45500070 PM 8650218 ER PT J AU Hemler, ME Mannion, BA Berditchevski, F AF Hemler, ME Mannion, BA Berditchevski, F TI Association of TM4SF proteins with integrins: Relevance to cancer SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID MONOCLONAL-ANTIBODIES; ANTIGEN; CELLS; FAMILY; EXPRESSION; MOLECULE; ADHESION; TAPA-1; CD9 AB Recent biochemical evidence has revealed that proteins in the TM4SF (transmembrane 4 superfamily; tetraspan family) form complexes with certain members of the integrin family of adhesion receptors. This convergence of two protein families has considerable relevance for tumor cells, since both growth and metastasis are regulated by adhesion receptors in the integrin family, and are modulated by TM4SF proteins. The aim of this review is to examine integrin/TM4SF associations in the context of tumor cell behavior. RP Hemler, ME (reprint author), DANA FARBER CANC INST,RM M-613,44 BINNEY ST,BOSTON,MA 02115, USA. NR 58 TC 171 Z9 181 U1 0 U2 4 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 JUN 7 PY 1996 VL 1287 IS 2-3 BP 67 EP 71 DI 10.1016/0304-419X(96)00007-8 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA UU597 UT WOS:A1996UU59700001 PM 8672529 ER PT J AU Hutchcroft, JE Tsai, B Bierer, BE AF Hutchcroft, JE Tsai, B Bierer, BE TI Differential phosphorylation of the T lymphocyte costimulatory receptor CD28 - Activation-dependent changes and regulation by protein kinase C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL TRANSDUCTION; TYROSINE KINASE; RESPONSES; ANTIGEN; CELLS AB Treatment of T lymphocytes with phorbol ester and anti-CD28 monoclonal antibody (mAb) can induce proliferation and interleukin 2 production by triggering still undefined intracellular signaling pathways. We have developed a deglycosylation procedure that allows the precise identification of a distinct CD28 protein band, facilitating the analysis of activation-dependent changes in the phosphorylation state of CD28. Phorbol 12-myristate 13-acetate (PMA) treatment induced the in vitro phosphorylation of CD28 on threonine as detected in immune complex kinase assays. This effect of PMA was (i) rapid, preceding a PMA-induced increase in CD28 surface expression; (ii) occurred using kinase buffer containing either manganese or magnesium; and cells, and in a Jurkat subclone, J. Cam1, that is deficient in Lek tyrosine kinase activity. In contrast, anti-CD28 monoclonal antibody stimulation led to in vitro phosphorylation of CD28 on tyrosine that was manganese-dependent and required Lek tyrosine kinase activity, as it was undetectable in J. Cam1 cells. Importantly, CD28 was phosphotyrosine antibodies after stimulation with anti-CD28 monoclonal antibody. The in vivo tyrosine phosphorylation of Cd28 was inhibited by PMA treatment and was absent in J. Cam1 cells. Thus, the CD28 coreceptor can trigger different intracellular signaling pathways, depending upon the nature of the initial co-stimulatory signal. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI35297] NR 25 TC 17 Z9 17 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 7 PY 1996 VL 271 IS 23 BP 13362 EP 13370 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UP385 UT WOS:A1996UP38500012 PM 8662792 ER PT J AU Baba, TW Trichel, AM An, L Liska, V Martin, LN MurpheyCorb, M Ruprecht, RM AF Baba, TW Trichel, AM An, L Liska, V Martin, LN MurpheyCorb, M Ruprecht, RM TI Infection and AIDS in adult macaques after nontraumatic oral exposure to cell-free SIV SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HOMOSEXUAL BISEXUAL MEN; RHESUS-MONKEYS; HIV SEROCONVERSION; HTLV-III; ACID-SECRETION; DISEASE STAGE; RISK-FACTORS; HUMAN SALIVA; TRANSMISSION AB Unprotected receptive anal intercourse is a well-recognized risk factor for infection with human immunodeficiency virus-type 1 (HIV-1). Isolated human case reports have implicated HIV-1 transmission by oral-genital exposure. Adult macaques exposed nontraumatically to cell-free simian immunodeficiency virus (SIV) through the oral route became infected and developed acquired immunodeficiency syndrome (AIDS). The minimal virus dose needed to achieve systemic infection after oral exposure was 6000 times lower than the minimal dose required to achieve systemic infection after rectal exposure. Thus, unprotected receptive oral intercourse, even in the absence of mucosal lesions, should be added to the list of risk behaviors for HIV-1 transmission. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,LAB VIRAL PATHOGENESIS,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT PEDIAT,DIV NEWBORN MED,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. TULANE UNIV,TULANE REG PRIMATE RES CTR,COVINGTON,LA 70433. FU NIAID NIH HHS [R01-AI32330, R01-AI34266, U01-AI24345] NR 66 TC 129 Z9 130 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 7 PY 1996 VL 272 IS 5267 BP 1486 EP 1489 DI 10.1126/science.272.5267.1486 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UP899 UT WOS:A1996UP89900049 PM 8633242 ER PT J AU Soloway, S Weissgold, D AF Soloway, S Weissgold, D TI Hypopyon SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 6 PY 1996 VL 334 IS 23 BP 1512 EP 1512 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UN799 UT WOS:A1996UN79900005 PM 8618606 ER PT J AU Frenette, PS Wagner, DD AF Frenette, PS Wagner, DD TI Adhesion molecules .1. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CELL C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Frenette, Paul/J-8272-2012 NR 4 TC 257 Z9 270 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 6 PY 1996 VL 334 IS 23 BP 1526 EP 1529 DI 10.1056/NEJM199606063342308 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA UN799 UT WOS:A1996UN79900008 PM 8618609 ER PT J AU Trimble, L Perales, MA Knazek, R Lieberman, J AF Trimble, L Perales, MA Knazek, R Lieberman, J TI Serum enhances the ex vivo generation of HIV-specific cytotoxic T cells SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE HIV; cytotoxic T lymphocytes (CTL); serum ID HUMAN-IMMUNODEFICIENCY-VIRUS; TOXIC LYMPHOCYTES-T; IMMUNOTHERAPY; INFECTION; EXPANSION; GENE; AIDS; LUNG AB The ex vivo expansion of antigen-specific cytotoxic T lymphocyte (CTL) lines is being developed for immunotherapy of viral infections and cancer and is critically dependent on the precise cell expansion and stimulation conditions. In this article, we investigate medium requirements for the development of HIV-specific CTL in cell lines generated from the peripheral blood of seven asymptomatic HIV-infected individuals. We find that HIV specific CTL do not readily develop in the serum-free medium AIM V but do develop if the medium is supplemented with 1% plasma or serum. T cell lines with antigen-specific cytolytic activity express more cell-surface CD57 than do cell lines grown in the absence of serum or plasma. Three sources of serum (human autologous, human AB, or fetal calf) are comparable. Human plasma is somewhat less effective than serum from an identical source. (C) 1996 John Wiley & Sons, Inc. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. RI Lieberman, Judy/A-2717-2015 NR 24 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUN 5 PY 1996 VL 50 IS 5 BP 521 EP 528 DI 10.1002/(SICI)1097-0290(19960605)50:5<521::AID-BIT6>3.0.CO;2-H PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA UH438 UT WOS:A1996UH43800007 PM 18627014 ER PT J AU Fava, M Abraham, M Alpert, J Nierenberg, AA Pava, JA Rosenbaum, JF AF Fava, M Abraham, M Alpert, J Nierenberg, AA Pava, JA Rosenbaum, JF TI Gender differences in Axis I comorbidity among depressed outpatients SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 147th Annual Meeting of the American-Psychiatric-Association CY MAY 21-26, 1994 CL PHILADELPHIA, PA SP Amer Psychiat Assoc DE major depression; gender; age of onset; comorbidity ID MENTAL-DISORDERS; PREVALENCE; ANXIETY; SITES AB Objective: The aim of our study was to assess gender differences in Axis I comorbidity in patients with a primary diagnosis of Major Depressive Disorder (MDD), as well as gender differences in age of onset of MDD. Methods: The presence of MDD, including age of onset, and of comorbid Axis I disorders were assessed in 396 depressed outpatients. Results: Women were significantly more likely than men to meet criteria for comorbid bulimia nervosa and for simple phobia, while men were significantly more likely than women to meet criteria for lifetime history of alcohol abuse/dependence and other substance abuse/dependence. No other significant gender differences in those comorbid Axis I disorders examined were observed. In addition, the age of onset of the first episode of MDD was significantly lower in women than in men. Conclusions: Our findings are consistent with those of previous studies showing a greater prevalence of alcohol and substance abuse and dependence in men and of earing disorders in women. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,DEPRESS CLIN & RES PROGRAM,BOSTON,MA 02114. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [MH4-8483-03] NR 10 TC 40 Z9 41 U1 3 U2 3 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 JUN 5 PY 1996 VL 38 IS 2-3 BP 129 EP 133 DI 10.1016/0165-0327(96)00004-3 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UR699 UT WOS:A1996UR69900006 PM 8791181 ER PT J AU Amsterdam, JD Fava, M Maislin, G Rosenbaum, J HornigRohan, M AF Amsterdam, JD Fava, M Maislin, G Rosenbaum, J HornigRohan, M TI TRH stimulation test as a predictor of acute and long-term antidepressant response in major depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE TRH stimulation test; thyrotropin response; depression; fluoxetine ID THYROTROPIN-RELEASING-HORMONE; ENDOGENOUS-DEPRESSION; PSYCHIATRIC-PATIENTS; UNIPOLAR DEPRESSION; THYROID AXIS; DISORDERS; SUBTYPES; ILLNESS; DRUGS AB We assessed the prognostic utility of the TRH stimulation test by examining (a) the relationship between pre-treatment Delta TSH and acute response to fluoxetine treatment, and (b) the relationship between the change in Delta TSH (Delta Delta TSH value) after repeated TRH testing at 6 weeks of fluoxetine treatment and long-term outcome during maintenance fluoxetine or placebo therapy. 43 MDD patients were studied with sequential TRH tests at 6-week intervals. Fluoxetine 'responders' were defined as patients with a Hamilton Depression Rating Scale score less than or equal to 7 by week 9 of treatment and who remained in remission at least 3 additional weeks. These subjects were then randomized to one of four fluoxetine/placebo treatment groups and long-term outcome assessed, Overall, there was no difference in the mean pre-treatment Delta TSH values between acute fluoxetine responders and nonresponders. Moreover, we observed similar Delta Delta TSH values in patients who maintained long-term remission compared to those who relapsed during maintenance with either fluoxetine or placebo. In contrast to prior reports of an higher Delta Delta TSH value in long-term remitters, the present observation of similar mean Delta Delta TSH values patients with long-term remission compared to those who relapsed suggest a limited prognostic utility for the TRH stimulation test in MDD. C1 MASSACHUSETTS GEN HOSP,PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. RP Amsterdam, JD (reprint author), UNIV PENN,SCH MED,DEPRESS RES UNIT,UNIV SCI CTR,8TH FLOOR,3600 MARKET ST,PHILADELPHIA,PA 19104, USA. FU NCRR NIH HHS [5-MO1-RR0040] NR 34 TC 23 Z9 23 U1 0 U2 0 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 JUN 5 PY 1996 VL 38 IS 2-3 BP 165 EP 172 DI 10.1016/0165-0327(96)00010-9 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UR699 UT WOS:A1996UR69900010 PM 8791185 ER PT J AU Cayrol, C Flemington, EK AF Cayrol, C Flemington, EK TI The Epstein-Barr virus bZIP transcription factor Zta causes G(0)/G(1) cell cycle arrest through induction of cyclin-dependent kinase inhibitors SO EMBO JOURNAL LA English DT Article DE EBV; growth arrest; p53; pRB; Zta ID ORAL HAIRY LEUKOPLAKIA; HUMAN PAPILLOMAVIRUS TYPE-16; LYMPHOCYTE GROWTH TRANSFORMATION; DNA-BINDING SPECIFICITY; TUMOR-ANTIGEN; SV40-TRANSFORMED CELLS; DIMERIZATION DOMAIN; EPITHELIAL-CELLS; MAMMALIAN-CELLS; SUPPRESSOR GENE AB While oncoproteins encoded by small DNA tumor viruses and Epstein-Barr virus (EBV) latent antigens facilitate G(1)/S progression, the EBV lytic switch transactivator Zta was found to inhibit growth by causing cell cycle arrest in G(0)/G(1) in several epithelial tumor cell lines. Expression of Zta results in induction of the tumor suppressor protein, p53, and the cyclin-dependent kinase inhibitors, p21 and p27, as well as accumulation of hypophosphorylated pRb. Up-regulation of p53 and p27 occurs by post-transcriptional mechanisms while expression of p21 is induced at the RNA level in a p53-dependent manner. Inactivation of pRb by transient overexpression of the human papillomavirus E7 oncoprotein indicates that pRb or pRb-related proteins are key mediators of the growth-inhibitory function of Zta. These findings suggest that EBV plays an active role in redirecting epithelial cell physiology to facilitate the viral replicative program through a Zta-mediated growth arrest function. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. RI CAYROL, Corinne/C-2106-2011 FU NCI NIH HHS [CA47554]; NIGMS NIH HHS [R29GM48045] NR 84 TC 148 Z9 149 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 3 PY 1996 VL 15 IS 11 BP 2748 EP 2759 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UQ620 UT WOS:A1996UQ62000015 PM 8654372 ER PT J AU Thomas, H AF Thomas, H TI Another nail in the coffin SO ACADEMIC EMERGENCY MEDICINE LA English DT Editorial Material DE circadian rhythm; biorhythm; occupational exposure; occupational injury; clinical shift duration; graduate medical education ID NEEDLESTICK INJURIES C1 PORTLAND VET AFFAIRS MED CTR,EMERGENCY CARE UNIT,PORTLAND,OR. RP Thomas, H (reprint author), OREGON HLTH SCI UNIV,DEPT EMERGENCY MED,UHN-52,3181 SW SAM JACKSON PK RD,PORTLAND,OR 97201, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 1996 VL 3 IS 6 BP 566 EP 567 DI 10.1111/j.1553-2712.1996.tb03465.x PG 2 WC Emergency Medicine SC Emergency Medicine GA UL916 UT WOS:A1996UL91600003 PM 8727626 ER PT J AU Montalbano, JM Lee, FT Grist, TM Rappe, AH Weiss, JW Kelcz, F Gribenko, V AF Montalbano, JM Lee, FT Grist, TM Rappe, AH Weiss, JW Kelcz, F Gribenko, V TI Magnetic resonance imaging detection of extraluminal enterally administered gadopentetate dimeglumine in a rat model of intestinal ischemia SO ACADEMIC RADIOLOGY LA English DT Article DE intestinal ischemia; gadopentetate dimeglumine; magnetic resonance imaging ID MESENTERIC ISCHEMIA AB Rationale and Objectives. We assessed whether intestinal ischemia would result in transudation of orally administered gadopentetate dimeglumine into the peritoneal cavity. Methods. Twenty-eight rats were anesthetized and midline laparotomy was performed. Animals were divided into four groups: control, ligation of a single mesenteric arcade, ligation of six consecutive arcades, and ligation of the anterior mesenteric artery (analogous to the superior mesenteric artery in humans). A 1.0-ml enteric bolus of gadopentetate dimeglumine diluted with sterile water (1:1) was given via gavage. Magnetic resonance imaging was performed 2 hr after laparotomy and reviewed for the presence of intraperitoneal gadopentetate dimeglumine by two experienced observers. Animals were sacrificed 24 hr after surgery for pathologic examination. Results. Four animals died prior to sacrifice. The bladder had a grossly high signal in all cases, implying some degree of intravascular absorption of the contrast material. A correlation was found between increasing mean radiology scores and increasing numbers of ligated vessels. The intraperitoneal signal tended to be higher in experimental animals than in control animals. Histologic damage was more severe in experimental animals (ischemic changes extending deeper into the intestinal wall) than in control animals. Conclusion. Direct visualization of spilled gastrointestinal gadopentetate dimeglumine helped discriminate ischemic from control rats in this model. C1 UNIV WISCONSIN HOSP & CLIN,DEPT RADIOL,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT PATHOL,MADISON,WI. FU NHLBI NIH HHS [K08HL02848] NR 20 TC 4 Z9 4 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUN PY 1996 VL 3 IS 6 BP 486 EP 492 DI 10.1016/S1076-6332(96)80008-0 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UN262 UT WOS:A1996UN26200006 PM 8796706 ER PT J AU Angst, J Kupfer, DJ Rosenbaum, JF AF Angst, J Kupfer, DJ Rosenbaum, JF TI Recovery from depression: Risk or reality? SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Review DE depression; recurrence; treatment outcome; disability ID ADULT OUTPATIENTS; MEDICAL OUTCOMES; DISORDER AB Depression is a serious condition associated with a high rate of recurrence in all populations of depressed patients. Research studies in the past have focused more on the criteria for onset of depressive disorder than on consistent criteria for outcome. However, the issue of concern to the patient is whether their depression is a lifelong condition or a condition from which they can reasonably expect to make a complete recovery. The issues surrounding recovery from depression are reviewed in the following article. The lifetime prognosis of depression is examined with reference to the Zurich follow-up study, and outcome criteria and the importance of assessing recovery in terms of quality of life as well as symptomatic improvement are considered. The relevance of clinical trial results to the clinical management of depression is also addressed. C1 UNIV PITTSBURGH,SCH MED,WESTERN PSYCHIAT INST & CLIN,DEPT PSYCHIAT,PITTSBURGH,PA. MASSACHUSETTS GEN HOSP,OUTPATIENT PSYCHIAT DIV,BOSTON,MA 02114. RP Angst, J (reprint author), UNIV ZURICH,HOSP PSYCHIAT,POSTFACH 68,CH-8029 ZURICH 8,SWITZERLAND. NR 18 TC 57 Z9 57 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JUN PY 1996 VL 93 IS 6 BP 413 EP 419 DI 10.1111/j.1600-0447.1996.tb10671.x PG 7 WC Psychiatry SC Psychiatry GA UV944 UT WOS:A1996UV94400001 PM 8831856 ER PT J AU Ott, BR Lafleche, G Whelihan, WM Buongiorno, GW Albert, MS Fogel, BS AF Ott, BR Lafleche, G Whelihan, WM Buongiorno, GW Albert, MS Fogel, BS TI Impaired awareness of deficits in Alzheimer disease SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE dementia; Alzheimer disease; insight; anosognosia ID MEMORY COMPLAINTS; NEUROPSYCHOLOGICAL SYNDROMES; DEMENTIA; DEPRESSION; ANOSOGNOSIA; CLINICIAN AB This study examined the relation between awareness of memory and functional decline and cognitive function in patients with Alzheimer disease (AD). Twenty-six patients with early AD and 16 nondemented elderly controls were studied. Awareness of deficits was determined by using (a) a discrepancy score between subject's and caregiver's ratings on a memory questionnaire, (b) a discrepancy score between subject's and caregiver's ratings on an activities-of-daily-living scale, and (c) a clinical rating of dementia awareness for patients. Whereas self-ratings of memory and activities of daily living were not significantly different between AD patients and controls, these two measures differed significantly when AD patients' ratings were compared with those of their caregivers. Measures of awareness of deficits correlated with one another and were primarily associated with performance on tests of executive and visuospatial functions but not with depression. Early AD is characterized by a failure of self-monitoring. Deficits in self-monitoring have been proposed to occur after damage to the frontal lobes and other cerebral areas. Impaired awareness of memory and functional deficits in AD is related to cognitive impairments, which may involve frontal and right hemisphere connections. C1 BROWN UNIV, SCH MED, DEPT PSYCHIAT, PROVIDENCE, RI 02912 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PSYCHIAT, BOSTON, MA USA. BROWN UNIV, CTR GERONTOL & HLTH CARE RES, PROVIDENCE, RI 02912 USA. RP Ott, BR (reprint author), BROWN UNIV, SCH MED, ROGER WILLIAMS MED CTR, DIV NEUROL, 50 MAUDE ST, PROVIDENCE, RI 02908 USA. NR 42 TC 122 Z9 125 U1 2 U2 7 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD SUM PY 1996 VL 10 IS 2 BP 68 EP 76 DI 10.1097/00002093-199601020-00003 PG 9 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA UM365 UT WOS:A1996UM36500003 PM 8727167 ER PT J AU Atlas, SJ Singer, DE Keller, RB Patrick, DL Deyo, RA AF Atlas, SJ Singer, DE Keller, RB Patrick, DL Deyo, RA TI Application of outcomes research in occupational low back pain: The Maine Lumbar Spine Study SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE outcomes research; low back pain; sciatica; occupational medicine; cohort study; lumbar disc surgery; natural history; workers' compensation ID SURGERY; HEALTH; DISABILITY; INDUSTRY; COST AB Outcomes research represents an expansion of traditional clinical research to include issues of cost and quality of care in usual clinical practice, emphasizing outcomes that matter most to patients. In low back disorders, outcomes research has focused on the lack of reliable information to support much of clinical practice and has demonstrated marked variability in the treatment of these common problems. The Maine Lumbar Spine Study represents an example of an outcomes research study to investigate the treatment of patients with sciatica in usual clinical practice. Because low back symptoms are a frequent cause of occupational disability, Workers' Compensation patients were explicitly oversampled. Baseline features were significantly different in those patients who were receiving Workers' Compensation versus those who were not. Efforts to compare outcomes by disability status need to control for these differences. Whereas most Workers' Compensation patients were still receiving disability compensation regardless of treatment at 6 months, patients who were tr eared surgically were more likely to have come off disability and returned to work than nonsurgically treated patients. Long-term follow-up is necessary to determine whether these differences persist. (C) 1996 Wiley-Liss, Inc. C1 HARVARD UNIV,GEN INTERNAL MED UNIT,MASSACHUSETTS GEN HOSP,SCH MED,MED SERV,BOSTON,MA 02114. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. MAINE MED ASSESSMENT FDN,AUGUSTA,GA. RP Atlas, SJ (reprint author), HARVARD UNIV,MED PRACTICES EVALUAT CTR,MASSACHUSETTS GEN HOSP,SCH MED,50 STANFORD ST,BOSTON,MA 02114, USA. FU AHRQ HHS [HS-08194, HS-06344] NR 24 TC 24 Z9 24 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 1996 VL 29 IS 6 BP 584 EP 589 DI 10.1002/(SICI)1097-0274(199606)29:6<584::AID-AJIM2>3.0.CO;2-K PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UP176 UT WOS:A1996UP17600002 PM 8773718 ER PT J AU Gatmaitan, Z Varticovski, L Ling, L Mikkelsen, R Steffan, AM Arias, IM AF Gatmaitan, Z Varticovski, L Ling, L Mikkelsen, R Steffan, AM Arias, IM TI Studies on fenestral contraction in rat liver endothelial cells in culture SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LIGHT CHAIN PHOSPHORYLATION; SMOOTH-MUSCLE CELLS; INOSITOL PHOSPHATES; PROTEIN-KINASE; MYOSIN; RECEPTOR; STIMULATION; CYTOSKELETON; LOCALIZATION; MICROSCOPY AB Liver endothelial cells possess fenestrae, which are pores supported by a cytoskeleton ring composed of actin and myosin. Fenestrae are dynamic structures that can contract or dilate, although the mechanism for this phenomenon remains to be elucidated. Staining of actin and/or of myosin permitted measurement of fenestral diameter and area in cultured rat liver endothelial cells using digitized video-intensified fluorescence microscopy with image analysis, Within 1 minute of incubation with 0.1 mu mol/L serotonin, fenestral diameter and area decreased by 24 +/- 5% and 56 +/- 7%, respectively. Contraction of fenestrae by serotonin was inhibited by chelation of extracellular Ca2+ with EGTA and by addition of Ca2+ channel blockers, such as dilthiazem and verapamil. The response of fenestrae to serotonin was mimicked by addition of a Ca2+ ionophore, A23187. Serotonin inhibited cAMP production, had no effect on inositol phosphate production, and activated phospholipase A(2), causing release of arachidonic acid. These results suggest that contraction of fenestrae is associated with Ca2+ influx. In response to 0.1 mu mol/L serotonin, intracellular Ca2+ levels increased within 3 to 5 seconds from 150 nmol/L to > 400 nmol/L followed by rapid phosphorylation of the 20-kd subunit of myosin light chain; both events depended on extracellular Ca2+. C1 ST ELIZABETH HOSP,DEPT HEMATOL,BRIGHTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT RADIAT ONCOL,RICHMOND,VA 23298. UNIV STRASBOURG 1,VIROL LAB,STRASBOURG,FRANCE. RP Gatmaitan, Z (reprint author), TUFTS UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02111, USA. FU NIDDK NIH HHS [DK35652, P30 DK 34928] NR 47 TC 63 Z9 64 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1996 VL 148 IS 6 BP 2027 EP 2041 PG 15 WC Pathology SC Pathology GA UN468 UT WOS:A1996UN46800031 PM 8669487 ER PT J AU Hozawa, S Holtzman, EJ Ausiello, DA AF Hozawa, S Holtzman, EJ Ausiello, DA TI cAMP motifs regulating transcription in the aquaporin 2 gene SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE aquaporin 2 gene promoter; adenosine 3',5'-cyclic monophosphate; gene transcription ID NEPHROGENIC DIABETES-INSIPIDUS; LLC-PK1 RENAL-CELLS; WATER CHANNEL; CYCLIC-AMP; RAT-KIDNEY; CCAAT BOX; VASOPRESSIN; EXPRESSION; PROMOTER; ELEMENT AB Genomic clones including the 5' flanking regions of the AQP2 (aquaporin 2) gene were isolated, and the promoter region was examined by transiently transfecting a promoter-luciferase reporter fusion gene into renal cultured epithelial cells. An orientation specific promoter for the AQP2 gene was found within the proximal 3 kb of 5'-flanking region. Minimal basal promoter activity of the AQP2 gene was found within 198 bp upstream from the transcription start site by deletion analysis. Sequencing the transcriptionally active region revealed a typical TATA box, adenosine 3',5'-cyclic monophosphate (cAMP) responsive element (CRE) and three putative CCAAT boxes in the proximal 1.2-kb region. Significantly, a GATA motif, AP1, AP2, and SP1 transcriptional factor consensus sites were also found in this region. Exposure to cAMP-enhancing agents (1 nM vasopressin or 20 mM forskolin and 250 mM 3-isobutyl-1-methylxanthine) showed that these agents increased luciferase activity in a parallel fashion, suggesting that vasopressin-induced AQP2 gene transcription is mediated through increases in intracellular cAMP in at least one renal cell type, the LLC-PK1 cells. The mechanism of cAMP responsiveness of AQP2 gene transcription was further studied using a series of deletion mutants in renal epithelial cells and other cell types. The cAMP regulatory motifs were shown to exist in a 50-bp sequence between -340 and -290 (containing CRE) and a 65-bp sequence (containing an AP2 site) between -150 and the ATG start site in LLC-PK1 cells. In rat inner medullary collecting duct (IMCD) cells, the cAMP regulatory motifs also exist in a 50-bp sequence between -340 and -290 (containing CRE) and in a 10-bp sequence between -160 and -150 (containing an SP1 site). These separate regions may cooperate to confer full cAMP inducibility to the AQP2 gene in a cell-specific manner. C1 MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. NR 29 TC 124 Z9 126 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUN PY 1996 VL 270 IS 6 BP C1695 EP C1702 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UU611 UT WOS:A1996UU61100015 ER PT J AU Unno, N Menconi, MJ Salzman, AL Smith, M Hagen, S Ge, YM Ezzell, RM Fink, MP AF Unno, N Menconi, MJ Salzman, AL Smith, M Hagen, S Ge, YM Ezzell, RM Fink, MP TI Hyperpermeability and ATP depletion induced by chronic hypoxia or glycolytic inhibition in Caco-2BBe monolayers SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE barrier function; mitochondria; adenosine 5'-triphosphate; acidosis; F-actin ID CELL-LINE CACO-2; INTESTINAL PERMEABILITY; GUT PERMEABILITY; RAT HEPATOCYTES; TIGHT JUNCTIONS; INJURY; DEATH; PH; CYTOSKELETON; OXYGENATION AB Previous studies have documented that the barrier function of epithelial or endothelial monolayers is deranged when cellular ATP levels are rapidly decreased to very low levels by inhibitors of mitochondrial and glycolytic function. We hypothesized that lesser degrees of ATP depletion also might affect epithelial permeability, particularly if the perturbation were sustained for a prolonged interval. Using Caco-2BBe cells grown on permeable supports: mounted in bicameral chambers, we assessed permeability by measuring the apical-to-basolateral clearance (flux divided by apical compartment concentration) of fluorescein disulfonic acid. ATP was depleted by incubating cells in glucose-free (Glu-) medium containing 10 mM 2-deosyglucose (2-DOG) for 12, 24, or 48 h or under an anoxic atmosphere for 24, 48, or 72 h. Although both models of energy depletion were characterized by significant derangements in barrier function, metabolic inhibition with 2-DOG/Glu- resulted in greater increases in permeability and more profound decrements in cellular ATP content. Morphological studies using electron and confocal fluorescence microscopy showed structural changes in individual cells and derangements in the normal distribution of perijunctional actin after monolayers were incubated with 2-DOG/Glu- but not after incubation under an anoxic atmosphere. Addition of 10 mM lactic acid (final pH 6.7) provided significant protection against both hyperpermeability and ATP depletion induced by 2-DOG/Glu-. We conclude that moderate degrees of ATP depletion are sufficient to increase the permeability of Caco-2BBe monolayers and that lactic acidosis helps to preserve ATP content, barrier function, and morphological integrity in hypoxic intestinal epithelial cells. C1 BETH ISRAEL HOSP, DEPT SURG, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. MASSACHUSETTS GEN HOSP, SURG RES LAB, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, CHARLESTOWN, MA 02129 USA. NR 42 TC 73 Z9 76 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 1996 VL 270 IS 6 BP G1010 EP G1021 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA UU990 UT WOS:A1996UU99000017 ER PT J AU Stepniakowski, KT Sallee, FR Goodfriend, TL Zhang, Z Egan, BM AF Stepniakowski, KT Sallee, FR Goodfriend, TL Zhang, Z Egan, BM TI Fatty acids enhance neurovascular reflex responses by effects on alpha(1)-adrenoceptors SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE nonesterified fatty acids; alpha-adrenergic receptors; low-pressure receptors ID ADRENERGIC RECEPTOR SUBTYPES; CARDIOPULMONARY MECHANORECEPTORS; BLOOD; CAPACITANCE; STIMULATION; IMPEDANCE; MECHANISM; RELEASE; ALPHA-2; INVIVO AB Abnormalities in plasma nonesterified fatty acids (NEFAs) may contribute to increased vascular alpha-adrenergic tone in obese hypertensive patients, because raising NEFAs locally enhances vascular reactivity to exogenously infused phenylephrine. However, responses to exogenous phenylephrine, a relatively selective alpha(1)-adrenoceptor agonist, may not reflect the physiologically more important response to endogenous norepinephrine, a nonselective alpha-adrenoceptor agonist. To study the effects of NEFAs on vascular responses to endogenously released norepinephrine, dorsal hand venoconstrictor responses to thigh cuff inflation were quantified in nine healthy volunteers during coinfusion of Intralipid with heparin to raise fatty acids locally. Intralipid-heparin, which approximately doubled local linoleic and oleic acid concentrations (P < 0.05), increased the magnitude and duration of the venoconstrictor response to thigh cuff inflation (P < 0.005) and also enhanced venoconstrictor responses to locally infused phenylephrine but not clonidine, a relatively selective partial alpha(2)-adrenoceptor agonist. The results of this study indicate that NEFAs enhance reflex vasoconstrictor responses largely through local effects on the vascular alpha(1)-adrenoceptor and raise the possibility that fatty acids contribute to increased neurovascular tone in obese hypertensive patients. C1 MED UNIV S CAROLINA, DIV CLIN PHARMACOL, DEPT PHARMACOL, CHARLESTON, SC 29425 USA. MED UNIV S CAROLINA, DEPT MED, CHARLESTON, SC 29425 USA. MED UNIV S CAROLINA, DEPT BIOMETRY & EPIDEMIOL, CHARLESTON, SC 29425 USA. UNIV WISCONSIN, WILLIAM S MIDDLETON MEM VET HOSP, DEPT MED, MADISON, WI 53705 USA. UNIV WISCONSIN, WILLIAM S MIDDLETON MEM VET HOSP, DEPT PHARMACOL, MADISON, WI 53705 USA. NR 36 TC 26 Z9 26 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JUN PY 1996 VL 270 IS 6 BP R1340 EP R1346 PG 7 WC Physiology SC Physiology GA UU589 UT WOS:A1996UU58900023 ER PT J AU Fitzgibbon, WR Webster, SK Imamura, A Ploth, DW Hutchison, FN AF Fitzgibbon, WR Webster, SK Imamura, A Ploth, DW Hutchison, FN TI Effect of dietary protein and enalapril on proximal tubular delivery and absorption of albumin in nephrotic rats SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE enalapril; passive Heymann nephritis; proximal tubule; protein absorption; tubular fluid ID CONVERTING ENZYME-INHIBITION; GLOMERULAR-FILTRATION; MICROPUNCTURE; ANGIOTENSIN; CHARGE; REABSORPTION; NEPHRITIS; RABBIT; KIDNEY AB In passive Heymann nephritis (PHN), angiotensin-converting enzyme inhibition (ACEI) or a low dietary protein intake decreases albuminuria (UA1bV). Although this reduction in albuminuria appears to result from an improvement in glomerular permselectivity, the effect of these treat; ments on albumin permeation and absorption by the nephron has not been clarified. This study used micropuncture techniques to examine the effect of these two treatments on albumin permeation (by measuring the delivery of albumin to the proximal tubule) and the tubular absorption of albumin. PHN rats (12-18 days after injection of FX1A) were switched from 23% to either 40% protein diet (HP), 40% protein diet and concomitantly treated with enalapril (40 mg . kg(-1). day(-1)) (HPE), or to 8% (LP) protein diet for 4-6 days. Although left kidney glomerular filtration rate (GFR) did not differ among the groups, UA1bV from the left kidney in LP and HPE was only 20-40% of that observed for the HP group. In protocol 1, the fractional recovery of albumin (FR(A1b)) in urine was calculated following injection of artificial tubular fluid containing [C-14]inulin and I-125-labeled albumin into the earliest identifiable proximal loops. There were no differences in FR(A1b) among the three groups. In protocol 2, timed quantitative collections of tubular fluid were obtained from proximal tubular loops. The rate of albumin delivery to the earliest accessible loops of the proximal tubule was significantly lower for the LP and HPE groups compared with the HP group. For each group, albumin concentration corrected for water absorption was not altered along the proximal tubule. The data indicate that alterations of dietary protein intake or ACEI treatment results in large changes in the delivery of albumin at the proximal tubule that could singularly account for the changes in urinary albumin excretion. C1 RALPH H JOHNSON VET AFFAIRS MED CTR, CHARLESTON, SC 29403 USA. RP Fitzgibbon, WR (reprint author), MED UNIV S CAROLINA, DEPT MED, DIV NEPHROL, 171 ASHLEY AVE, CHARLESTON, SC 29425 USA. NR 23 TC 1 Z9 2 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD JUN PY 1996 VL 270 IS 6 BP F986 EP F996 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA UT492 UT WOS:A1996UT49200009 PM 8764318 ER PT J AU Bowden, CL Janicak, PG Orsulak, P Swann, AC Davis, JM Calabrese, JR Goodnick, P Small, JG Rush, AJ Kimmel, SF Risch, SC Morris, DD AF Bowden, CL Janicak, PG Orsulak, P Swann, AC Davis, JM Calabrese, JR Goodnick, P Small, JG Rush, AJ Kimmel, SF Risch, SC Morris, DD TI Relation of serum valproate concentration to response in mania SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-16, 1994 CL SAN JUAN, PR SP Amer Coll Neuropsychopharmacol ID SODIUM VALPROATE; PREDICTION; EPILEPSY; ACID AB Objective: This study was designed to determine the relation of valproate serum levels to clinical improvement and development of adverse effects in hospitalized patients with acute mania. The initial fixed-dose escalation design, the monotherapy with divalproex, and the control of variables that is possible only with hospitalized patients reduced the confounding factors present in most outpatient studies of serum level-response relationships. Method: Sixty-five hospitalized patients who met the Research Diagnostic Criteria for bipolar disorder with mania were treated with divalproex, 750 mg/day for 2 days and then 1,000 mg/day on days 3-5; the dosage was subsequently adjusted as clinically indicated for the remainder of the 21-day study. Manic symptoms were assessed with the Mania Rating Scale, which is derived from the Schedule for Affective Disorders and Schizophrenia. Results: At day 5, patients with serum valproate levels greater than or equal to 45 mu g/ml were two to seven times as likely as patients with levels <45 mu g/ml to show 20% or greater improvement in scores on the manic syndrome subscale, the behavior and ideation subscale, elevated mood, increased activity, motor hyperactivity, and psychosis. Endpoint analyses yielded similar results. Adverse experiences characteristic of divalproex treatment were disproportionately associated with serum levels greater than or equal to 225 mu g/ml. Conclusions: Acutely manic patients treated with divalproex who have valproate serum levels between 45 and 100-125 mu g/ml are much more likely to have efficacious and well-tolerated responses than patients with lower ol higher levels of valproate. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV ILLINOIS,DEPT PSYCHIAT,CHICAGO,IL 60612. UNIV TEXAS,SW MED CTR,DEPT PSYCHIAT,DALLAS,TX. VET AFFAIRS MED CTR,DALLAS,TX. CASE WESTERN RESERVE UNIV,SCH MED,DEPT PSYCHIAT,CLEVELAND,OH 44106. UNIV TEXAS,SCH MED,DEPT PSYCHIAT,HOUSTON,TX. UNIV MIAMI,DEPT PSYCHIAT,CORAL GABLES,FL 33124. MED UNIV S CAROLINA,INST PSYCHIAT,CHARLESTON,SC 29425. ABBOTT LABS,CLIN RES SECT,N CHICAGO,IL 60064. RP Bowden, CL (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,DIV BIO PSYCHIAT,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. OI Rush, Augustus/0000-0003-2004-2382 NR 17 TC 127 Z9 129 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1996 VL 153 IS 6 BP 765 EP 770 PG 6 WC Psychiatry SC Psychiatry GA UN632 UT WOS:A1996UN63200005 PM 8633687 ER PT J AU Centorrino, F Baldessarini, RJ Frankenburg, FR Kando, J Volpicelli, SA Flood, JG AF Centorrino, F Baldessarini, RJ Frankenburg, FR Kando, J Volpicelli, SA Flood, JG TI Serum levels of clozapine and norclozapine in patients treated with selective serotonin reuptake inhibitors SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: The selective serotonin reuptake inhibitor (SSRI) fluoxetine can increase serum levels of clozapine and norclozapine, but effects of other SSRIs are unknown. Thus, the authors evaluated interactions of clozapine with fluoxetine, paroxetine, and sertraline. Method: Serum clozapine and norclozapine concentrations were assayed in 80 psychiatric patients, matched for age and clozapine dose, given clozapine (mean dose=279 mg/day) alone or with fluoxetine (mean dose=39.3 mg/day), paroxetine (mean=31.2 mg/day), or sertraline (mean=92.5 mg/day). Each patient's dose of clozapine was stable for at least a month before serum sampling. Results: Concentrations of clozapine plus norclozapine averaged 43% higher; and the risk of levels higher than 1000 ng/ml was 10-fold greater (25%), in the patients taking SSRIs, with minor differences between patients taking the individual SSRIs. Conclusions: SSRIs can increase circulating concentrations of clozapine and norclozapine, sometimes to potentially toxic levels. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CLIN CHEM LAB,BOSTON,MA 02114. RP Centorrino, F (reprint author), MCLEAN HOSP,MAILMAN RES CTR,PSYCHIAT RES LABS,115 MILL ST,BELMONT,MA 02178, USA. FU NIMH NIH HHS [MH-31154, MH-47370] NR 10 TC 129 Z9 132 U1 1 U2 4 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1996 VL 153 IS 6 BP 820 EP 822 PG 3 WC Psychiatry SC Psychiatry GA UN632 UT WOS:A1996UN63200016 PM 8633698 ER PT J AU Bostic, JQ Shadid, LG Blotcky, MJ AF Bostic, JQ Shadid, LG Blotcky, MJ TI Our time is up: Forced terminations during psychotherapy training SO AMERICAN JOURNAL OF PSYCHOTHERAPY LA English DT Article AB Psychiatry residents often must terminate psychotherapy before patients complete their treatment goals, introducing a stressful event into the therapist-patient relationship. Determining what, how, and when to announce the impending termination, anticipating patient responses, managing resident reactions and countertransference, and planning the forced termination to the patient's benefit require careful consideration. The literature on forced terminations is reviewed, two cases illustrate common issues encountered, and nine guidelines are described. C1 UNIV TEXAS,SW MED SCH,DALLAS,TX 75230. DALLAS PSYCHOANALYT INST,DALLAS,TX. RP Bostic, JQ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,15 PARKMAN ST,WAC725,BOSTON,MA 02114, USA. NR 26 TC 12 Z9 12 U1 1 U2 3 PU ASSN ADVAN PSYCHOTHERAPY PI BRONX PA BELFER EDUC CENTER, ROOM 402 ALBERT EINSTEIN COLL MED 1300 MORRIS PARK AVE, BRONX, NY 10461-1602 SN 0002-9564 J9 AM J PSYCHOTHER JI Am. J. Psychother. PD SUM PY 1996 VL 50 IS 3 BP 347 EP 359 PG 13 WC Psychology, Clinical; Psychiatry; Psychology; Psychology, Psychoanalysis SC Psychology; Psychiatry GA VJ659 UT WOS:A1996VJ65900009 PM 8886234 ER PT J AU Horinouchi, H Wang, CC Shepherd, KE Jones, R AF Horinouchi, H Wang, CC Shepherd, KE Jones, R TI TNF alpha gene and protein expression in alveolar macrophages in acute and chronic hyperoxia-induced lung injury SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; POLYPEPTIDE GROWTH-FACTORS; PULMONARY-HYPERTENSION; OXYGEN-TOXICITY; MESSENGER-RNA; POLYMORPHONUCLEAR LEUKOCYTES; ENDOTHELIAL-CELLS; RAT; INTERLEUKIN-1; MICROVESSELS AB Alveolar-capillary membrane remodeling, including microvessel wall thickening and interstitial fibrosis, is a well-known sequela of cell proliferation in the hyperoxia-injured lung. The array of growth molecules released locally that potentially mediate this response, and their cell(s) of origin, are currently being defined. To elucidate the role of tumor necrosis factor alpha (TNF alpha), an effector molecule of cell injury and proliferation, and the role of the alveolar macrophage (AM) as its source during the acute (1 to 24 h) and chronic stages (3 to 28 days) of hyperoxia-induced injury, we have analyzed gene and protein expression in cells recovered from rat lung by bronchoalveolar lavage, In the hyperoxic lung, cell number was similar to that in normal lung (1 x 10(6)) except on day 7, when it was higher (5 x 10(6)). Virtually all cells recovered from the normal and hyperoxic lung were AMs, with the exception that on days 3 and 7 of hyperoxia these cells represented 69% and 55% of the population, respectively, and polymerphonuclear leukocytes and lymphocytes the remainder, Probe specificity was confirmed by detection of TNF alpha RNA (1.6 kb) from lung cells recovered after lipopolysaccharide (LPS) treatment (positive control) and from the hyperoxic lung (at day 3), with an extremely low level of constitutive expression detected in cells from normal lung. In cytospin preparations, TNF alpha mRNA transcripts were detected in few AMs recovered from normal lung and in most AMs after LPS treatment. In the hyperoxic lung, a signal was detected at 3 h, when similar to 25% of the population was positive. The number of hybridizing cells then increased, being highest on day 7 (day 1 similar to 30%, day 3 similar to 58%, day 7 similar to 90%, day 28 similar to 65%). No expression of TNF alpha protein was detected in AMs from normal lung; positive cells were detected in the hyperoxic lung from day 1 and thereafter. We conclude from upregulation of the TNF alpha gene in a significant number of cells, and from the increase in the number expressing biologically active protein, that AMs are an important source of this molecule both in the acute and chronic stages of hyperoxic lung injury. It is anticipated that an increased understanding of the cellular sources of mediators effecting vascular and alveolar wall remodeling in vivo will contribute to the development of strategies to inhibit the response. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,MOL & CELL BIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU PHS HHS [R0I 34552] NR 51 TC 32 Z9 37 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN PY 1996 VL 14 IS 6 BP 548 EP 555 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA UR399 UT WOS:A1996UR39900006 PM 8652183 ER PT J AU Papanicolaou, N Eisenberg, PJ Silverman, SG McNicholas, MMJ Althausen, AF AF Papanicolaou, N Eisenberg, PJ Silverman, SG McNicholas, MMJ Althausen, AF TI Prostatic biopsy after proctocolectomy: A transgluteal, CT-guided approach SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,UROL SERV,BOSTON,MA 02114. RP Papanicolaou, N (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 6 TC 14 Z9 15 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 1996 VL 166 IS 6 BP 1332 EP 1334 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UM261 UT WOS:A1996UM26100022 PM 8633443 ER PT J AU Bramson, RT Cleveland, R Blickman, JG Kinane, TB AF Bramson, RT Cleveland, R Blickman, JG Kinane, TB TI Radiographic appearance of follicular bronchitis in children SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB OBJECTIVE. The purpose of this study was to present the first radiographic description of a newly described disease in children, follicular bronchitis. MATERIALS AND METHODS. We retrospectively reviewed the medical history and radiographs of eight children with biopsy evidence of follicular bronchitis. RESULTS. All eight infants had findings on initial radiographs that were consistent with viral inflammatory disease. The clinical features of follicular bronchitis started by 6-8 weeks old and peaked between about 2 and 3 years old. After several months of the disease, the infants' radiographs showed a more obvious interstitial pattern. When these children were approximately 3 years old, the radiographic findings began to return to normal. Four children have been followed up for at least 8 years. By that age, the clinical symptoms of respiratory disease have disappeared. All four children tested after they were 8 years old had abnormal results of pulmonary function tests. CONCLUSION. The combination of unique clinical features associated with the radiographic appearances we describe should allow radiologists to suggest the diagnosis of follicular bronchitis. C1 CHILDRENS HOSP,DEPT RADIOL,BOSTON,MA 02115. BOSTON CITY HOSP,DEPT RADIOL,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,PEDIAT PULM DIV,BOSTON,MA 02114. RP Bramson, RT (reprint author), MASSACHUSETTS GEN HOSP,DIV PEDIAT IMAGING,WHITE 2,BOSTON,MA 02114, USA. NR 4 TC 11 Z9 12 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 1996 VL 166 IS 6 BP 1447 EP 1450 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UM261 UT WOS:A1996UM26100041 PM 8633461 ER PT J AU Qureshi, AA Asahina, A Ohnuma, M Tajima, M Granstein, RD Lerner, EA AF Qureshi, AA Asahina, A Ohnuma, M Tajima, M Granstein, RD Lerner, EA TI Immunomodulatory properties of maxadilan, the vasodilator peptide from sand fly salivary gland extracts SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID GENE-RELATED PEPTIDE; LUTZOMYIA-LONGIPALPIS; IN-VITRO; CELLS; PROLIFERATION; LEISHMANIASIS; TRANSMISSION; INHIBITION; INFECTION AB Sand flies are the arthropod vector of leishmaniasis and salivary gland extracts from these flies exacerbate leishmaniasis in vivo. The mechanism of exacerbation appears to be due to immunomodulatory effects of the saliva on host immune function but the active component is unknown. The following studies reveal that maxadilan, the vasodilatory peptide present in sand fly salivary gland extracts, has immunomodulatory properties. To examine the effect of maxadilan on T cell proliferation, the peptide was added to murine spleen cells stimulated with either concanavalin A or plate-bound anti-T cell receptor antibody. Inhibition of proliferation was noted in a dose-dependent manner for both sets of experiments (P < 0.05). To examine the effect of maxadilan on alloantigen presentation, the peptide was added to mixed lymphocyte and mixed epidermal cell lymphocyte reactions. Inhibition of proliferation was found in these culture systems. Maxadilan also inhibited the delayed-type hypersensitivity reaction in mice (P < 0.05). These observations suggest a role for maxadilan in the pathogenesis of leishmaniasis since the peptide may inhibit the immune response at the site of parasite inoculation, allowing the infection to proceed. C1 SHISEIDO RES CTR,LIFE SCI RES LABS,KANAZAWA KU,YOKOHAMA,KANAGAWA,JAPAN. RP Qureshi, AA (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,BLDG 149,CHARLESTOWN,MA 02139, USA. FU NIAMS NIH HHS [R01-AR42005] NR 21 TC 61 Z9 62 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 1996 VL 54 IS 6 BP 665 EP 671 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA UX379 UT WOS:A1996UX37900022 PM 8686790 ER PT J AU Tuner, K Wexler, HM Reeves, D Finegold, SM AF Tuner, K Wexler, HM Reeves, D Finegold, SM TI Penicillin-binding proteins in Fusobacterium species SO ANAEROBE LA English DT Article DE penicillin-binding proteins; Fusobacterium; anaerobic bacteria; antimicrobials ID BETA-LACTAM ANTIBIOTICS; CEFOXITIN RESISTANCE; SUSCEPTIBILITY; MECHANISM; BACTERIA; FRAGILIS AB PBPs were identified in four species of Fusobacterium. Each species had a distinctive PBP pattern, although some intra-species variation was noted. Most species had five or six PBPs, ranging in molecular weight from similar to 100 kDa to similar to 40 kDa. The two strains of F. nucleatum tested had characteristic ''wavy'' PBP patterns. F. mortiferum was distinctive in possessing a very major band or complex at the PBP-2 position, whereas F. varium and F. necrophorum had only minor or average bands. The antibiotics tested had varying affinities for the different PBPs and distinctive morphological changes were seen upon exposure of the organisms to certain beta-lactam agents. Cefotaxime, which caused elongation in strains of two species, had greater affinity for PBPs 1 and 4 than for the other PBPs in those strains. Aztreonam, which caused elongation in F. varium, also had affinity for PBP-4 in that strain. (C) 1996 Academic Press C1 HUDDINGE UNIV HOSP,KAROLINSKA INST,DEPT MICROBIOL,S-14186 HUDDINGE,SWEDEN. HUDDINGE UNIV HOSP,KAROLINSKA INST,DEPT PATHOL,S-14186 HUDDINGE,SWEDEN. HUDDINGE UNIV HOSP,KAROLINSKA INST,DEPT INFECT DIS,S-14186 HUDDINGE,SWEDEN. W LOS ANGELES VET AFFAIRS MED CTR,WADSWORTH DIV,MED SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,WADSWORTH DIV,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. MED PROD AGCY,S-75103 UPPSALA,SWEDEN. RP Tuner, K (reprint author), HUDDINGE UNIV HOSP,KAROLINSKA INST,DEPT IMMUNOL,S-14186 HUDDINGE,SWEDEN. NR 16 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1075-9964 J9 ANAEROBE JI Anaerobe PD JUN PY 1996 VL 2 IS 3 BP 155 EP 162 PG 8 WC Microbiology SC Microbiology GA UW535 UT WOS:A1996UW53500005 ER PT J AU Fihn, SD Callahan, CM Martin, DC McDonell, MB Henikoff, JG White, RH AF Fihn, SD Callahan, CM Martin, DC McDonell, MB Henikoff, JG White, RH TI The risk for and severity of bleeding complications in elderly patients treated with warfarin SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE warfarin; hemorrhage; age factors; prothrombin time; atrial fibrillation ID ORAL ANTICOAGULANT-THERAPY; ATRIAL-FIBRILLATION; THROMBOEMBOLIC COMPLICATIONS; FOLLOW-UP; OUTPATIENTS; PREVENTION; STROKE; HEMORRHAGE AB Objective: To determine whether increasing age is associated with an increased risk for bleeding during warfarin treatment. Design: Combined retrospective and prospective cohort studies. Setting: 6 anticoagulation clinics. Patients: 2376 patients receiving warfarin for various indications. Measurements: Bleeding events categorized as minor (resulting in no costs or consequences), serious (requiring testing or treatment), life-threatening, or fatal. Results: 812 first bleeding events (4 fatal, 33 life-threatening, 222 serious, and 553 minor) occurred during 3702 patient-years. Age was inversely related to the mean warfarin dose and dose-adjusted prothrombin time ratio. The unadjusted incidence of minor bleeding complications did not vary according to age group: 18.0 per 100 patient-years for patients younger than 50 years of age, 21.5 for patients 50 to 59 years of age, 24.0 for patients 60 to 69 years of age; 23.5 for patients 70 to 79 years of age, and 16.3 for patients 80 years of age and older. The unadjusted incidence of serious bleeding complications also did not vary according to age group: 9.3 per 100 patient-years for patients younger than 50 years of age, 7.1 for patients 50 to 59 years of age, 6.6 for patients 60 to 69 years of age, 5.1 for patients 70 to 79 years of age, and 4.4 for patients 80 years of age and older. The unadjusted incidence of life-threatening or fatal complications combined was significantly higher among the oldest patients: 0.75 per 100 patient-years for patients younger than 50 years of age, 0.97 for patients 50 to 59 years of age, 1.10 for patients 60 to 69 years of age, 0.68 for patients 70 to 79 years of age, and 3.38 for patients 80 years of age and older. Patients 80 years of age and older had a relative risk of 4.5 (95% CI, 1.3 to 15.6) compared with patients younger than 50 years of age. After adjustment for the intensity of anticoagulation therapy and the deviation in the prothrombin time ratio using Cox and Poisson regression, age was not generally associated with the occurrence of bleeding; relative risk estimates ranged from 0.99 to 1.03 per year of age (lower-bound 95% CI, 0.97 to 1.01; upper-bound 95% CI, 1.00 to 1.09). The single exception was life-threatening and fatal complications in patients 80 years of age or older (relative risk, 4.6 [CI, 1.2 to 18.1]). Conclusions: Age did not appear to be an important determinant of risk for bleeding in patients receiving warfarin, with the possible exception of age 80 years or older. The intensity of anticoagulation therapy and the deviation in the prothrombin time ratio were much stronger predictors of risk for bleeding. C1 PRIMARY CARE CTR,DIV GEN INTERNAL MED,SACRAMENTO,CA 95817. RP Fihn, SD (reprint author), VET AFFAIRS PUGET SOUND HEALTHCARE SYST,NW VET AFFAIRS HLTH SERV RES & DEV FIELD PROGRAM,SEATTLE,WA 98108, USA. NR 49 TC 412 Z9 430 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 1 PY 1996 VL 124 IS 11 BP 970 EP & PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA UL905 UT WOS:A1996UL90500004 PM 8624064 ER PT J AU Griffin, JW Griggs, RC Barchi, R Schneck, SA Moses, H Pedley, T Collins, RC Foley, KM Rowland, LP Ringel, S Konkol, RJ Booss, J Viste, K Pleasure, D Cascino, TL Caplan, L Wooten, F McDonald, R Choi, D McArthur, JC Waxman, S Young, A Parry, G Whitaker, J Percy, A Hanley, D AF Griffin, JW Griggs, RC Barchi, R Schneck, SA Moses, H Pedley, T Collins, RC Foley, KM Rowland, LP Ringel, S Konkol, RJ Booss, J Viste, K Pleasure, D Cascino, TL Caplan, L Wooten, F McDonald, R Choi, D McArthur, JC Waxman, S Young, A Parry, G Whitaker, J Percy, A Hanley, D TI Opportunities and challenges in academic neurology: Report of the long range planning committee of the American Neurological Association SO ANNALS OF NEUROLOGY LA English DT Article AB By most measures, academic neurology is thriving as never before, yet convening forces are changing the face of academic neurology. This report focuses on changes that academic neurology and the American Neurological Association could undertake to seize new opportunities and resist damaging potential changes, These proposals can be categorized in the following four major goals: (1) enhance the quality of a smaller neurology workforce and augment the recruitment of gifted young neuroscientists into neurology; (2) foster new diversity in neurological investigation, including clinical research in neurology; (3) document the benefits and relative costs of neurological care, in general, and of academic neurology, in particular; and (4) foster the role of neurologists as teachers to medical caregivers at all levels, including medical students, nonneurological house staff, and primary practitioners. C1 JOHNS HOPKINS UNIV, BALTIMORE, MD 21218 USA. COLUMBIA UNIV, NEW YORK, NY 10027 USA. UNIV ROCHESTER, ROCHESTER, NY 14627 USA. UNIV CALIF LOS ANGELES, LOS ANGELES, CA 90024 USA. CORNELL UNIV, ITHACA, NY 14853 USA. UNIV COLORADO, BOULDER, CO 80309 USA. AMER ACAD NEUROL, MINNEAPOLIS, MN 55414 USA. UNIV PENN, PHILADELPHIA, PA 19104 USA. MAYO CLIN, ROCHESTER, MN 55905 USA. UNIV VIRGINIA, CHARLOTTESVILLE, VA 22903 USA. TUFTS UNIV, MEDFORD, MA 02155 USA. UNIV MICHIGAN, ANN ARBOR, MI 48109 USA. WASHINGTON UNIV, ST LOUIS, MO 63130 USA. YALE UNIV, NEW HAVEN, CT 06520 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. NR 4 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1996 VL 39 IS 6 BP 693 EP 699 DI 10.1002/ana.410390604 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UQ881 UT WOS:A1996UQ88100003 PM 8651640 ER PT J AU PericakVance, MA Johnson, CC Rimmler, JB Saunders, AM Robinson, LC DHondt, EG Jackson, CE Haines, JL AF PericakVance, MA Johnson, CC Rimmler, JB Saunders, AM Robinson, LC DHondt, EG Jackson, CE Haines, JL TI Alzheimer's disease and apolipoprotein E-4 allele in an Amish population SO ANNALS OF NEUROLOGY LA English DT Article ID MINI-MENTAL STATE; E POLYMORPHISM; TYPE-4 ALLELE; PREVALENCE; FREQUENCY; LINKAGE; GENE AB Alzheimer's Disease (AD) is a complex genetic disorder with four loci already identified. Mutations in three of these, the amyloid precursor protein, presenilin I, and presenilin II, cause early-onset AD. The apolipoprotein E (APOE) gene contributes primarily to late-onset AD. The APOE-4 allele acts in a dose-related fashion to increase risk and decrease the age-of-onset distribution in AD. We examined the effect of APOE on AD in a previously unstudied Amish population that has a lower prevalence of dementia compared with other populations. We sampled a large inbred family with 6 late-onset AD members. We also genotyped 53 individuals from the general Amish population as controls for the APOE allele frequency estimates. The frequency of the APOE-4 allele ire the Amish controls was 0.037 +/- 0.02. This differed significantly compared with three independent sets of non-Amish white controls (p < 2 x 10(-4), p < 6 x 10(-5), and p < 2 x 10(-6)). In addition, all Amish AD-affected individuals had APOE 3/3 genotypes; no APOE X/4 or 4/4 individuals were observed. We suggest that the lower frequency of dementia in the Amish may be partially explained by the decreased frequency of the APOE-4 allele in this population, and that the inbred nature of this pedigree, with its strong clustering of cases contrasted against the lower frequency of dementia, indicates that additional genetic factors influence late-onset AD. C1 HENRY FORD HOSP,DETROIT,MI 48202. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA. RP PericakVance, MA (reprint author), DUKE UNIV,MED CTR,DEPT MED,DIV NEUROL,BOX 2900,DURHAM,NC 27710, USA. RI Haines, Jonathan/C-3374-2012; OI Johnson, Christine Cole/0000-0002-6864-6604 FU NINDS NIH HHS [NS26630, NS531153] NR 43 TC 39 Z9 40 U1 2 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1996 VL 39 IS 6 BP 700 EP 704 DI 10.1002/ana.410390605 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UQ881 UT WOS:A1996UQ88100004 PM 8651641 ER PT J AU Chung, H Roberts, CT Greenberg, S Rebeck, GW Christie, R Wallace, R Jacob, HJ Hyman, BT AF Chung, H Roberts, CT Greenberg, S Rebeck, GW Christie, R Wallace, R Jacob, HJ Hyman, BT TI Lack of association of trinucleotide repeat polymorphisms in the very-low-density lipoprotein receptor gene with Alzheimer's disease SO ANNALS OF NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E; ALLELE AB Inheritance of the apolipoprotein E epsilon 4 allele is a risk factor for Alzheimer's disease (AD). A recent report studying Japanese patients suggested that a polymorphism of a trinucleotide repeat in the 5' untranslated region of an apolipoprotein E receptor, the very-low-density lipoprotein receptor, is genetically associated with AD, with overrepresentation of the allele containing five copies of the repeat. We determined the allele frequencies of the very-low-density lipoprotein receptor in 3 white populations totaling 469 individuals. In contrast to the previous report, we found no differences in allele frequencies between case patients and control subjects. The discrepancy could be due to differences in Japanese and white populations. Nonetheless, these data weaken the likelihood that this polymorphism in the very-low-density lipoprotein receptor gene is strongly associated with AD. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. UNIV IOWA,COLL MED,DEPT BIOSTAT & EPIDEMIOL,IOWA CITY,IA 52242. FU NIA NIH HHS [AG10127, AG02100, AG12406] NR 15 TC 29 Z9 29 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1996 VL 39 IS 6 BP 800 EP 803 DI 10.1002/ana.410390617 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UQ881 UT WOS:A1996UQ88100016 PM 8651653 ER PT J AU RodriguezDeVelasquez, A Weber, AL Montgomery, W AF RodriguezDeVelasquez, A Weber, AL Montgomery, W TI Extramedullary laryngeal plasmacytoma SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID HEAD; NECK C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP RodriguezDeVelasquez, A (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114, USA. NR 16 TC 17 Z9 17 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUN PY 1996 VL 105 IS 6 BP 483 EP 486 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA UP635 UT WOS:A1996UP63500013 PM 8638902 ER PT J AU Jacobson, JM Davidian, M Rainey, PM Hafner, R Raasch, RH Luft, BJ AF Jacobson, JM Davidian, M Rainey, PM Hafner, R Raasch, RH Luft, BJ TI Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ENCEPHALITIS; AIDS; SULFADIAZINE; COMBINATION; SULFADOXINE; EFFICACY; THERAPY; SERUM AB Pyrimethamine pharmacokinetics were studied in 11 human immunodeficiency virus (HIV)-positive patients who were seropositive for exposure to Toxoplasma gondii and were taking zidovudine (AIDS Clinical Trials Group Protocol 102), Pyrimethamine was administered at 50 mg daily for 3 weeks to achieve steady state, and pharmacokinetic profiles were determined after administration of the last dose, Noncompartmental and compartmental analyses were performed. Population pharmacokinetic analysis assuming a one-compartment model yielded the following estimates: area under the 24-h concentration-time curve, 42.7 +/- 12.3 mu g . h/ml; half-life, 139 +/- 34 h; clearance, 1.28 +/- 0.41 liters/h; volume of distribution, 246 +/- 641; and absorption rate constant, 1.5 +/- 1.3 liters/h. These values are similar to those seen in subjects without HIV infection, Pyrimethamine pharmacokinetics did not differ significantly in those subjects who were intravenous drug users. Adverse effects were noted in 73% of those initially enrolled in this study, leading to discontinuation for 38%. No association was noted between pyrimethamine levels and the incidence of adverse events. No significant differences were seen in zidovudine pharmacokinetic parameters obtained from studies performed before and during treatment with pyrimethamine. In summary, pyrimethamine exhibited pharmacokinetics in HIV-infected patients that were similar to those in non-HIV-infected subjects and it did not alter the pharmacokinetics of zidovudine in these patients. C1 MT SINAI SCH MED,NEW YORK,NY. SUNY STONY BROOK,DEPT MED,STONY BROOK,NY 11794. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT LAB MED,NEW HAVEN,CT 06510. NIAID,DIV AIDS,WASHINGTON,DC. UNIV N CAROLINA,SCH MED,DEPT MED,CHAPEL HILL,NC. RP Jacobson, JM (reprint author), BRONX VET AFFAIRS MED CTR,DEPT MED,DIV INFECT DIS,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. OI Luft, Benjamin/0000-0001-9008-7004 NR 25 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1996 VL 40 IS 6 BP 1360 EP 1365 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA UP107 UT WOS:A1996UP10700007 PM 8726001 ER PT J AU Whitman, MS Pitsakis, PG DeJesus, E Osborne, AJ Levison, ME Johnson, CC AF Whitman, MS Pitsakis, PG DeJesus, E Osborne, AJ Levison, ME Johnson, CC TI Gastrointestinal tract colonization with vancomycin-resistant Enterococcus faecium in an animal model SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CLOSTRIDIUM-DIFFICILE; INVITRO ACTIVITY; RAMOPLANIN; GENTAMICIN; TEICOPLANIN; PENICILLIN; INFECTIONS; FAECALIS AB Vancomycin-resistant enterococci have become important nosocomial pathogens in many institutions, The gastrointestinal tract of susceptible hosts serves as the likely reservoir from which the organism is disseminated. To study factors promoting colonization and the efficacy of decontamination therapy,vith antimicrobial agents, a model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecium was developed in CF1 mice. At baseline, all animals were colonized with non-vancomycin-resistant enterococci (5.0 log(10) CFU/g), but vancomycin-resistant organisms were not detectable. Following gastric inoculation,vith 5 x 10(8) CFU of a clinical isolate of vancomycin-resistant E. faecium, the strain transiently colonized the gastrointestinal tract of 100% of mice but was undetectable by Day 14 (less than or equal to 2.7 log(10) mean CFU/g). In animals who received 5 mg of streptomycin per mi or 250 mu g of vancomycin per mi in drinking water, colonization with the organism occurred at significantly higher bacterial counts than in controls at 7 days following inoculation (9.4 for vancomycin, 9.2 for streptomycin, and 5.1 log(10) mean CFU/g for controls; P < 0.05), Fecal concentrations of vancomycin-resistant E. faecium persisted at high counts through Day 22 in mice receiving these antibiotics, but low counts were also still detected in 3 of 10 control animals. In mice with previously established vancomycin-resistant E. faecium colonization, oral administration of ramoplanin, a lipoglycodepsipeptide to which the strain was susceptible, suppressed growth of all enterococci in feces, including the vancomycin-resistant strain after 7 days of therapy (less than or equal to 3.1 and less than or equal to 3.3 log(10) mean CFU/g for vancomycin and streptomycin groups, respectively). All mice had a recurrence of colonization with vancomycin-resistant E. faecium after the ramoplanin was discontinued, In summary, this animal model demonstrates the importance of antibiotics in predisposing to gastrointestinal colonization with vancomycin-resistant Enterococcus spp, Although treatment with ramoplanin temporarily suppressed the organism, recurrence of colonization due to relapse or reinfection occurred. C1 MED COLL PENN & HAHNEMANN UNIV,DIV INFECT DIS,DEPT MED,PHILADELPHIA,PA 19129. VET AFFAIRS MED CTR,DEPT MED,PHILADELPHIA,PA. NR 27 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1996 VL 40 IS 6 BP 1526 EP 1530 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA UP107 UT WOS:A1996UP10700037 PM 8726031 ER PT J AU Garrison, MW Malone, CL Eiland, JE AF Garrison, MW Malone, CL Eiland, JE TI Activity of once-daily cefpodoxime regimens against Haemophilus influenzae and Streptococcus pneumoniae with an in vitro pharmacodynamic chamber model SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PROXETIL AB To characterize the in vitro effectiveness of once-daily dosing with cefpodoxime against Haemophilus influenzae and Streptococcus pneumoniae infections, an in vitro pharmacodynamic chamber model was used to compare the bacterial killing activities of three cefpodoxime regimens: 100 mg twice daily (BID), 200 mg once daily (QD), and 400 mg QD. At the end of 24 h, the regrowth of H. influenzae isolates in the QD regimens was of concern, and the total logarithmic reduction was greatest in the BID regimen (3.1 log). Against S. pneumoniae isolates, the largest reductions in bacterial counts were observed in the 100-mg BID (5.5 log) and 400-mg QD (4.0 log) regimens. These data suggest that 400 mg of cefpodoxime given QD may have a role in the therapy of infections involving S. pneumoniae isolates. C1 DEACONESS MED CTR,SPOKANE,WA 99204. RP Garrison, MW (reprint author), WASHINGTON STATE UNIV,COLL PHARM,601 W 1ST AVE,SPOKANE,WA 99204, USA. NR 19 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1996 VL 40 IS 6 BP 1545 EP 1547 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA UP107 UT WOS:A1996UP10700042 PM 8726036 ER PT J AU HolmHansen, C Ayehunie, S Johansson, B Nkya, W Shao, J Haukenes, G AF HolmHansen, C Ayehunie, S Johansson, B Nkya, W Shao, J Haukenes, G TI HIV-1 proviral DNA sequences of env gp41 PCR amplificates from Tanzania SO APMIS LA English DT Article DE HIV-1 gp41; PCR; DNA sequencing; Tanzania ID IMMUNODEFICIENCY-VIRUS TYPE-1; NUCLEOTIDE-SEQUENCE; GENETIC DIVERSITY; V3 LOOP; SUBTYPE; STRAINS; IDENTIFICATION; VARIABILITY; SENSITIVITY; REACTIVITY AB The polymerase chain reaction (PCR) and direct DNA sequencing were used to detect and characterize selected regions of the HIV-1 proviral genome in whole blood samples from Tanzania. Specific PCR amplification products were obtained in gag and/or env (gp41) regions from 15 of the 19 HIV-1 seropositive samples investigated. Env regions from 12 different amplificates were further characterized using the dideoxy sequencing method. Preliminary results indicate that, despite scattered nucleotide mismatches, HIV-1 gp41 amino acid sequences from Tanzania conform to the 1990 Los Alamos African consensus sequence and resemble the HIV-1 subtype A or D consensus sequences in the characterized regions. C1 UNIV BERGEN,DEPT MICROBIOL & IMMUNOL,GADE INST,N-5021 BERGEN,NORWAY. HARVARD UNIV,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HUDDINGE HOSP,DIV CLIN VIROL,S-14186 HUDDINGE,SWEDEN. KILIMANJARO CHRISTIAN MED CTR,MOSHI,TANZANIA. RP HolmHansen, C (reprint author), UNIV BERGEN,CTR INT HLTH,N-5021 BERGEN,NORWAY. NR 35 TC 12 Z9 12 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PD JUN PY 1996 VL 104 IS 6 BP 459 EP 464 PG 6 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA VC885 UT WOS:A1996VC88500009 PM 8774676 ER PT J AU Kane, KS Quirk, DM MacLean, J Mackool, BT AF Kane, KS Quirk, DM MacLean, J Mackool, BT TI Perirectal hematoma presenting as purpura SO ARCHIVES OF DERMATOLOGY LA English DT Article RP Kane, KS (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, BOSTON, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-987X EI 1538-3652 J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 1996 VL 132 IS 6 BP 615 EP 616 DI 10.1001/archderm.132.6.615 PG 2 WC Dermatology SC Dermatology GA UQ751 UT WOS:A1996UQ75100002 PM 8651711 ER PT J AU Stiller, MJ Bartolone, J Stern, R Smith, S Kollias, N Gillies, R Drake, LA AF Stiller, MJ Bartolone, J Stern, R Smith, S Kollias, N Gillies, R Drake, LA TI Topical 8% glycolic acid and 8% L-lactic acid creams for the treatment of photodamaged skin - A double-blind vehicle-controlled clinical trial SO ARCHIVES OF DERMATOLOGY LA English DT Article ID ALPHA-HYDROXY-ACIDS; AMMONIUM LACTATE; DERMAL DAMAGE; TRETINOIN; LOTION; SUNSCREENS; XEROSIS AB Objective: To evaluate the efficacy and tolerability of 2 widely used topical alpha-hydroxy acids at low concentrations, 8% glycolic acid and 8% lactic (L-isoform) acid creams, in the treatment of photodamaged skin. Design: A single-center, 22-week, double-blind, vehicle-controlled, randomized clinical trial assessed the overall severity of photodamage on the faces and forearms of volunteers, based on 7 individual clinical components of cutaneous photodamage. Setting: The study was performed in an outpatient clinical research unit at the Massachusetts General Hospital, Boston. Patients: Seventy-four women, aged 40 to 70 years, with moderately severe photodamaged facial skin were enrolled in the study. One subject withdrew from the study early because of skin irritation, and 6 subjects withdrew from the study for personal reasons. Interventions: Glycolic acid, L-lactic acid, or vehicle creams were applied twice daily to the face and outer aspect of the forearms. Main Outcome Measures: Improvement in alpha-hydroxy acid-treated photodamaged skin as determined by patient self-assessments and physician evaluations of efficacy and irritancy. Results: The percentage of patients using either 8% glycolic acid or 8% L-lactic acid creams on the face achieving at least 1 grade of improvement (using a scale from 0 through 9) in overall severity of photodamage was significantly greater than with the vehicle cream (76% glycolic acid, 71% lactic acid, and 40% vehicle; P<.05). On the forearms, after 22 weeks, treatment with glycolic acid cream was superior to the vehicle in improving the overall severity of photodamage and sallowness (P<.05). L-lactic acid cream was significantly superior to the vehicle in reducing the overall severity of photodamage (P<.05), mottled hyperpigmentation (P<.05), sallowness (P<.05), and roughness on the forearms (P<.05) at week 22. Conclusions: Topical 8% glycolic acid and 8% L-lactic acid creams are modestly useful in ameliorating some of the signs of chronic cutaneous photodamage. These agents are well tolerated and available without prescription. C1 BETH ISRAEL HOSP,DEPT DERMATOL,BOSTON,MA 02215. UNILEVER RES CORP,EDGEWATER,NJ. RP Stiller, MJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,DERMATOL CLIN INVEST UNIT,WEL-224,BOSTON,MA 02114, USA. NR 25 TC 79 Z9 81 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 1996 VL 132 IS 6 BP 631 EP 636 DI 10.1001/archderm.132.6.631 PG 6 WC Dermatology SC Dermatology GA UQ751 UT WOS:A1996UQ75100005 PM 8651713 ER PT J AU Bigby, M AF Bigby, M TI Ruling out the diagnosis SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID PATHOLOGY RP Bigby, M (reprint author), MASSACHUSETTS GEN HOSP EAST, 149 13TH ST, CHARLESTOWN, MA 02129 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-987X EI 1538-3652 J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 1996 VL 132 IS 6 BP 697 EP 698 DI 10.1001/archderm.132.6.697 PG 2 WC Dermatology SC Dermatology GA UQ751 UT WOS:A1996UQ75100014 ER PT J AU Duncan, LM Baden, HP AF Duncan, LM Baden, HP TI Vascular papules on the dorsum of the hands SO ARCHIVES OF DERMATOLOGY LA English DT Article ID MULTINUCLEATE CELL ANGIOHISTIOCYTOMA C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Duncan, LM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 5 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 1996 VL 132 IS 6 BP 703 EP & PG 2 WC Dermatology SC Dermatology GA UQ751 UT WOS:A1996UQ75100015 PM 8651724 ER PT J AU Aarsland, D Tandberg, E Larsen, JP Cummings, JL AF Aarsland, D Tandberg, E Larsen, JP Cummings, JL TI Frequency of dementia in Parkinson disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID DEPRESSION AB Objective: To investigate the frequency of dementia in patients with Parkinson disease (PD). Design: Community-based prevalence study. Setting: The study population comprised 220 858 inhabitants from the Rogaland County, Norway. Participants: Almost 400 participants were examined by a neurologist, and 245 were given the diagnosis of PD and included in the study. Measurements: Mental functioning was rated with the Mini-Mental State Examination; Gottfries, Brane, and Steen scale; and the intellectual subscale of the Unified Parkinson's Disease Rating Scale. Criteria from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, were applied during a semistructured interview to determine the diagnosis of dementia. Results: Dementia was found in 67 patients (27.7%). Patients with dementia were older at the time of the study and at onset of PD and had had PD longer than the patients without dementia. Major depression was more common among patients with dementia (23%) than among patients without dementia (2.3%) (chi(2), P<.001), and patients with dementia were more often institutionalized than those without dementia (62% vs 6%, respectively, chi(2), P<.001). Atypical neurologic features for idiopathic PD tie, early occurrence of autonomic failure, symmetrical disease presentation, and only moderate response to a dopamine agonist) were associated with more severe dementia of a higher frequency rate and with lower scores on cognitive rating scales. Conclusion: Approximately one quarter of the patients with PD had dementia with the motor manifestations of PD. Dementia was associated with depression, institutionalization, older age at onset of PD, and atypical neurologic features. C1 CENT HOSP ROGALAND,DEPT NEUROL,N-4000 STAVANGER,NORWAY. HOSP PSYCHIAT,SECT GERIATR PSYCHIAT,ROGALAND,NORWAY. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,BEHAV NEUROSCI SECT,LOS ANGELES,CA 90073. OI Aarsland, Dag/0000-0001-6314-216X NR 26 TC 196 Z9 207 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 1996 VL 53 IS 6 BP 538 EP 542 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA UR158 UT WOS:A1996UR15800014 PM 8660156 ER PT J AU Pless, M Lessell, S AF Pless, M Lessell, S TI Spontaneous visual improvement in orbital apex tumors SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID MENINGIOMAS; PALSY AB Objective: To describe patients with orbital apex masses involving the optic nerve who enjoyed spontaneous improvement in visual function without therapy. Methods: A retrospective chart review of cases in an academic neuro-ophthalmology practice identified three cases of tumorous compression of the optic nerve in which there was spontaneous improvement in visual function. Each patient had undergone a full neuro-ophthalmologic evaluation, followed up with serial imaging. Results: The first patient initially had a visual acuity of 2/200 and central visual field defects. Over a 4-year period, her visual acuity improved to 20/40 and her visual field expanded centrally. The second patient initially had a visual acuity of 20/40 and a cecocentral visual field defect. After a 4-year follow-wp, her visual acuity had improved to 20/15 and her cecocentral defect had shrunk. The third patient had an initial visual acuity of 20/25, an afferent pupillary defect, and optic atrophy. Over a 2-year period she developed a paracentral scotoma and her visual acuity worsened in 20/30. In the next 2 years her visual acuity improved to 20/10 and her visual field normalized. Conclusions: In exceptional instances, visual dysfunction from tumorous compression of the optic nerve in the orbital apex may spontaneously improve. Clinicians who use the natural history of visual loss in differential diagnosis should be a aware that spontaneous remission is compatible with the presence of tumor. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. RP Pless, M (reprint author), BRIGHAM & WOMENS HOSP,DIV NEUROL,NEUROOPHTHALMOL UNIT,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 11 TC 17 Z9 17 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 1996 VL 114 IS 6 BP 704 EP 706 PG 3 WC Ophthalmology SC Ophthalmology GA UP245 UT WOS:A1996UP24500010 PM 8639082 ER PT J AU Endo, EG Walton, DS Albert, DM AF Endo, EG Walton, DS Albert, DM TI Neonatal hepatoblastoma metastatic to the choroid and iris SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID NEUROBLASTOMA AB A newborn boy was diagnosed with hepatoblastoma after a systemic workup was prompted because of abnormal-appearing eyes. Radiological examination revealed mass lesions involving the liver, brain, eyes, and ribs. A liver biopsy was performed before death and results showed hepatoblastoma, an unusual solid tumor of childhood, At autopsy, hepatoblastoma was also found histopathologically in the irides and choroid of both eyes. No previous report of hepatoblastoma metastatic to the eye could be found in the medical literature. In addition, we believe this is the first report in a child of a solid tumor metastatic to the choroid and iris, and of a solid tumor metastatic to the iris that is confirmed histopathologically. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. UNIV WISCONSIN,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,MADISON,WI. FU NEI NIH HHS [EY01917] NR 24 TC 10 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 1996 VL 114 IS 6 BP 757 EP 761 PG 5 WC Ophthalmology SC Ophthalmology GA UP245 UT WOS:A1996UP24500022 PM 8639094 ER PT J AU Eavey, RD Ryan, DP AF Eavey, RD Ryan, DP TI Refinements in pediatric microtia reconstruction SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article AB Auricular construction for a child born with microtia is a rewarding endeavor that can provide the patient with a realistic pinna. However, not all reconstructive problems have been solved. For example, the donor sites for the rib harvest and for subsequent skin grafting are not without morbidity and scar formation. Furthermore, in some children, an unexpected shortage of rib can be encountered. Surgical techniques that address these problems are described. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV PEDIAT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP Eavey, RD (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 7 TC 17 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUN PY 1996 VL 122 IS 6 BP 617 EP 620 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA UP737 UT WOS:A1996UP73700007 PM 8639292 ER PT J AU MacLean, CH Knight, KK Shekelle, PG Paulus, HE Brook, RH AF MacLean, CH Knight, KK Shekelle, PG Paulus, HE Brook, RH TI Drug use in rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 VALUE HLTH SCI,SANTA MONICA,CA 90407. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90095. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1996 VL 39 IS 6 SU S BP R5 EP R5 PG 1 WC Rheumatology SC Rheumatology GA UQ616 UT WOS:A1996UQ61600010 ER PT J AU MacLean, CH Knight, KK Shekelle, PG Paulus, HE Brook, RH AF MacLean, CH Knight, KK Shekelle, PG Paulus, HE Brook, RH TI Costs attributable to arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 VALUE HLTH SCI,SANTA MONICA,CA 90407. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90095. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1996 VL 39 IS 6 SU S BP R4 EP R4 PG 1 WC Rheumatology SC Rheumatology GA UQ616 UT WOS:A1996UQ61600005 ER PT J AU Roger, L Masi, AT Luther, M AF Roger, L Masi, AT Luther, M TI Clinical remission in rheumatoid arthritis correlates with entry status: A longitudinal study of 191 patients treated with aurothioglucose and low-dose triamcinolone. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV ILLINOIS,COLL MED,PEORIA,IL 61656. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1996 VL 39 IS 6 SU S BP R23 EP R23 PG 1 WC Rheumatology SC Rheumatology GA UQ616 UT WOS:A1996UQ61600090 ER PT J AU Roger, L Masi, AT Luther, M AF Roger, L Masi, AT Luther, M TI Early aggressive therapy in the treatment of rheumatoid arthritis (RA). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV ILLINOIS,COLL MED,PEORIA,IL 61656. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1996 VL 39 IS 6 SU S BP R23 EP R23 PG 1 WC Rheumatology SC Rheumatology GA UQ616 UT WOS:A1996UQ61600089 ER PT J AU Otto, MW Pollack, MH Sabatino, SA AF Otto, MW Pollack, MH Sabatino, SA TI Maintenance of remission following cognitive behavior therapy for panic disorder: Possible deleterious effects of concurrent medication treatment SO BEHAVIOR THERAPY LA English DT Article ID BENZODIAZEPINE TREATMENT; AGORAPHOBIA; IMIPRAMINE; DISCONTINUATION; EXPOSURE; ALPRAZOLAM AB In a prospective, naturalistic study, we examined the long-term outcome of patients with panic disorder who entered remission following cognitive behavior therapy (CBT) alone or CBT plus medications (combined treatment). Similar to previous studies, severity of the panic disorder and agoraphobic avoidance served as predictors of relapse in a survival analysis. However, the most powerful predictor of maintenance of remission was treatment type. Despite ongoing pharmacotherapy, patients who entered remission with combined treatment and continued their pharmacologic treatment relapsed sooner than patients treated with CBT who entered remission medication-free. Consideration of baseline levels of anxiety severity, comorbidity, and history of previous remissions did not account for the prediction afforded by consideration of treatment type. These findings are discussed in the context of other evidence for deleterious effects of concomitant pharmacotherapy on the long-term outcome of patients with panic disorder treated with CBT. Treatment implications are discussed. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Otto, MW (reprint author), MASSACHUSETTS GEN HOSP,BEHAV THERAPY UNIT,WACC-815,BOSTON,MA 02114, USA. NR 33 TC 56 Z9 57 U1 2 U2 10 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD SUM PY 1996 VL 27 IS 3 BP 473 EP 482 DI 10.1016/S0005-7894(96)80028-1 PG 10 WC Psychology, Clinical SC Psychology GA WC752 UT WOS:A1996WC75200010 ER PT J AU Cohen, LS Sichel, DA Faraone, SV Robertson, LM Dimmock, JA Rosenbaum, JF AF Cohen, LS Sichel, DA Faraone, SV Robertson, LM Dimmock, JA Rosenbaum, JF TI Course of panic disorder during pregnancy and the puerperium: A preliminary study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE panic disorder; pregnancy; puerperium; treatment; anxiety ID POSTPARTUM MOOD DISORDERS; DEPRESSION; ATTACKS AB Pregnancy has been referred to as a time of well-being for patients with psychiatric disorder, However, this impression is derived primarily from anecdotal reports and retrospective studies, rather than systematic prospective evaluation. In this study, 10 pregnant women with previous histories of panic disorder were evaluated prospectively across pregnancy and the postpartum period using the Structured Clinical Interview for DSM-III-R and the Clinical Global Impression. Information regarding pharmcotherapy received was also recorded. Seven of 10 subjects continued to meet DSM-III-R criteria for panic disorder at all trimester visits. Symptoms persisted for some patients even in the context of treatment with antipanic medications. Most subjects (n = 9) met DSM-III-R criteria at 1-3 months postpartum despite nearly uniform intensification of antipanic treatment. Although some women may experience diminished symptoms of panic during pregnancy, in this sample most continued to experience panic attacks and to require antipanic treatment to control symptoms. C1 HARVARD UNIV,SCH MED,BOSTON,MA. BROCKTON VET ADM HOSP,BROCKTON,MA. UNIV VIRGINIA,DEPT CLIN PSYCHOL,CHARLOTTESVILLE,VA. RP Cohen, LS (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPT PSYCHIAT,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-19445] NR 24 TC 38 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 1996 VL 39 IS 11 BP 950 EP 954 DI 10.1016/0006-3223(95)00300-2 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UK321 UT WOS:A1996UK32100006 PM 9162207 ER PT J AU Sammel, MD Ryan, LM AF Sammel, MD Ryan, LM TI Latent variable models with fixed effects SO BIOMETRICS LA English DT Article DE factor analysis; hierarchical models; variance components ID LONGITUDINAL DATA-ANALYSIS AB We discuss latent variable models that allow for fixed effect covariates, as well as covariates affecting the latent variable directly. Restricted maximum likelihood and maximum likelihood are used to estimate model parameters. A generalized likelihood ratio test can be used to test significance of the covariates effecting the latent outcomes. Special cases of the proposed model correspond to factor analysis, mixed models, random effects models, and simultaneous equations. The model is applied to birth defects data, where continuous data on the size of infants who were exposed to anticonvulsant medications in utero are compared to controls. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RP Sammel, MD (reprint author), HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DIV BIOSTAT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA48061]; NIEHS NIH HHS [ES07142] NR 23 TC 43 Z9 44 U1 0 U2 9 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1996 VL 52 IS 2 BP 650 EP 663 DI 10.2307/2532903 PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA UR160 UT WOS:A1996UR16000023 PM 8672706 ER PT J AU Lipsitz, SR Fitzmaurice, GM AF Lipsitz, SR Fitzmaurice, GM TI The score test for independence in RxC contingency tables with missing data SO BIOMETRICS LA English DT Article DE Mantel-Haenszel statistic; ordinal dat; Pearson's chi-squared statistic AB In this paper, the score test statistic for testing independence in R x C contingency tables with missing data is proposed. Under the null hypothesis of independence, the statistic has an approximate chi-squared distribution with (R - 1)(C - 1) degrees of freedom. The proposed test statistic is quite similar to the Pearson chi-squared statistic with complete data and, unlike the likelihood ratio statistic for testing independence, its computation is simple and noniterative. In addition, a score test statistic is proposed for testing independence when the rows and columns of the R x C table are ordinal. Finally, extensions of the scare statistics to test for conditional independence in a set of (R x C) contingency tables with missing data are described. This yields score test statistics that are natural extensions of the Mantel-Haenszel statistic. An example, using a subset of data from the Six Cities Study, is presented to illustrate the methods. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. UNIV OXFORD NUFFIELD COLL,OXFORD OX1 1NF,ENGLAND. RP Lipsitz, SR (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 55576]; NIAID NIH HHS [AI 24643]; NIGMS NIH HHS [GM 29745] NR 8 TC 8 Z9 8 U1 2 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1996 VL 52 IS 2 BP 751 EP 762 DI 10.2307/2532915 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA UR160 UT WOS:A1996UR16000035 PM 8672711 ER PT J AU Venugopalan, V Nishioka, NS Mikic, BB AF Venugopalan, V Nishioka, NS Mikic, BB TI Thermodynamic response of soft biological tissues to pulsed infrared-laser irradiation SO BIOPHYSICAL JOURNAL LA English DT Article ID THERMAL-DAMAGE; ABLATION RATE; CORNEA; SKIN; ER; ABSORPTION; POLYMERS; DYNAMICS; DURATION; WATER AB The physical mechanisms that achieve tissue removal through the delivery of short pulses of high-intensity infrared laser radiation, in a process known as laser ablation, remain obscure. The thermodynamic response of biological tissue to pulsed infrared laser irradiation was investigated by measuring and analyzing the stress transients generated by Q-sw Er:YSGG (lambda = 2.79 mu m) and TEA CO2 (lambda = 10.6 mu m) laser irradiation of porcine dermis using thin-film piezoelectric transducers. For radiant exposures that do not produce material removal, the stress transients are consistent with thermal expansion of the tissue samples. The temporal structure of the stress transients generated at the threshold radiant exposure for ablation indicates that the onset of material removal is delayed with respect to irradiation. Once material removal is achieved, the magnitude of the peak compressive stress and its variation with radiant exposure are consistent with a model that considers this process as an explosive event occurring after the laser pulse. This mechanism is different from ArF- and KrF-excimer laser ablation where absorption of ultraviolet radiation by the collagenous tissue matrix leads to tissue decomposition during irradiation and results in material removal via rapid surface vaporization. It appears that under the conditions examined in this study, explosive boiling of tissue water is the process that mediates the ablation event. This study provides evidence that the dynamics and mechanism of tissue ablation processes can be altered by targeting tissue water rather than the tissue structural matrix. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. MIT,DEPT MECH ENGN,CAMBRIDGE,MA 02139. NR 58 TC 57 Z9 58 U1 0 U2 11 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1996 VL 70 IS 6 BP 2981 EP 2993 PG 13 WC Biophysics SC Biophysics GA UP428 UT WOS:A1996UP42800050 PM 8744336 ER PT J AU Kim, JH Puder, M Soberman, RJ AF Kim, JH Puder, M Soberman, RJ TI Joining of DNA fragments by repeated cycles of denaturation, annealing and extension SO BIOTECHNIQUES LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; LEUKOTRIENE-B4 20-HYDROXYLASE; IDENTIFICATION C1 MASSACHUSETTS GEN HOSP,ARTHRITIS UNIT,CHARLESTOWN,MA 02129. RI Kim, Jae-Hong/B-2530-2009 FU NIEHS NIH HHS [ES-50859] NR 6 TC 6 Z9 6 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUN PY 1996 VL 20 IS 6 BP 954 EP 955 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UP432 UT WOS:A1996UP43200001 PM 8780860 ER PT J AU Ku, H Yonemura, Y Kaushansky, K Ogawa, M AF Ku, H Yonemura, Y Kaushansky, K Ogawa, M TI Thrombopoietin, the ligand for the Mpl receptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; BLAST CELL COLONIES; C-KIT; GROWTH-FACTOR; INTERLEUKIN-3-DEPENDENT PROLIFERATION; MURINE HEMATOPOIESIS; CULTURE; DIFFERENTIATION; ENHANCEMENT; INTERLEUKIN-11 AB Recently, the ligand for the MpI receptor (ML) was identified to be thrombopoietin, the principal regulator of megakaryocytopoiesis and thrombopoiesis. We examined the effects of ML, as a single factor or in combinations with early acting factors such as steel factor (SF), interleukin (IL)-3, IL-ll, IL-6, and granulocyte colony-stimulating factor (G-CSF), on colony formation from primitive progenitors of mice. Cells enriched for cell cycle dormant primitive progenitors were isolated from bone marrow cells of li-fluorouracil (5-FU)-treated mice by a combination of Nycodenz density gradient separation, immunomagnetic selection for lineage-negative cells, and fluorescence-activated cell sorter (FAGS) sorting for Ly-6A/E(+)Kit(+) cells. ML, in the presence of erythropoietin, could support the formation of only a few megakaryocyte colonies. However, ML acted synergistically with SF or IL-3 to support the formation of multiple types of hematopoietic colonies including multilineage colonies. Effects of the combination of ML and SF on multipotential progenitors were not mediated through other cells, as demonstrated by micromanipulation of individual progenitors. In suspension culture, the combination of ML and SF increased the number of multipotential progenitors. ML also acted synergistically with IL-ll, IL-6, or G-CSF to support colony formation in serum-containing, but not in serum-free, cultures. However, the multilineage colony formation seen in serum-containing culture was completely abrogated by addition of ACK2, a neutralizing antibody to Kit protein. Serial observation (mapping studies) of colony development from multipotential progenitors suggested that ML triggers the cell division of dormant progenitors. Based on these observations, we propose that ML can function as an early acting cytokine and stimulate the proliferation of cell cycle dormant progenitors by shortening their G(0) period. (C) 1996 by The American Society of Hematology. C1 MED UNIV S CAROLINA,RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,DEPT MED,CHARLESTON,SC 29425. WASHINGTON UNIV,DEPT MED,SEATTLE,WA. FU NIDDK NIH HHS [DK 48714, DK 32294, DK 49855] NR 38 TC 214 Z9 219 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1996 VL 87 IS 11 BP 4544 EP 4551 PG 8 WC Hematology SC Hematology GA UN797 UT WOS:A1996UN79700009 PM 8639822 ER PT J AU Friedrich, C Zausch, E Sugrue, SP GutierrezRamos, JC AF Friedrich, C Zausch, E Sugrue, SP GutierrezRamos, JC TI Hematopoietic supportive functions of mouse bone marrow and fetal liver microenvironment: Dissection of granulocyte, B-lymphocyte, and hematopoietic progenitor support at the stroma cell clone level SO BLOOD LA English DT Article ID C-KIT RECEPTOR; STEM-CELLS; LINES; DIFFERENTIATION; PROLIFERATION; CULTURES; ANTIGEN; PRECURSORS; GROWTH; GENE AB We dissected the functions of the microenvironment of bone marrow (BM) and fetal liver (FL) at the cellular level by cloning individual stromal cells and characterizing their phenotypical and functional features. Stromal cell clones derived from FL are large in size (mean forward light scatter intensity [mFSC] of 450), express the surface antigen Thy-1 but not Sca-l and 6 out of 6 are able to differentiate into fat accumulating adipocytes. BM derived stromal cell clones are either small (mFSC of 250) or large (mFSC of 450), express Sca-1 but not Thy-1 and only 2 out of 7 differentiate towards adipocytes. Heterogeneity in terms of vascular adhesion molecule-1, intracellular adhesion molecule-1 and heat stable antigen expression was found among the different cell clones. Functional assays using long- and short-term cocultures of stromal and hematopoietic cells revealed: (1) the capacity of 8 out of 12 stromal cell clones to support the expansion of primitive hematopoietic progenitors (colony forming unit spleen day 12) more than 10 weeks. Fat accumulation but not expression of stem cell factor by stromal cells did correlate with this supportive function. (2) Better support of granulocyte maturation and proliferation by BM-compared to FL-derived stromal cell clones. However, stromal cell clones from both organs expressed macrophage-colony stimulating factor, (3) The ability of 4 out of 12 stromal cell clones (derived from both, FL and BM) to support the expansion of interleukin-7 dependent pre-B cells from the BM. Pre-B cell growth stimulating factor was not restricted to supporters. (4) Mutual exclusiveness of myeloid and lymphoid support in that a given stromal cell clone supported either pre Ei-cell or granulocyte expansion. Experiments comparing the support of BM- and FL-derived hematopoietic progenitors showed identical responses of late (B220(+)/c-kit(-)) but strikingly different responses of early (B220(+)/c-hit(+)) pre-B cells, revealing different proliferation requirements for FL- versus BM- derived early pre-B cells in vitro. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT ANAT & CELLULAR BIOL,BOSTON,MA 02115. UNIV FREIBURG,DEPT BIOL,FREIBURG,GERMANY. FU NHLBI NIH HHS [HL148675-02] NR 50 TC 49 Z9 51 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1996 VL 87 IS 11 BP 4596 EP 4606 PG 11 WC Hematology SC Hematology GA UN797 UT WOS:A1996UN79700015 PM 8639828 ER PT J AU Gribben, JG Guinan, EC Boussiotis, VA Ke, XY Linsley, L Sieff, C Gray, GS Freeman, GJ Nadler, LM AF Gribben, JG Guinan, EC Boussiotis, VA Ke, XY Linsley, L Sieff, C Gray, GS Freeman, GJ Nadler, LM TI Complete blockade of B7 family-mediated costimulation is necessary to induce human alloantigen-specific anergy: A method to ameliorate graft-versus-host disease and extend the donor pool SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; T-CELL DEPLETION; CHRONIC MYELOGENOUS LEUKEMIA; HEMATOPOIETIC STEM-CELLS; HLA-IDENTICAL SIBLINGS; LIMITING DILUTION; ACTIVATION; CD28; PROLIFERATION; INTERLEUKIN-2 AB Graft-versus-host disease (GVHD) is initiated by adoptively transferred donor T cells that recognize host alloantigens. Whereas the absence of donor T-cell proliferation to host alloantigens in a mixed-leukocyte reaction does not predict freedom from GVHD, the frequency of alloreactive precursor helper T lymphocytes (pHTL) is predictive. Complete blockade of B7 family-mediated costimulation, but not of major histocompatibility complex recognition or adhesion, induces host alloantigen-specific anergy by reducing cytokine production below threshold levels necessary for common gamma-chain signaling. The associated reduction of alloreactive pHTL frequency below that predictive for GVHD, without depletion of either nonallospecific T cells or hematopoietic progenitors, has led us to embark upon human clinical trials of haplomismatched allogeneic bone marrow transplantation. (C) 1996 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA. REPLIGEN CORP,CAMBRIDGE,MA 02139. RP Gribben, JG (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA40216]; NIAID NIH HHS [AI35225] NR 35 TC 96 Z9 96 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1996 VL 87 IS 11 BP 4887 EP 4893 PG 7 WC Hematology SC Hematology GA UN797 UT WOS:A1996UN79700050 PM 8639863 ER PT J AU Schultze, J Nadler, LM Gribben, JG AF Schultze, J Nadler, LM Gribben, JG TI B7-mediated costimulation and the immune response SO BLOOD REVIEWS LA English DT Review ID T-CELL ACTIVATION; VERSUS-HOST DISEASE; ANTIGEN-PRESENTING-CELL; RECEPTOR GAMMA-CHAIN; BONE-MARROW TRANSPLANTATION; B-CELLS; TUMOR-ANTIGENS; CLONAL ANERGY; LYMPHOCYTES-T; FUNCTIONAL COMPONENT AB In addition to presentation of antigen, T cells require additional or 'costimulatory' signals from antigen-presenting cells. Failure to receive costimulation following antigen presentation renders T cells anergic, and these cells are functionally incapable of proliferating or secreting cytokines in response to subsequent rechallenge. Recent evidence has demonstrated that a critical costimulatory signal is delivered by members of the B7 family. B7-1 (CD80) and B7-2 (CD86) provide costimulation through CD28, their ligand on the T cell. Dysregulation of expression of B7 may be implicated in the pathogenesis of autoimmune disease. In contrast, lack of expression of B7 on tumor cells may explain in part the lack of immune response against the majority of tumors. It may now be possible to exploit this pathway to induce immunological response against tumors. Blockade of this pathway will likely have significant impact on transplantation biology, to induce T-cell anergy and prevent graft rejection and graft-versus-host disease. RP Schultze, J (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115, USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 107 TC 103 Z9 106 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0268-960X J9 BLOOD REV JI Blood Rev. PD JUN PY 1996 VL 10 IS 2 BP 111 EP 127 DI 10.1016/S0268-960X(96)90040-5 PG 17 WC Hematology SC Hematology GA UY657 UT WOS:A1996UY65700007 PM 8813343 ER PT J AU DeVincenzo, JP Leombruno, D Soiffer, RJ Siber, GR AF DeVincenzo, JP Leombruno, D Soiffer, RJ Siber, GR TI Immunotherapy of respiratory syncytial virus pneumonia following bone marrow transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE immunotherapy; BMT; respiratory syncytial virus ID IMMUNE GLOBULIN; IMMUNOCOMPROMISED ADULTS; PROTECTIVE ACTIVITY; VIRAL-INFECTION; COTTON RATS; ANTIBODY; THERAPY; CHILDREN; INFANTS AB Respiratory syncytial virus (RSV) pneumonia is a well-recognized complication of bone marrow transplantation with a high mortality rate. We describe two patients who developed RSV pneumonia within the first 3 weeks following allogeneic bone marrow transplantation. These patients had significant oxygen requirements and radiographic infiltrates. Both were treated with aerosolized ribavirin and given a single 1.5 gm/kg dose of intravenous immune globulin containing high levels of RSV neutralizing activity (RSV-IG). Both patients showed subjective and objective improvement after RSV-IG, never required mechanical ventilation, and were discharged without an oxygen requirement within 2 weeks after therapy. RSV microneutralization activity was measured in serum and nasal secretions. Mean serum microneutralization activity increased from 2279 microneutralization units (Mu)/ml to 18 082 Mu/ml after RSV-IG. Peak serum microneutralization activity achieved with RSV-IG was higher than that achieved in a series of other immunocompromised adults with RSV pneumonia given either multiple doses of standard IVIG or no immune globulin therapy. RSV-IG may be beneficial in the treatment of RSV pneumonia in severely immunocompromised patients. C1 DANA FARBER CANC INST,DIV INFECT DIS,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. MASSACHUSETTS PUBL HLTH BIOL LABS,BOSTON,MA. NR 30 TC 36 Z9 36 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 1996 VL 17 IS 6 BP 1051 EP 1056 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA UW587 UT WOS:A1996UW58700023 PM 8807113 ER PT J AU Molrine, DC Guinan, EC Antin, JH Wheeler, C Parsons, SK Weinstein, HJ McGarigle, C Blanding, P Phillips, NR Ciamarra, A George, S Ambrosino, DM AF Molrine, DC Guinan, EC Antin, JH Wheeler, C Parsons, SK Weinstein, HJ McGarigle, C Blanding, P Phillips, NR Ciamarra, A George, S Ambrosino, DM TI Haemophilus influenzae type b (HIB)-conjugate immunization before bone marrow harvest in autologous bone marrow transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE bone marrow transplantation; immunization; active; vaccines; conjugate; polysaccharides; bacterial ID BLOOD STEM-CELL; ACUTE LYMPHOBLASTIC-LEUKEMIA; NON-HODGKINS LYMPHOMA; CONJUGATE VACCINE; CAPSULAR POLYSACCHARIDE; MONOCLONAL-ANTIBODY; INFECTION; RECONSTITUTION; OLIGOSACCHARIDE; ENGRAFTMENT AB Immune reconstitution following autologous bone marrow transplantation (ABMT) is characterized by defects in B cell and T cell function and loss of specific antibody. In the late post-transplant period, patients are at risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We examined whether immunizing ABMT patients before bone marrow (BM) harvest enhanced the early recovery of specific antibody. Twelve patients were immunized before BM harvest with Haemophilus influenzae type b (HIB)-conjugate, tetanus toroid and polysaccharide pneumococcal vaccines. Forty-one comparable ABMT patients not immunized prior to BM harvest were also studied. Following ABMT, both groups of patients were immunized with HIB-conjugate and tetanus toroid vaccines at 3, 6, 12 and 24 months and with pneumococcal vaccine at 12 and 24 months. Patients immunized before BM harvest had higher HIB antibody concentrations during the first 2 years posttransplant, the differences reaching significance at 3 months (P = 0.0001) and following the 24-month dose (P = 0.048). Tetanus toroid antibody concentrations were also significantly higher at 3 months (P = 0.001) and 6 months (P = 0.032) in patients immunized before BM harvest. There were no differences in pneumococcal antibody concentrations between the two groups. Immunization of patients before bone marrow harvest resulted in higher anti-HIB antibody concentrations following ABMT and may he an effective strategy to prevent infectious complications. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PHARM,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL & ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. BETH ISRAEL HOSP,BOSTON,MA 02215. RP Molrine, DC (reprint author), DANA FARBER CANC INST,INFECT DIS LAB,44 BINNEY ST,JFB ROOM 424,BOSTON,MA 02115, USA. FU NCI NIH HHS [CAO1730]; PHS HHS [A129623] NR 38 TC 17 Z9 18 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 1996 VL 17 IS 6 BP 1149 EP 1155 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA UW587 UT WOS:A1996UW58700038 PM 8807128 ER PT J AU Litvan, I DeLeo, JM Hauw, JJ Daniel, SE Jellinger, K McKee, A Dickson, D Horoupian, DS Lantos, PL Tabaton, M AF Litvan, I DeLeo, JM Hauw, JJ Daniel, SE Jellinger, K McKee, A Dickson, D Horoupian, DS Lantos, PL Tabaton, M TI What can artificial neural networks teach us about neurodegenerative disorders with extrapyramidal features? SO BRAIN LA English DT Article DE artificial neural networks; dystal; neurodegenerative disorders; neuropathology; progressive supranuclear palsy ID PROGRESSIVE SUPRANUCLEAR PALSY; ALZHEIMERS-DISEASE; CORTICOBASAL DEGENERATION; DIAGNOSIS; CLASSIFICATION; DEMENTIA; PATHOLOGY; TANGLES; CANCER AB Artificial neural networks (ANNs), computer paradigms that can learn, excel in pattern recognition tasks such as disease diagnosis. Artificial neural networks operate in two different learning modes: supervised, in which a known diagnostic outcome is presented to the ANN, and unsupervised, in which the diagnostic outcome is not presented. A supervised learning ANN could emulate human expert diagnostic performance and identify relevant predictive markers in the diagnostic task, while an unsupervised learning ANN could suggest reasonable alternative diagnostic classification criteria. In the present study, we used ANN methodology to try to overcome the neuropathological difficulties in differentiating the subtypes of progressive supranuclear palsy (PSP), and in differentiating PSP from postencephalitic parkinsonism (PEP) and corticobasal degeneration, or Pick's disease from corticobasal degeneration. First, we applied supervised learning ANN to classify 62 cases of these disorders and to identify diagnostic markers that distinguish them. In a second experiment, we used unsupervised learning ANN to investigate possible alternative nosological classifications. Artificial neural networks input data for each case consisted of values representing histological features, including neurofibrillary tangles, neuronal loss and gliosis found in multiple brain sampling areas. The supervised learning ANN achieved excellent accuracy in classifying PSP but had difficulty classifying the other disorders. This method identified a few features that might help to differentiate PEP, supported currently proposed criteria for Pick's disease, corticobasal degeneration and typical PSP, but detected no features to characterize the atypical subtype of PSP. In general, unsupervised learning ANN supported the present nosological classification for PSP, PEP, Pick's disease and corticobasal degeneration, although it overlapped some groups. Artificial neural networks methodology appears promising for studying neurodegenerative disorders. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. ALBERT EINSTEIN COLL MED,DEPT NEUROPATHOL,NEW YORK,NY. STANDFORD SCH MED,DEPT PATHOL NEUROPATHOL,STANFORD,CA. CASE WESTERN RESERVE UNIV,DIV NEUROPATHOL,CLEVELAND,OH 44106. HOP LA PITIE SALPETRIERE,ASSOC CLAUDE BERNARD,INSERM U360,RAYMOND ESCOUROLLE NEUROPATHOL LAB,PARIS,FRANCE. LUDWIG BOLTZMANN INST CLIN NEUROBIOL,VIENNA,AUSTRIA. INST PSYCHIAT,PARKINSONS DIS SOC BRAIN TISSUE BANK,LONDON,ENGLAND. INST PSYCHIAT,INST NEUROL,DEPT NEUROPATHOL,LONDON,ENGLAND. RP Litvan, I (reprint author), NINCDS,NIH,NEUROEPIDEMIOL BRANCH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Dickson, Dennis W/0000-0001-7189-7917; Litvan, Irene/0000-0002-3485-3445 NR 47 TC 15 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 1996 VL 119 BP 831 EP 839 DI 10.1093/brain/119.3.831 PN 3 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UX947 UT WOS:A1996UX94700013 PM 8673495 ER PT J AU Caplan, D Hildebrandt, N Makris, N AF Caplan, D Hildebrandt, N Makris, N TI Location of lesions in stroke patients with deficits in syntactic processing in sentence comprehension SO BRAIN LA English DT Article DE localization of language functions; syntactic comprehension deficits; localization of syntactic processing; syntactic comprehension in stroke patients ID POSITRON EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; CEREBRAL LATERALIZATION; BIOLOGICAL MECHANISMS; GLUCOSE-METABOLISM; BRAIN POTENTIALS; APHASIA; LOCALIZATION; ASSOCIATIONS; AGRAMMATISM AB Sixty patients, 46 with left-hemisphere strokes and 14 with right-hemisphere strokes, and 21 normal control subjects were tested for the ability to use syntactic structures to determine the meaning of sentences. Patients enacted thematic roles (the agent, recipient and goal of an action) in 12 examples of each of 25 sentence types, which were designed to test a wide variety of syntactic operations. Both right- and left-hemisphere damaged patients performed worse than control subjects on syntactically complex sentences, and left-hemisphere patients performed worse than right-hemisphere patients. Eighteen patients with left-hemisphere strokes underwent CT scanning to image the perisylvian association cortex. There was no difference between the performance of patients with anterior and posterior lesions, and no correlation between the degree of impairment and the size of lesions in different regions of the perisylvian cortex. There results are consistent with the view that syntactic processing involves an extensive neural system, whose most important region is the left perisylvian cortex. When these results are combined with those of other studies, the picture that emerges is one in which, within this cortical region, this system manifests features of both distributed and localized processing. C1 MASSACHUSETTS GEN HOSP, NEUROPSYCHOL LAB, BOSTON, MA USA. FU NIDCD NIH HHS [DC00942] NR 70 TC 139 Z9 142 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 1996 VL 119 BP 933 EP 949 DI 10.1093/brain/119.3.933 PN 3 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UX947 UT WOS:A1996UX94700021 PM 8673503 ER PT J AU Gruss, HJ Rollins, BJ Herrmann, F AF Gruss, HJ Rollins, BJ Herrmann, F TI Human fibroblasts express functional interleukin (IL)-2 receptors formed by the IL-2R-alpha- and -beta-chain subunits: Association of IL-2 binding with secretion of the monocyte chemoattractant protein-1 SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 UNIV ULM,MED KLIN,W-7900 ULM,GERMANY. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 SU 2 BP 372 EP 372 PG 1 WC Hematology SC Hematology GA UP114 UT WOS:A1996UP11400372 ER PT J AU Kalina, U Ganser, A Hoelzer, D Griffin, JD Eder, M AF Kalina, U Ganser, A Hoelzer, D Griffin, JD Eder, M TI GM-CSF induced oligomerization of chimeric alpha/beta GM-CSF receptors in vitro SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract C1 UNIV FRANKFURT,DEPT HEMATOL,W-6000 FRANKFURT,GERMANY. HANNOVER MED SCH,W-3000 HANNOVER,GERMANY. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1996 VL 93 SU 2 BP 373 EP 373 PG 1 WC Hematology SC Hematology GA UP114 UT WOS:A1996UP11400373 ER PT J AU Schnitt, SJ Harris, JR Smith, BL AF Schnitt, SJ Harris, JR Smith, BL TI Developing a prognostic index for ductal carcinoma in situ of the breast - Are we there yet? SO CANCER LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,COMPREHENS BREAST CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP Schnitt, SJ (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 14 TC 52 Z9 56 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1996 VL 77 IS 11 BP 2189 EP 2192 DI 10.1002/(SICI)1097-0142(19960601)77:11<2189::AID-CNCR1>3.0.CO;2-L PG 4 WC Oncology SC Oncology GA UM089 UT WOS:A1996UM08900001 PM 8635082 ER PT J AU Fidias, P Wright, C Harris, NL Urba, W Grossbard, ML AF Fidias, P Wright, C Harris, NL Urba, W Grossbard, ML TI Primary tracheal non-Hodgkin's lymphoma - A case report and review of the literature SO CANCER LA English DT Article DE non-Hodgkin's lymphoma; tracheal neoplasms; extranodal lymphoma; tracheobronchial ID FIELD RADIATION-THERAPY; MALIGNANT-LYMPHOMA; ENDOBRONCHIAL INVOLVEMENT; CELL LYMPHOMA; LIMITED-STAGE; CHEMOTHERAPY; NEOPLASMS; TUMORS AB BACKGROUND. Primary tracheobronchial non-Hodgkin's lymphoma (NHL) is an uncommon occurrence. The authors report a patient who presented with primary tracheal NHL, the sixth such patient described in the literature. METHODS. Using a MEDLINE search, 41 additional patients presenting with symptomatic primary or secondary tracheobronchial NHL were identified. The characteristics, management, and outcome of these patients are described. RESULTS. Patients with NHL of the upper respiratory tract present with dyspnea, wheezing, and cough, and frequently are misdiagnosed as having asthma. The majority of patients have additional sites of intrathoracic disease with tracheobronchial involvement occurring in the setting of advanced or relapsed NHL. Low grade histology is seen most commonly in patients with primary tracheal NHL. Several patients demonstrate the typical histologic features of mucosa-associated lymphoid tissue. Surgery, chemotherapy, and radiation therapy have been used alone or in combination for treatment. The outcome of these patients does not appear different from that observed in patients with lymphomas of similar histology and stage that do not involve the tracheobronchial tree. CONCLUSIONS. Thoracic surgeons, pulmonologists, and oncologists should recognize that NHL can rarely be confined to the trachea or bronchi. NHL should be considered in the differential diagnosis of airway obstruction, because it represents a highly treatable malignancy. (C) 1996 American Cancer Society. C1 MASSACHUSETTS GEN HOSP,HEMATOL ONCOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV THORAC SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. PROVIDENCE PORTLAND MED CTR,EARLE A CHILES RES INST,PORTLAND,OR. NR 38 TC 26 Z9 32 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1996 VL 77 IS 11 BP 2332 EP 2338 DI 10.1002/(SICI)1097-0142(19960601)77:11<2332::AID-CNCR23>3.0.CO;2-X PG 7 WC Oncology SC Oncology GA UM089 UT WOS:A1996UM08900023 PM 8635104 ER PT J AU Kumar, P Herndon, J Langer, M Kohman, LJ Elias, AD Kass, FC Eaton, WL Seagren, SL Green, MR Sugarbaker, DJ AF Kumar, P Herndon, J Langer, M Kohman, LJ Elias, AD Kass, FC Eaton, WL Seagren, SL Green, MR Sugarbaker, DJ TI Patterns of disease failure after trimodality therapy of nonsmall cell lung carcinoma pathologic stage IIIA (N2) - Analysis of cancer and leukemia group B protocol 8935 SO CANCER LA English DT Article; Proceedings Paper CT 77th Meeting of the American-Radium-Society CY APR 29-MAY 03, 1995 CL PARIS, FRANCE SP Amer Radium Soc DE nonsmall cell lung carcinoma; Stage IIIA (N2); trimodality therapy; failure pattern ID PHASE-II; NEOADJUVANT CHEMOTHERAPY; RADIOTHERAPY; CISPLATIN; TRIAL AB BACKGROUND. The impact of sequential trimodality therapy on the pattern of first site disease failure in pathologic Stage IIIA (N2) nonsmall cell lung carcinoma (NSCLC) was analyzed. METHODS. Seventy-four eligible patients with histologically documented Stage IIIA (N2) NSCLC underwent sequential trimodality therapy on Cancer and Leukemia Group B (CALGB) Protocol 8935. Treatment consisted of 2 cycles of induction cisplatin at 100 mg/m(2) intravenously (i.v.) (Days 1 and 29) and vinblastine at 5 mg/m(2) i.v. weekly for 5 weeks followed by surgery. Surgery included a thoracotomy with resection of the primary tumor and hilar lymph nodes and a mediastinal lymph node dissection. Patients with resected disease then received an additional 2 cycles of cisplatin at 100 mg/m(2) i.v. and vinblastine at 5 mg/m(2) i.v. biweekly for a total of 4 doses followed by consolidative thoracic irradiation. Patients with completely resected disease received 54 Gray (Gy) whereas those with incompletely resected disease received 59.4 Gy at 1.8 Gy/fraction (fx) once a day. Patients with unresectable disease underwent thoracic radiation therapy (TRT) treatments only to 59.4 Gy at 1.8 Gy/fx without any additional chemotherapy, Disease recurrence was determined by clinical, radiographic, or histologic criteria. Pattern of disease failure was identified by site of involvement at first recurrence as indicated by the CALGB Respiratory Follow-Up Form. RESULTS. Sixty-three of the 74 patients completed the induction chemotherapy as planned. Forty-six of the 63 patients underwent resection of disease whereas the remaining 17 were unresectable. Thirty-three of the 46 resected patients completed the entire adjuvant postoperative chemoradiation treatment as planned. Ten of 17 patients with unresectable disease completed postsurgical TRT. At a median follow-up interval of 27 months (range, 4-43), the 3-year overall survival and failure-free survival were 23% and 18%, respectively, for all 74 eligible patients. Overall, disease failure has occurred in 52 (70%) of the 74 eligible patients: local only: 13 (25%); distant only: 16 (31%); and both local and distant: 23 (44%), (P = not significant [NS]). Ten patients progressed during induction chemotherapy: local only: six patients; and both local and distant failure: four patients. Twenty eight of 46 resected patients recurred: local only: 1 (4%); both local and distant failure: 11 (39%); and distant only: 16 (57%); (P < 0.001). Disease progression occurred in 14 of 17 patients with unresectable disease: local only: 6; both local and distant sites: 8. Among the 52 total patients experiencing disease relapse, isolated or combined local failure occurred commonly among patients during induction chemotherapy (n = 10, [28%]), in those with unresectable disease (n = 14, [39%]), or in those with resected disease (n = 12, [33%]), (P = NS). However, isolated or combined distant failure was more likely to occur among patients with resected disease (n = 27, [69%]) than either during induction chemotherapy (n = 4, [10%]) or in those with unresected disease (n = 8, [21%]), (P < 0.05). Among patients who relapsed, brain metastases occurred in 13 of 52 (25%) patients overall and in 12 of 28 (43%) patients with resected disease. CONCLUSIONS. Overall, disease failure was just as likely to occur in local, distant, or combined sites on CALGB Protocol 8935 using sequential trimodality therapy in the treatment of pathologic Stage IIIA (N2) NSCLC. Isolated or combined local failure occurred commonly during sequential tri-modality therapy whereas isolated or combined distant relapse was prevalent among patients with resected disease. In addition, isolated local failure was rare among patients with resected disease. The pattern of disease failure on CALGB Protocol 8935 reflects the biology of locoregional NSCLC as much as the therapeutic impact of trimodality therapy. (C) 1996 American Cancer Society. C1 UNIV TENNESSEE,MEMPHIS,TN. DUKE UNIV,MED CTR,DEPT BIOSTAT,DURHAM,NC. HARVARD JOINT CTR RADIAT THERAPY,BOSTON,MA. SUNY HLTH SCI CTR,DEPT SURG,SYRACUSE,NY 13210. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. SANTA BARBARA COTTAGE HOSP,SANTA BARBARA,CA. DARTMOUTH HITCHCOCK MED CTR,HANOVER,NH. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. HARVARD UNIV,SCH MED,DIV THORAC SURG,BRIGHAM & WOMENS HOSP,BOSTON,MA. RP Kumar, P (reprint author), VET ADM MED CTR,RADIAT ONCOL SERV,114A,1030 JEFFERSON AVE,MEMPHIS,TN 38104, USA. NR 12 TC 48 Z9 48 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1996 VL 77 IS 11 BP 2393 EP 2399 DI 10.1002/(SICI)1097-0142(19960601)77:11<2393::AID-CNCR31>3.3.CO;2-8 PG 7 WC Oncology SC Oncology GA UM089 UT WOS:A1996UM08900031 PM 8635112 ER PT J AU Jain, RK Koenig, GC Dellian, M Fukumura, D Munn, LL Melder, RJ AF Jain, RK Koenig, GC Dellian, M Fukumura, D Munn, LL Melder, RJ TI Leukocyte-endothelial adhesion and angiogenesis in tumors SO CANCER AND METASTASIS REVIEWS LA English DT Review DE adhesion molecules; angiogenesis; leukocyte-endothelial interactions; selectins; integrins ID ACTIVATED KILLER-CELLS; GROWTH-FACTOR-BETA; MICROVASCULAR ENDOTHELIUM; NECROSIS-FACTOR; IFN-GAMMA; EXPRESSION; LYMPHOCYTE; MOLECULE-1; INVIVO; IL-4 AB Leukocyte-endothelial adhesion and angiogenesis, until recently considered as separate processes, have been shown to be linked by two recent findings: soluble cellular adhesion molecules (CAMs) involved in leukocyte-endothelial interactions are angiogenic and well known angiogenic molecules secreted by cancer or immune cells can modulate the endothelial CAMs. This molecular link may partially explain why the overall leukocyte-endothelial interaction is often low and heterogeneous in angiogenic tumor vessels and why activated lymphocytes adhere nonuniformly to tumor vessels when injected into the tumor's blood supply. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Jain, RK (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,STEELE LAB,BOSTON,MA 02114, USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R35-CA-56591] NR 63 TC 78 Z9 79 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 1996 VL 15 IS 2 BP 195 EP 204 DI 10.1007/BF00437472 PG 10 WC Oncology SC Oncology GA UW384 UT WOS:A1996UW38400008 PM 8842491 ER PT J AU Teicher, BA AF Teicher, BA TI A systems approach to cancer therapy (antiangiogenics plus standard cytotoxics->mechanism(s) of interaction) SO CANCER AND METASTASIS REVIEWS LA English DT Review DE antiangiogenic agents; combined modality therapy; TNP-470; minocycline; Lewis lung carcinoma ID FIBROBLAST GROWTH-FACTOR; ACQUIRED IMMUNODEFICIENCY SYNDROME; TUMOR-NECROSIS-FACTOR; LEWIS LUNG-CARCINOMA; ANGIOGENESIS INHIBITOR AGM-1470; SQUAMOUS-CELL CARCINOMA; ENDOTHELIAL-CELLS; BETA-CAROTENE; IV COLLAGENASE; QUINOLINE-3-CARBOXAMIDE LINOMIDE C1 JOINT CTR RADIAT THERAPY, BOSTON, MA 02115 USA. RP Teicher, BA (reprint author), DANA FARBER CANC INST, 44 BINNEY ST, BOSTON, MA 02115 USA. NR 314 TC 89 Z9 91 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 1996 VL 15 IS 2 BP 247 EP 272 DI 10.1007/BF00437479 PG 26 WC Oncology SC Oncology GA UW384 UT WOS:A1996UW38400015 PM 8842498 ER PT J AU Teicher, BA Holden, SA Ara, G Korbut, T Menon, K AF Teicher, BA Holden, SA Ara, G Korbut, T Menon, K TI Comparison of several antiangiogenic regimens alone and with cytotoxic therapies in the Lewis lung carcinoma SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Review DE antiangiogenic agents; combination therapy; TNP-470; suramin; genistein; minocycline ID FIBROBLAST GROWTH-FACTOR; ANGIOGENESIS INHIBITOR TNP-470; MICROVASCULAR ENDOTHELIAL-CELLS; CHICK CHORIOALLANTOIC MEMBRANE; INVASIVE BREAST-CARCINOMA; TUMOR STROMA GENERATION; EXTRACELLULAR-MATRIX; IN-VITRO; INVITRO DIFFERENTIATION; PLASMINOGEN-ACTIVATOR AB The efficacy of several potential antiangiogenic agents, TNP-470, minocycline, suramin, genistein, interferon delta 4, 14(sulfated)-beta-cyclodextrin and tetrahydrocortisol, alone and in combination with cytotoxic therapies was examined against primary and metastatic Lewis lung carcinoma. The antiangiogenic agents when administered as single agents or in two-agent combinations were only modestly active as antitumor agents. Three antiangiogenic agent combinations, TNP-470/minocycline, TNP-470/14(SO4)beta CD/THC and minocycline/14(SO4)beta CD/THC, produced significant increases in tumor growth delay and decreases in the number of lung metastases when administered along with cyclophosphamide compared with cyclophosphamide alone. Two antiangiogenic agent combinations, minocycline/interferon delta 4 and minocycline/14 (SO4)beta CD/THC, produced significant decreases in the number of lung metastases when administered alone with adriamycin compared with adriamycin alone. The antiangiogenic combinations of TNP-470/minocycline, TNP-470/suramin, TNP-470/genistein, TNP-470/interferon delta 4 and TNP-470/14(SO4)beta CD/THC, resulted in increased tumor growth delays when administered along with CDDP, BCNU, fractionated radiation or 5-fluorouracil. There was not always a direct correlation between the antiangiogenic regimen that was most beneficial against the primary tumor as compared with disease metastatic to the lungs. These studies establish that a broad range of antiangiogenic therapies can interact in a positive manner with cytotoxic therapies. RP Teicher, BA (reprint author), DANA FARBER CANC INST, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [P01-CA19589, P01-CA31303, R01-CA50174] NR 120 TC 67 Z9 69 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1996 VL 38 IS 2 BP 169 EP 177 DI 10.1007/s002800050466 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA UH686 UT WOS:A1996UH68600009 PM 8616908 ER PT J AU Chou, D Miyashita, T Mohrenweiser, HW Ueki, K Kastury, K Druck, T vonDeimling, A Huebner, K Reed, JC Louis, DN AF Chou, D Miyashita, T Mohrenweiser, HW Ueki, K Kastury, K Druck, T vonDeimling, A Huebner, K Reed, JC Louis, DN TI The BAX gene maps to the glioma candidate region at 19q13.3, but is not altered in human gliomas SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID HUMAN CHROMOSOME-19; HUMAN ASTROCYTOMAS; HIGH-RESOLUTION; LIBRARIES AB The box protein regulates apoptosis in a cellular pathway that involves both bcl-2 and p53, two molecules associated with human glioma tumorigenesis. We therefore evaluated the possibility that BAX functions as a glioma tumor suppressor gene. Somatic cell hybrid panels, fluorescence in situ hybridization and cosmid mapping localized the BAX gene to 19q13.3, approximately 300 kb centromeric to HRC. Thus BAX maps to the region of chromosome 19 most frequently deleted in gliomas. Routine and pulsed-field gel electrophoresis/Southern blotting studies, however, failed to reveal large-scale deletions or rearrangements of the BAX gene in gliomas, In addition, single strand conformation polymorphism analysis of all six BAX exons and flanking intronic sequences did not disclose mutations in 20 gliomas with allelic loss of the other copy of 19q. A C/T polymorphism was defected in intron 3 and was common in the general population. Therefore, although BAX maps to the glioma candidate region on the long arm of chromosome 19, BAX is probably not the 19q glioma tumor suppressor gene. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,NEUROSURG SERV,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. LA JOLLA CANC RES FDN,LA JOLLA,CA 92037. LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,LIVERMORE,CA 94550. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. UNIV HOSP,INST NEUROPATHOL,BONN,GERMANY. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [CA 51083, CA 57683, CA 60181] NR 28 TC 49 Z9 50 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUN PY 1996 VL 88 IS 2 BP 136 EP 140 DI 10.1016/0165-4608(95)00341-X PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA UR929 UT WOS:A1996UR92900007 PM 8640722 ER PT J AU Tangir, J Loughridge, NS Berkowitz, RS Muto, MG Bell, DA Welch, WR Mok, SC AF Tangir, J Loughridge, NS Berkowitz, RS Muto, MG Bell, DA Welch, WR Mok, SC TI Frequent microsatellite instability in epithelial borderline ovarian tumors SO CANCER RESEARCH LA English DT Article ID CANCER; HETEROZYGOSITY; CARCINOMAS AB To further define the genetic events that could lead to the development of borderline ovarian tumors (BOTs), we analyzed 13 microsatellite markers on chromosomes 3p and q in 18 BOTs and compared the results to 31 serous invasive epithelial ovarian cancers (IEOCs), Five of the 18 BOTs showed microsatellite instability (MSI) at one or more loci, compared to only 2 of the 31 IEOCs studied (P < 0.04), In two of these five BOTs, MSI was found in multiple loci, All BOTs with MSI were serous, while none of the mucinous type showed any alteration, Loss of heterozygosity was found in only 1 of the 18 BOTs, but in 12 of the 31 IEOCs (P < 0.01), This first report of a relatively high percentage of MSI in BOTs opens a wide spectrum of new hypotheses for borderline ovarian tumorigenesis as well as several new research avenues. C1 BRIGHAM & WOMENS HOSP,GYNECOL ONCOL LAB,DIV GYNECOL ONCOL,DEPT OBSTET GYNECOL & REPROD BIOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [R01CA63381] NR 32 TC 74 Z9 75 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1996 VL 56 IS 11 BP 2501 EP 2505 PG 5 WC Oncology SC Oncology GA UN250 UT WOS:A1996UN25000011 PM 8653685 ER PT J AU Royal, I Raptis, L Druker, BJ Marceau, N AF Royal, I Raptis, L Druker, BJ Marceau, N TI Down-regulation of cytokeratin 14 gene expression by the polyoma virus middle T antigen is dependent on c-Src association but independent of full transformation in rat liver nonparenchymal epithelial cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; PROTEIN PHOSPHATASE-2A; MONOCLONAL-ANTIBODIES; HUMAN KERATIN-18; TUMOR-ANTIGEN; MESSENGER-RNA; SOFT-AGAR; PP60C-SRC; 3-KINASE; PRODUCT AB Polyoma virus middle T antigen (mT) transforms the T51B cell line and induces the loss of the cytokeratin 8 and 14 pair (CK8/CK14) present in these rat nonparenchymal liver epithelial cells (LECs), because of the selective down-regulation of CK14 gene expression. To identify the initial steps of the mT-induced signaling pathway(s) leading to this inhibition, T51B cells were transfected with vectors encoding the NG59, dl23, and 248M mT mutants, which are known to interact in a differential manner with c-Src, PI3-kinase, and Shc. Immunofluorescence microscopy and Northern blot analysis showed a loss of cytokeratins in dl23 or 248M but not in NG59 mT mutant-containing cells. An in vitro kinase assay demonstrated that only the dl23 and 248M mT mutants could associate with c-Src. This c-Src-mediated action of mT on CK14 gene expression was further confirmed by adding the v-src gene product in T51B cells. The assessment of the transforming capacity of the mT mutants demonstrated that the NG59 and dl23 mT mutants were nontransformant, whereas the 248M mT mutant expressed an appreciable transforming activity, These results show that the down-regulation of CK14 gene expression by mT in the LEC line T51B is dependent on the association with the c-Src tyrosine kinase, but interestingly, this c-Src-mediated action of mT can occur in the absence of transformation, Furthermore, when coupled with recent data on the plasticity of LECs, the present findings provide the first essential element in our definition of the signaling pathway(s) that link growth/differentiation events with CK gene regulation in typical simple epithelial cells. C1 UNIV LAVAL,HOTEL DIEU QUEBEC,CTR RECH CANCEROL,QUEBEC CITY,PQ G1R 2J6,CANADA. QUEENS UNIV,DEPT MICROBIOL & IMMUNOL,KINGSTON,ON K7L 3N6,CANADA. DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. OI Royal, Isabelle/0000-0002-7548-1182 NR 58 TC 4 Z9 4 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUN PY 1996 VL 7 IS 6 BP 737 EP 743 PG 7 WC Cell Biology SC Cell Biology GA UP341 UT WOS:A1996UP34100006 PM 8780887 ER PT J AU Force, T Pombo, CM Avruch, JA Bonventre, JV Kyriakis, JM AF Force, T Pombo, CM Avruch, JA Bonventre, JV Kyriakis, JM TI Stress-activated protein kinases in cardiovascular disease SO CIRCULATION RESEARCH LA English DT Review ID PHOSPHORYLATION C1 MASSACHUSETTS GEN HOSP EAST,RENAL UNIT,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP EAST,DIABET UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP Force, T (reprint author), MASSACHUSETTS GEN HOSP EAST,CARDIAC UNIT,SUITE 4002,149 13TH ST,CHARLESTOWN,MA 02129, USA. OI Force, Thomas/0000-0002-0450-8659 FU NIDDK NIH HHS [DK-39773, DK-38452]; NINDS NIH HHS [NS-10828] NR 39 TC 180 Z9 183 U1 1 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN PY 1996 VL 78 IS 6 BP 947 EP 953 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA UN375 UT WOS:A1996UN37500001 PM 8635244 ER PT J AU Pavri, BB Ruskin, JN Brooks, R AF Pavri, BB Ruskin, JN Brooks, R TI The yield of head-up tilt testing is not significantly increased by repeating the baseline test SO CLINICAL CARDIOLOGY LA English DT Article DE tilt table testing; syncope ID UNEXPLAINED SYNCOPE; UPRIGHT TILT; UNKNOWN ORIGIN; TABLE TEST; ISOPROTERENOL; METHODOLOGY; BRADYCARDIA; HYPOTENSION; MANAGEMENT AB Background and hypothesis: Head-up tilt is widely used in evaluating patients with syncope. Data suggest that baseline tilt without isoproterenol is asscociated with few (less than or equal to 10%) positive results in normals. However, there is considerable day-today variability in patients with syncope, resulting in low reproducibility. We hypothesized that repeating the baseline tilt would increase the total number of positive responses. Methods: In all, 193 patients with syncope of unknown etiology prospectively underwent serial baseline tilt (Tilt-1 and Tilt-2) at 70 degrees for 25 min on two consecutive days. Results: Of 193 patients, 39 (20%) had a positive Tilt-1. Of these, 19 had a positive Tilt-2, (positive concordance rate: 19/39 = 49%). Of 154 patients with a negative Tilt-1, 145 had a negative Tilt-2 (negative concordance rate: 142/151=94%). Only 9 of 154 patients (6%) with a negative Tilt-1 had a positive Tilt-2. Thus, the yield increased from 20% (39/193) after Tilt-1, and to 25% (48/193) after Tilt-1 plus Tilt-2, p = NS. Conclusions: (1) Reproducibility of a positive Tilt-1 is moderate. (2) Reproducibility of a negative Tilt-1 is high. (3) Repetition of tilt in patients with a negative Tilt-1 does not significantly increase the number of positive results. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. NR 22 TC 4 Z9 5 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUN PY 1996 VL 19 IS 6 BP 494 EP 496 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UP660 UT WOS:A1996UP66000010 PM 8790955 ER PT J AU Butts, WC Lilje, DJ McClung, JW Flood, JG Long, WH Abbott, TJ Ng, KM AF Butts, WC Lilje, DJ McClung, JW Flood, JG Long, WH Abbott, TJ Ng, KM TI Evaluation of endocrine testing with the BMC-Hitachi 917: Thyroid and diabetes panels SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 GRP HLTH,SEATTLE,WA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BOEHRINGER MANNHEIM CORP,INDIANAPOLIS,IN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 SU S BP 596 EP 596 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UR522 UT WOS:A1996UR52200596 ER PT J AU Brown, EN McDermott, TJ Bloch, KJ McCollom, AD AF Brown, EN McDermott, TJ Bloch, KJ McCollom, AD TI Defining the smallest analyte concentration an immunoassay can measure SO CLINICAL CHEMISTRY LA English DT Article DE Bayesian statistics; detection limit; enzyme immunoassay; minimal detectable dose; prostate disease; sensitivity ID PROSTATE-SPECIFIC ANTIGEN; RESOLVED IMMUNOFLUOROMETRIC ASSAY; DETECTABLE CONCENTRATION; DETECTION LIMIT; SENSITIVITY AB An immunoassay's minimal detectable concentration ((MDC), the smallest analyte concentration the assay can reliably measure, is one of its most important properties. Bayes' theorem is used to unify the five current mathematical MDC definitions. The unified definition has significant implications for defining positive results for screening and diagnostic tests, setting criteria for immunoassay quality control and optimal design, reliably measuring biological substances at low concentrations, and, in general, measuring small analyte concentrations with calibrated analytic methods, As an illustration, we apply the unified definition to the microparticle capture enzyme immunoassay for prostate-specific antigen (PSA) developed for the Abbott IMxm(TM) automated immunoassay system. The MDC of this assay as estimated by our unifying approach is shown to be 4.1-7.1 times greater than currently reported, As a consequence, the ability of the assay to measure reliably small concentrations of PSA to detect early recurrences of prostate cancer is probably overstated. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STAT RES LAB,ANESTHESIA SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CLIN IMMUNOL UNIT,GEN MED SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ALLERGY UNIT,GEN MED SERV,BOSTON,MA 02114. NR 50 TC 24 Z9 24 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1996 VL 42 IS 6 BP 893 EP 903 PN 1 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UQ783 UT WOS:A1996UQ78300011 PM 8665681 ER PT J AU McNicholas, MMJ Saini, S Echeverri, J Foley, M Kaufman, J McFarland, E Hahn, PF AF McNicholas, MMJ Saini, S Echeverri, J Foley, M Kaufman, J McFarland, E Hahn, PF TI T2 relaxation times of hypervascular and non-hypervascular liver lesions: Do hypervascular lesions mimic haemangiomas on heavily T2-weighted MR images? SO CLINICAL RADIOLOGY LA English DT Article ID FOCAL HEPATIC-LESIONS; HEPATOCELLULAR-CARCINOMA; CAVERNOUS HEMANGIOMA; DIFFERENTIATION; METASTASES; ERRORS; VALUES; US AB Aim: To correlate the T2 relaxation times of liver lesions with their vascularity at angiography and to determine whether hypervascular lesions have similar signal intensity to haemangiomas on heavily T2-weighted MR images, Patients and methods: Thirty-four patients with histologically proven malignant liver lesions had both angiography and T2W (SE 3000/80,160) MR imaging (1.5 T) of the liver, Angiographically, the lesions mere hypervascular in 15 and non-hypervascular in 19 patients, Fifteen additional patients with proven haemangioma also had MR imaging during the same time period, The T2 relaxation time of a representative lesion was calculated for each patient and the results compared, Results: The mean T2 time for hypervascular lesions was 76+/-21 ms compared with 79+/-18 ms for non-hypervascular lesions (P=0.61), The mean T2 relaxation time for haemangiomas was significantly longer than either group: 147+/-46 ms (P=0.0001). Conclusion: The T2 relaxation times of hypervascular and non-hypervascular liver lesions are similar and are significantly shorter than those of haemangiomas, Therefore, hypervascular lesions should not mimic haemangiomas on heavily Ta-weighted images. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BETH ISRAEL HOSP,DEPT RADIOL,BOSTON,MA 02215. JEWISH HOSP ST LOUIS,MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110. NR 23 TC 12 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD JUN PY 1996 VL 51 IS 6 BP 401 EP 405 DI 10.1016/S0009-9260(96)80157-7 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UP490 UT WOS:A1996UP49000003 PM 8654003 ER PT J AU Goldfinger, SM Schutt, RK Turner, W Tolomiczenko, G Abelman, M AF Goldfinger, SM Schutt, RK Turner, W Tolomiczenko, G Abelman, M TI Assessing homeless mentally ill persons for permanent housing: Screening for safety SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article ID COMMUNITY; SUPPORTS; LIFE AB Although placement in community housing is a frequent intervention with populations of seriously mentally ill homeless individuals, there has been little formal investigation of the criteria used by clinicians in screening individuals for such placement. In this paper, we describe screening a population of 303 homeless people with severe mental illness for placement in independent apartments. We assess subjects' level of risk along multiple dimensions and determine the contribution of each risk dimension to the final safety decision. In addition, we evaluate the validity of the risk measures with other measures of clinical condition. Two-thirds of the sample were judged as safe for independent living. Assaultiveness was the most frequent risk identified, followed by self-destructiveness, substance abuse, and medication non-compliance. The final safety decision was associated most strongly with assaultiveness, self-destructiveness, and medication non-compliance. We conclude that it is possible to assess risk with measures that are available from shelter and medical records, and call for more research on the role of medication non-compliance in safety decisions and for longitudinal research to validate risk assessments. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,CAMBRIDGE,MA 02138. MASSACHUSETTS DEPT MENTAL HLTH,BOSTON,MA. UNIV MASSACHUSETTS,DEPT SOCIOL,BOSTON,MA 02125. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,ADDICT SERV,BOSTON,MA 02114. SOLOMON CARTER FULLER MENTAL HLTH CTR,BOSTON,MA. FU NIMH NIH HHS [1R18MH4808001] NR 20 TC 8 Z9 8 U1 1 U2 1 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD JUN PY 1996 VL 32 IS 3 BP 275 EP 288 DI 10.1007/BF02249428 PG 14 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA UQ458 UT WOS:A1996UQ45800010 PM 8790969 ER PT J AU Kirchhausen, T Rosen, FS AF Kirchhausen, T Rosen, FS TI Disease mechanism - Unravelling Wiskott-Aldrich syndrome SO CURRENT BIOLOGY LA English DT Article ID T-CELLS; LYMPHOCYTES AB The gene responsible for Wiskott-Aldrich syndrome, a disease affecting platelets and lymphocytes, has been cloned and its protein product (WASp) found to interact with the GTPase Cdc42. WASp seems to provide a link between Cdc42 and the actin cytoskeleton, perhaps explaining the cellular defects underlying the disease. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP Kirchhausen, T (reprint author), HARVARD UNIV,SCH MED,DEPT CELL BIOL,200 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 19 TC 42 Z9 42 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 1 PY 1996 VL 6 IS 6 BP 676 EP 678 DI 10.1016/S0960-9822(09)00447-3 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UR928 UT WOS:A1996UR92800022 PM 8793292 ER PT J AU Mashal, RD Sklar, J AF Mashal, RD Sklar, J TI Practical methods of mutation detection SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID SINGLE BASE SUBSTITUTIONS; GRADIENT GEL-ELECTROPHORESIS; POLYMERASE CHAIN-REACTION; DNA HETERODUPLEXES; POINT MUTATIONS; RAPID DETECTION; P53 MUTATIONS; PCR; HYBRIDIZATION; AMPLIFICATION AB The past few years have seen a marked increase in the demand for practical methods of mutation detection. Over this period of time, both the development of new methods and improvements in existing methods have made mutation detection in the research setting a less cumbersome task. Nevertheless, all of the commonly used approaches to this problem are labor intensive, and truly practical mutation detection methods in the clinical setting will depend on the development of more fully automated technology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. RP Mashal, RD (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV MOLEC ONCOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 39 TC 30 Z9 31 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD JUN PY 1996 VL 6 IS 3 BP 275 EP 280 DI 10.1016/S0959-437X(96)80002-5 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA UR931 UT WOS:A1996UR93100002 PM 8791513 ER PT J AU Limmroth, V Cutrer, M Moskowitz, MA AF Limmroth, V Cutrer, M Moskowitz, MA TI Neurotransmitters and neuropeptides in headache SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID GENE-RELATED PEPTIDE; RAT DURA-MATER; PLASMA-PROTEIN EXTRAVASATION; SUBSTANCE-P; BLOOD-VESSELS; TRIGEMINOVASCULAR SYSTEM; TRIGEMINAL GANGLIA; ANTIMIGRAINE DRUG; SODIUM VALPROATE; MAST-CELLS AB For many decades, headache and migraine were thought to evolve from dilated cranial blood vessels. Vasoconstrictors such as ergotamine and, more recently, sumatriptan were considered appropiate treatments. With the introduction of animal models and the emergence of molecular pharmacology, this traditional concept has been challenged, and an important role for neuropeptides, neuronal receptors and neurogenic inflammation is emerging, Neurogenic inflammation develops within the meninges as a consequence of neuropeptide release from primary afferent fibers and has been hypothesized to be of importance in migraine. Neurogenic inflammation provides protection for many organs, contributes to tissue repair and serves as a useful model to define the receptor population and peptide mechanisms of relevance to drug discovery in migraine. The possible role played by neurotransmitters and neuropeptides in migraine and their receptors as potential targets for treatment will be discussed. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE NEUROVASC REGULAT NEUROSCI CTR,BOSTON,MA. RP Limmroth, V (reprint author), UNIV CLIN ESSEN,DEPT NEUROL,HUFELANDSTR 55,D-45147 ESSEN,GERMANY. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS21558] NR 53 TC 18 Z9 18 U1 0 U2 2 PU CURRENT SCIENCE PI PHILADELPHIA PA 400 MARKET STREET,SUITE 750 ATTN:SARAH WHEALEN/SUB MGR, PHILADELPHIA, PA 19106 SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD JUN PY 1996 VL 9 IS 3 BP 206 EP 210 DI 10.1097/00019052-199606000-00009 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UY146 UT WOS:A1996UY14600009 PM 8839612 ER PT J AU Jenkins, AJ Klein, RL Chassereau, CN Hermayer, KL LopesVirella, MF AF Jenkins, AJ Klein, RL Chassereau, CN Hermayer, KL LopesVirella, MF TI LDL from patients with well-controlled IDDM is not more susceptible to in vitro oxidation SO DIABETES LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; CULTURED HUMAN-FIBROBLASTS; DIABETIC-PATIENTS; INVITRO OXIDATION; ATHEROSCLEROSIS; GLYCATION; GLYCOSYLATION; ANTIOXIDANTS; STRESS AB Increased susceptibility of LDL to oxidation has been shown to be associated with the presence of coronary heart disease and may account for the accelerated vascular disease seen in diabetes, The response of LDL to in vitro oxidative stress has been proposed as a measure of the predisposition of LDL to the in vivo subendothelial oxidative stress, Increased susceptibility to oxidation has been demonstrated recently in diabetic patients with poorly controlled IDDM, Thus, we conducted studies to determine whether the increased susceptibility of LDL to oxidation was secondary to diabetes per se or to the level of glycemic control, Fifteen IDDM patients with good glycemic control and with no evidence of macrovascular disease or proteinuria were compared with healthy age-, sex-, race-, and BMI-matched nondiabetic subjects, Fasting blood glucose levels averaged 12.1 +/- 1.1 (mean +/- SE) vs, 4.9 +/- 0.1 mmol/l in the diabetic versus the control groups, respectively, HbA(1c) levels averaged 7.7 +/- 0.5 vs, 4.4 +/- 0.2%, reflecting well-controlled diabetes (P < 0.0001), Total, LDL, VLDL, and HDL cholesterol, triglyceride, and lipoprotein(a) levels did not differ between the groups, The particle size, lipid composition, fatty acid content, antioxidant content, and glycation were similar for LDL isolated from both groups, A rapid LDL preparation technique was used to compare LDL susceptibility to oxidation under the following conditions: final LDL cholesterol concentration of 100 mu g/ml, 5 mu mol/l of CuCl2 at 25 degrees C, There was no difference in the susceptibility to in vitro oxidation of LDL isolated from IDDM patients compared with control subjects, There was no correlation of glycemic control with any of the parameters of the in vitro oxidation of LDL, LDL from patients with well-controlled IDDM does not differ in composition or in susceptibility to in vitro oxidative stress compared with LDL from nondiabetic subjects. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,RES SERV 1515,CHARLESTON,SC 29401. NR 52 TC 53 Z9 55 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1996 VL 45 IS 6 BP 762 EP 767 DI 10.2337/diabetes.45.6.762 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UN724 UT WOS:A1996UN72400010 PM 8635650 ER PT J AU Brown, SA Winter, M Upchurch, S Ramirez, G Anding, R AF Brown, SA Winter, M Upchurch, S Ramirez, G Anding, R TI Promoting weight loss in type II diabetes SO DIABETES CARE LA English DT Review ID LOW-CALORIE DIET; INSULIN-DEPENDENT DIABETICS; NEWLY DIAGNOSED NIDDM; LONG-TERM USE; OBESE PATIENTS; GLYCEMIC CONTROL; METABOLIC CONTROL; META-ANALYSIS; LIPOPROTEIN-LIPASE; GLUCOSE-TOLERANCE AB OBJECTIVE - To examine strategies-behavioral therapies, exercise, diet, anorectic drugs, surgery, or a combination of strategies-used for promoting weight loss in people with type Ii diabetes. RESEARCH DESIGN AND METHODS - Meta-analysis was used to synthesize research of promoting weight loss in this population. Literature search strategies involved reviewing bibliographies, conducting computer starches and surveys of relevant master's degree programs, and contacting representatives of the Centers for Disease Control. The final sample consisted of 89 studies involving 1,800 subjects. Data were extracted on 80 variables characterizing the sample of studies/subjects and on 23 outcome variables, including weight, metabolic control, lipids. and other physiological parameters. RESULTS - Diet alone had the largest statistically significant impact on weight loss (-20 lb) and metabolic control (-2.7% in glycosylated hemoglobin). All diets significantly improved fasting blood sugar. Behavioral programs alone had a statistically significant impact on weight loss (-6.4 Ib) and metabolic control (-1.5 SS) but effects were less than for dit alone. Data from the few exercise studies indicated that weighted average effects for exercise on weight loss (-3.4 Ib) and metabolic control (-0.8%) were less than diet alone. Behavioral therapy plus diet plus exercise was associated with statistically significant enter size estimates for weight loss 1-8.5 Ib) and metabolic control (-1.6%). Diet alone achieved better results. Effects of weight promotion strategies, in general, were smaller in experimental studies and for individuals over age 55. CONCLUSIONS - Dietary strategies are most effective for promoting short-term weight loss in type II diabetes. A number of gaps exist in the extant literature-descriptions of subjects, interventions, or longitudinal outcomes beyond 12 months after intervention. C1 UNIV TEXAS,HLTH SCI CTR,SCH NURSING,HOUSTON,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO COCHRANE CTR,SAN ANTONIO,TX 78284. RP Brown, SA (reprint author), UNIV TEXAS,SCH NURSING,1700 RED RIVER,AUSTIN,TX 78701, USA. FU NINR NIH HHS [NR02773] NR 109 TC 100 Z9 100 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1996 VL 19 IS 6 BP 613 EP 624 DI 10.2337/diacare.19.6.613 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UN440 UT WOS:A1996UN44000011 PM 8725861 ER PT J AU Lorenz, RA Bubb, J Davis, D Jacobson, A Jannasch, K Kramer, J Lipps, J Schlundt, D AF Lorenz, RA Bubb, J Davis, D Jacobson, A Jannasch, K Kramer, J Lipps, J Schlundt, D TI Practical lessons from the Diabetes Control and Complications Trial SO DIABETES CARE LA English DT Article C1 VANDERBILT UNIV, SCH MED, NASHVILLE, TN 37212 USA. WASHINGTON UNIV, SCH MED, ST LOUIS, MO USA. JOSLIN DIABET CTR, BOSTON, MA 02215 USA. UNIV IOWA, SCH MED, IOWA CITY, IA 52242 USA. NR 17 TC 56 Z9 56 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1996 VL 19 IS 6 BP 648 EP 652 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UN440 UT WOS:A1996UN44000016 PM 8725866 ER PT J AU Brownell, HL Narsimhan, RP Corbley, MJ Mann, VM Whitfield, JF Raptis, L AF Brownell, HL Narsimhan, RP Corbley, MJ Mann, VM Whitfield, JF Raptis, L TI Ras is involved in gap junction closure in proliferating fibroblasts or preadipocytes but not in differentiated adipocytes SO DNA AND CELL BIOLOGY LA English DT Article ID TO-CELL COMMUNICATION; INTERCELLULAR COMMUNICATION; SIGNAL-TRANSDUCTION; ADHERENT CELLS; POTENTIAL ROLE; CYCLIC-AMP; SRC GENE; EXPRESSION; TRANSFORMATION; ONCOGENE AB A decrease in gap junctional, intercellular communication (GJIC) has been associated with cells neoplastically transformed by a variety of factors, To investigate the role of the Ras oncogene product in gap junction function, a panel of murine C3H10T 1/2 (10T 1/2) fibroblasts was constructed in which the levels of ras gene expression could be effectively up- or down-regulated, Intercellular communication was measured using a novel technique of in situ electroporation of adherent cells on a partly conductive slide. The introduction of increasing amounts of activated Ras(leu61) in mouse 10T 1/2 fibroblasts proportionally reduced GJIC, while the downregulation of endogenous c-ras gene expression increased junctional permeability, These results indicate that Ras plays an important role in the junction closure pathway leading to the proliferation of normal cells. However, differentiation of c-Ras-deficient preadipocytes entirely abolished their initially extensive GJIC, indicating that junction closure in response to adipocytic differentiation is independent of Ras. C1 QUEENS UNIV,DEPT MICROBIOL & IMMUNOL,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NATL RES COUNCIL CANADA,INST BIOL SCI,OTTAWA,ON K1A 0R6,CANADA. NR 46 TC 18 Z9 20 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUN PY 1996 VL 15 IS 6 BP 443 EP 451 DI 10.1089/dna.1996.15.443 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA UW627 UT WOS:A1996UW62700002 PM 8672240 ER PT J AU Byrne, D Dirks, D AF Byrne, D Dirks, D TI Effects of acclimatization and deprivation on non-speech auditory abilities SO EAR AND HEARING LA English DT Article; Proceedings Paper CT 1st Eriksholm Consensus Conference CY AUG, 1995 CL COPENHAGEN, DENMARK SP Oticon Fdn AB This article reviews the evidence for acclimatization and deprivation with respect to non-speech auditory abilities. Although this subject has not been studied extensively, clear evidence exists for acclimatization and/or deprivation effects on intensity discrimination, binaural masking level difference, and auditory localization and lateralization. There is also some argument for such effects with regard to changes in tolerance for intense sounds or preferred levels of amplification. However, the main evidence for these effects, changes in loudness discomfort levels with repeated testing, may reasonably be explained as procedural or task-related effects rather than changes in auditory abilities. On the other hand, the successful use of tinnitus maskers to treat hyperacusis suggests that particularly low tolerance levels may be improved by exposure to certain types of auditory stimulation. Overall, this retrospective review of changes in nonspeech auditory abilities, associated with the presence or absence of listening experience, indicates that acclimatization or deprivation effects may have influenced the results of some of the experiments reviewed. This suggests that experiments designed to study acclimatization or deprivation are timely and useful. In addition, acclimatization and deprivation are potential variables that should be considered, and preferably controlled, within experiments on auditory abilities. Clinically, the review adds weight to the argument for considering acclimatization and/or deprivation in hearing aid fitting and evaluation. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Byrne, D (reprint author), NATL ACOUST LABS,126 GREVILLE ST,CHATSWOOD,NSW 2067,AUSTRALIA. NR 0 TC 15 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD JUN PY 1996 VL 17 IS 3 SU S BP S29 EP S37 DI 10.1097/00003446-199617031-00004 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA UV121 UT WOS:A1996UV12100006 PM 8807274 ER PT J AU Lowe, GN Fu, YH McDougall, S Polendo, R Williams, A Benya, PD Hahn, TJ AF Lowe, GN Fu, YH McDougall, S Polendo, R Williams, A Benya, PD Hahn, TJ TI Effects of prostaglandins on deoxyribonucleic acid and aggrecan synthesis in the RCJ 3.1C5.18 chondrocyte cell line: Role of second messengers SO ENDOCRINOLOGY LA English DT Article ID OSTEOBLAST-LIKE CELLS; PROTEOGLYCAN SYNTHESIS; ARTICULAR CHONDROCYTES; PARATHYROID-HORMONE; RETINOIC ACID; CORE PROTEIN; CARTILAGE; MODULATION; ACTIVATION; EXPRESSION AB PGs play an important role in regulating articular chondrocyte function in both normal and pathological states. However, the mechanisms of the the effects of PG on chondrocyte function remain undefined. We, therefore, examined tile effects of PGE(1), PGE(2), and PGF(2 alpha) on second messenger generation in relation to DNA and aggrecan synthesis in the nontransformed rat RCJ 3.1C5.18 (RCJ) chondrocyte cell line. RCJ cells were grown under minimal attachment conditions on a composite collagen-agarose (0.15%/0.8%) gel to maintain a differentiated phenotype. PGE(1) and PGE(2) (0.001-100 mu M) produced a similar dose-related increase in cAMP accumulation, with a maximal 8-fold increase over basal values, whereas PGF2 alpha produced a minimal 1.3-fold increase in cAMP levels only at 100 mu M. On the other hand, both PGE(2) and PGF(2 alpha) raised the intracellular Free calcium ([Ca2+](i)) concentration, derived primarily from extracellular sources, whereas PGE(1) was without effect on [Ca2+](i). These three PGs also had divergent effects on DNA synthesis, as measured by [H-3]thymidine ([H-3]TdR) incorporation. PGF(2 alpha) (0.001-5 mu M) produced a dose-related increase in [H-3]TdR incorporation, with a maximal 1.6-fold increase over baseline values at 5 mu M and a slight decline to below maximal levels at 10 mu M PGE(2) exhibited a contrasting inverse biphasic response, with an initial small suppressive effect that was maximal at 0.1 mu M and a secondary stimulatory phase producing a small increase over control values at 5 mu M. PGE(1) had a uniformly suppressive effect, producing a 30% decrease at 10 mu M Despite the divergent effects of PGE(1), PGE(2), and PGF(2 alpha) on second messenger generation and DNA synthesis, all three PGs produced a dose-related stimulation of angrecan synthesis. PGF(2 alpha) was the most potent, producing significant stimulation at 0.001 mu M and a maximal 104% increase at 5 mu M. PGE(1) and PGE(2) were approximately equipotent and approximately 60% as effective as PGF(2 alpha) in stimulating aggrecan synthesis. Northern analysis demonstrated that the effects of PG on aggrecan synthesis were not accompanied by changes in aggrecan core protein steady state messenger RNA levels. Thus, the effects of PG on aggrecan production in RCJ cells appear to be regulated at the posttranscriptional level. Forskolin and (Bu)(2)cAMP mimicked the suppressive effects of PGE(1) on [H-3]TdR incorporation, as well as the stimulatory effect of PGE(1) on aggrecan synthesis. In addition, the phorbol ester 12-O-tetradecanoyl phorbol acetate mimicked PGF(2 alpha) stimulation of [H-3]TdR incorporation and aggrecan synthesis, and the effects of PGF(2 alpha) on these processes were unlocked bg protein kinase C inhibitors. Therefore. it appears that in mammalian chondrocytes, PGE(1) primarily activates the cAMP-protein kinase a second messenger system, PGF(2 alpha) affects primarily the Ca2+-protein kinase C system, and PGE(2) activates both pathways. Moreover, PG posttranscriptional regulation of aggrecan synthesis in chondrocytes involves both the cAMP-protein kinase A and Ca2+-protein kinase C second messenger systems. C1 W LOS ANGELES VET AFFAIRS MED CTR, CTR GERIATR RES EDUC & CLIN, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA 90073 USA. ORTHOPED HOSP LOS ANGELES, J VERNON LUCK ORTHOPED RES CTR, LOS ANGELES, CA 90007 USA. UNIV SO CALIF, DEPT ORTHOPED, LOS ANGELES, CA 90033 USA. RI Benya, Paul/I-3449-2015 OI Benya, Paul/0000-0002-1060-7127 FU NIA NIH HHS [AG-00489]; NIAMS NIH HHS [AR-38463, AR-42894] NR 44 TC 42 Z9 46 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1996 VL 137 IS 6 BP 2208 EP 2216 DI 10.1210/en.137.6.2208 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UM802 UT WOS:A1996UM80200003 PM 8641167 ER PT J AU Kowluru, A Seavey, SE Rabaglia, ME Nesher, R Metz, SA AF Kowluru, A Seavey, SE Rabaglia, ME Nesher, R Metz, SA TI Carboxylmethylation of the catalytic subunit of protein phosphatase 2A in insulin-secreting cells: Evidence for for functional consequences on enzyme activity and insulin secretion SO ENDOCRINOLOGY LA English DT Article ID GTP-BINDING PROTEINS; RAT ISLETS; PANCREATIC-ISLETS; OKADAIC ACID; PHOSPHORYLATION; LANGERHANS; CAMP; ACTIVATION; INHIBITORS; CA-2+ AB We report the carboxylmethylation of a 36-kDa protein in intact normal rat islets and clonal beta (INS-1) cells. This protein was predominantly cytosolic. Its carboxylmethylation, as assessed by vapor phase equilibration assay, was resistant to inhibition by N-acetyl-S-trans,trans-farnesyl-L-cysteine, a competitive substrate for cysteine methyl transferases. These data suggest that the methylated C-terminal amino acid is not cysteine. The methylated protein was identified as the catalytic subunit of protein phosphatase 2A (PP2Ac) by immunoblotting. The carboxylmethylation of the PP2Ac increased its catalytic activity, suggesting a key role in the functional regulation of PP2A. Therefore, we studied okadaic acid, a selective inhibitor of PP2A that acts by an unknown mechanism. Okadaic acid (but not 1-nor-okadaone, its inactive analog) inhibited (K-i = 10 nM) the carboxylmethylation of PP2Ac and phosphatase activity in the cytosolic fraction (from normal rat islets and clonal beta-cells) as well as in intact rat islets. Furthermore, methylated PP2Ac underwent rapid demethylation (t(1/2) = 40 min) catalyzed by a methyl esterase localized in islet homogenates. Ebelactone, a purported inhibitor of methyl esterases, significantly delayed (>200 min) the demethylation of PP2Ac. Furthermore, ebelactone reversibly inhibited glucose- and ketoisocaproate-induced insulin secretion from normal rat islets. These data identify, for the first time, a methylation-demethylation cycle for PP2Ac in the beta-cell and suggest a key functional relationship between PP2A activity and the carboxylmethylation of its catalytic subunit. These findings thus suggest a negative modulatory role for PP2A in nutrient-induced insulin exocytosis. C1 UNIV WISCONSIN, SCH MED, ENDOCRINOL SECT, MADISON, WI 53792 USA. UNIV WISCONSIN, SCH MED, DEPT MED, MADISON, WI 53792 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MADISON, WI 53705 USA. HEBREW UNIV JERUSALEM, HADASSAH MED CTR, DEPT ENDOCRINOL & METAB, IL-91120 JERUSALEM, ISRAEL. FU NIDDK NIH HHS [DK-37312] NR 45 TC 58 Z9 59 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1996 VL 137 IS 6 BP 2315 EP 2323 DI 10.1210/en.137.6.2315 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UM802 UT WOS:A1996UM80200017 PM 8641181 ER PT J AU Krolewski, AS Warram, JH Freire, MBS AF Krolewski, AS Warram, JH Freire, MBS TI Epidemiology of late diabetic complications - A basis for the development and evaluation of preventive programs SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID CORONARY HEART-DISEASE; INSULIN-DEPENDENT DIABETICS; GLYCOSYLATION END-PRODUCTS; IMPAIRED GLUCOSE-TOLERANCE; URINARY ALBUMIN EXCRETION; RISK-FACTORS; PIMA-INDIANS; BLOOD-PRESSURE; ARTERY DISEASE; RENAL-DISEASE AB This article examines the relationship glycemia in patients with diabetes and the occurrence of complications in the eyes, kidneys, and heart. Emphasis is placed on those aspects that are relevant to the development and evaluation of preventive and therapeutic programs against these complications. Data on patients with insulin-dependent diabetes mellitus are reviewed, and the similarities and differences with the data on patients with non-insulin-dependent diabetes mellitus are discussed. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. HARVARD UNIV, SCH PUBL HLTH, DEPT EPIDEMIOL, BOSTON, MA 02115 USA. RP Krolewski, AS (reprint author), JOSLIN DIABET CTR, SECT EPIDEMIOL & GENET, DIV RES, 1 JOSLIN PL, BOSTON, MA 02215 USA. FU PHS HHS [R01 41526] NR 144 TC 42 Z9 43 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 EI 1558-4410 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD JUN PY 1996 VL 25 IS 2 BP 217 EP + DI 10.1016/S0889-8529(05)70322-4 PG 0 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UT273 UT WOS:A1996UT27300003 PM 8799698 ER PT J AU King, GL Brownlee, M AF King, GL Brownlee, M TI The cellular and molecular mechanisms of diabetic complications SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID GLYCOSYLATION END-PRODUCTS; GLUCOSE-MODIFIED PROTEINS; GLOMERULAR-BASEMENT-MEMBRANE; ALDOSE REDUCTASE INHIBITION; EXTRACELLULAR-MATRIX; GALACTOSEMIC DOGS; ENDOTHELIAL-CELLS; MESANGIAL CELLS; GROWTH-FACTOR; NITRIC-OXIDE AB Hyperglycemia-induced mechanisms that may induce diabetic vascular dysfunction include increased polyol pathway flux, altered cellular redox state, increased formation of diacylglycerol, the subsequent activation of protein kinase C isoforms, and accelerated nonenzymatic formation of advanced glycation end products. Growth factor abnormalities and insulin resistance also may have a role. C1 HARVARD UNIV,SCH MED,DEPT INTERNAL MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT INTERNAL MED,BOSTON,MA 02115. ALBERT EINSTEIN COLL MED,DEPT MED,BRONX,NY 10467. ALBERT EINSTEIN COLL MED,DIABET RES CTR,BRONX,NY 10467. RP King, GL (reprint author), JOSLIN DIABET CTR,VASC CELL BIOL SECT,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NEI NIH HHS [EY09178, EY05110]; NIDDK NIH HHS [DK23811] NR 80 TC 196 Z9 209 U1 0 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD JUN PY 1996 VL 25 IS 2 BP 255 EP & DI 10.1016/S0889-8529(05)70324-8 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UT273 UT WOS:A1996UT27300005 PM 8799700 ER PT J AU Aiello, LP Cavallerano, J Bursell, SE AF Aiello, LP Cavallerano, J Bursell, SE TI Diabetic eye disease SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RETINAL BLOOD-FLOW; PROTEIN-KINASE-C; LASER DOPPLER VELOCIMETRY; GLYCEMIC CONTROL; RAT RETINA; RETINOPATHY; COMPLICATIONS; PROGRESSION; MELLITUS AB Diabetic retinopathy accounts for most visual loss in the United States among working-age individuals. With appropriate detection, evaluation, and treatment, the risk for severe visual loss from this condition is dramatically reduced. This article details the natural history, pathophysiology, complications, grading, evaluation, and treatment for patients with diabetic retinopathy and discusses potential novel treatment modalities currently under investigation. C1 HARVARD UNIV, SCH MED, BEETHAM EYE INST, BOSTON, MA 02215 USA. RP Aiello, LP (reprint author), HARVARD UNIV, SCH MED, JOSLIN DIABET CTR, 1 JOSLIN PL, BOSTON, MA 02215 USA. NR 97 TC 14 Z9 14 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 EI 1558-4410 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD JUN PY 1996 VL 25 IS 2 BP 271 EP + DI 10.1016/S0889-8529(05)70325-X PG 0 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UT273 UT WOS:A1996UT27300006 PM 8799701 ER PT J AU Brownlee, M King, GL AF Brownlee, M King, GL TI Chronic complications of diabetes - Preface SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 JOSLIN DIABET CTR,BOSTON,MA 02215. RP Brownlee, M (reprint author), ALBERT EINSTEIN COLL MED,DIABET RES CTR,1300 MORRIS PK AVE,BRONX,NY 10461, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD JUN PY 1996 VL 25 IS 2 BP R13 EP R14 DI 10.1016/S0889-8529(05)70321-2 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UT273 UT WOS:A1996UT27300002 ER PT J AU Pegues, CF Pegues, DA Ford, DS Hibberd, PL Carson, LA Raine, CM Hooper, DC AF Pegues, CF Pegues, DA Ford, DS Hibberd, PL Carson, LA Raine, CM Hooper, DC TI Burkholderia cepacia respiratory tract acquisition: Epidemiology and molecular characterization of a large nosocomial outbreak SO EPIDEMIOLOGY AND INFECTION LA English DT Article ID PSEUDOMONAS-CEPACIA; CYSTIC-FIBROSIS; RISK-FACTORS; MEDICATION NEBULIZERS; COLONIZATION; INFECTIONS; PNEUMONIA; VENTILATION; DISEASE AB In 1994 we investigated a large outbreak of Burkholderia (formerly Pseudomonas) cepacia respiratory tract acquisition. A case patient was defined as any patient with at least one sputum culture from which B. cepacia was isolated from 1 January to 31 December 1994. Seventy cases were identified. Most (40 [61%]) occurred between 1 February and 31 March 1994; of these, 35 (86%) were mechanically ventilated patients, 30 of whom were in an intensive-care unit (ICU) when B. cepacia was first isolated. Compared with control patients who were mechanically ventilated in an ICU, these 30 case-patients were significantly more likely to have been ventilated for 2 or more days (30/30 v. 15/30; P < 0.001) or to have been intubated more than once (12/30 v. 2/30; OR = 9.3, 95% CI 1.6-68.8; P = 0.002) before the first isolation of B. cepacia. By multivariate analysis, the 35 mechanically ventilated case-patients were significantly more likely to have received a nebulized medication (OR = 11.9, 95% CI = 1.6-553.1; P < 0.001) and a cephalosporin antimicrobial (OR = 11.9, 95% CI = 1.6-553.1) in the 10 days before the first isolation of B, cepacia, compared with B, cepacia-negative control-patients matched by date and duration of most recent mechanical ventilation. Although B, cepacia was not cultured from medications or the hospital environment, all outbreak strains tested had an identical DNA restriction endonuclease digestion pattern by pulsed-field gel electrophoresis. Review of respiratory therapy procedures revealed opportunities for contamination of nebulizer reservoirs. This investigation suggests that careful adherence to standard procedures for administration of nebulized medications is essential to prevent nosocomial respiratory infections. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. CTR DIS CONTROL & PREVENT,HOSP INFECT PROGRAM,ATLANTA,GA 30341. NR 31 TC 35 Z9 36 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD JUN PY 1996 VL 116 IS 3 BP 309 EP 317 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA UV211 UT WOS:A1996UV21100011 PM 8666075 ER PT J AU Meier, CA AF Meier, CA TI Molecular pathology of familial central diabetes insipidus SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article RP Meier, CA (reprint author), MASSACHUSETTS GEN HOSP,DIV ENDOCRINE,WEL 501,FRUIT ST,BOSTON,MA 02114, USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JUN PY 1996 VL 134 IS 6 BP 683 EP 684 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UV660 UT WOS:A1996UV66000005 PM 8766934 ER PT J AU Kono, K SalazarOnfray, F Petersson, M Hansson, J Masucci, G Wasserman, K Nakazawa, T Anderson, P Kiessling, R AF Kono, K SalazarOnfray, F Petersson, M Hansson, J Masucci, G Wasserman, K Nakazawa, T Anderson, P Kiessling, R TI Hydrogen peroxide secreted by tumor-derived macrophages down-modulates signal-transducing zeta molecules and inhibits tumor-specific T cell- and natural killer cell-mediated cytotoxicity SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD3 zeta; hydrogen peroxide; cytotoxic T lymphocyte; natural killer cell ID HUMAN-LYMPHOCYTES; RECEPTOR COMPLEX; BEARING MICE; SUPPRESSION; EXPRESSION; CARCINOMA; P56(LCK); OXYGEN; CHAIN AB Although alterations in CD3-associated signal-transducing molecules in tumorinfiltrating T cells of patients with advanced cancer have been previously described, the mechanism behind these changes is not known. We demonstrate that macrophages isolated from metastatic lymph nodes of patients with malignant melanoma down-regulate levels of CD3 zeta; in autologous peripheral blood T cells. Lipopolysaccharide (LPS)- or phorbol 12-myristate 13-acetate (PMA)stimulated monocytes derived from peripheral blood of healthy donors also induced decreased expression of CD3 and CD16-associated zeta chains similar to that observed in T cells and natural killer (NK) cells of patients with advanced cancer. Go-culture with activated monocytes impaired Ca2+ mobilization in peripheral blood derived-T cells when stimulated with monoclonal antibodies to CD3 and also strongly inhibited melanoma-specific cytotoxic T lymphocyte (CTL) activity and NK activity. The presence of catalase, a scavenger of H2O2, during co-culture almost totally abrogated the inhibitory effect of activated monocytes on melanoma-specific CTL lines and on NK cells. Pre-treatment of CTL or NK cells with nontoxic concentrations (1 x 10(-5) M) of H2O2 also severely reduced their cytotoxic activity which could be prevented by catalase. The decrease in CD3 zeta and in CD16 zeta expression, induced by macrophages isolated from metastatic lymph nodes or by LPS-stimulated monocytes, was also prevented by catalase when maintained throughout the co-culture period. The possibility that monocyte/macrophage-derived reactive oxygen metabolites contribute directly to alterations in signal transducing molecules of T cells and NK cells and to the mechanism of immunosuppression in individuals with cancer should be considered. C1 KAROLINSKA INST,MICROBIOL & TUMOR BIOL CTR,S-17177 STOCKHOLM,SWEDEN. KAROLINSKA HOSP,DEPT ONCOL RADIUMHEMMET,STOCKHOLM,SWEDEN. DANA FARBER CANC INST,BOSTON,MA 02115. NR 31 TC 263 Z9 276 U1 1 U2 8 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1996 VL 26 IS 6 BP 1308 EP 1313 DI 10.1002/eji.1830260620 PG 6 WC Immunology SC Immunology GA UQ062 UT WOS:A1996UQ06200019 PM 8647210 ER PT J AU Duerinckx, AJ Valentino, DJ Hayrapetian, A Hagan, G Grant, EG AF Duerinckx, AJ Valentino, DJ Hayrapetian, A Hagan, G Grant, EG TI Ultrafast networks (ATM): First clinical experiences SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE picture archiving and communication system, (PACS); images, transmission; radiology and radiologists ID ASYNCHRONOUS TRANSFER MODE; LOS-ANGELES; PACS; TELERADIOLOGY; RADIOLOGY; IMPLEMENTATION; COMMUNICATION; INFORMATION; IMPACT; COST AB Ultrafast networks using asynchronous transfer mode (ATM) technology can provide the bandwidth and throughput that may be sufficient to satisfy the medical imaging community. Several trials are underway to assess the effect of ATM network capabilities on the clinical practice of radiology, by providing immediate interactive radiology consultations between subspecialists and general radiologists at affiliated academic institutions. The hardware to build such networks is now commercially available and its cost is decreasing steadily, but the monthly charges for ATM bandwidth use are still high. Nevertheless, given the tremendous increase in communication capability and data transfer rates possible with ATM networks, cost alone should not be the determining factor for selecting this technology. The ATM concept in general is first reviewed, followed by a description of early clinical ATM network installation in four medical environments worldwide. These medical clusters include: the UCLA affiliated hospitals (UCLA Medical Center, West LA VAMC and Olive-View UCLA Medical Center), the UCSF affiliated hospitals, Duke University Hospitals and a cluster of medical centers in Berlin which have all been connected via ATM networks. The use of ATM technology in these realistic clinical environments is discussed and evaluated for its potential impact on patient care and clinical teaching within radiology departments. From this preliminary study it is concluded that image communications over a regional PACS using an ATM network can allow interactive consultations between different subspecialist and general radiologists or other specialized radiologists spread over different medical centers. RP Duerinckx, AJ (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,SERV RADIOL,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 62 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD JUN PY 1996 VL 22 IS 3 BP 186 EP 196 DI 10.1016/0720-048X(96)00763-2 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UY879 UT WOS:A1996UY87900005 PM 8832233 ER PT J AU Neben, S Donaldson, D Fitz, L Calvetti, J Neben, T Turner, K Hirayama, F Ogawa, M AF Neben, S Donaldson, D Fitz, L Calvetti, J Neben, T Turner, K Hirayama, F Ogawa, M TI Interleukin-4 (IL-4) in combination with IL-11 or IL-6 reverses the inhibitory effect of IL-3 on early B lymphocyte development SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE lymphohematopoietic progenitor; pre-B cell colony; PWM-SCM; interleukins; inhibition ID PRIMITIVE HEMATOPOIETIC PROGENITORS; CELL COLONY FORMATION; STIMULATORY FACTOR-I; C-KIT; STEM-CELLS; PROLIFERATION; CULTURE; ENHANCEMENT; LIGAND; MAST AB We have previously described a two-step methylcellulose culture system in which individual primitive progenitors from 5-fluorouracil (5-FU)-treated mice were shown to have both myeloid and B lymphoid differentiation capacity. Highly enriched Lin(-)Sca(+)FU(2d) BM cells were cultured in methylcellulose in the presence of Steel factor (SF), interleukin-7 (IL-7), and pokeweed mitogen stimulated spleen cell conditioned medium (PWM-SCM). Primary mixed myeloid colonies were replated after 8-11 days into secondary cultures containing SF and IL-7, which supported the generation of B220(+)sIgM(-) pre-B cell colonies. A number of growth factors, including IL-6, IL-11, granulocyte colony-stimulating factor (G-CSF), and IL-12 were shown to be capable of substituting for PWM-SCM to support the B lymphoid potential of primary colonies. B lymphoid potential was not supported, however, in SF + IL-3 or in SF + IL-3 plus any single growth factor (IL-1 to -12, granulocyte-macrophage colony-stimulating factor [GM-CSF], G-CSF, erythropoietin [Epo], leukemia inhibitory factor [LIF], tumor necrosis factor-alpha: [TNF-alpha], transforming growth factor-beta [TGF-beta], gamma interferon [IFN-gamma], or insulin-like growth factor-1 [IGF-1]), but was supported in SF + IL-3 + 5% PWM-SCM. Experiments were designed to identify the factor or factors in PWM-SCM that reverse the inhibitory effects of IL-3 on B lymphoid potential. By substituting various cytokine combinations for PWM-SCM, we determined that combinations of IL-4 + IL-6 or IL-4 + IL-11, but not IL-4 alone, can substitute for PWM-SCM to reverse the inhibitory effect of IL-3 on B lymphoid potential. Neutralizing antibodies to IL-4 completely eliminated the activity in PWM-SCM, but antibodies to IL-6 only partially inhibited the activity. IL-11 was not detected in PWM-SCM, and the activity co-purified with IL-4, but not with IL-6. Thus, IL-4 plus IL-6, IL-11, or one or more unidentified growth factors in PWM-SCM can reverse the inhibitory effects of IL-3 on early B lymphocyte development in culture. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC 29425. RP Neben, S (reprint author), GENET INST INC,87 CAMBRIDGE PK DR,CAMBRIDGE,MA 02140, USA. FU NIDDK NIH HHS [DK32294] NR 25 TC 13 Z9 13 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUN PY 1996 VL 24 IS 7 BP 783 EP 789 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA UQ816 UT WOS:A1996UQ81600004 PM 8647228 ER PT J AU Brugge, WR Lee, MJ Kelsey, PB Schapiro, RH Warshaw, AL AF Brugge, WR Lee, MJ Kelsey, PB Schapiro, RH Warshaw, AL TI The use of EUS to diagnose malignant portal venous system invasion by pancreatic cancer SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ENDOSCOPIC ULTRASONOGRAPHY; ADENOCARCINOMA; CARCINOMA; CT AB Background: CT scanning and mesenteric angiography are insensitive tests for diagnosing vascular invasion by pancreatic cancer. Endoscopic ultrasound (EUS) has been proposed as an alternative. The sensitivity, specificity, and accuracy of specific EUS criteria for diagnosing malignant invasion of the branches of the portal venous system have not been determined. Methods: This is a prospective blinded evaluation of EUS and angiography to diagnose malignant invasion of the portal venous system by pancreatic cancer in 45 patients, 28 of whom underwent surgery. Surgical staging was used as the gold standard for determining the accuracy of EUS and angiography. Results: Four EUS criteria were studied and the overall accuracy rates were as follows: irregular venous wall (87%), loss of interface (78%), proximity of mass (73%), and size (39%). Although ''irregular venous wall'' was the most accurate, it suffered from a low sensitivity rate (47%) because of its relative inability to detect superior mesenteric vein invasion (sensitivity of 17%). The angiographic criteria had accuracy rates of 73% to 90% with low sensitivity rates (20% to 77%). The clean resection rate was 86% when all tests were used, 78% if EUS was used without angiography, and 60% if only angiography was used. Conclusion: EUS is highly sensitive far detecting portal and splenic vein invasion by pancreatic cancer, but may be insensitive for superior mesenteric vein involvement. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP Brugge, WR (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BULFINCH BLDG 127,BOSTON,MA 02114, USA. NR 12 TC 112 Z9 122 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUN PY 1996 VL 43 IS 6 BP 561 EP 567 DI 10.1016/S0016-5107(96)81585-9 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UT907 UT WOS:A1996UT90700003 PM 8781933 ER PT J AU Wong, DA Davis, EM LeBeau, M Springer, TA AF Wong, DA Davis, EM LeBeau, M Springer, TA TI Cloning and chromosomal localization of a novel gene-encoding a human beta(2)-integrin alpha subunit SO GENE LA English DT Article DE recombinant DNA; polymerase chain reaction; ITGAD; sequence homology ID CELL-ADHESION; P150,95 MOLECULE; LEUKOCYTE; FAMILY; LFA-1; IDENTIFICATION; INTEGRINS; MAC-1 AB We isolated a partial genomic clone encoding ITGAD, a novel beta(2)-integrin alpha subunit. The ITGAD gene is highly homologous to the three previously known alpha subunit-encoding genes, that compose the beta(2) integrin family, in deduced amino acid sequence, intron/exon structure and mapping location (chromosome 16p11). C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. FU NCI NIH HHS [CA40046, CA31799] NR 10 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 1 PY 1996 VL 171 IS 2 BP 291 EP 294 DI 10.1016/0378-1119(95)00869-1 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA UR518 UT WOS:A1996UR51800026 PM 8666289 ER PT J AU Manome, Y Wen, PY Chen, L Tanaka, T Dong, Y Yamazoe, M Hirshowitz, A Kufe, DW Fine, HA AF Manome, Y Wen, PY Chen, L Tanaka, T Dong, Y Yamazoe, M Hirshowitz, A Kufe, DW Fine, HA TI Gene therapy for malignant gliomas using replication incompetent retroviral and adenoviral vectors encoding the cytochrome P450 2B1 gene together with cyclophosphamide SO GENE THERAPY LA English DT Article DE gene therapy; gliomas cytochrome P450; cyclophosphamide; retroviral; adenoviral vectors ID THYMIDINE KINASE GENES; BRAIN-TUMOR MODEL; RAT-BRAIN; INVIVO; SYSTEM; CELLS; XENOGRAFTS AB Cyclophosphamide is an inactive prodrug which is converted by hepatic cytochrome P450 2B1 to cytotoxic metabolites which produce interstrand DNA cross-linking in a cell cycle-independent fashion. The limited ability of these metabolites to cross the blood-brain barrier contributes to the poor activity of cyclophosphamide against brain tumors. In this study we demonstrate that replication deficient retroviral and adenoviral vector-mediated gene transfer of cytochrome P450 2B1 into 9L glioma cells significantly increases the sensitivity of these tumor cells to cyclophosphamide in vitro, and prolongs the survival of animals bearing intracerebral 9L tumors treated with cyclophosphamide in vivo. Attempts to improve the effectiveness of retrovirally mediated transduction of the P450 2B1 gene by increasing the concentration cyclophosphamide delivered to the tumors using intracarotid and intratumoral injections did not prolong animal survival, although survival was increased when a second treatment with P450-expressing retroviral vectors and cyclophosphamide was administered These results suggest that in situ transduction of firmer cells with the P450 281 gene using retroviral and adenoviral vectors increases their sensitivity to cyclophosphamide and may have a potential role in the therapy of malignant gliomas. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV NEUROL,BOSTON,MA 02115. NR 34 TC 47 Z9 49 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUN PY 1996 VL 3 IS 6 BP 513 EP 520 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA UR302 UT WOS:A1996UR30200009 PM 8789801 ER PT J AU Baumeister, R Liu, YX Ruvkun, G AF Baumeister, R Liu, YX Ruvkun, G TI Lineage-specific regulators couple cell lineage asymmetry to the transcription of the Caenorhabditis elegans POU gene unc-86 during neurogenesis SO GENES & DEVELOPMENT LA English DT Article DE POU homeo domain protein; C-elegans; neurogenesis; unc-86; asymmetric cell division; transcriptional regulation ID TOUCH RECEPTOR NEURONS; CENTRAL-NERVOUS-SYSTEM; C-ELEGANS; HOMEOPROTEINS UNC-86; DOMAIN PROTEIN; MOTOR NEURONS; BODY REGION; EXPRESSION; HOMEODOMAIN; NEMATODE AB The POU homeo box gene unc-86 specifies neuroblast and neural identities in the developing Caenorhabditis elegans nervous system. After an asymmetric neuroblast division, unc-86 is expressed in one of two daughter cells in 27 lineage classes that are not obviously related by function or position. We show here that unc-86 transcriptional regulatory regions detect cell lineage asymmetry to activate unc-86 expression in one of two neuroblast daughter cells. Distinct regulatory regions activate unc-86 expression in particular sets of sublineages. Therefore the unc-86 regulatory region integrates distinct cell lineage asymmetry cues to activate unc-86 expression in the many classes of neuroblast cell lineages. In agreement with such lineage-specific regulation of unc-86 asymmetric activation, mutations in lin-11 (LIM homeo box), ham-1, and lin-17 affect the asymmetry of unc-86 expression in particular cell lineages, and mutations in lin-32 (achaete/scute family), vab-3 (Pax-G homolog) and egl-5 (Abd-B homolog) affect the establishment of unc-86 expression in other cell lineages. Homologs of unc-86 and many of these unc-86 regulators have been implicated in control of neurogenesis in vertebrates and invertebrates. These data suggest that unc-86 acts in a phylogenetically conserved pathway that couples neuroblast cell lineage asymmetry to the generation of diverse neural types. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT BIOL MOLEC,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. NR 65 TC 54 Z9 70 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 1996 VL 10 IS 11 BP 1395 EP 1410 DI 10.1101/gad.10.11.1395 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UR824 UT WOS:A1996UR82400008 PM 8647436 ER PT J AU Glazebrook, J Rogers, EE Ausubel, FM AF Glazebrook, J Rogers, EE Ausubel, FM TI Isolation of Arabidopsis mutants with enhanced disease susceptibility by direct screening SO GENETICS LA English DT Article ID PATHOGENESIS-RELATED PROTEINS; AVIRULENCE GENE AVRRPT2; ACQUIRED-RESISTANCE; BIOLOGICAL FUNCTION; SALICYLIC-ACID; FUNGAL GROWTH; PLANT; TOBACCO; CHITINASES; SYRINGAE AB To discover which components of plant defense responses make significant contributions to limiting pathogen attack, we screened a mutagenized population of Arabidopsis thaliana for individuals that exhibit increased susceptibility to the moderately virulent bacterial pathogen Pseudomonas synigae pv. maculicola ES4326 (Psm ES4326). The 12 enhanced disease Susceptibility (eds) mutants isolated included alleles of two genes involved in phytoalexin biosynthesis (pad2, which had been identified previously, and pad4, which had not been identified previously), two alleles of the previously identified npr1 gene, which affects expression of other defense genes, and alleles of seven previously unidentified genes of unknown function. The npr1 mutations caused greatly reduced expression of the PR1 gene in response to PsmES4326 infection, but had little effect on expression of two other defense genes, BGL2 and PR5, suggesting that PR1 expression may be important for limiting growth of PsmES4326. While direct screens for mutants with quantitative pathogen-susceptibility phenotypes have not been reported previously, our finding that mutants isolated in this way include those affected in known defense responses supports the notion that this type of screening strategy allows genetic dissection of the roles of various plant defense responses in disease resistance. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RI Rogers, Elizabeth/D-2087-2009; OI Rogers, Elizabeth/0000-0002-0545-4744; Glazebrook, Jane/0000-0001-5167-736X FU PHS HHS [48707] NR 39 TC 371 Z9 389 U1 1 U2 17 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 1996 VL 143 IS 2 BP 973 EP 982 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA UN684 UT WOS:A1996UN68400031 PM 8725243 ER PT J AU Sanderson, IR Xu, Z Chu, SW Xie, QY Levine, LJ Walker, WA AF Sanderson, IR Xu, Z Chu, SW Xie, QY Levine, LJ Walker, WA TI Developmental differences in the expression of the cholera toxin sensitive subunit (Gs alpha) of adenylate cyclase in the rat small intestine SO GUT LA English DT Article DE Gs alpha subunit; development; cholera toxin; ADP-ribosylation ID MESSENGER-RNA; ADP-RIBOSYLATION; ACTIVATION; PROTEINS; CELLS; EPITHELIUM; RECEPTORS; REQUIRES; LIVER; BRAIN AB Background-The stimulatory guanosine triphosphate (GTP) binding protein alpha subunit (Gs alpha) of adenylate cyclase is the target protein for cholera toxin. Aims/methods-The expression of this signal transducer was analysed in the small intestine of developing rats by RNA transfer (northern blot) analysis by immunoblotting, and by ADP-ribosylation of membrane proteins. Results-Intestinal Gs alpha mRNA (about 1 . 9 kb) was increased in the neonate compared with the adult rat. Two isoforms of Gs alpha proteins, a 45 000 and a 52 000 form, were expressed in the small intestinal epithelial cell and both were ADP-ribosylated by cholera toxin. A significant increase in the larger isoform (52 000) and in its ribosylation was noted in the 2 week old suckling compared with post-weaned older animals. The protein content or ribosylation of the smaller form (45 000) did not significantly change with age. Conclusion-These data show that a developmental decline of intestinal Gs alpha expression seems to be, in part, regulated at the mRNA level. An increased Gs alpha expression in the immature intestine may help to explain a previously reported, dose dependent increased adenylate cyclase response and an increase in fluid secretion to cholera toxin in neonates compared with adults. C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. RP MASSACHUSETTS GEN HOSP EAST, DEV GASTROENTEROL LAB, COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR, CHARLESTOWN, MA 02129 USA. FU NICHD NIH HHS [R01 HD12437, R01 HD31852] NR 37 TC 6 Z9 6 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JUN PY 1996 VL 38 IS 6 BP 853 EP 858 DI 10.1136/gut.38.6.853 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UT633 UT WOS:A1996UT63300013 PM 8984023 ER PT J AU Blumenthal, D AF Blumenthal, D TI Effects of market reforms on doctors and their patients SO HEALTH AFFAIRS LA English DT Article; Proceedings Paper CT Conference on the New Competition - Dynamics Shaping the Health Care Market CY NOV 09, 1995 CL WASHINGTON, DC SP Robert Wood Johnson Fdn, Alpha Ctr ID PRIMARY-CARE; HEALTH-CARE; PHYSICIANS; COSTS; CAPITATION AB The outcome of the competitive revolution in health care will depend critically on how it affects physicians' behavior and their interaction with patients. From the standpoint of physicians, competition often seems mediated by three influences affecting their day-to-day practice environment: the organizational phenomenon, the customer phenomenon, and the commodification phenomenon. A careful examination of these three phenomena offers reasons to believe that both the supporters and detractors of competition may be partially correct. Competitive markets may work extraordinarily well for some consumers and very poorly for others. The competitive restructuring of our health care system will accentuate the divisions and inequalities that existed in our society before the transition to a market-based health care system. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Blumenthal, D (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114, USA. NR 36 TC 42 Z9 42 U1 0 U2 1 PU PROJECT HOPE-HEALTH AFFAIRS PI SYRACUSE PA PO BOX 8015, SYRACUSE, NY 13217 SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SUM PY 1996 VL 15 IS 2 BP 170 EP 184 DI 10.1377/hlthaff.15.2.170 PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA VB839 UT WOS:A1996VB83900014 PM 8690374 ER PT J AU Blumenthal, D Meyer, GS AF Blumenthal, D Meyer, GS TI Academic health centers in a changing environment SO HEALTH AFFAIRS LA English DT Article ID MEDICAL-CENTERS; RAPID CHANGES; CARE AB To evaluate the potential problems facing academic health centers (AHCs) as a result of market-driven health care reforms, we conducted case studies of seven nationally prominent AHCs during 1994. Findings suggest that although AHCs were not yet feeling the predicted impact of competition on their financial health and ability to sustain their academic missions of teaching, research, and care of vulnerable populations, they were adopting a variety of strategies for responding to those perceived threats, especially networking and cost reduction. They were placing considerably less emphasis on restructuring their research and teaching missions to prepare for anticipated fiscal pressure. Our analysis suggests that even the most successful AHCs are likely to be fundamentally altered by the revolutionary changes occurring in health care markets. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIFORMED SERV UNIV HLTH SCI,SCH MED,BETHESDA,MD 20814. RP Blumenthal, D (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114, USA. NR 19 TC 64 Z9 64 U1 0 U2 1 PU PROJECT HOPE-HEALTH AFFAIRS PI SYRACUSE PA PO BOX 8015, SYRACUSE, NY 13217 SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SUM PY 1996 VL 15 IS 2 BP 200 EP 215 DI 10.1377/hlthaff.15.2.200 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA VB839 UT WOS:A1996VB83900016 PM 8690376 ER PT J AU Hartford, AC Zietman, AL AF Hartford, AC Zietman, AL TI Prostate cancer - Who is best benefited by external beam radiation therapy? SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID RADICAL PROSTATECTOMY; FOLLOW-UP; LOCAL-CONTROL; PROGNOSTIC FACTORS; CLINICAL STAGE; ANTIGEN LEVELS; SERUM PSA; CARCINOMA; RADIOTHERAPY; ADENOCARCINOMA AB The major indications for radical radiation therapy of prostate cancer for both early-stage and locally advanced disease are discussed. Important issues in the interpretation of long-term treatment series are reviewed. The outcomes of therapy are analyzed for both early-stage and locally advanced disease, including alternative therapeutic strategies. On the basis of this review of the literature, current treatment recommendations delineate patients most likely to benefit from radiation therapy as opposed to alternative therapeutic modalities. RP Hartford, AC (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,COX BLDG,BOSTON,MA 02114, USA. NR 65 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1996 VL 10 IS 3 BP 595 EP & DI 10.1016/S0889-8588(05)70355-5 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA UP066 UT WOS:A1996UP06600006 PM 8773499 ER PT J AU Talcott, JA AF Talcott, JA TI Quality of life in early prostate cancer - Do we know enough to treat? SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID RADICAL PROSTATECTOMY; URINARY CONTINENCE; INSTRUMENT AB Informed consent is especially important for patients with early (nonmetastatic) prostate cancer. Because it occurs in older men and usually grows slowly, most newly diagnosed patients are likely to live many years and most likely will die without symptoms of metastatic cancer. The complications of treatment, however, may begin within months and be permanent. Recent studies using modem survey techniques are beginning to provide accurate information on treatment complications. A careful, thorough discussion between doctor and patient is necessary to identify the best available therapy for each patient. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Talcott, JA (reprint author), DANA FARBER CANC INST,DIV MED ONCOL,D1118,44 BINNEY ST,BOSTON,MA 02115, USA. FU AHRQ HHS [HS06824] NR 32 TC 14 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1996 VL 10 IS 3 BP 691 EP & DI 10.1016/S0889-8588(05)70361-0 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA UP066 UT WOS:A1996UP06600012 PM 8773505 ER PT J AU Jacobson, JO Kantoff, PW AF Jacobson, JO Kantoff, PW TI Untitled - Preface SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Jacobson, JO (reprint author), VET ADM MED CTR W ROXBURY,HEMATOL ONCOL PROGRAM,1400 VFW PKWY,BOSTON,MA 02132, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1996 VL 10 IS 3 BP R13 EP R13 DI 10.1016/S0889-8588(05)70350-6 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA UP066 UT WOS:A1996UP06600001 ER PT J AU Lohi, J Leivo, I Tani, T Kiviluoto, T Kivilaakso, E Burgeson, RE Virtanen, I AF Lohi, J Leivo, I Tani, T Kiviluoto, T Kivilaakso, E Burgeson, RE Virtanen, I TI Laminins, tenascin and type VII collagen in colorectal mucosa SO HISTOCHEMICAL JOURNAL LA English DT Article ID HUMAN SMALL-INTESTINE; EXTRACELLULAR-MATRIX PROTEINS; CRYPT-VILLUS AXIS; A-CHAIN ISOFORMS; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODIES; ANCHORING FIBRILS; BASEMENT-MEMBRANE; TISSUES; LOCALIZATION AB The distribution of different laminin polypeptides, type VII collagen and tenascin has been studied in adult and foetal colorectal mucosa by using the indirect immunofluorescence technique. Immunoreactivity for laminin al chain was located to basement membranes of epithelia, muscularis mucosae, and blood vessels, respectively in different segments of adult colon and rectum. Laminin beta 1 and gamma 1 chains were additionally expressed in lamina propria. Laminin alpha 2 chain was also found in lamina propria around the pericryptal fibroblasts. Immunoreactivity for laminin beta 2 chain was restricted to basement membranes in the muscularis mucosae and arteries. Laminin alpha 3 and beta 3 chains, suggestive for laminin-5, were confined especially to surface epithelial basement membranes. Immunoreactivity for type VII collagen was confined to basement membrane of surface epithelium in a punctate manner, while that for tenascin was seen slightly more broadly in the basement membrane zone and also in the muscular layer. The distribution of laminin chains in 16-week-foetal colon mostly resembled that of corresponding adult tissue, although immunoreactivities for laminin alpha 2 and beta 2 chains were lacking. Type VII collagen and the high molecular weight isoform of tenascin were also absent from the foetal colon. The results show that the basement membrane of the surface epithelium of colon and rectum express the components of epithelial adhesion complex, laminin-5 (alpha 3-beta 3-gamma 2) and type VII collagen, resembling in this respect small intestine and stomach while laminin-2 (alpha 2-beta 1-gamma 1) appears to be associated with pericryptal fibroblasts, and laminin-l (alpha 1-beta 1-gamma 1) widely in most basement membranes. C1 UNIV HELSINKI, DEPT PATHOL, FIN-00014 HELSINKI, FINLAND. UNIV HELSINKI, CENT HOSP, DEPT SURG 2, FIN-00290 HELSINKI, FINLAND. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, CUTANEOUS BIOL RES CTR, CHARLESTOWN, MA 02129 USA. RP Lohi, J (reprint author), UNIV HELSINKI, DEPT ANAT, INST BIOMED, POB 9 SILTAVUORENPENGER 20A, FIN-00014 HELSINKI, FINLAND. NR 51 TC 37 Z9 37 U1 0 U2 3 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0018-2214 J9 HISTOCHEM J JI Histochem.J. PD JUN PY 1996 VL 28 IS 6 BP 431 EP 440 DI 10.1007/BF02331434 PG 10 WC Cell Biology SC Cell Biology GA VB816 UT WOS:A1996VB81600002 PM 8863048 ER PT J AU Yunis, EJ AF Yunis, EJ TI The Rose Payne Award lecture of 1992 revisited SO HUMAN IMMUNOLOGY LA English DT Editorial Material ID MAJOR HISTOCOMPATIBILITY COMPLEX; HEPATITIS-B VACCINE; CELL-MEDIATED LYMPHOLYSIS; EXTENDED MHC HAPLOTYPES; PEMPHIGUS-VULGARIS; IMMUNE-RESPONSE; UNRELATED INDIVIDUALS; RESTRICTION FRAGMENT; JEWISH PATIENTS; C2 DEFICIENCY C1 AMER RED CROSS,NEW ENGLAND REG,DEDHAM,MA. RP Yunis, EJ (reprint author), DANA FARBER CANC INST,44 BINNEY ST,LHRRB203,BOSTON,MA 02115, USA. NR 82 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 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD JUN-JUL PY 1996 VL 48 IS 1-2 BP 139 EP 147 DI 10.1016/0198-8859(96)00015-8 PG 9 WC Immunology SC Immunology GA UY579 UT WOS:A1996UY57900017 PM 8824583 ER PT J AU VanOrsouw, NJ Li, DZ vanderVlies, P Scheffer, H Eng, C Buys, CHCM Li, FP Vijg, J AF VanOrsouw, NJ Li, DZ vanderVlies, P Scheffer, H Eng, C Buys, CHCM Li, FP Vijg, J TI Mutational scanning of large genes by extensive PCR multiplexing and two-dimensional electrophoresis: Application to the RB1 gene SO HUMAN MOLECULAR GENETICS LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; POLYMERASE CHAIN-REACTION; SINGLE-BASE CHANGES; CYSTIC-FIBROSIS GENE; GC-CLAMP; DNA FRAGMENTS; IDENTIFICATION; RETINOBLASTOMA; SUBSTITUTIONS; EFFICIENT AB With the rapid increase in the number of identified human disease genes, the development of accurate and cost-efficient mutation tests has become opportune. Here we present a combination of extensive PCR multiplexing and two dimensional (2-D) DNA electrophoresis to screen for mutations in 26 exons of the retinoblastoma (RBI) tumor suppressor gene. In 2-D electrophoresis, fragments are separated according to size and base pair sequence in non-denaturing and denaturing gradient gels, respectively. All target fragments, designed to have optimal melting characteristics, were prepared in a two-step PCR (a 6-plex long-PCR pre-amplification and a subsequent 25-plex short-PCR) followed by heteroduplexing. The mixture of PCR amplicons was then subjected to 2-D electrophoresis under a single set of experimental conditions. With this design, 35 previously identified mutations in 18 different exons were detected in 33 bilateral retinoblastoma patients. These results suggest that 2-D electrophoresis in this format provides a generally applicable, practical and fast way to diagnose with high accuracy large genes for a broad spectrum of possible disease-causing mutations. C1 BETH ISRAEL HOSP,DEPT MED,GERONTOL DIV,MOLEC GENET SECT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. UNIV GRONINGEN,DEPT MED GENET,9713 AW GRONINGEN,NETHERLANDS. DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. RI Scheffer, Hans/E-4644-2012; OI Scheffer, Hans/0000-0002-2986-0915; Eng, Charis/0000-0002-3693-5145 FU NEI NIH HHS [EY05321] NR 26 TC 26 Z9 27 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1996 VL 5 IS 6 BP 755 EP 761 DI 10.1093/hmg/5.6.755 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA UQ072 UT WOS:A1996UQ07200005 PM 8776589 ER PT J AU Karlsson, JOM Eroglu, A Toth, TL Cravalho, EG Toner, M AF Karlsson, JOM Eroglu, A Toth, TL Cravalho, EG Toner, M TI Fertilization and development of mouse oocytes cryopreserved using a theoretically optimized protocol SO HUMAN REPRODUCTION LA English DT Article DE cryopreservation; mouse oocytes; optimization; rational design; theoretical modelling ID INTRACELLULAR ICE FORMATION; INVITRO FERTILIZATION; DIMETHYL-SULFOXIDE; BIOLOGICAL CELLS; LOW-TEMPERATURES; COOLING RATES; EMBRYOS; EGGS; CONSEQUENCES; PREGNANCY AB Rational design of a cryopreservation protocol was demonstrated by using theoretical models of the cryopreservation process to develop an optimal freezing protocol for mouse oocytes, A coupled mechanistic model of the processes of freeze-induced cell dehydration and intracellular ice formation was developed, and cryomicroscopical measurements of intracellular ice formation kinetics were used to determine biophysical parameters required by the model, and to test model predictions of the freezing behaviour of mouse oocytes, A simple phenomenological model for oocyte damage resulting from exposure to concentrated electrolyte and cryoprotectant solutions during cryopreservation was obtained by defining a cost function equal to the duration of the freezing protocol, A two-step freezing protocol was theoretically optimized by using a sequential simplex algorithm to minimize the cost function, subject to the constraint that the predicted probability of intracellular ice formation remain below 5%, yielding a putative optimum at the cooling rate B = 0.59 degrees C/min, and plunge temperature T-p = -67 degrees C, By systematically varying B and T-p about these values in experiments with mouse oocytes cryopreserved in 1.5 M dimethyl sulphoxide, the maximal recovery of intact oocytes with a normal morphology (82%) was obtained for B = 0.5 degrees C/min and T-p = -80 degrees C, Further evaluation of the fertilizability and developmental capacity of oocytes cryopreserved using the optimized protocol yielded cleavage to the 2-cell stage in 65% of oocytes inseminated, and blastocyst formation in 50% of these 2-cell embryos. C1 MASSACHUSETTS GEN HOSP,CTR ENGN MED & SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,OBSTET & GYNECOL SERV,BOSTON,MA. MIT,DEPT MECH ENGN,CAMBRIDGE,MA 02139. NR 44 TC 82 Z9 86 U1 2 U2 10 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 1996 VL 11 IS 6 BP 1296 EP 1305 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA UZ657 UT WOS:A1996UZ65700037 PM 8671443 ER PT J AU ParhamiSeren, B Keel, T Reed, GL AF ParhamiSeren, B Keel, T Reed, GL TI Structural characterization of immunodominant regions of streptokinase recognized by murine monoclonal antibodies SO HYBRIDOMA LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; INTRAVENOUS STREPTOKINASE; NEUTRALIZATION TITERS; PLASMINOGEN; CELLS AB In order to determine the nature of the antigenic and functional determinants of streptokinase (SK), we produced monoclonal antibodies (MAbs) by immunizing A/J mice with native SK protein. By virtue of their differential binding to a large panel of recombinant SK truncated proteins, and their effect on the formation of functional SK-plasminogen activator complex (SKPAC), these MAbs were found to recognize 6 unique and minimally overlapping epitopes on the SK protein, The fine epitope specificity of the anti-SK MAbs derived from A/J mice was compared with that of MAbs derived from BALB/c mice. A number of MAbs from both inbred strains of mice were directed against the same sequences of SK (1-13, 1-253, 120-352) suggesting that these regions of the molecule contain peptide sequences that are immunodominant. Two of the ''immunodominant'' sequences of SK protein appeared to be important for SK function, since the formation of SKPAC could be inhibited by MAbs against these sequences. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP ParhamiSeren, B (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA24432]; NHLBI NIH HHS [HL-02348] NR 24 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1996 VL 15 IS 3 BP 169 EP 176 DI 10.1089/hyb.1996.15.169 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA UX055 UT WOS:A1996UX05500001 PM 8823613 ER PT J AU ParhamiSeren, B AF ParhamiSeren, B TI MAb antistreptokinase monoclonal antibodies SO HYBRIDOMA LA English DT Article RP ParhamiSeren, B (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,JACKSON 14,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1996 VL 15 IS 3 BP 242 EP 242 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA UX055 UT WOS:A1996UX05500014 ER PT J AU Stec, DE Trolliet, MR Krieger, JE Jacob, HJ Roman, RJ AF Stec, DE Trolliet, MR Krieger, JE Jacob, HJ Roman, RJ TI Renal cytochrome P4504A activity and salt sensitivity in spontaneously hypertensive rats SO HYPERTENSION LA English DT Article DE hydroxyeicosatetraenoic acids; rats, inbred strains; sodium, dietary; genotype; cytochrome P450 ID ARACHIDONIC-ACID; BLOOD-PRESSURE; ARCUATE ARTERIES; VASCULAR TONE; METABOLISM; PREVENTS; KIDNEY; GENES AB Differences in the renal metabolism of arachidonic acid by cytochrome P450 have been reported in the spontaneously hypertensive rat (SHR) and Wistar-Koyto rats, but the contribution of this system to the development of hypertension is unclear. The present study compared renal P450 activity and blood pressure in SHR and Brown-Norway rats (BN) under control conditions and in response to an elevation in sodium intake; genetic linkage analysis was performed in an F-2 population (n=219) derived from these strains. Basal renal P4504A enzyme activity measured by conversion of [C-14]arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) was significantly greater in the kidneys of adult SHR (n=7) than of BN (n=8) (82+/-7 versus 60+/-5 pmol/min per milligram protein). Renal 20-HETE production fell 45% in SHR and 22% in BN in which salt intake was elevated by drinking of saline instead of water for 2 weeks. Mean arterial pressure averaged 157+/-3 mm Hg in SHR (n=9) and 100+/-2 mm Hg in BN fed a normal salt diet, and it rose to 170+/-7 mm Hg (P<.05) in SHR and fell to 90+/-3 mm Hg (P<.05) in BN (n=8) after sodium intake was elevated. A polymorphic marker, D5Rjrl, that spanned a repeated element in the P4504A1 gene on chromosome 5, where all three P4504A isoforms are located, was used for genotyping of the F-2 population. The P4504A genotype did not cosegregate with baseline mean arterial pressure in the F-2 population; however, significant linkage was observed with the change in mean arterial pressure after sodium intake of the rats was elevated. The degree of linkage differed in male and female rats, and the highest LOD score (3.6) was observed in male F-2 rats with a BN grandfather. These findings suggest that the difference in renal P450 activity in SHR and BN does not contribute to the development of hypertension in this F-2 population, but it may play some role in determining the blood pressure response to an elevation in salt intake. C1 MED COLL WISCONSIN,DEPT PHYSIOL,MILWAUKEE,WI 53226. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA. UNIV SAO PAULO,SAO PAULO HEART INST,SCH MED,BR-05508 SAO PAULO,BRAZIL. RI Krieger, Jose/C-3117-2011; OI Krieger, Jose/0000-0001-5464-1792 FU NHLBI NIH HHS [HL36279] NR 30 TC 55 Z9 53 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 1996 VL 27 IS 6 BP 1329 EP 1336 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UP223 UT WOS:A1996UP22300022 PM 8641744 ER PT J AU Ullian, ME HazenMartin, DJ Walsh, LG Davda, RK Egan, BM AF Ullian, ME HazenMartin, DJ Walsh, LG Davda, RK Egan, BM TI Carbenoxolone damages endothelium and enhances vasoconstrictor action in aortic rings SO HYPERTENSION LA English DT Article DE carbenoxolone; endothelium; muscle, smooth, vascular; vasoconstriction; receptors, adrenergic; angiotensin II ID NITRIC-OXIDE; MINERALOCORTICOID ACTION; HYPERTENSION; RAT; GLUCOCORTICOIDS; ALDOSTERONE; ANGIOTENSIN; DEXAMETHASONE; INHIBITION; RESPONSES AB Carbenoxolone causes hypertension indirectly by inhibition of 11 beta-hydroxysteroid dehydrogenase and consequent elevation of intracellular glucocorticoid levels and enhancement of vasoconstrictor action. We performed the present study to determine whether carbenoxolone also enhances vascular tone directly by mechanisms independent of glucocorticoids and other systemic influences. Exposure of rat aortic rings to 10 to 100 mu mol/L carbenoxolone in aerated Krebs-Henseleit buffer for 24 hours resulted in concentration-dependent increases in angiotensin II (Ang II) (100 nmol/L)-stimulated contractions and significant shifting of the phenylephrine cumulative contraction curve to the left but not increases in KCl (120 mmol/L)-stimulated contractions. Maximal enhancement of Ang II contraction was 39%. In contrast, brief (15-minute) exposure to 100 mu mol/L carbenoxolone did not alter Ang II contractions. Mechanical denudation of the endothelium obviated enhancement of Ang II contractions by carbenoxolone, suggesting interaction of carbenoxolone with the endothelium. Endothelium-dependent relaxation of precontracted rings to acetylcholine of ATP was reduced by more than 90% by 24-hour pretreatment with 100 mu mol/L carbenoxolone but not with 100 mu mol/L deoxycorticosterone acetate (a mineralocorticoid) or 100 mu mol/L glycyrrhizic acid (a natural 11 beta-hydroxysteroid dehydrogenase inhibitor). Vascular smooth muscle relaxation with sodium nitroprusside was not inhibited by carbenoxolone. Incubation of cultured endothelial cells with 100 mu mol/L carbenoxolone for 24 hours did not inhibit nitric oxide synthase activity, as measured by conversion of [H-3]L-citrulline. Electron micrography demonstrated that endothelial cell ultrastructure but not vascular smooth muscle cell ultrastructure was abnormal after incubation of rings for 24 hours with 100 mu mol/L carbenoxolone. These studies suggest that carbenoxolone concentrations higher than 10 mu mol/L enhance vasoconstrictor action via selective toxicity to the endothelium and elimination of endothelium-dependent relaxation. C1 MED UNIV S CAROLINA,DEPT PATHOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT PHARMACOL,CHARLESTON,SC 29425. RALPH H JOHNSON VET ADM HOSP,CHARLESTON,SC. RP Ullian, ME (reprint author), MED UNIV S CAROLINA,DIV NEPHROL,DEPT MED,CLIN SCI BLDG 829,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 32 TC 22 Z9 22 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 1996 VL 27 IS 6 BP 1346 EP 1352 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UP223 UT WOS:A1996UP22300025 PM 8641747 ER PT J AU Rudd, CE AF Rudd, CE TI Upstream-downstream: CD28 cosignaling pathways and T cell function SO IMMUNITY LA English DT Review ID SIGNAL-TRANSDUCTION; ACTIVATION; RECEPTOR; COSTIMULATION; MOLECULES RP Rudd, CE (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 70 TC 178 Z9 179 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 1996 VL 4 IS 6 BP 527 EP 534 DI 10.1016/S1074-7613(00)80479-3 PG 8 WC Immunology SC Immunology GA UU443 UT WOS:A1996UU44300001 PM 8673699 ER PT J AU Shang, ES Summers, TA Haake, DA AF Shang, ES Summers, TA Haake, DA TI Molecular cloning and sequence analysis of the gene encoding LipL41, a surface-exposed lipoprotein of pathogenic Leptospira species SO INFECTION AND IMMUNITY LA English DT Article ID INTERROGANS SEROVAR HARDJO; TREPONEMA-PALLIDUM DETERMINES; OUTER-MEMBRANE PROTEIN; BORRELIA-BURGDORFERI; ESCHERICHIA-COLI; BOVIS INFECTION; VACCINATION; IMMUNOGEN; CATTLE; ANTIGENS AB We report the cloning of the gene encoding a surface-exposed leptospiral lipoprotein, designated LipL41. In a previous study, a 41-kDa protein antigen was identified on the surface of Leptospira kirschneri (D. A. Haake, E. M. Walker, D. R. Blanco, C. A. Bolin, J. N. Miller, and M. A. Lovett, Infect. Immun. 59:1131-1140, 1991), We obtained the N-terminal amino acid sequence of a staphylococcal V8 proteolytic-digest fragment in order to design an oligonucleotide probe. A Lambda ZAP II library containing EcoRI fragments of L. kirschneri DNA was Screened, and a 2.3-kb DNA fragment which contained the entire structural lipL41 gene was identified. The deduced amino acid sequence of LipL41 would encode a 355-amino-acid polypeptide with a 19-amino-acid signal peptide, followed by an L-X-Y-C lipoprotein signal peptidase cleavage site, A recombinant His(6)-LipL41 fusion protein was expressed in Escherichia coli in order to generate specific rabbit antiserum. LipL41 is solubilized by Triton X-114 extraction of L. kirschneri; phase separation results in partitioning of LipL41 exclusively into the detergent phase. At least eight proteins, including LipL41 and the other major Triton X-114 detergent phase proteins, are intrinsically labeled during incubation of L. kirschneri in media containing [H-3] palmitate, Processing of LipL41 is inhibited by globomycin, a selective inhibitor of lipoprotein signal peptidase. Triton X-100 extracts of L. kirschneri contain immunoprecipitable OmpL1 (porin), LipL41, and another lipoprotein, LipL36, However, in contrast to LipL36, only LipL41 and OmpL1 were exposed on the surface of intact organisms. Immunoblot analysis of a panel of Leptospira species reveals that LipL41 expression is highly conserved among leptospiral pathogens. C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV INFECT DIS,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90095. FU NCI NIH HHS [CA16042]; NIAID NIH HHS [2-T32-AI07323-06] NR 56 TC 104 Z9 141 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1996 VL 64 IS 6 BP 2322 EP 2330 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UN189 UT WOS:A1996UN18900062 PM 8675344 ER PT J AU Chanock, SJ Gorlin, JB AF Chanock, SJ Gorlin, JB TI Granulocyte transfusions - Time for a second look SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; COLONY-STIMULATING FACTOR; PROGRAMMED CELL-DEATH; LEUKOCYTE TRANSFUSIONS; POLYMORPHONUCLEAR LEUKOCYTES; HUMAN NEUTROPHILS; INFECTION; SURVIVAL; THERAPY; NEUTROPENIA AB Among the available therapies to support neutropenic patients with infection, granulocyte transfusions have generated considerable controversy. Plagued by the inconvenience of harvesting cells, infusion-associated toxicity, and marginal efficacy, granulocyte transfusions, once in vogue in the 1980s, had been relegated to a secondary role. Several recent developments, however, have given new impetus to re-evaluating the role of granulocyte transfusions. The two most notable reasons include the ability to increase the number of circulating granulocytes in the donor by treatment with one or two doses of recombinant hematopoietic growth factors, such as granulocyte- and granulocyte-macrophage colony stimulating factor, and improvements in the efficiency of the collection process. Armed with these advances, it is an appropriate time to review the existing data and consider studies designed to determine the appropriate role of granulocyte transfusions in neutropenic hosts. C1 CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA. RP Chanock, SJ (reprint author), NCI,NIH,PEDIAT BRANCH,10-13N240,BETHESDA,MD 20892, USA. NR 66 TC 26 Z9 27 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 1996 VL 10 IS 2 BP 327 EP & DI 10.1016/S0891-5520(05)70301-9 PG 18 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UV398 UT WOS:A1996UV39800006 PM 8803623 ER PT J AU Sandin, RL Rinaldi, M AF Sandin, RL Rinaldi, M TI Special considerations for the clinical microbiology laboratory in the diagnosis of infections in the cancer patient SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID CYTOMEGALO-VIRUS; MYCOBACTERIUM-TUBERCULOSIS; RAPID DIAGNOSIS; BLOOD CULTURES; CELL-CULTURES; BACT ALERT; IDENTIFICATION; AMPLIFICATION; SPECIMENS AB The clinical microbiology laboratory faces enormous challenges in diagnosing infections that cause morbidity and mortality in cancer patients. Such laboratories face several issues that surpass those faced by laboratories that perform more routine work. Issues such as sources of clinical specimens, I-reed for correlation and interaction between laboratory and clinical services, blood cultures, susceptibility testing, and the role of new molecular diagnostic techniques are considered in this article. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP Sandin, RL (reprint author), UNIV S FLORIDA,COLL MED,H LEE MOFFITT CANC CTR & RES INST,ROOM 2071,12902 MAGNOLIA DR,TAMPA,FL 33612, USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 1996 VL 10 IS 2 BP 413 EP & DI 10.1016/S0891-5520(05)70305-6 PG 20 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UV398 UT WOS:A1996UV39800010 PM 8803627 ER PT J AU Hamada, Y Kobayashi, K Podolsky, DK Brown, WR AF Hamada, Y Kobayashi, K Podolsky, DK Brown, WR TI Increased cytoplasmic accumulation of goblet cell glycoproteins in ulcerative colitis SO INFLAMMATORY BOWEL DISEASES LA English DT Article ID HUMAN COLONIC MUCIN; FC BINDING-SITE; INTESTINAL EPITHELIUM; SAGUINUS-OEDIPUS; DISEASE C1 DEPT VET AFFAIRS MED CTR, DEPT MED, DENVER, CO USA. UNIV COLORADO, SCH MED, DENVER, CO USA. MASSACHUSETTS GEN HOSP, GASTROINTESTINAL UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NR 15 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 EI 1536-4844 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SUM PY 1996 VL 2 IS 2 BP 97 EP 104 DI 10.1002/ibd.3780020205 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UL244 UT WOS:A1996UL24400004 PM 23282515 ER PT J AU Winter, HS AF Winter, HS TI When does a child with severe ulcerative colitis need a surgeon? SO INFLAMMATORY BOWEL DISEASES LA English DT Article C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CHILDRENS HOSP,BOSTON,MA. RP Winter, HS (reprint author), BOSTON CITY HOSP,BOSTON,MA 02118, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SUM PY 1996 VL 2 IS 2 BP 159 EP 159 DI 10.1002/ibd.3780020217 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UL244 UT WOS:A1996UL24400016 PM 23282527 ER PT J AU Kemper, P Blumenthal, D Corrigan, JM Cunningham, PJ Felt, SM Grossman, JM Kohn, LT Metcalf, CE StPeter, RF Strouse, RC Ginsburg, PB AF Kemper, P Blumenthal, D Corrigan, JM Cunningham, PJ Felt, SM Grossman, JM Kohn, LT Metcalf, CE StPeter, RF Strouse, RC Ginsburg, PB TI The design of the community tracking study: A longitudinal study of health system change and its effects on people SO INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Health-Services-Research CY JUN 09-11, 1996 CL ATLANTA, GA SP Assoc Hlth Serv Res C1 MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114. RP Kemper, P (reprint author), CTR STUDYING HLTH SYST CHANGE,600 MARYLAND AVE SW,SUITE 550,WASHINGTON,DC 20024, USA. NR 0 TC 186 Z9 186 U1 0 U2 3 PU BLUE CROSS BLUE SHIELD ASSN PI CHICAGO PA 676 N ST CLAIR ST, CHICAGO, IL 60611 SN 0046-9580 J9 INQUIRY-J HEALTH CAR JI Inquiry-J. Health Care Organ. Provis. Financ. PD SUM PY 1996 VL 33 IS 2 BP 195 EP 206 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA UW893 UT WOS:A1996UW89300011 PM 8675282 ER PT J AU Pollack, MH Gould, RA AF Pollack, MH Gould, RA TI The pharmacotherapy of social phobia SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 4th International Symposium on Moclobemide CY SEP 15-16, 1995 CL OSLO, NORWAY SP Hoffmann La Roche DE social phobia; monoamine oxidase inhibitors; moclobemide; reverse inhibitors of monoamine oxidase A; selective serotonin reuptake inhibitors ID PSYCHOPHARMACOLOGICAL TREATMENT; DOUBLE-BLIND; CLONAZEPAM; FLUOXETINE; PHENELZINE; PLACEBO; COMORBIDITY; IMIPRAMINE; SERTRALINE; ALPRAZOLAM AB Social phobia has been recognized as a discrete diagnostic condition only relatively recently. Epidemiological studies have shown that social phobia is associated with significant impairment and an increasing body of evidence has now indicated that pharmacological treatment is effective. Placebo-controlled studies have demonstrated the efficacy of the monoamine oxidase inhibitor phenelzine. A reversible inhibitor of monoamine oxidase A, moclobemide, is better tolerated and safer than the irreversible monoamine oxidase inhibitors and placebo-controlled studies have also demonstrated efficacy for this compound; moreover, positive results from a small study of brofaromine also support the efficacy of this class of compounds. It has been reported that a high-potency benzodiazepine, clonazepam, is effective but there is little placebo-controlled evidence to support the use of other benzodiazepines. Selective serotonin reuptake inhibitors are also being tested in social phobia with encouraging results. More studies are now needed on the long-term treatment of social phobia. RP Pollack, MH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,ANXIETY DISORDERS PROGRAM,ACC-815,BOSTON,MA 02114, USA. NR 41 TC 10 Z9 10 U1 2 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD JUN PY 1996 VL 11 SU 3 BP 71 EP 75 DI 10.1097/00004850-199606003-00012 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA VQ799 UT WOS:A1996VQ79900012 PM 8923113 ER PT J AU Wang, BP Hollander, GA Nichogiannopoulou, A Simpson, SJ Orange, JS GutierrezRamos, JC Burakoff, SJ Biron, CA Terhorst, C AF Wang, BP Hollander, GA Nichogiannopoulou, A Simpson, SJ Orange, JS GutierrezRamos, JC Burakoff, SJ Biron, CA Terhorst, C TI Natural killer cell development is blocked in the context of aberrant T lymphocyte ontogeny SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE bone marrow transplantation; thymus; tumor necrosis factor; tg epsilon 26 mice ID GROWTH-FACTOR-BETA; BONE-MARROW; CYTOKINE PRODUCTION; CD8 THYMOCYTES; NK CELLS; MICE; DIFFERENTIATION; MATURE; ALPHA; INTERFERON AB Over-expression of human or mouse CD3-epsilon transgenes profoundly disturbs T lymphocyte and natural killer (NK) cell development, One of these transgenic strains, termed tg epsilon 26, displays a very early block in T lymphocyte and NK cell development, We showed previously that the absence of early thymocyte progenitors results in an abnormal thymic microenvironment, Due to this thymic defect, T cell development could not be restored by bone marrow (BM) transplantation in adult tg epsilon 26 mice but could in fetal tg epsilon 26 mice, Here we examine the effect of this abnormal thymic environment on NK cell development, We demonstrate that NK cell maturation in tg epsilon 26 mice was reconstituted by BM derived from completely T cell-deficient mice, i,e, RAG-2(-/-) and TCR beta x delta(-/-), but not from wild-type mice, Moreover, tg epsilon 26 mice transplanted with BM from partially T cell-deficient mice, i,e, TCR alpha(-/-), TCR beta(-/-) and TCR delta(-/-) mice, did not reconstitute their NK cell compartment. We conclude from these studies that the thymic environment is not required for NK cell development, but that aberrantly educated alpha beta or gamma delta T lymphocytes can influence NK cell ontogeny, Furthermore, high serum levels of tumor necrosis factor (TNF) were detected in the vast majority of tg epsilon 26 mice transplanted with BM cells derived from partially T cell-deficient mice, but never from tg epsilon 26 mice transplanted with BM cells derived from completely T cell-deficient mice, The high levels of TNF may play an important role in the observed inhibition of NK cell development, since in vivo treatment with an anti-TNF antibody restored NK cell development. C1 HARVARD UNIV,DANA FARBER CANC INST,DIV PEDIAT ONCOL,SCH MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02215. BROWN UNIV,DIV BIOL & MED,PROVIDENCE,RI 02912. RP Wang, BP (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,DIV IMMUNOL,SCH MED,BOSTON,MA 02215, USA. RI Orange, Jordan/D-5239-2009; OI orange, jordan/0000-0001-7117-7725 FU NCI NIH HHS [CA41268]; NIAID NIH HHS [AI-35714, AI-17651] NR 62 TC 23 Z9 23 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 1996 VL 8 IS 6 BP 939 EP 949 DI 10.1093/intimm/8.6.939 PG 11 WC Immunology SC Immunology GA UU915 UT WOS:A1996UU91500014 PM 8671683 ER PT J AU Young, EW Forti, EM Preston, DB AF Young, EW Forti, EM Preston, DB TI Rural nurses' use of universal precautions in relation to perceived knowledge of patient's HIV status SO INTERNATIONAL JOURNAL OF NURSING STUDIES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-B VIRUS; RISK; WORKERS; AIDS; INFECTION; BLOOD; PREVENTION; ATTITUDES; EMERGENCY AB The increased incidence of AIDS in rural areas of the United States has called attention to the practice of universal precautions by rural nurses. The purpose of this research was to determine protective barrier use by 555 nurses living in rural counties in Pennsylvania and New York State and the effect on this use of their knowledge of their patients' HIV status. Findings suggest that nurses increased their use of protection if they knew their patients were HIV-positive. However, if they thought that their patients were HIV-negative or if they did not know their patients' HIV status, they did not always use adequate protection. Findings are discussed as they relate to the context of rural nursing practice, Copyright (C) 1996 Elsevier Science Ltd. C1 MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. PENN STATE UNIV,UNIVERSITY PK,PA 16802. PENN STATE UNIV,DEPT HLTH EDUC & NURSING,UNIVERSITY PK,PA 16802. NR 47 TC 4 Z9 5 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0020-7489 J9 INT J NURS STUD JI Int. J. Nurs. Stud. PD JUN PY 1996 VL 33 IS 3 BP 249 EP 258 DI 10.1016/0020-7489(95)00057-7 PG 10 WC Nursing SC Nursing GA UM745 UT WOS:A1996UM74500002 PM 8736470 ER PT J AU Wang, CC Efird, J Nakfoor, B Martins, P AF Wang, CC Efird, J Nakfoor, B Martins, P TI Local control of T3 carcinomas after accelerated fractionation: A look at the ''gap'' SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE accelerated hyperfractionated radiation therapy; treatment gaps; BID radiation therapy; oropharyngeal carcinoma; laryngeal carcinoma ID SQUAMOUS-CELL CARCINOMA AB Purpose: To study the effects of midcourse treatment break or gaps related to the local control of T3 carcinoma of the oropharynx and larynx following accelerated hyperfractionated radiation therapy. Methods and Materials: All patients were treated at the Massachusetts General Hospital from 1979 through 1994 with treatment consisting of 1.6 Gy per fraction, two fractions a day for the treatment of T3 carcinoma of the oropharynx and larynx. They were entered in the head and neck data base, Their treatment dates, treatment breaks, and doses vs, local control were analyzed and compared, A p-value of 0.05 was considered statistically significant. Results: A total of 162 patients were available for review, Due to the acute severe mucosal effects, most of the patients required a midcourse pause or ''break'' after a dose of 38.4-48 Gy before treatment could be resumed and completed, The data indicate that (a) prolongation of the treatment gap for more than 14 days, (b) total treatment course longer than 45 days, (c) total dose less than 67 Gy, and (d) male gender adversely affected local control. In spite of the gaps, the female patients with advanced carcinomas enjoyed the benefits of improved local control after the accelerated hyperfractionated radiation therapy. Conclusions: Accelerated hyperfractionation radiation therapy using 1.6 Gy per fraction/twice-a-day (b.i.d.) for a total dose of 70.4 Gy in 6 weeks is effective in achieving high local control of T3 squamous cell carcinoma of the oropharynx and larynx. The midcourse treatment gap should be as short as possible with the projected total dose and time, Should the gaps be unduly prolonged due to various circumstances, further increase in the total dose, for example, 72-75 Gy, and/or increase of the fraction sizes, for example, 1.8-2.0 Gy/f b.i.d. after the gap may be necessary to compensate for the adverse effects of the tumor regeneration from the prolonged gap. RP Wang, CC (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 7 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 1996 VL 35 IS 3 BP 439 EP 441 DI 10.1016/S0360-3016(96)80004-6 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA UT724 UT WOS:A1996UT72400003 PM 8655365 ER PT J AU Abad, JC Foster, CS AF Abad, JC Foster, CS TI Fungal keratitis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID FUSARIUM-SOLANI KERATITIS; AMPHOTERICIN-B; CANDIDA KERATITIS; TOPICAL KETOCONAZOLE; ANTIFUNGAL AGENTS; SOUTH FLORIDA; KERATOMYCOSIS; MICONAZOLE; PENETRATION; THERAPY RP Abad, JC (reprint author), MASSACHUSETTS EYE & EAR INFIRM,CORNEA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 70 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 1 EP 15 DI 10.1097/00004397-199603630-00003 PG 15 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500002 PM 8989596 ER PT J AU Chang, EJ Dreyer, EB AF Chang, EJ Dreyer, EB TI Herpesvirus infections of the anterior segment SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID ZOSTER OPHTHALMICUS; ORAL ACYCLOVIR; SIMPLEX VIRUS; KERATITIS; THERAPY RP Chang, EJ (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 31 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 17 EP 28 DI 10.1097/00004397-199603630-00004 PG 12 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500003 PM 8989597 ER PT J AU Huang, MC Dreyer, E AF Huang, MC Dreyer, E TI Parinaud's oculoglandular conjunctivitis and cat-scratch disease SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID ROCHALIMAEA-HENSELAE INFECTION; BACILLARY ANGIOMATOSIS; ANTIBIOTIC-THERAPY; DOMESTIC CAT; SP-NOV; ANTIBODIES; DIAGNOSIS; ANTIGENS; DNA RP Huang, MC (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 30 TC 2 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 29 EP 36 DI 10.1097/00004397-199603630-00005 PG 8 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500004 PM 8989598 ER PT J AU Pineda, R Dohlman, CH AF Pineda, R Dohlman, CH TI Adjunctive therapy and surgical considerations in the management of bacterial ulcerative keratitis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID EXPERIMENTAL PSEUDOMONAS KERATITIS; INFECTIOUS KERATITIS; AERUGINOSA ELASTASE; MICROBIAL KERATITIS; CORNEAL BIOPSY; CRYOTHERAPY; INHIBITION; COLLAGEN; ADHESIVE RP Pineda, R (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,CORNEA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 32 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 37 EP 48 DI 10.1097/00004397-199603630-00006 PG 12 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500005 PM 8989599 ER PT J AU Young, JA Ryan, ET AF Young, JA Ryan, ET TI Parasitic infections of the anterior segment SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID LINKED IMMUNOELECTROTRANSFER BLOT; ACANTHAMOEBA-KERATITIS; MICROSPORIDIAL KERATOCONJUNCTIVITIS; POLYHEXAMETHYLENE BIGUANIDE; INTRAOCULAR CYSTICERCOSIS; EOSINOPHILIC MENINGITIS; TOPICAL FUMAGILLIN; OCULAR INVOLVEMENT; CHAGAS-DISEASE; UNITED-STATES RP Young, JA (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,CORNEA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 86 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 49 EP 71 DI 10.1097/00004397-199603630-00007 PG 23 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500006 PM 8989600 ER PT J AU Braun, C AF Braun, C TI Late infections associated with glaucoma surgery SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID TERM FOLLOW-UP; MITOMYCIN-C; FILTERING SURGERY; POSTOPERATIVE ENDOPHTHALMITIS; ADJUNCTIVE 5-FLUOROURACIL; INTRAOPERATIVE MITOMYCIN; PSEUDOPHAKIC PATIENTS; MOLTENO IMPLANTATION; FILTRATION SURGERY; BLEB INFECTION C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. NR 56 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 73 EP 85 DI 10.1097/00004397-199603630-00008 PG 13 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500007 PM 8989601 ER PT J AU Kanellopoulos, AJ Dreyer, EB AF Kanellopoulos, AJ Dreyer, EB TI Postoperative infection following current cataract extraction surgery SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID INTRAOCULAR-LENS IMPLANTATION; PROPIONIBACTERIUM ENDOPHTHALMITIS; AQUEOUS-HUMOR; BLEPHARITIS; ANTIBIOTICS; PENETRATION; TOXICITY; COMPLICATIONS; CIPROFLOXACIN; PROPHYLAXIS C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA. NR 47 TC 10 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 97 EP 107 DI 10.1097/00004397-199603630-00010 PG 11 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500009 PM 8989603 ER PT J AU Ng, EWM Baker, AS DAmico, DJ AF Ng, EWM Baker, AS DAmico, DJ TI Postoperative endophthalmitis: Risk factors and prophylaxis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Review ID COAGULASE-NEGATIVE STAPHYLOCOCCI; CHAMBER ASPIRATE CULTURES; PARS-PLANA VITRECTOMY; EXTRACAPSULAR CATARACT-EXTRACTION; INTRAOCULAR-LENS IMPLANTATION; COLLAGEN-SHIELD DELIVERY; BACTERIAL ENDOPHTHALMITIS; INFECTIOUS ENDOPHTHALMITIS; OPHTHALMIC SURGERY; POVIDONE-IODINE RP Ng, EWM (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,RETINA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 113 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 109 EP 130 DI 10.1097/00004397-199603630-00011 PG 22 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500010 PM 8989604 ER PT J AU Harooni, M Lashkari, K Freilich, JM Schepens, CL AF Harooni, M Lashkari, K Freilich, JM Schepens, CL TI Cytomegalovirus retinitis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID RHEGMATOGENOUS RETINAL-DETACHMENT; IMMUNE-DEFICIENCY SYNDROME; VIRUS RETINITIS; GANCICLOVIR; MANIFESTATIONS; INFECTIONS; AIDS C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA. NR 28 TC 0 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 131 EP 140 DI 10.1097/00004397-199603630-00012 PG 10 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500011 PM 8989605 ER PT J AU Freilich, JM Ryan, EA Lou, PL Kroll, AJ Brockhurst, RJ Harooni, M AF Freilich, JM Ryan, EA Lou, PL Kroll, AJ Brockhurst, RJ Harooni, M TI Acute retinal necrosis syndrome: Findings, management, and differential diagnosis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID ZOSTER DERMATITIS; VIRUS; ASSOCIATION; THERAPY C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. NR 32 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 141 EP 146 DI 10.1097/00004397-199603630-00013 PG 6 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500012 PM 8989606 ER PT J AU Samiy, N DAmico, DJ AF Samiy, N DAmico, DJ TI Endogenous fungal endophthalmitis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID CANDIDA ENDOPHTHALMITIS; AMPHOTERICIN-B; ASPERGILLUS ENDOPHTHALMITIS; HEMATOGENOUS ENDOPHTHALMITIS; CRYPTOCOCCAL CHORIORETINITIS; HISTOPLASMA-CAPSULATUM; ORAL FLUCONAZOLE; INFECTIONS; ITRACONAZOLE; MANAGEMENT RP Samiy, N (reprint author), HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM,SCH MED, DEPT OPHTHALMOL,RETINA SERV, 243 CHARLES ST, BOSTON, MA 02114 USA. NR 90 TC 29 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 147 EP 162 DI 10.1097/00004397-199603630-00014 PG 16 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500013 PM 8989607 ER PT J AU Weissgold, DJ DAmico, DJ AF Weissgold, DJ DAmico, DJ TI Rare causes of endophthalmitis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID PROPIONIBACTERIUM-ACNES ENDOPHTHALMITIS; EXTRACAPSULAR CATARACT-EXTRACTION; INTRAOCULAR-LENS IMPLANTATION; METASTATIC BACTERIAL ENDOPHTHALMITIS; NOCARDIA-ASTEROIDES ENDOPHTHALMITIS; B STREPTOCOCCAL BACTEREMIA; PARS-PLANA VITRECTOMY; STRABISMUS SURGERY; POSTOPERATIVE ENDOPHTHALMITIS; PNEUMONIAE ENDOPHTHALMITIS RP Weissgold, DJ (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,RETINA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 86 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 163 EP 177 DI 10.1097/00004397-199603630-00015 PG 15 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500014 PM 8989608 ER PT J AU McMillan, TA Lashkari, K AF McMillan, TA Lashkari, K TI Ocular histoplasmosis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID SUBFOVEAL NEOVASCULARIZATION; NATURAL-HISTORY; CAPSULATUM; CHOROIDITIS C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. NR 41 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 179 EP 186 DI 10.1097/00004397-199603630-00016 PG 8 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500015 PM 8989609 ER PT J AU Samy, CN DAmico, DJ AF Samy, CN DAmico, DJ TI Infectious choroiditis in the acquired immune deficiency syndrome SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID PNEUMOCYSTIS-CARINII CHOROIDITIS; AEROSOLIZED PENTAMIDINE THERAPY; IMMUNODEFICIENCY-SYNDROME; TOXOPLASMIC RETINOCHOROIDITIS; OCULAR TOXOPLASMOSIS; PATIENT; AIDS; CYTOMEGALOVIRUS; MANIFESTATIONS; CHOROIDOPATHY C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RETINA SERV,BOSTON,MA 02114. NR 33 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 187 EP 196 DI 10.1097/00004397-199603630-00017 PG 10 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500016 PM 8989610 ER PT J AU March, GA Lessell, S AF March, GA Lessell, S TI Infectious optic neuropathy SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY-SYNDROME; CYTOMEGALO-VIRUS RETINITIS; HERPES-ZOSTER OPHTHALMICUS; CRYPTOCOCCAL MENINGITIS; CEREBROSPINAL-FLUID; SYNDROME AIDS; NERVE; NEURITIS; DISEASE C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,NEUROOPHTHALMOL SERV,BOSTON,MA. NR 52 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 197 EP 205 DI 10.1097/00004397-199603630-00018 PG 9 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500017 PM 8989611 ER PT J AU Rumelt, S Rubin, PAD AF Rumelt, S Rubin, PAD TI Potential sources for orbital cellulitis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID CAVERNOUS SINUS THROMBOSIS; RHINOCEREBRAL MUCORMYCOSIS; DIAGNOSIS; PANOPHTHALMITIS; COMPLICATIONS; FRACTURES; ABSCESS; SPREAD RP Rumelt, S (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,EYE PLAST & ORBIT SERV,BOSTON,MA 02114, USA. NR 55 TC 16 Z9 20 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP 207 EP 221 DI 10.1097/00004397-199603630-00019 PG 15 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500018 PM 8989612 ER PT J AU Jakobiec, FA Lucarelli, MJ AF Jakobiec, FA Lucarelli, MJ TI Ocular and adnexal infections - Preface SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1996 VL 36 IS 3 BP R17 EP R18 DI 10.1097/00004397-199603630-00002 PG 2 WC Ophthalmology SC Ophthalmology GA WC965 UT WOS:A1996WC96500001 ER PT J AU Takagi, H King, GL Ferrara, N Aiello, LP AF Takagi, H King, GL Ferrara, N Aiello, LP TI Hypoxia regulates vascular endothelial growth factor receptor KDR/Flk gene expression through adenosine A(2) receptors in retinal capillary endothelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE endothelial cell; KDR; Flk; receptor; retina; vascular endothelial growth factor (VEGF); vascular permeability factor (VPF) ID TYROSINE KINASE; STIMULATE PROLIFERATION; ANOXIC HEPATOCYTES; ANGIOGENESIS; NUCLEOTIDES; SECRETION; CLONING; FAMILY; RNA AB Purpose, Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic factor that serves an important role in numerous ischemic retinopathies. The authors studied the hypoxic gene regulation of two known VEGF receptors (KDR and Fit) and its mechanism in cultured bovine retinal endothelial cells (BREC). Methods, Confluent monolayers of BREC were exposed to various oxygen concentrations using a computer-controlled, infrared, water-jacked CO2 incubator with reduced oxygen control. Northern blot analysis and I-125-VEGF binding analysis were used to identify hypoxia-induced alterations of VEGF receptor at mRNA and protein levels. Results. KDR was detectable by Northern blot analysis in BREC, whereas Fit was not. Hypoxia decreased KDR gene expression in a dose- and time-dependent manner with maximal inhibition to 0.5 +/- 0.2% (P = 0.019) of normoxic control observed after 24 hours exposure to 0% oxygen and with significant inhibition at oxygen concentrations below 5%. Blockade of oxygen respiration decreased KDR mRNA expression to 58% +/- 7.1% of control (P = 0.001) after 3 hours. CPA a stable adenosine A, receptor (AIR) agonist, did not affect KDR mRNA expression at AIR stimulatory concentrations, but it decreased KDR mRNA levels to 30% +/- 4.9% (P = 0.002) of control at higher concentrations that react with A(2)R DPMA, an adenosine A(2) receptor (A(2)R) agonist, decreased KDR mRNA in a dose-dependent manner with an EC(50) of 5 to 10 nM. A(1)R antagonists, 8-cyclolentyl-1,3-dipropylxanthine and 8-phenyltheophylline, did not inhibit the hypoxic response of KDR mRNA at A(1)R inhibitory concentrations but did inhibit the response at A(2)R effective doses (P = 0.001), The A(2)R antagonist, CSC, inhibited the KDR hypoxic response by 42% +/- 7.8% (P = 0.008) at 10 mu M. Specific VEGF binding to BREC was decreased from 15.1% +/- 0.3% to 12.7% +/- 0.4% per milligram protein (P < 0.001) after exposure to 1% oxygen for 24 hours. In contrast, long-term exposure to 1% oxygen (72 hours) resulted in an increase of VEGF binding from 13.5% +/- 1.1% to 18.3% +/- 0.8% per milligram protein (P < 0.001). Scatchard analysis detected a decrease of receptor binding sites without change in binding affinity after 30 hows of exposure to hypoxia but demonstrated an increase in specific binding sites (4.2 +/- 0.6 x 10(4) sites/cell to 6.7 +/- 1.0 x 10(4) sites/cell, P = 0.049) with unaltered receptor affinity after 72 hours of hypoxic exposure. Conclusions. These data suggest that hypoxia induces an initial decline in KDR mRNA levels and VEGF binding sites as mediated through adenosine binding to the A(2)R. Exposure to prolonged periods of hypoxia, however, results in an increase in VEGF binding sites by an as yet unidentified mechanism. C1 JOSLIN DIABET CTR,BEETHAM EYE INST,DIV RES,BOSTON,MA 02215. JOSLIN DIABET CTR,BEETHAM EYE INST,DEPT OPHTHALMOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. GENENTECH INC,SAN FRANCISCO,CA 94080. FU NEI NIH HHS [EY09178, EY10827] NR 47 TC 100 Z9 104 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1996 VL 37 IS 7 BP 1311 EP 1321 PG 11 WC Ophthalmology SC Ophthalmology GA UP572 UT WOS:A1996UP57200012 PM 8641834 ER PT J AU Shima, DT Gougos, A Miller, JW Tolentino, M Robinson, G Adamis, AP DAmore, PA AF Shima, DT Gougos, A Miller, JW Tolentino, M Robinson, G Adamis, AP DAmore, PA TI Cloning and mRNA expression of vascular endothelial growth factor in ischemic retinas of Macaca fascicularis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE angiogenesis; ganglion cells; hypoxia; in situ hybridization; neovascularization ID ANGIOGENESIS; HYPOXIA AB Purpose. To identify and isolate cDNAs for the alternatively spliced vascular endothelial growth factor (VEGF) mRNAs present in retina and to compare the relative levels of the splice variants and localization of VEGF mRNA in nonischemic and ischemic adult simian retinas. Methods, Retinas of cynomolgous monkeys were made ischemic by laser occlusion of the main branch retinal veins. Reverse transcription-polymerase chain reaction was used to amplify the VEGF coding region of RNA from ischemic and control retinas, and amplification products were analyzed by agarose gel electrophoresis, Southern blot, and nucleotide sequencing. Analysis of VEGF mRNA expression was accomplished by in situ hybridization. Results, Control and ischemic retinas produce mRNAs that correspond to the 121 and 165 amino acid diffusible isoforms of VEGF, and relatively low levels of VEGF(189), the heparin-binding isoform. There was no significant difference in the levels of the alternatively spliced VEGF transcripts between control and ischemic retinas, Cloning and sequencing revealed that simVEGF cDNAs are 99% identical to human VEGFs and are predicted to encode proteins identical to their respective human homologues, In situ hybridization of nonischemic retinas revealed a low level of VEGF mRNA in retinal ganglion cells and in the inner nuclear layer. VEGF mRNA levels were elevated in ischemic retinas as early as 1 day after laser vein occlusion, when there was a small but reproducible increase in signal. The expression peaked at approximately 13 days, coincident with maximal iris neovascularization, and was significantly reduced by 28 days, when the iris vessels largely regressed. Conclusions, The elevation of simVEGF(121) and VEGF(165) in ischemic retinas is consistent with a role for diffusible, retina-derived angiogenic factors in the development of ocular neovascularization. C1 CHILDRENS HOSP,SURG RES LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM BIOL & BIOMED SCI,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,RETINA SERV,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. HYBRIDON INC,WORCESTER,MA. FU NCI NIH HHS [CA45548]; NEI NIH HHS [EY05985] NR 22 TC 94 Z9 100 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1996 VL 37 IS 7 BP 1334 EP 1340 PG 7 WC Ophthalmology SC Ophthalmology GA UP572 UT WOS:A1996UP57200014 PM 8641836 ER PT J AU Liu, CJL Chaturvedi, N Barnstable, CJ Dreyer, EB AF Liu, CJL Chaturvedi, N Barnstable, CJ Dreyer, EB TI Retinal Thy-1 expression during development SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE immunohistochemistry; neural development; retinal ganglion cells; reverse transcription-polymerase chain reaction(RT-PCR); Thy-1 ID NERVOUS-TISSUE; AXONS AB Purpose. To evaluate the developmental expression of Thy-1 in the retina. Thy-1, the most abundant mammalian neuronal surface glycoprotein, is likely to play a significant role in retinal development. In the mammalian retina, it is found predominantly, if not exclusively, on retinal ganglion cells. Methods. Rat retinae of various ages were stained immunohistochemically for Thy-1 with 2G12, a monoclonal Thy-1 antibody. Sections were analyzed digitally to quantify bound antibody. Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), the expression of Thy-1 protein was compared with the levels of mRNA detected. Results. Thy-1-dependent fluorescence was detected in rat retinae from birth, albeit at low levels. Thy-1 labeling was localized predominantly to the ganglion cell layer. Minimal, fine patterns of linear and reticular fluorescence were noted in the inner nuclear layer. Thy-1 levels reached a maximal level at approximately postnatal day 14. RT-PCR measurements showed a similar time course for the increase in Thy-1 expression. Conclusions. The Thy-1 antigen is present in the inner retina at birth. Its level increases steadily after birth and peaks during the second week of life. Thy-1 expression is approximately coterminous with synaptogenesis of the inner plexiform layer and may play a role in synaptogenesis of the inner retina or in other developmental milestones in the formation of the visual system. C1 HARVARD UNIV,DEPT OPHTHALMOL,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. YALE UNIV,DEPT OPHTHALMOL & VISUAL SCI,NEW HAVEN,CT. OI Barnstable, Colin/0000-0002-7011-4068 FU NEI NIH HHS [R01-EY10009] NR 11 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1996 VL 37 IS 7 BP 1469 EP 1473 PG 5 WC Ophthalmology SC Ophthalmology GA UP572 UT WOS:A1996UP57200028 PM 8641850 ER PT J AU ShimizuSasamata, M AF ShimizuSasamata, M TI Clinical development of excitatory amino acid antagonists for acute ischemic stroke. SO JAPANESE JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA Japanese DT Article ID TOLERABILITY; SAFETY; TRIAL C1 YAMANOUCHI PHARMACEUT CO LTD,INST DRUG DISCOVERY RES,TSUKUBA,IBARAKI 305,JAPAN. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. NR 26 TC 0 Z9 0 U1 0 U2 0 PU SEIWA SHOTEN PUBL LTD PI TOKYO PA 2-5 KAMITAKAIDO 1-CHOME, SUGINAMI-KU, TOKYO 168, JAPAN SN 0388-7588 J9 JPN J NEUROPSYCHOPH JI Jpn. J. Neuropsychopharmacol. PD JUN PY 1996 VL 18 IS 6 BP 427 EP 434 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VN661 UT WOS:A1996VN66100003 ER PT J AU Biswas, DK Tius, MA Zhuo, JC Pardee, AB AF Biswas, DK Tius, MA Zhuo, JC Pardee, AB TI Canventol inhibits HIV-1 replication by a Tat-induced Tar-independent mechanism SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE canventol, inhibitor of TNF-alpha; NF-kappa B activation; and HIV-1 transcription ID HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; LONG TERMINAL REPEAT; T-CELLS; EXPRESSION; PROTEIN; TYPE-1; INDUCTION; ACTIVATION AB Canventol (2-isopropyl-4-isopropyldencyclohex-2-ene-1-ol), a blocker of tumor necrosis factor alpha (TNF-alpha) release, inhibits human immunodeficiency virus type (HIV-1) production in chronically and acutely infected cells. This effect of Canventol on virus replication could be correlated with its inhibitory influence on necrosis factor (NF)-kappa B activation and HIV-1 long terminal repeat (LTR)-driven reporter gene expression in Jurkat cells and these could be overcome by the administration of TNF-alpha. Canventol inhibits activation of the promoter by the viral protein Tat through a TAR-independent mechanism. The HIV-1 promoter is synergistically upregulated when both the TAR-independent and the TAR-dependent modes of Tat action are in operation, Tat-induced downstream events, such as the production of cytokines like TNF-alpha and NF-kappa B activation, are central for this upregulation. Inhibitors of the respective modes of action of Tat downregulate HIV-1 LTR activation and virus replication. C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. UNIV HAWAII, DEPT CHEM, HONOLULU, HI 96822 USA. RP Biswas, DK (reprint author), DANA FARBER CANC INST, DIV CELL GROWTH & REGULAT, 44 BINNEY ST, BOSTON, MA 02115 USA. NR 26 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD JUN 1 PY 1996 VL 12 IS 2 BP 120 EP 127 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UP366 UT WOS:A1996UP36600004 PM 8680882 ER PT J AU Lu, YC Salvato, MS Pauza, CD Li, J Sodroski, J Manson, K Wyand, M Letvin, N Jenkins, S Touzjian, N Chutkowski, C Kushner, N LeFaile, M Payne, LG Roberts, B AF Lu, YC Salvato, MS Pauza, CD Li, J Sodroski, J Manson, K Wyand, M Letvin, N Jenkins, S Touzjian, N Chutkowski, C Kushner, N LeFaile, M Payne, LG Roberts, B TI Utility of SHIV for testing HIV-1 vaccine candidates in macaques SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE simian/human immunodeficiency virus chimera; rhesus monkeys; HIV-1 vaccine ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEINS; PROTECTION; INFECTION; CHIMPANZEES; CHALLENGE; PRIMATES; MONKEYS; GP120; AIDS AB Intravenous injection of SHIV (simian/human immunodeficiency virus, chimeric virus) into rhesus macaques resulted in a viremia in peripheral blood lymphocytes (PBL) and the generation of anti-HIV-1 (human immuno-deficiency virus type 1) envelope immune responses. A challenge stock of a SHIV containing HIV-1 HXBc2 envelope glycoproteins was prepared from infected rhesus monkey peripheral blood mononuclear cells (PBMC). The minimum animal infectious dose of the SHIV stock was determined and used in a challenge experiment to test protection. The vaccination of two rhesus monkeys with whole inactivated HIV-1 plus polydicarboxylatophenoxy phosphazene (PCPP) as the adjuvant protected the animals from becoming infected by a SHIV challenge. This experiment demonstrated for the first time that monkeys immunized with HIV-1 antigens can be protected against an HIV-1 envelope-containing virus. As the challenge virus was prepared from monkey PBMC, human antigens were unlikely to be involved in the protection. Protection of rhesus monkeys from SHIV challenge may help define protective immune responses stimulated by HIV-1 vaccine candidates. C1 UNIV WISCONSIN,DEPT PATHOL & LAB MED,MADISON,WI. DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. TSI MASON LABS,WORCESTER,MA. BETH ISRAEL HOSP,DIV VIRAL PATHOGENESIS,BOSTON,MA 02215. RP Lu, YC (reprint author), INST VIRUS RES,61 MOULTON ST,CAMBRIDGE,MA 02138, USA. FU NIAID NIH HHS [AI28691, AI35478] NR 20 TC 62 Z9 64 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUN 1 PY 1996 VL 12 IS 2 BP 99 EP 106 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UP366 UT WOS:A1996UP36600001 PM 8680896 ER PT J AU Lieberman, JR Dorey, F Shekelle, P Schumacher, L Thomas, BJ Kilgus, DJ Finerman, GA AF Lieberman, JR Dorey, F Shekelle, P Schumacher, L Thomas, BJ Kilgus, DJ Finerman, GA TI Differences between patients' and physicians' evaluations of outcome after total hip arthroplasty SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB The purpose of this study was to compare patients' and physicians' evaluations of the results of 147 total hip arthroplasties, The patients and physicians independently evaluated pain and over-all satisfaction,vith the outcome of the procedure using a 10.0-centimeter visual-analog scale, They also answered a questionnaire with which they assessed general health, functional ability, and pain, The mean (and standard deviation) analog rating for pain (with 0.0 centimeters indicating no pain and 10.0 centimeters, severe pain) was 1.7 +/- 2.6 centimeters as assessed by the patients and 1.1 +/- 1.8 centimeters as assessed by the physicians (p < 0.001, paired t test), The mean analog rating for over-all satisfaction (with 0.0 centimeters indicating poor and 10.0 centimeters, excellent) was 8.6 +/- 2.1 centimeters as assessed by the patients and 8.8 +/- 1.7 centimeters as assessed by the physicians (p = 0.07, paired t test), There was a marked disparity between the patients' and the physicians' scores when the patients assigned a low score to a particular area, For the thirty patients who rated the pain as more than 4.0 centimeters, the mean analog rating was 6.8 +/- 2.1 centimeters according to the patients, while it was 3.6 +/- 2.7 centimeters according to the physicians (p < 0.001, linear regression), The mean analog rating for over-all satisfaction according to the nineteen patients who rated this parameter as less than 7.0 centimeters was 3.8 +/- 2.0 centimeters, while the mean rating according to the physicians was 6.5 +/- 2.8 centimeters (p < 0.001, linear regression), The patients' and physicians' evaluations were similar regarding the results of the total hip arthroplasty when the patients had little or no pain and were satisfied with the result. However, the disparity increased as the patients' ratings for pain increased and their ratings for over-all satisfaction decreased. This study highlights a discrepancy between patients' and physicians' evaluations of the results of total hip arthroplasty. This discrepancy increased when the patient was not satisfied with the outcome, The use of patients' self-administered questionnaires as well as traditional physician-generated assessments may provide a more complete evaluation of the results of total hip arthroplasty. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,VET AFFAIRS HLTH SERV,RES & DEV SERV,LOS ANGELES,CA 90073. RP Lieberman, JR (reprint author), UNIV CALIF LOS ANGELES,MED CTR,DEPT ORTHOPAED SURG,CHS 76-134,10833 LE CONTE AVE,LOS ANGELES,CA 90095, USA. NR 5 TC 198 Z9 200 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUN PY 1996 VL 78A IS 6 BP 835 EP 838 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA UT143 UT WOS:A1996UT14300005 PM 8666600 ER PT J AU Koepp, DM Wong, DH Corbett, AH Silver, PA AF Koepp, DM Wong, DH Corbett, AH Silver, PA TI Dynamic localization nuclear import receptor and its interactions with transport factors SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CHROMOSOME CONDENSATION; PROTEIN RAN/TC4; MESSENGER-RNA; GENE-PRODUCT; YEAST; MUTANT; RCC1; MAINTENANCE; MUTATIONS AB Characterization of the interactions between soluble factors required for nuclear transport is key to understanding the process of nuclear trafficking. Using a synthetic lethal screen with the rnal-1 strain, we have identified a genetic interaction between Rnalp, a GTPase activating protein required for nuclear transport, and yeast importin-beta, a component of the nuclear localization signal receptor. By the use of fusion proteins, we demonstrate that Rnalp physically interacts with importin-beta. Mutants in importin-beta exhibit in vivo nuclear protein import defects, and importin-beta localizes to the nuclear envelope along with other proteins associated with the nuclear pore complex. In addition, we present evidence that importin-alpha, but not importin-beta, mislocalizes to the nucleus in cells where the GTPase Ran is likely to be in the GDP-bound state. We suggest a model of nuclear transport in which Ran-mediated hydrolysis of GTP is necessary for the import of importin-alpha and the nuclear localization signal-bearing substrate into the nucleus, while exchange of GDP for GTP on Ran is required for the export of both mRNA and importin-alpha from the nucleus. C1 DANA FARBER CANC INST, DIV MOL & CELLULAR BIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. NR 63 TC 114 Z9 114 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD JUN PY 1996 VL 133 IS 6 BP 1163 EP 1176 DI 10.1083/jcb.133.6.1163 PG 14 WC Cell Biology SC Cell Biology GA UT407 UT WOS:A1996UT40700003 PM 8682856 ER PT J AU Locke, JL AF Locke, JL TI Why do infants begin to talk? Language as an unintended consequence SO JOURNAL OF CHILD LANGUAGE LA English DT Article ID INDIVIDUAL-DIFFERENCES; SPEECH-PERCEPTION; NATIVE LANGUAGE; SOUND PATTERNS; RECOGNITION; ACQUISITION; VOCALIZATIONS; SPECIFICITY; CONTINUITY; IMITATION AB Scholars have addressed a range of questions about language development, but for some reason have neglected to ask why infants begin to talk. Biologists often prefer 'how' to 'why' questions, but it is possible to ask about the immediate consequences of developing behaviours - an acceptable strategy for attacking causation - and psycholinguists can study the immediate consequences to the infant of behaviours that lead to linguistic competence. This process is demonstrated with a series of illustrative proposals as to the short- and long-term consequences of vocal learning and utterance storage, two developmental phases that lead to talking, as well as the act of talking itself. The goal is to encourage investigation of behavioural dispositions that nudge the child, by degrees, towards proficiency in the use of spoken language. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. NR 86 TC 33 Z9 33 U1 3 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0305-0009 J9 J CHILD LANG JI J. Child Lang. PD JUN PY 1996 VL 23 IS 2 BP 251 EP 268 PG 18 WC Psychology, Developmental; Linguistics; Psychology, Experimental SC Psychology; Linguistics GA VR672 UT WOS:A1996VR67200002 PM 8936686 ER PT J AU Hinkin, CH vanGorp, WG Satz, P Marcotte, T Durvasula, RS Wood, S Campbell, L Baluda, MR AF Hinkin, CH vanGorp, WG Satz, P Marcotte, T Durvasula, RS Wood, S Campbell, L Baluda, MR TI Actual versus self-reported cognitive dysfunction in HIV-1 infection: Memory-metamemory dissociations SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; NEUROPSYCHOLOGICAL PERFORMANCE; ANOSOGNOSIA; INDIVIDUALS; LESIONS; UNAWARENESS; HEMIPLEGIA; NEGLECT; TESTS AB The relationship between subjective awareness and objective neuropsychological status in HIV-1 infection remains unclear. Forty-six HIV-1 seropositive males were administered a battery of neuropsychological measures assessing episodic memory, metacognition, and depression. Results of ANOVA revealed a dissociation between subjects' self-complaint of neuropsychological impairment and objective performance, with subjects who denied cognitive impairment performing worse on memory testing. Three subgroups were identified: A group whose self-reported cognitive impairment exceeded deficits demonstrated on memory testing (37% of subjects); a group who denied impairment but evidenced deficits on memory testing (26% of subjects); and a group whose self-appraisal was consistent with performance (37% of subjects). These data suggest that self-report of cognitive dysfunction among HIV-1 infected subjects is frequently at variance with objective neuropsychological testing and that diminished awareness of decline among medically symptomatic HIV-1 infected subjects can be identified. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT PSYCHIAT & BIOBEHAV SCI, LOS ANGELES, CA 90024 USA. W LOS ANGELES VET AFFAIRS MED CTR, DEPT VET AFFAIRS, LOS ANGELES, CA USA. UNIV CALIF SAN DIEGO, SCH MED, DEPT PSYCHIAT, LA JOLLA, CA 92093 USA. FU CSR NIH HHS [RG000974]; NIMH NIH HHS [R03MH54465-01] NR 46 TC 51 Z9 52 U1 1 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD JUN PY 1996 VL 18 IS 3 BP 431 EP 443 DI 10.1080/01688639608408999 PG 13 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA VF466 UT WOS:A1996VF46600010 PM 8877626 ER PT J AU Ali, HH Lien, CA Witkowski, T Brull, SJ Stout, RG Bartkowski, R Silverman, DG Patel, S Ascher, JA Goudsouzian, NG AF Ali, HH Lien, CA Witkowski, T Brull, SJ Stout, RG Bartkowski, R Silverman, DG Patel, S Ascher, JA Goudsouzian, NG TI Efficacy and safety of divided dose administration of mivacurium for a 90-second tracheal intubation SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Induction agents, propofol, fentanyl; intubation, rapid tracheal intubation; neuromuscular relaxants, d-tubocurarine, mivacurium, succinylcholine ID NONDEPOLARIZING MUSCLE RELAXANTS; ADULT PATIENTS; SUCCINYLCHOLINE; ANESTHESIA; ROCURONIUM; VECURONIUM; INDUCTION; CHLORIDE; PROPOFOL AB Study Objective: To compare the safety and effectiveness of 0.25 mg divided doses of mivacurium chloride to succinylcholine for a 90-second tracheal intubation. Design: Randomized, double-blind, multicenter study in two groups. Setting: Operating rooms at four university medical centers. Patients: 200 healthy ASA status I and II adult patients scheduled for elective surgery with general anesthesia and endotracheal intubation. Interventions: Patients were premedicated with 1 to 2 mg midazolam and 2 mu g/kg fentanyl. Anesthesia was induced with 2 mg/kg propofol. Group A received 0.25 mg/kg mivacurium given as a divided dose (0.15 mg/kg followed in 30 seconds with 0.1 mg/kg). Group B (control) received 1.5 mg/kg succinylcholine (SCh) preceded two minutes earlier by 50 mu g/kg d-tubocurarine (dtc). Measurements and Main Results: Tracheal intubation grading, train-of-four response of the adductor pollicis, heart rate (HR) and mean arterial blood pressure (MAP) were measured and evaluated. Chi-square analysis was performed for comparison between Group A and Group B with respect to the frequency distribution of intubation using the scores excellent, good, and poor and not possible (combined). Group B had a significantly higher excellent score of intubation than Group A, 84% versus 56% (p < 0.001). No significant difference was found between the two groups when the scores excellent and good were combined (Fisher's Exact test, p = 0.28). The changes in MAP and HR were similar for the two groups. Conclusions: When Sch is not desirable, mivacurium 0.25 mg/kg given as a divided dose provides good to excellent intubation conditions 90 seconds after the initial dose without significant changes in MAP or HR. It can be an appropriate alternative for short surgical procedures. It must be emphasized that this conclusion does not apply to rapid-sequence induction-intubation. RP Ali, HH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. RI Brull, Sorin/E-8578-2010 OI Brull, Sorin/0000-0003-2607-2590 NR 16 TC 15 Z9 15 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD JUN PY 1996 VL 8 IS 4 BP 276 EP 281 DI 10.1016/0952-8180(96)85617-0 PG 6 WC Anesthesiology SC Anesthesiology GA UN114 UT WOS:A1996UN11400003 PM 8695129 ER PT J AU ChristinMaitre, S Taylor, AE Khoury, RH Hall, JE Martin, KA Smith, PC Albanese, C Jameson, JL Crowley, WF Sluss, PM AF ChristinMaitre, S Taylor, AE Khoury, RH Hall, JE Martin, KA Smith, PC Albanese, C Jameson, JL Crowley, WF Sluss, PM TI Homologous in vitro bioassay for follicle-stimulating hormone (FSH) reveals increased FSH biological signal during the mid- to late luteal phase of the human menstrual cycle SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PREMATURE OVARIAN FAILURE; CELL AROMATASE BIOASSAY; INVITRO BIOASSAY; LUTEINIZING-HORMONE; NORMAL WOMEN; RECEPTOR; SERUM; SECRETION; BINDING; MICROHETEROGENEITY AB Monitoring of the secretory dynamics of FSH during the human menstrual cycle has demonstrated conflicting results between the amounts of FSH measured by dimer-specific immunoassays and previous heterologous in vitro bioassays. These differences suggest somewhat different models of the steroidal and nonsteroidal regulation of FSH secretion and its control of folliculogenesis in the human. We have developed a homologous in vitro bioassay, using the recombinant human FSH receptor cotransfected into Chinese hamster ovary cells with a cAMP-responsive luciferase reporter gene, that overcomes many of the theoretic shortfalls of previous assays and allows reevaluation of the changes in bioactive FSH across the menstrual cycle. Bioactive FSH levels measured across 12 menstrual cycles in 11 normal women ranged from 4-40 IU/L. FSH bioactivity was constant during the menstrual cycle, with elevations noted only during the mid- to late luteal phase. Bioactive FSH levels were similar to immunoactive FSH levels across the cycle as indicated by a ratio of bioactive to immunoreactive FSH (FSH B/I) of 1.10 +/- 0.04 across the follicular and early luteal phases. However, during the mid- to late luteal phase, the mean FSH B/I rose to 1.65 +/- 0.07, which significantly exceeded that during the rest of the cycle (P < 0.001). This change in FSH B/I occurs at a critical time during folliculogenesis when the next cohort of follicles is being recruited and appears to be secondary to a decrease in immunoreactive FSH unaccompanied by a similar decrease in in vitro bioactivity. There was good agreement between immunoassay and bioassay results on the day of the midcycle gonadotropin surge (FSH B/I = 1.07 +/- 0.14), which was not different from that in the follicular phase (days -17 to -2; FSH B/I = 1.06 +/- 0.05) or the FSH B/I measured in postmenopausal women (0.93 +/- 0.2). These observations using a novel homologous human FSH in vitro bioassay indicate that bioactive FSH levels are not declining during the time of active corpus luteum formation and secretory activity. Thus, there is a previously undetected increased biologic signal during the mid- to late luteal phase, suggesting that the influence of elevated FSH on the cohort of developing follicles (including the subsequent dominant follicle) begins earlier during the luteal-follicular transition than previously predicted by FSH immunoreactivity. C1 MASSACHUSETTS GEN HOSP, DEPT MED, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [P30 HD028138, R01-HD-19302, U54-HD-29164, R01 HD015788, P30-HD-28138] NR 46 TC 32 Z9 32 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1996 VL 81 IS 6 BP 2080 EP 2088 DI 10.1210/jc.81.6.2080 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UQ022 UT WOS:A1996UQ02200014 PM 8964832 ER PT J AU Biller, BMK Molitch, ME Vance, ML Cannistraro, KB Davis, KR Simons, JA Schoenfelder, JR Klibanski, A AF Biller, BMK Molitch, ME Vance, ML Cannistraro, KB Davis, KR Simons, JA Schoenfelder, JR Klibanski, A TI Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LONG-TERM THERAPY; HYPERPROLACTINEMIC DISORDERS; BROMOCRIPTINE; MULTICENTER; MACROPROLACTINOMAS; TOLERABILITY; WITHDRAWAL; TUMOR; SIZE AB Dopamine agonist administration is the primary therapy for macroprolactinomas, but bromocriptine is the only agent approved in the United States. Its use is limited by a high incidence of side effects, a short duration of action, and a lack of effectiveness in some patients. Cabergoline is a long-acting dopamine agonist specific for the D2 receptor that is more effective and better tolerated than bromocriptine in women with microadenomas or idiopathic hyperprolactinemia. However, experience with cabergoline in the treatment of patients with macroadenomas is limited. We report the first study of chronic administration of cabergoline conducted exclusively in patients with macroprolactinomas. Fifteen patients (8 women, 7 men) ages 18-76 yr were studied in an open-label 48-week dose escalation trial of cabergoline administered once per week. Eleven patients had received prior therapy with other dopamine agonists. Mean prolactin (PRL) levels decreased by 93.6%, and normal levels were attained in 73% of patients at doses of 0.5-3.0 mg per week, Three of five patients who had failed to normalize PRL on prior dopamine agonists achieved normal levels. Gonadal function was restored in all hypogonadal men and in 76% of premenopausal women with amenorrhea. Tumor size decreased in 11 of the 15 patients. Side effects were minimal. Of the 5 patients who had experienced side effects on prior dopamine agonists, 4 had none on cabergoline, and the fifth had milder symptoms. During two further years of follow up, the improvement in PRL levels, gonadal function, and tumor size has persisted during cabergoline administration, and three patients have experienced a further decline in PRL and/or tumor size. This study demonstrates the effectiveness and minimal side effects of once-weekly cabergoline for treatment of macroprolactinomas. C1 UNIV VIRGINIA, DEPT MED, CHARLOTTESVILLE, VA 22902 USA. PHARMACIA AB, COLUMBUS, OH 43216 USA. NORTHWESTERN UNIV, MED CTR, CHICAGO, IL 60611 USA. MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. RP Biller, BMK (reprint author), MASSACHUSETTS GEN HOSP, NEUROENDOCRINE UNIT, FRUIT ST, BUL 457B, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-00847, RR-01066] NR 21 TC 128 Z9 131 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1996 VL 81 IS 6 BP 2338 EP 2343 DI 10.1210/jc.81.6.2338 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UQ022 UT WOS:A1996UQ02200057 PM 8964874 ER PT J AU Millen, BE Franz, MM Quatromoni, PA Gagnon, DR Sonnenberg, LM Ordovas, JM Wilson, PWF Schaefer, EJ Cupples, LA AF Millen, BE Franz, MM Quatromoni, PA Gagnon, DR Sonnenberg, LM Ordovas, JM Wilson, PWF Schaefer, EJ Cupples, LA TI Diet and plasma lipids in women .1. Macronutrients and plasma total and low-density lipoprotein cholesterol in women: The Framingham nutrition studies SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE diet; plasma lipids; lipoproteins; apo E phenotype; estrogen; menopausal status ID CORONARY HEART-DISEASE; MONOUNSATURATED FATTY-ACIDS; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; NUTRIENT INTAKE; BLOOD-LIPIDS; SERUM-LIPIDS; HEALTHY-MEN; APOLIPOPROTEIN; PREVALENCE AB This study examined relationships between diet and plasma total and LDL cholesterol levels in a population based sample of 695 premenopausal and 727 postmenopausal women participating in the Framingham Offspring/Spouse Study. Regression analyses controlled for age, caloric intake, apolipoprotein E isoform type, estrogen use, and important CVD risk factors indicated that plasma total and LDL cholesterol levels were directly associated with consumption of saturated fat and inversely associated with total calorie intake. In contrast, dietary cholesterol was not a predictor of plasma total or LDI, cholesterol levels. Total cholesterol levels were also directly associated with total fat, oleic acid, and animal fat, and inversely associated with carbohydrate intake. Stepwise regressions with key nutrients indicated that saturated fat was consistently associated with total and LDL cholesterol levels in Framingham women. These analyses suggest that diet explains 2% of the variability in these lipid levels in a cross sectional sample of women; the full model explains 22-27%. C1 BOSTON UNIV,SCH PUBL HLTH,DEPT SOCIAL & BEHAV SCI,BOSTON,MA 02118. BOSTON UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,DEPT DIETET,BOSTON,MA 02118. TUFTS UNIV,SCH MED,USDA,HUMAN NUTR RES CTR AGING,LIPID METAB LAB,BOSTON,MA 02111. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. RP Millen, BE (reprint author), BOSTON UNIV,SCH PUBL HLTH,OFF DIRECTOR,85 E NEWTON ST,BOSTON,MA 02118, USA. OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [N01 HC 38038, N01-HV-38038, R01 HL 40423-02] NR 48 TC 16 Z9 17 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUN PY 1996 VL 49 IS 6 BP 657 EP 663 DI 10.1016/0895-4356(96)00030-3 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA UR415 UT WOS:A1996UR41500011 PM 8656227 ER PT J AU Rosen, FS AF Rosen, FS TI The enigma of the Wiskott-Aldrich syndrome begins to unravel SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,CAMBRIDGE,MA 02138. RP Rosen, FS (reprint author), HARVARD UNIV,SCH MED,CHILDRENS HOSP,DIV IMMUNOL,CTR BLOOD RES,CAMBRIDGE,MA 02138, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 1 PY 1996 VL 97 IS 11 BP 2407 EP 2407 DI 10.1172/JCI118686 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UQ238 UT WOS:A1996UQ23800003 PM 8647931 ER PT J AU Tang, T Frenette, PS Hynes, RO Wagner, DD Mayadas, TN AF Tang, T Frenette, PS Hynes, RO Wagner, DD Mayadas, TN TI Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE endothelium; leukocytes; inflammation; cerebrospinal fluid; blood-brain barrier ID TUMOR-NECROSIS-FACTOR; CEREBROSPINAL-FLUID; FACTOR-ALPHA; P-SELECTIN; BACTERIAL-MENINGITIS; MENINGEAL INFLAMMATION; MONOCLONAL-ANTIBODIES; INTERLEUKIN-1; RABBITS; INFECTION AB Leukocyte accumulation in cerebrospinal fluid and disruption of the blood-brain barrier are central components of meningitis and are associated with a poor prognosis. Genetically engineered deficiencies or functional inhibition of endothelial leukocyte adhesion receptors P-, or P- plus E-selectins, lead to deficits in leukocyte rolling and extravasation. However, their impact on meningeal inflammation has not been tested previously. An acute cytokine-induced meningitis model associated with significant cerebrospinal fluid leukocyte accumulation (averaging 14,000 leukocytes/mu l as early as 4 h) and blood-brain barrier permeability was developed in adult mice. This model was applied to mice deficient in P-selectin and mice doubly deficient in P- and E-selectins. Partial inhibition of cerebrospinal fluid leukocyte influx and permeability was noted in P-selectin-deficient mice. Mice doubly deficient in P- and E-selectins displayed a near complete inhibition of these parameters. Our results suggest that P- and E-selectins cooperatively contribute to meningitis and that functional blocking of both endothelial selectins in conjunction with antibiotics may provide a therapeutic approach for treatment of bacterial meningitis. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. MIT,HOWARD HUGHES MED INST,BOSTON,MA 02139. MIT,CTR CANC RES,BOSTON,MA 02139. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [HL53756, HL41002]; NINDS NIH HHS [NS33296] NR 37 TC 117 Z9 117 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 1 PY 1996 VL 97 IS 11 BP 2485 EP 2490 DI 10.1172/JCI118695 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UQ238 UT WOS:A1996UQ23800012 PM 8647940 ER PT J AU VidalPuig, A JimenezLinan, M Lowell, BB Hamann, A Hu, E Spiegelman, B Flier, JS Moller, DE AF VidalPuig, A JimenezLinan, M Lowell, BB Hamann, A Hu, E Spiegelman, B Flier, JS Moller, DE TI Regulation of PPAR gamma gene expression by nutrition and obesity in rodents SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE peroxisome proliferator-activated receptor; obesity; nutrition; insulin; gene regulation ID HORMONE RECEPTOR SUPERFAMILY; PEROXISOME PROLIFERATOR; INSULIN-RESISTANCE; ADIPOSE-TISSUE; FATTY-ACIDS; MEMBER; THIAZOLIDINEDIONES; ADIPOCYTE; BINDING; FAMILY AB The orphan nuclear receptor, peroxisome proliferator-activated receptor (PPAR) gamma, is implicated in mediating expression of fat-specific genes and in activating the program of adipocyte differentiation. The potential for regulation of PPAR gamma gene expression in vivo is unknown. We cloned a partial mouse PPAR gamma cDNA and developed an RNase protection assay that permits simultaneous quantitation of mRNAs for both gamma 1 and gamma 2 isoforms encoded by the PPAR gamma gene. Probes for detection of adipocyte P2, the obese gene product, leptin, and 18S mRNAs were also employed. Both gamma 1 and gamma 2 mRNAs were abundantly expressed in adipose tissue. PPAR gamma 1 expression was also detected at lower levels in liver, spleen, and heart; whereas, gamma 1 and gamma 2 mRNA were expressed at low levels in skeletal muscle. Adipose tissue levels of gamma 1 and gamma 2 were not altered in two murine models of obesity (gold thioglucose and ob/ob), but were modestly increased in mice with toxigene-induced brown fat ablation uncoupling protein diphtheria toxin A mice. Pasting (12-48 h) was associated with an 80% fall in PPAR gamma 2 and a 50% fall in PPAR gamma 1 mRNA levels in adipose tissue. Western blot analysis demonstrated a marked effect of fasting to reduce PPAR gamma protein levels in adipose tissue. Similar effects of fasting on PPAR gamma mRNAs were noted in all three models of obesity. Insulin-deficient (streptozotocin) diabetes suppressed adipose tissue gamma 1 and gamma 2 expression by 75% in normal mice with partial restoration during insulin treatment. Levels of adipose tissue PPAR gamma 2 mRNA were increased by 50% in normal mice exposed to a high fat diet. In obese uncoupling protein diphtheria toxin A mice, high fat feeding resulted in de novo induction of PPAR gamma 2 expression in liver. We conclude (a) PPAR gamma 2 mRNA expression is most abundant in adipocytes in normal mice, but lower level expression is seen in skeletal muscle; (b) expression of adipose tissue gamma 1 or gamma 2 mRNAs is increased in only one of the three models of obesity; (c) PPAR gamma 1 and gamma 2 expression is downregulated by fasting and insulin-deficient diabetes; and (d) exposure of mice to a high fat diet increases adipose tissue expression of PPAR gamma (in normal mice) and induces PPAR gamma 2 mRNA expression in liver (in obese mice). These findings demonstrate in vivo modulation of PPAR gamma mRNA levels over a fourfold range and provide an additional level of regulation for the control of adipocyte development and function. C1 BETH ISRAEL HOSP,DIV ENDOCRINE,DEPT MED,BOSTON,MA 02215. DANA FARBER CANC INST,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. MERCK & CO INC,MERCK SHARP & DOHME RES LABS,DEPT MOLEC ENDOCRINOL,RAHWAY,NJ 07065. FU NIDDK NIH HHS [DK 28082, R01 DK 46930]; PHS HHS [R01 45878] NR 45 TC 435 Z9 442 U1 3 U2 26 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 1 PY 1996 VL 97 IS 11 BP 2553 EP 2561 DI 10.1172/JCI118703 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UQ238 UT WOS:A1996UQ23800020 PM 8647948 ER PT J AU Almind, K Inoue, G Pedersen, O Kahn, CR AF Almind, K Inoue, G Pedersen, O Kahn, CR TI A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling - Evidence from transfection studies SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE diabetes mellitus; IRS-1; insulin resistance; genetics; PI 3-kinase ID PHOSPHATIDYLINOSITOL 3'-KINASE; HEMATOPOIETIC-CELLS; DIABETES-MELLITUS; ANIMAL-MODELS; IRS-1; EXPRESSION; MUSCLE; GENE; ASSOCIATION; RESISTANCE AB Insulin receptor substrate-1 (IRS-1) is the major cytoplasmic substrate of the insulin and IGF-1 receptors. Recent studies have identified multiple sequence variants of IRS-1, especially in patients with non-insulin-dependent diabetes mellitus. In the present study, we have examined insulin-stimulated processes in 32D(IR) cells, a myeloid progenitor cell stably overexpressing the insulin receptor, transfected with wild-type human-IRS-1 or the most common human variant of IRS-1 in which glycine 972 is replaced by arginine. As compared to wild-type IRS-1, insulin stimulation of cells transfected with mutant IRS-1 exhibited a 32% decrease in incorporation of [H-3]thymidine into DNA (P = 0.002), a 36% decrease in IRS-1 associated phosphatidylinositol (PI) 3-kinase activity (P = 0.004) and a 25% decrease in binding of the p85 regulatory subunit of PI 3-kinase to IRS-1 (P = 0.002). There was also a tendency for a decrease in Grb2 binding to IRS-1 and insulin-stimulated mitogen-activated protein kinase activity, however, these were not statistically significant. The changes occurred with no change in insulin receptor or IRS-1 tyrosine phosphorylation. These data indicate that the mutation in codon 972 in IRS-1 impairs insulin-stimulated signaling, especially along the PI 3-kinase pathway, and may contribute to insulin resistance in normal and diabetic populations. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. STENO DIABET CTR,DK-2820 GENTOFTE,COPENHAGEN,DENMARK. HAGEDORN RES INST,DK-2820 GENTOFTE,COPENHAGEN,DENMARK. FU NIDDK NIH HHS [DK33201] NR 45 TC 185 Z9 191 U1 1 U2 13 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 1 PY 1996 VL 97 IS 11 BP 2569 EP 2575 DI 10.1172/JCI118705 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UQ238 UT WOS:A1996UQ23800022 PM 8647950 ER PT J AU CastiglioneGertsch, M Goldhirsch, A Gusterson, B Bettelheim, R Reed, R Gussett, H Geiser, K Hurny, C Bernhard, J Hangartner, A Maibach, R Pedowski, R Gelber, R Price, K Peterson, H Zelen, M Isley, M Hinkle, R Kay, RG Holdaway, IM Harvey, VJ Jagusch, MF Neave, L Mason, BM Evans, B Benjamin, CS Carter, JF Gillman, JC Mack, D BensonCooper, D Monfardini, S Galligioni, E Crivellari, D Buonadonna, A Massarut, S Rossi, C Candiani, E Carbone, A Volpe, R Trovo, MG Roncadin, M Santini, GF Villalta, D Coran, F Morassut, S Marini, G Simoncini, E Marpicati, P Zaniboni, A Sartori, U Barni, A Cerutti, L Alghisi, A Raffaglio, E Garattini, MP Albertini, A Grigolato, P Morassi, L Bergonzini, R Lauriola, C Gudgeon, A Dent, DM Tiltman, A Hacking, A Dowdle, E Steynor, P Toop, J Schnurch, HG Mosny, D Bender, HG Bojar, H Veronesi, A Foladore, S Pamich, G Bianchi, G Torretta, A Rudenstam, CM Wallgren, A Persson, S Mattsson, J Cahlin, E Hafstrom, LO Holmberg, S Hultborn, R ColldahlJaderstrom, G Gustavsson, B Carlsson, G Ivarsson, L Thoren, O Ruusvik, O Nicklasson, LG Dahlin, S Karlsson, G Lindberg, B Sundback, A Bergegardh, S Salander, H Andersson, C Hessman, Y Nelzen, O Heideman, M Ramhult, T Svensson, JH Lidberg, P Bjork, S Lindtner, J Erzen, D Cerar, O Stabuc, B Golouh, R Lamovec, J Sebek, S Kramberger, M Vrhovec, I CortesFunes, H MartinezTello, F Mendiola, C CruzVigo, F Larrodera, ML Sierra, A Miranda, P Alonso, S Collins, J Snyder, R Gregory, P Burns, WI Green, M Gale, T Henderson, M Hart, S Neil, S Kitchen, P Lovell, R McLennan, R Russell, I Schwarz, M Basser, R Robertson, A Gill, P Carter, ML Malycha, P Yeoh, E Ward, G Leong, ASY LommaxSmith, J Hoosfall, D DAngelo, R Byrne, M vanHazel, G Dewar, J Buck, M Sheiner, HJ Ingram, D Sterrett, G Hahnel, R Forbes, JF Steward, J Darbar, SW Bishop, JM Simms, B Ziogas, V Tattersall, MHN Coates, A Niesche, F West, R Renwick, S Donovan, J Duval, P Simes, RJ Ng, A Glenn, D North, RA Beith, J OConnor, RG Rice, M Stevens, G Fey, M Barth, A Dreher, E Isenschmid, M Schneider, H Buser, K Ludin, J Luthi, JM Altermatt, HJ Laissue, JA Markwalder, R Burg, H Senn, HJ Thurlimann, B Jungi, WF Morant, R Oehlschlegel, C Hardmeier, T Luscher, K Ries, G Topfer, M Lorenz, U Benz, D Schiltknecht, O Spati, B Schmid, L Cavalli, F Sessa, C Bronz, L Martinelli, G Muller, W Luscieti, P Passega, E Pedrinis, E Rey, P Martinoli, S Spinelli, A Galfetti, MA Lombardi, A Pedrazzini, A Losa, G Varini, M Ginier, M Herrmann, R Harder, JF Laffer, U Almendral, AC Eppenberger, U Torhorst, J Siegenthaler, P Piguet, D Barrelet, V Baumann, RP Joss, R Sauter, C Metzger, U Engeler, V Haller, U Kochli, O Leyvraz, S Perey, L Anani, P Gomez, F Mirimanoff, RO Chapuis, G DeGrandi, P Reymond, P Alberto, P Schafer, P Krauer, F Forni, M Aapro, M Egeli, R Megevand, R JacotdesCombes, E Schindler, A Noseda, G Weber, W Lehmann, W AF CastiglioneGertsch, M Goldhirsch, A Gusterson, B Bettelheim, R Reed, R Gussett, H Geiser, K Hurny, C Bernhard, J Hangartner, A Maibach, R Pedowski, R Gelber, R Price, K Peterson, H Zelen, M Isley, M Hinkle, R Kay, RG Holdaway, IM Harvey, VJ Jagusch, MF Neave, L Mason, BM Evans, B Benjamin, CS Carter, JF Gillman, JC Mack, D BensonCooper, D Monfardini, S Galligioni, E Crivellari, D Buonadonna, A Massarut, S Rossi, C Candiani, E Carbone, A Volpe, R Trovo, MG Roncadin, M Santini, GF Villalta, D Coran, F Morassut, S Marini, G Simoncini, E Marpicati, P Zaniboni, A Sartori, U Barni, A Cerutti, L Alghisi, A Raffaglio, E Garattini, MP Albertini, A Grigolato, P Morassi, L Bergonzini, R Lauriola, C Gudgeon, A Dent, DM Tiltman, A Hacking, A Dowdle, E Steynor, P Toop, J Schnurch, HG Mosny, D Bender, HG Bojar, H Veronesi, A Foladore, S Pamich, G Bianchi, G Torretta, A Rudenstam, CM Wallgren, A Persson, S Mattsson, J Cahlin, E Hafstrom, LO Holmberg, S Hultborn, R ColldahlJaderstrom, G Gustavsson, B Carlsson, G Ivarsson, L Thoren, O Ruusvik, O Nicklasson, LG Dahlin, S Karlsson, G Lindberg, B Sundback, A Bergegardh, S Salander, H Andersson, C Hessman, Y Nelzen, O Heideman, M Ramhult, T Svensson, JH Lidberg, P Bjork, S Lindtner, J Erzen, D Cerar, O Stabuc, B Golouh, R Lamovec, J Sebek, S Kramberger, M Vrhovec, I CortesFunes, H MartinezTello, F Mendiola, C CruzVigo, F Larrodera, ML Sierra, A Miranda, P Alonso, S Collins, J Snyder, R Gregory, P Burns, WI Green, M Gale, T Henderson, M Hart, S Neil, S Kitchen, P Lovell, R McLennan, R Russell, I Schwarz, M Basser, R Robertson, A Gill, P Carter, ML Malycha, P Yeoh, E Ward, G Leong, ASY LommaxSmith, J Hoosfall, D DAngelo, R Byrne, M vanHazel, G Dewar, J Buck, M Sheiner, HJ Ingram, D Sterrett, G Hahnel, R Forbes, JF Steward, J Darbar, SW Bishop, JM Simms, B Ziogas, V Tattersall, MHN Coates, A Niesche, F West, R Renwick, S Donovan, J Duval, P Simes, RJ Ng, A Glenn, D North, RA Beith, J OConnor, RG Rice, M Stevens, G Fey, M Barth, A Dreher, E Isenschmid, M Schneider, H Buser, K Ludin, J Luthi, JM Altermatt, HJ Laissue, JA Markwalder, R Burg, H Senn, HJ Thurlimann, B Jungi, WF Morant, R Oehlschlegel, C Hardmeier, T Luscher, K Ries, G Topfer, M Lorenz, U Benz, D Schiltknecht, O Spati, B Schmid, L Cavalli, F Sessa, C Bronz, L Martinelli, G Muller, W Luscieti, P Passega, E Pedrinis, E Rey, P Martinoli, S Spinelli, A Galfetti, MA Lombardi, A Pedrazzini, A Losa, G Varini, M Ginier, M Herrmann, R Harder, JF Laffer, U Almendral, AC Eppenberger, U Torhorst, J Siegenthaler, P Piguet, D Barrelet, V Baumann, RP Joss, R Sauter, C Metzger, U Engeler, V Haller, U Kochli, O Leyvraz, S Perey, L Anani, P Gomez, F Mirimanoff, RO Chapuis, G DeGrandi, P Reymond, P Alberto, P Schafer, P Krauer, F Forni, M Aapro, M Egeli, R Megevand, R JacotdesCombes, E Schindler, A Noseda, G Weber, W Lehmann, W TI Duration and reintroduction of adjuvant chemotherapy for node-positive premenopausal breast cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article AB Purpose: The optimal duration and timing of adjuvant chemotherapy for breast cancer patients remain uncertain and were prospectively studied. Patients and Methods: We randomly assigned 1,554 premenopausal breast cancer patients with node-positive disease in ct 2 x 2 factorial design to receive the following: (A) cyclophosphamide, methotrexate, and fluorouracil for 6 consecutive courses on months 1 to 6 (CMFx6); (B) CMFx6 plus three single courses of reintroduction CMF given on months 9, 12, and 15; (C) CMF for three consecutive courses on months 1 to 3 (CMFx3); or (D) CMFx3 plus three single courses of reintroduction CMF given on months 6, 9, and 12. Accrual was between July 1986 and April 1993. A total of 1,475 patients (95%) were eligible and assessable. The median follow-up duration was 60 months. Results: Patients who received CMFx3 without reintroduction had a 5-year disease-free survival (DFS) rate of 53% compared with 58% for the other three treatment groups (hazards ratio [HR], 1.20; 95% confidence interval [CI], 1.00 to 1.45; P = .04). The increased risk of relapse with CMFx3 was more marked for women aged less than 40 years (308 patients; HR, 1.32; 95% CI, 0.94 to 1.84; P = .11) and for patients with estrogen receptor (ER)-negative tumors (455 patients; HR, 1.45; 95% CI, 1.06 to 2.00; P = .02). Reintroduction chemotherapy provided additional benefit (HR, 0.86; 95% CI, 0.73 to 1.01; P = .07), especially for women greater than or equal to 40 years of age (1,167 patients; HR, 0.82; 95% CI, 0.68 to 0.99; P =.04). Conclusion: Three courses of adjuvant CMF chemotherapy are not sufficient compared with longer duration CMF chemotherapy, especially in younger women and in patients with ER-negative primary tumors. Reintroduction chemotherapy showed some evidence of additional benefit, bur remains investigational. (C) 1996 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. FRONTIER SCI & TECHNOL RES FDN INC,AMHERST,NY. AUCKLAND BREAST CANC STUDY GRP,AUCKLAND,NEW ZEALAND. CTR RIFERIMENTO ONCOL,I-33081 AVIANO,ITALY. SPEDALI CIVILI & FDN BERETTA,BRESCIA,ITALY. GROOTE SCHUUR HOSP,CAPE TOWN 7925,SOUTH AFRICA. UNIV DUSSELDORF,W-4000 DUSSELDORF,GERMANY. PRESIDIO OSPEDALIERO,GORIZIA,ITALY. W SWEDISH BREAST CANC STUDY GRP,GOTHENBURG,SWEDEN. INST ONCOL,LJUBLJANA,SLOVENIA. MADRID BREAST CANC GRP,MADRID,SPAIN. ANTICANC COUNCIL VICTORIA,MELBOURNE,VIC,AUSTRALIA. ROYAL ADELAIDE HOSP,ADELAIDE,SA 5000,AUSTRALIA. RI gusterson, barry/D-3752-2009 NR 21 TC 72 Z9 72 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1996 VL 14 IS 6 BP 1885 EP 1894 PG 10 WC Oncology SC Oncology GA UP725 UT WOS:A1996UP72500016 ER PT J AU Chapple, ILC Socransky, SS Dibart, S Glenwright, DH Matthews, JB AF Chapple, ILC Socransky, SS Dibart, S Glenwright, DH Matthews, JB TI Chemiluminescent assay of alkaline phosphatase in human gingival crevicular fluid: Investigations with an experimental gingivitis model and studies on the source of the enzyme within crevicular fluid SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE alkaline phosphatase; gingival fluid; gingivitis; periodontal bacteria; isoenzymes; source; levamisole AB The purpose of this study was to investigate how levels of gingival crevicular fluid (GCF) alkaline phosphatase (ALP) changes in relation to levels of plaque and gingival inflammation in 20 adults during a 21 day period of experimental gingivitis. The source of ALP within GCF was also investigated using a repeat sampling protocol; by determining enzyme levels derived from 30 putative periodontal pathogenic and non-pathogenic species; and by examining inhibition profiles from a variety of host and bacterial ALP isoenzymes. Total 30-s GCF ALP levels increased significantly (p<0.002) during experimental gingivitis and preceded an increase in gingival index (GI) by approximately 7 days. Enzyme levels correlated with GCF volume (R = 0.7; p<0.0001), but repeat sampling indicated that entry of ALP into the gingival crevice was independent of the rates of fluid flow. Only 5 of the bacterial species investigated produced clearly detectable levels of ALP in culture supernatants, there were P. gingivalis (381), P. intermedia (581), P. nigrescens (8944), Dentin P. gingivalis (TW 471: clinical isolate) and C. ochracea (25). Levamisole inhibition and studies on suspensions of washed plaque demonstrated that host-derived ALP contributed to >80% of the enzyme in GCF. We conclude that elevated 30-s GCF ALP levels measured using the chemiluminescent assay reported, are detected before increase in gingival indices and appear to be a better marker of gingival inflammation than ALP concentrations. The Major source of ALP within GCF is host derived and in early inflammatory disease is likely to be polymophonuclear leukocyte origin. C1 FORSYTH DENT CTR,BOSTON,MA 02115. RP Chapple, ILC (reprint author), UNIV BIRMINGHAM,PERIODONTAL UNIT,BIRMINGHAM DENT SCH,DEPT DENT,ST CHADS QUEENSWAY,BIRMINGHAM B4 6NN,W MIDLANDS,ENGLAND. NR 22 TC 25 Z9 25 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD JUN PY 1996 VL 23 IS 6 BP 587 EP 594 DI 10.1111/j.1600-051X.1996.tb01829.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UU676 UT WOS:A1996UU67600013 PM 8811480 ER PT J AU Horowitz, SL Mandel, ID AF Horowitz, SL Mandel, ID TI An interview with Coenraad F. A. Moorrees SO JOURNAL OF DENTAL RESEARCH LA English DT Editorial Material C1 FORSYTH DENT CTR,BOSTON,MA 02115. COLUMBIA UNIV,SCH DENT & ORAL SURG,NEW YORK,NY. RP Horowitz, SL (reprint author), HARVARD UNIV,SCH DENT MED,CAMBRIDGE,MA 02138, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 1996 VL 75 IS 6 BP 1342 EP 1345 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VK230 UT WOS:A1996VK23000003 ER PT J AU Weeks, MR Himmelgreen, DA Singer, M Woolley, S RomeroDaza, N Grier, M AF Weeks, MR Himmelgreen, DA Singer, M Woolley, S RomeroDaza, N Grier, M TI Community-based aids prevention: Preliminary outcomes of a program for African American and Latino injection drug users SO JOURNAL OF DRUG ISSUES LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the American-Anthropological-Association CY NOV 30-DEC 04, 1994 CL ATLANTA, GA SP Amer Anthr Assoc ID RISK SEXUAL-BEHAVIOR; SELF-EFFICACY; UNITED-STATES; CRACK USERS; CONDOM USE; WOMEN; INFECTION; SYRINGES; MODEL AB This paper presents preliminary outcomes of a community-based AIDS prevention program for drug users called Project COPE II, the National Institute on Drug Abuse (NIDA) cooperative agreement study in Hartford, Connecticut. COPE II's efficacy study compares the NIDA standard intervention against two culturally targeted, enhanced interventions, one for African Americans and one for Puerto Ricans, A sample of 188 out-of-treatment injection drug users (IDUs) with matched baseline and 6-month follow-up interviews were compared for changes in monthly injection rates and proportionate use of new and pre-used needles and used injection supplies, Effects of injection outliers, attrition, and ethnic differences were examined for impact on outcome measures and to identify subgroups within the study population for whom the intervention had differential effects. These preliminary analyses suggest that attendance in culturally targeted enhanced interventions may increase the likelihood of positive program outcome, including drug-related risk reduction for some populations, However, subgroups of IDUs, such as extremely high injectors or individuals who drop out before initiating or completing the program, may require different intervention approaches. Further research is needed to understand the relationship between intervention and behavior change, reasons for attrition, and moderating factors affecting project outcomes. C1 UNIV CONNECTICUT,SCH MED,STORRS,CT 06269. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. OI Weeks, Margaret R./0000-0001-7493-0276 NR 59 TC 24 Z9 24 U1 0 U2 0 PU J DRUG ISSUES INC PI TALLAHASSEE PA PO BOX 4021, TALLAHASSEE, FL 32315 SN 0022-0426 J9 J DRUG ISSUES JI J. Drug Issues PD SUM PY 1996 VL 26 IS 3 BP 561 EP 590 PG 30 WC Substance Abuse SC Substance Abuse GA VM056 UT WOS:A1996VM05600004 ER PT J AU Grellier, P Feliers, D Yee, D Woodruff, K Abboud, SL AF Grellier, P Feliers, D Yee, D Woodruff, K Abboud, SL TI Interaction between insulin-like growth factor-I and insulin-like growth factor-binding proteins in TC-1 stromal cells SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER CELLS; IGF-I; HUMAN FIBROBLASTS; PROLIFERATION; EXPRESSION; MECHANISMS; MODULATION; SECRETION; INHIBITOR; IGFBP-1 AB IGF-I and -II play an important role in regulating bone formation. Bone marrow stromal cells, particularly those with osteoblast-like features, may act in concert with osteoblasts to increase IGF-I and -II levels in the bone microenvironment. Local bioavailability of IGFs, however, is modulated by IGF binding proteins (IGFBPs). We have previously demonstrated that murine TC-1 stromal cells constitutively secrete IGF-I and IGFBPs. In the present study, we determined the phenotype of these cells and used them as a model to explore the effect of IGFBPs on IGF-I-induced mitogenesis. The effect of IGF-I on IGFBPs expressed by TC-1 was also determined. When grown under conditions that promote osteogenic differentiation, TC-1 cells showed high alkaline phosphatase activity and mRNA levels, weakly expressed osteocalcin mRNA, and formed mineralized bone-like nodules. TC-1 cells expressed IGF-I and IGF-II mRNAs, while other stromal phenotypes preferentially expressed IGF-I. TGF-I stimulated TC-1 DNA synthesis in a dose-dependent manner and this effect was inhibited by recombinant IGFBP-1 and -4. Since IGF-I may regulate IGFBP production, the effect of EGF-I on IGFBPs expressed by TC-1 cells was determined. IGF-I increased the abundance of IGFBP-3, -4 and -5 in TC-1 conditioned medium; this correlated with induction of IGFBP-3 mRNA, but not with that of IGFBP-4 or -5 mRNAs. The findings demonstrate that most stromal cells express IGF-I which. may act in an autocrine and/or paracrine fashion. The local effects of IGF-I, however, may be blocked by IGFBP-1 or -4. IGF-I regulates the relative abundance of IGFBPs in stromal cells which, in turn, may influence IGF-I-mediated effects on bone remodeling. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NCI NIH HHS [CA52952]; NIAMS NIH HHS [AR42306] NR 37 TC 6 Z9 6 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JUN PY 1996 VL 149 IS 3 BP 519 EP 529 DI 10.1677/joe.0.1490519 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UP485 UT WOS:A1996UP48500018 PM 8691111 ER PT J AU Costa, JJ Demetri, GD Harrist, TJ Dvorak, AM Hayes, DF Merica, EA Menchaca, DM Gringeri, AJ Schwartz, LB Galli, SJ AF Costa, JJ Demetri, GD Harrist, TJ Dvorak, AM Hayes, DF Merica, EA Menchaca, DM Gringeri, AJ Schwartz, LB Galli, SJ TI Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GROWTH-FACTOR; INVIVO; DIFFERENTIATION; MASTOCYTOSIS; BASOPHILS; RECEPTOR; IL-3 AB Stem cell factor (SCF), also known as mast cell growth factor, kit ligand, and Steel factor, is the ligand for the tyrosine kinase receptor (SCFR) that is encoded by the c-kit proto-oncogene. We analyzed the effects of recombinant human SCF (r-hSCF, 5-50 mu g/kg/day, injected subcutaneously) on mast cells and melanocytes in a phase I study of 10 patients with advanced breast carcinoma. A wheal and flare reaction developed at each r-hSCF injection site; by electron microscopy, most dermal mast cells at these sites exhibited extensive, anaphylactic-type degranulation. A 14-d course of r-hSCF significantly increased dermal mast cell density at sites distant to those injected with the cytokine and also increased both urinary levels of the major histamine metabolite, methyl-histamine, and serum levels of mast cell a-tryptase. Five subjects developed areas of persistent hyperpigmentation at r-hSCF injection sites; by light microscopy, these sites exhibited markedly increased epidermal melanization and increased numbers of melanocytes. The demonstration that r-hSCF can promote both the hyperplasia and the functional activation of human mast cells and melanocytes in vivo has implications for our understanding of the role of endogenous SCF in health and disease. These findings also indicate that the interaction between SCF and its receptor represents a potential therapeutic target for regulating the numbers and functional activity of both mast cells and cutaneous melanocytes. C1 BETH ISRAEL HOSP,DEPT PATHOL,DIV EXPTL PATHOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. PATHOL SERV INC,CAMBRIDGE,MA 02139. AMGEN INC,THOUSAND OAKS,CA 91320. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. FU NCI NIH HHS [CA/AI-72074]; NIAID NIH HHS [AI/GM-23990, AI-31982] NR 27 TC 186 Z9 187 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 1 PY 1996 VL 183 IS 6 BP 2681 EP 2686 DI 10.1084/jem.183.6.2681 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UT401 UT WOS:A1996UT40100031 PM 8676090 ER PT J AU Miller, JB AF Miller, JB TI Red-breasted Mergansers in an urban winter habitat SO JOURNAL OF FIELD ORNITHOLOGY LA English DT Article ID BEHAVIOR AB During the winters of 1991-95, I determined population densities, proportions of adult males, activity budgets, and foraging by Red-breasted Mergansers (Mergus serrator) during mid-day on the urbanized inner harbor at Boston Massachusetts. Red-breasted Mergansers arrived at Boston in mid-to-late December, reached peak densities of 1-3/ha in late January or early February, and left by the first week of April. The mid-winter proportion of adult males was 60-80% in the three winters of 1991-92 through 1993-94, but only approximately 30% during the warmer than average winter of 1994-95. Foraging, preening, and alert/swimming each accounted for about 20-30% of observations. Red-breasted Mergansers surfaced with and ingested fish after 6.4% of dives, and, when gulls attempted to pirate fish, the mergansers escaped under piers. RP Miller, JB (reprint author), MASSACHUSETTS GEN HOSP,NEUROMUSCULAR LAB,149 13TH ST,CHARLESTOWN,MA 02129, USA. NR 19 TC 0 Z9 0 U1 2 U2 2 PU ASSOC FIELD ORNITHOLOGISTS PI BELOIT PA BELOIT COLLEGE, DEPT BIOLOGY, 700 COLLEGE ST, BELOIT, WI 53511 SN 0273-8570 J9 J FIELD ORNITHOL JI J. Field Ornithol. PD SUM PY 1996 VL 67 IS 3 BP 477 EP 483 PG 7 WC Ornithology SC Zoology GA VA954 UT WOS:A1996VA95400021 ER PT J AU Netland, PA Feke, GT Konno, S Goger, DG Fujio, N AF Netland, PA Feke, GT Konno, S Goger, DG Fujio, N TI Optic nerve head circulation after topical calcium channel blocker SO JOURNAL OF GLAUCOMA LA English DT Article DE calcium channel blocker; verapamil; glaucoma; ocular blood flow; laser Doppler ID OPEN-ANGLE GLAUCOMA; RETINAL BLOOD-FLOW; INTRAOCULAR-PRESSURE; LOW-TENSION; MANAGEMENT; INCREASES; DILTIAZEM; VERAPAMIL; ATROPHY AB Purpose: Our purpose was to investigate the effects of the calcium channel blocker verapamil on intraocular pressure and blood circulation in the human optic nerve head. Methods: The effects of three different concentrations of topical verapamil (0.063%, 0.125%, and 0.25%) on intraocular pressure and optic nerve head capillary blood speed were measured in 12 healthy normal subjects, In a randomized, double-masked design, each subject received one drop of either verapamil or placebo in one eye and the opposite treatment in the fellow eye. Anterior optic nerve circulation was assessed at baseline and 90 min after instillation of the drops using the laser Doppler technique. Results: The intraocular pressure was significantly reduced compared with baseline in both verapamil- and placebo-treated eyes at each concentration. The reductions of intraocular pressure were greater in verapamil-treated eyes (12-17%) than in placebo-treated eyes (9-12%). No systemic effect on heart rate or blood pressure was detected after administration of topical verapamil, The capillary blood speed in the optic nerve head was increased in both verapamil- and placebo-treated eyes at each concentration, although the only statistically significant increases were with the 0.25% concentration. The mean +/- SEM increase compared with baseline at the 0.25% concentration was 10.4 +/- 3.6% in verapamil-treated eyes (p = 0.017), and 11.6 +/- 4.4% in placebo-treated eyes (p = 0.026). Conclusions: These results indicate that topical administration of verapamil lowers the intraocular pressure and increases the capillary blood speed in the optic nerve head in normal subjects. Changes measured in verapamil-treated eyes were also observed in placebo-treated eyes, indicating a crossover effect. C1 HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA. RP Netland, PA (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 30 TC 46 Z9 47 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD JUN PY 1996 VL 5 IS 3 BP 200 EP 206 PG 7 WC Ophthalmology SC Ophthalmology GA UP799 UT WOS:A1996UP79900010 PM 8795760 ER PT J AU Hutchcroft, JE Bierer, BE AF Hutchcroft, JE Bierer, BE TI Signaling through CD28/CTLA-4 family receptors - Puzzling participation of phosphatidylinositol-3 kinase SO JOURNAL OF IMMUNOLOGY LA English DT Editorial Material ID HUMAN T-CELLS; PROTEIN-KINASE; LYMPHOCYTES-T; CTLA-4; CD28; EXPRESSION; ACTIVATION; GENE; TRANSDUCTION; HOMOLOG C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV PEDIAT ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED,BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL, DEPT MED, BOSTON, MA 02115 USA. FU NIAID NIH HHS [AI35297] NR 69 TC 53 Z9 53 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1996 VL 156 IS 11 BP 4071 EP 4074 PG 4 WC Immunology SC Immunology GA UM244 UT WOS:A1996UM24400001 PM 8666770 ER PT J AU Hohmann, EL Oletta, CA Killeen, KP Miller, SI AF Hohmann, EL Oletta, CA Killeen, KP Miller, SI TI phoP/phoQ-deleted Salmonella typhi (Ty800) is a safe and immunogenic single-dose typhoid fever vaccine in volunteers SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PHOP-VIRULENCE REGULON; IMMUNE-RESPONSE; TYPHIMURIUM VIRULENCE; GENE; MUTATIONS; INVASION; STRAINS; MUTANT; CELLS; TY21A AB The phoP/phoQ virulence regulatory genes of Salmonella typhi Ty2 were deleted, and the resultant strain (Ty800) was tested as a live attenuated typhoid fever vaccine in human volunteers. Groups of 2 or 3 subjects received single oral doses of 10(7), 10(8), 10(9), or 10(10) cfu. Two volunteers who received the largest dose had self-limited side effects; no bacteremias were detected. Ten of 11 subjects had evidence of intestinal immune responses to the vaccine as measured by increases in S. typhi lipopolysaccharide-specific IgA-secreting cells in peripheral blood samples. Humoral immune responses were measured and compared with those of control vaccinees who received 4 oral doses of S, typhi Ty21a. In the most sensitive assays, 9 of 11 volunteers and 5 of 8 Ty21a control vaccinees had evidence of IgG directed against S. typhi antigens. Ty800 is safe, and single oral doses are highly immunogenic in humans. C1 INST VIRUS RES,CAMBRIDGE,MA. RP Hohmann, EL (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,GRAY 5,BOSTON,MA 02114, USA. FU NCRR NIH HHS [RR-01066]; NIAID NIH HHS [AI-30497]; PHS HHS [DJ-01410] NR 31 TC 185 Z9 190 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1996 VL 173 IS 6 BP 1408 EP 1414 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UM115 UT WOS:A1996UM11500014 PM 8648213 ER PT J AU Gupta, RK Griffin, P Xu, J Rivera, R Thompson, C Siber, GR AF Gupta, RK Griffin, P Xu, J Rivera, R Thompson, C Siber, GR TI Diphtheria antitoxin levels in US blood and plasma donors SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ANTIBODIES AB Plasma samples from 500 blood donors were titrated for diphtheria antitoxin (DAT) by the toxin neutralization (TN) test. Only 1.6% of donors had <0.01 IU/mL DAT, the minimum protective level against diphtheria; 15% had levels between 0.01 and <0.1 IU/mL, indicating basic protection, and 83.4% had levels greater than or equal to 0.1 IU, indicating full protection, Three hundred fifty samples were studied by ELISA for diphtheria toroid IgG antibodies to assess the utility of the assay as a quick, convenient method for evaluating diphtheria immunity, Although the correlation between TN and ELISA titers for the 350 samples was high (r = .80), there was no correlation (r = .07) for samples with antitoxin titers <0.1 IU/mL, the level of special interest for serosurveys for protection, Titration of 62 immune globulin samples (prepared from 1957 to 1994) showed that DAT levels in Massachusetts blood donors increased concurrently with increased use of tetanus-diphtheria vaccine in the state. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Gupta, RK (reprint author), MASSACHUSETTS PUBL HLTH BIOL LABS,305 SOUTH ST,BOSTON,MA 02130, USA. NR 16 TC 22 Z9 23 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1996 VL 173 IS 6 BP 1493 EP 1497 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UM115 UT WOS:A1996UM11500029 PM 8648228 ER PT J AU Halaban, R Bohm, M Dotto, P Moellmann, G Cheng, E Zhang, YH AF Halaban, R Bohm, M Dotto, P Moellmann, G Cheng, E Zhang, YH TI Growth regulatory proteins that repress differentiation markers in melanocytes also downregulate the transcription factor microphthalmia SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE basic FGF; FGF2; dominantly acting oncogenes; E1A ID MURINE MELANOCYTES; MALIGNANT-MELANOMA; TRANSGENIC MICE; CYCLIN-A; GENE; CELLS; TRANSFORMATION; MUTATIONS; CULTURE; E1A AB Expression of basic fibroblast growth factor cDNA or dominantly acting oncogenes, e.g,, E1A, in immortalized mouse melanocytes leads to autonomous growth in vitro, depigmentation, and in the case of the oncogenes, tumorigenesis, Because downregulation of pigmentation is a common event in human metastatic melanoma cells grown in culture, we determined the molecular basis of depigmentation in a mouse melanocyte model system. We tested the effect of E1A mutants deficient in their ability to neutralize several regulatory proteins and determined changes in melanogenic gene expression, We identified Microphthalmia as the affected, downregulated transcription factor in melanocytes rendered amelanotic by E1A, basic fibroblast growth factor, or the oncogenes ras or neu, and in an amelanotic cell variant of Cloudman S91 mouse melanoma. Against expectations, sequestration of p300, a transcriptional adaptor that mediates responses to cyclic adenosine monophosphate, was not required for the full transforming effects of E1A. Our results suggest that in addition to controlling tyrosinase (albino locus) and tyrosinase-related protein 1 (TRP1/gp75/brown locus), both known to possess the DNA consensus site for binding the Microphthalmia protein, this transcription factor also controls other melanocyte-specific genes such as pink-eyed dilution and Pmel 17 (silver), but not tyrosinase-related protein 2 (slaty locus), Furthermore, these findings show that nicr crophthalmia is downregulated not only by experimentally introduced dominantly acting oncogenes but also by the aberrant expression of basic fibroblast growth factor and by spontaneous tumorigenic transformation. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT DERMATOL,CHARLESTOWN,MA 02129. RP Halaban, R (reprint author), YALE UNIV,SCH MED,DEPT DERMATOL,POB 208059,NEW HAVEN,CT 06520, USA. FU NCI NIH HHS [CA 44542]; NIAMS NIH HHS [AR 41942, AR 39848] NR 44 TC 39 Z9 39 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1996 VL 106 IS 6 BP 1266 EP 1272 DI 10.1111/1523-1747.ep12348972 PG 7 WC Dermatology SC Dermatology GA UR404 UT WOS:A1996UR40400018 PM 8752668 ER PT J AU Rosenzweig, M Marks, DF Hempel, D Johnson, RP AF Rosenzweig, M Marks, DF Hempel, D Johnson, RP TI In vitro T lymphopoiesis: A model system for stem cell gene therapy for AIDS SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 13th Annual Primate Center Meeting - Nonhuman Primate Models for AIDS VIII CY NOV 05-08, 1995 CL MONTEREY, CA SP Calif Reg Primate Res Center, Davis DE HIV; SIV; rhesus; macaque ID IMMUNODEFICIENCY-VIRUS TYPE-1; BONE-MARROW CELLS; RETROVIRAL VECTOR; PERIPHERAL-BLOOD; PROGENITOR CELLS; LEUKEMIA-VIRUS; HUMAN THYMUS; IN-VIVO; EXPRESSION; INFECTION AB Stable introduction of therapeutic genes into hematopoietic stem cells has the potential to reconstitute immunity in individuals with HIV infection. However, many important questions regarding the safety and efficacy of this approach remain unanswered and may be addressed in a non-human primate model. To facilitate evaluation of expression of foreign genes in T cells derived from transduced hematopoietic progenitor cells, we have established a culture system that supports the differentiation of rhesus macaque and human CD34(+) bone marrow derived cells into mature T cells. Thymic stromal monolayers were prepared from the adherent cell fraction of collagenase digested fetal or neonatal thymus. After 10-14 days, purified rhesus CD34(+) bone marrow-derived cells cultured on thymic stromal monolayers yielded CD3(+)CD4(+)CD8(+), CD3(+)CD4(+)CD8(-), and CD3(+)CD4(-)CD8(+) cells. Following stimulation with mitogens, these T cells derived from CD34(+) cells could be expanded over 1,000-fold and maintained in culture for up to 20 weeks. We next evaluated the ability of rhesus CD34(+) cells transduced with a retroviral vector containing the marker gene neo to undergo in vitro T cell differentiation. CD34(+) cells transduced in the presence of bone marrow stroma and then cultured on rhesus thymic stroma resulted in T cells containing the retroviral marker gene. These studies should facilitate both in vitro and in vivo studies of hematopoietic stem cell therapeutic strategies for AIDS. C1 HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,DIV IMMUNOL,SOUTHBOROUGH,MA 01772. MASSACHUSETTS GEN HOSP,CTR AIDS RES,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,CHARLESTOWN,MA. FU NCRR NIH HHS [RR-00168, RR-00055]; NIAID NIH HHS [AI-36550] NR 51 TC 7 Z9 7 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD JUN PY 1996 VL 25 IS 3 BP 192 EP 200 PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA VH065 UT WOS:A1996VH06500007 PM 8892040 ER PT J AU Cui, YN Shen, YT Kalthof, B Iwase, M Sato, N Uechi, M Vatner, SF Vatner, DE AF Cui, YN Shen, YT Kalthof, B Iwase, M Sato, N Uechi, M Vatner, SF Vatner, DE TI Identification and functional role of beta-adrenergic receptor subtypes in primate and rodent: In vivo versus isolated myocytes SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE beta-adrenergic receptor subtypes; isolated myocytes; contractility; baboon; rat ID HUMAN VENTRICULAR MYOCARDIUM; HUMAN-HEART; ADRENOCEPTOR SUBTYPES; ADENYLATE-CYCLASE; DOWN-REGULATION; RAT-HEART; CONTRACTILE-FORCE; CYCLIC-AMP; GUINEA-PIG; BETA-2-ADRENOCEPTORS AB We determined the relationship between the beta(1)- and beta(2)-adrenergic receptor subtypes in isolated myocytes and their physiological responsiveness in chronically instrumented conscious baboons and rats. In conscious baboons, isoproterenol (ISO) (0.02 mu g/kg) increased left ventricular (LV) dP/dt by 89 +/- 6.7% from 2898 +/- 370 mmHg/s and only by 13 +/- 3.3% from 2491 +/- 146 mmHg/s after beta(1)-adrenergic receptor blockade, indicating that the predominant physiological response was mediated by beta(1)-adrenergic receptors. Decreases in mean arterial pressure (-11 +/- 0.5 mmHg v -16 +/- 4.6 mmHg) and coronary vascular resistance (-3.1 +/- 0.4 v -3.6 +/- 0.4 mmHg/ml/min) induced ISO were not different before and after beta(1)-blockade, indicating that beta(2)-adrenergic receptors were not blocked. In conscious rats, ISO (0.4 mu g/kg) increased LV dP/dt by 50 +/- 4.9% from 13 252 +/- 2002 mmHg/s and only by 10 +/- 3.9% from 10 793 +/- 1364 mmHg/s after beta(1)-adrenergic receptor blockade; whereas decreases in mean arterial pressure induced by ISO were not different before and after beta(1) blockade (-19 +/- 2.4 mmHg v -16 +/- 2.2 mmHg), i.e. very consistent with the physiological responses in baboons. In vitro studies of isolated myocytes, using radioligand binding with I-125-cyanopindolol (I-125-cyp) and the subtype beta(1)-selective antagonist betaxolol and the beta(2)-selective antagonist ICI 118 551 indicated that the beta(1)/beta(2) ratio of rat myocytes was 92/8; whereas baboon myocytes were more equally distributed (59/41). Thus, in both species the preponderance of effects of ISO on ventricular function was beta(1)-adrenergic receptor mediated, which is consistent with the beta(1)/beta(2) ratio in rat myocytes but not in baboon myocytes, where a significant fraction of beta(2)-adrenergic receptors does not appear to exert an effect on conctractility in vivo. (C) 1996 Academic Press Limited C1 NEW ENGLAND REG PRIMATE RES CTR, SOUTHBOROUGH, MA 01772 USA. HARVARD UNIV, SCH MED,DEPT MED,BRIGHAM & WOMENS HOSP, MASSACHUSETTS GEN HOSP,CHILDRENS SERV, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [P01-HL-38070, HL-33107, HL-37404] NR 50 TC 18 Z9 18 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUN PY 1996 VL 28 IS 6 BP 1307 EP 1317 DI 10.1006/jmcc.1996.0121 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA UN561 UT WOS:A1996UN56100012 PM 8782072 ER PT J AU Warner, JEA Rizzo, JF Brown, EW Ogilvy, CS AF Warner, JEA Rizzo, JF Brown, EW Ogilvy, CS TI Recurrent chiasmal apoplexy due to cavernous malformation SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article DE chiasmal apoplexy; cavernous malformation; pregnancy; recurrent hemorrhage; surgery ID OPTIC CHIASM; ARTERIOVENOUS-MALFORMATIONS; VASCULAR MALFORMATION; HEMANGIOMA; ANGIOMA; HEMORRHAGE; NERVE; PREGNANCY; TRACT AB We report a case of chiasmal apoplexy due to a cavernous malformation (CM). Surgery was delayed because of the patient's advanced pregnancy, and nearly complete recovery of vision occurred spontaneously. Recurrent hemorrhage prompted surgical extirpation. The patient was left with a residual deficit. The literature pertaining to chiasmal apoplexy and CMs is reviewed. Nearly half of the reported cases of chiasmal CM had recurrent hemorrhages. The co-occurrence of hemorrhage from CM and pregnancy is too cause and effect. C1 UNIV UTAH,DEPT OPHTHALMOL,SALT LAKE CITY,UT. UNIV UTAH,DEPT NEUROL,SALT LAKE CITY,UT. HARVARD UNIV,MASSACHUSETTS GEN HOSP,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT NEUROSURG,BOSTON,MA 02115. DEPT OPHTHALMOL,BOSTON,MA. DEPT RADIOL,BOSTON,MA. NR 33 TC 20 Z9 22 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD JUN PY 1996 VL 16 IS 2 BP 99 EP 106 PG 8 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA UT349 UT WOS:A1996UT34900004 PM 8797165 ER PT J AU Borchert, MS Lessell, S Hoyt, WF AF Borchert, MS Lessell, S Hoyt, WF TI Hemifield slide diplopia from altitudinal visual field defects SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article DE Hemifield slide; diploplia; visual field defects AB We report two cases in which heteronymous, altitudinal visual field defects resulted in loss of fusion and transient overlap of preserved hemifields. This phenomenon resulted in complaints of diplopia similar to that described as ''hemifield'' slide previously described by temporal hemianopsias. These cases illustrate that generalized loss of fusion, and not the particular type of hemianopic field defect, is responsible for the symptoms known as hemifield slide. C1 UNIV SO CALIF,SCH MED,DEPT OPHTHALMOL,LOS ANGELES,CA 90033. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,DEPT OPHTHALMOL,SAN FRANCISCO,CA 94143. RP Borchert, MS (reprint author), CHILDRENS HOSP LOS ANGELES,DIV OPHTHALMOL,4650 SUNSET BLVD,MS88,LOS ANGELES,CA 90027, USA. NR 6 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD JUN PY 1996 VL 16 IS 2 BP 107 EP 109 PG 3 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA UT349 UT WOS:A1996UT34900005 PM 8797166 ER PT J AU Harr, SD Uint, L Hollister, R Hyman, BT Mendez, AJ AF Harr, SD Uint, L Hollister, R Hyman, BT Mendez, AJ TI Brain expression of apolipoproteins E, J, and A-I in Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; senile plaques; apolipoproteins; beta-amyloid peptide ID SULFATED GLYCOPROTEIN-2; CEREBROSPINAL-FLUID; MESSENGER-RNA; PROTEIN; BINDING; IDENTIFICATION; HIPPOCAMPUS; CLEAVAGE; RAT AB Inheritance of the epsilon 4 allele of apolipoprotein (apo) E is associated with increased risk of Alzheimer's disease (AD) and with increased beta-amyloid peptide (A beta) deposition in the cortex. Apo E is a member of a family of exchangeable apos, characterized by the presence of amphipathic alpha-helical segments that allow these molecules to act as surfactants on the surface of lipoprotein particles. Two members of this family, apo E and apo J, have been shown to bind soluble A beta, and both are associated with senile plaques in the AD cortex. We now have studied the pattern of brain apo expression and found that five members of this class are present: apo AI, A-IV, D, E, and J, By contrast, apos A-II, B, and C-II were not detectable. Immunohistochemistry revealed that, in addition to apo E and apo J, apo A-I immunostained occasional senile plaques in AD cortex. Immunoblot analysis showed no difference in the relative amounts of any of these apos in tissue homogenates of frontal lobe from AD or control patients. Comparison by APO E genotype showed no differences in the amount of apo E in brain among APO E epsilon 3/3, epsilon 3/4, or epsilon 4/4 individuals; however, a significant decrease in the amount of apo J was associated with the APO E epsilon 4 allele. No differences in apo J levels were detected in CSF samples of AD subjects, We propose that several members of the exchangeable apo family may interact with A beta deposits in senile plaques through common amphipathic alpha-helical domains. Competition among these molecules for binding of A beta or A beta aggregates may influence the deposition of A beta in senile plaques. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. FU NIA NIH HHS [50AG05134, AG08487, AG12406] NR 44 TC 127 Z9 127 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1996 VL 66 IS 6 BP 2429 EP 2435 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UL589 UT WOS:A1996UL58900024 PM 8632166 ER PT J AU Litvan, I Mangone, CA McKee, A Verny, M Parsa, A Jellinger, K DOlhaberriague, L Chaudhuri, KR Pearce, RKB AF Litvan, I Mangone, CA McKee, A Verny, M Parsa, A Jellinger, K DOlhaberriague, L Chaudhuri, KR Pearce, RKB TI Natural history of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) and clinical predictors of survival: A clinicopathological study SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE progressive supranuclear palsy; natural history; survival ID GAZE PALSY; DISEASE; MANIFESTATION; PARKINSONISM; DEMENTIA AB Objective-To analyse the natural history of progressive supranuclear palsy (PSP or Steele-Richardson-Olszewski syndrome) and clinical predictors of survival in 24 patients with PSP confirmed by necropsy, who fulfilled the NINDS criteria for a neuropathological diagnosis of typical PSP. Methods-Patients were selected from the research and clinical files of seven medical centres involving tertiary centres of Austria, England, France, and the United States. Clinical features were analysed in detail. The patients' mean age at onset of PSP was 63 (range 45-73) years. Results-The most frequent clinical features (occurring in at least 75% of the patients) were early postural instability and falls, vertical supranuclear palsy, akinetic-rigid predominant parkinsonian disorder characterised by symmetric bradykinesia and axial rigidity unrelieved by levodopa, pseudobulbar palsy, and frontal release signs. Occasionally, segmental dystonia or myoclonus were described, but neither aphasia nor alien limb syndrome was reported. Fractures occurred in 25% of the patients hut were unrelated to the severity of the gait or to the presence of falls. Median survival time was 5.6 (range 2-16.6) years. Onset of falls during the first year, early dysphagia, and incontinence predicted a shorter survival time. Age at onset, sex, early onset of dementia, vertical supranuclear palsy, or axial rigidity had no effect on prognosis of survival. Pneumonia was the most common immediate cause of death. PSP was most often clinically misdiagnosed as Parkinson's disease. Errors in diagnosis suggest that PSP is underdiagnosed. Conclusion-Progressive onset of early postural instability with falls or supranuclear vertical palsy in the fifth decade, should suggest the diagnosis of PSP. Onset of falls during the first year are emphasised, as they could lead to an early diagnosis and influence the prognosis of patients with PSP. Whether appropriate treatment of the dysphagia could prolong the survival of PSP patients needs to be explored. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA. HOP LA PITIE SALPETRIERE,INSERM U360,RAYMOND ESCOUROLLE NEUROPATHOL LAB,PARIS,FRANCE. LUDWIG BOLTZMANN INST CLIN NEUROBIOL,VIENNA,AUSTRIA. INST PSYCHIAT,DEPT NEUROL,LONDON SE5 8AF,ENGLAND. INST NEUROL,PARKINSONS DIS SOC,BRAIN TISSUE BANK,LONDON WC1N 3BG,ENGLAND. RP Litvan, I (reprint author), NINCDS,NIH,NEUROEPIDEMIOL BRANCH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 54 TC 200 Z9 206 U1 0 U2 5 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUN PY 1996 VL 60 IS 6 BP 615 EP 620 DI 10.1136/jnnp.60.6.615 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA UP452 UT WOS:A1996UP45200004 PM 8648326 ER PT J AU Mendez, MF Engebrit, B Doss, R Grau, R AF Mendez, MF Engebrit, B Doss, R Grau, R TI The relationship of epileptic auras and psychological attributes SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID COMPLEX PARTIAL SEIZURES; TEMPORAL-LOBE EPILEPSY; INTERICTAL DEPRESSION; PERSONALITY-INVENTORY; GLUCOSE-METABOLISM; PSYCHO-PATHOLOGY; LATERALITY; VARIABLES; ANXIETY; FOCUS AB Studies suggest a high frequency of epileptic auras with intellectual content among epileptic patients with psychopathology and personality disorders. This study compared measures of personality and psychosocial functioning between epileptic patients with cognitive auras and epileptic patients with noncognitive auras. Ten patients with complex partial seizures who experienced cognitive auras had consistently more depressive traits and psychosocial difficulties than 50 patients with other psychic or nonpsychic auras, particularly if the patients with cognitive auras had left hemisphere epilepti-form foci. Cognitive auras may be associated with depressive traits among epileptic patients. The findings were also in agreement with studies that relate the left hemisphere to depression. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT PSYCHIAT,LOS ANGELES,CA 90073. ST PAUL RAMSEY MED CTR,DEPT NEUROL,ST PAUL,MN 55101. ST PAUL RAMSEY MED CTR,DEPT PSYCHIAT,ST PAUL,MN 55101. RP Mendez, MF (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEUROBEHAV UNIT 691116AF,DEPT NEUROL,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 46 TC 18 Z9 19 U1 1 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 1996 VL 8 IS 3 BP 287 EP 292 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VB219 UT WOS:A1996VB21900006 PM 8854300 ER PT J AU McConnell, H Snyder, PJ Duffy, JD Weilburg, J Valeriano, J Brillman, J Cress, K Cavalier, J AF McConnell, H Snyder, PJ Duffy, JD Weilburg, J Valeriano, J Brillman, J Cress, K Cavalier, J TI Neuropsychiatric side effects related to treatment with felbamate SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID ANTIEPILEPTIC DRUGS; NMDA ANTAGONISTS; PARTIAL SEIZURES; ANTICONVULSANT; RECEPTORS; TRIAL AB Seven patients with refractory seizure disorders and neuropsychiatric symptoms believed secondary to felbamate are presented. Five were on concomitant valproic acid (rind other agents). Anergia, apathy, bradyphrenia, and increased irritability were prominent. One patient on felbamate monotherapy had a new-onset psychosis. Felbamate's NMDA receptor antagonism and GABA potentiation (perhaps enhanced by valproic acid use) are discussed as possible mechanisms of these side effects. C1 ALLEGHENY NEUROPSYCHIAT INST, OAKDALE, PA USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. ALLEGHENY GEN HOSP, DEPT MED NEUROL, PITTSBURGH, PA 15212 USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. OI Snyder, Peter/0000-0003-0555-4654 NR 17 TC 27 Z9 27 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 EI 1545-7222 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 1996 VL 8 IS 3 BP 341 EP 346 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VB219 UT WOS:A1996VB21900014 PM 8854308 ER PT J AU Matsumae, M Kikinis, R Morocz, I Lorenzo, AV Albert, MS Black, PM Jolesz, FA AF Matsumae, M Kikinis, R Morocz, I Lorenzo, AV Albert, MS Black, PM Jolesz, FA TI Intracranial compartment volumes in patients with enlarged ventricles assessed by magnetic resonance-based image processing SO JOURNAL OF NEUROSURGERY LA English DT Article DE hydrocephalus; magnetic resonance imaging; computerized image processing; brain; gray and white matter volume; cerebrospinal fluid volume ID NORMAL-PRESSURE HYDROCEPHALUS; MR SIGNAL ABNORMALITIES; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; GRAY-MATTER; CEREBRAL ATROPHY; BRAIN-WEIGHT; DEMENTIA; STENOSIS; WHITE AB Magnetic resonance image-based computerized segmentation was used to measure the volumes of the brain, gray and white matter components, and to identify regions with prolonged enhancement on T-2-weighted imaging, such as periventricular or deep white matter hyperintensities. The authors also determined the volumes of the ventricles and subarachnoid space in control subjects and in patients with: 1) aqueductal stenosis (AS); 2) other causes of obstructive hydrocephalus (OH); 3) Alzheimer's disease (AD); and 3) normal-pressure hydrocephalus (MPH). In AS the volume of the brain was smaller, whereas that of ventricles and subarachnoid cerebrospinal fluid space was larger than that of controls. The decrease in brain volume was due primarily to white matter loss. Although in OH the ventricles were larger, the subarachnoid space was smaller than in controls, presumably due to encroachment by the brain, in which the volume remained unchanged. In AD, loss of both gray and white matter resulted in a smaller brain volume, whereas that of ventricles and subarachnoid space was larger than in controls. in NPH patients, only ventricular volume was greater, whereas all other compartments were similar to controls. The brain normally occupies 87% to 92% of the intracranial volume and conse quently, as observed in our patients, relatively small decrements in brain markedly among our patient groups, and whether such changes prove useful in clinical assessment and differentiation needs to be determined. C1 BRIGHAM & WOMENS HOSP, DEPT RADIOL, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DEPT NEUROSURG, BOSTON, MA 02115 USA. CHILDRENS HOSP, DEPT NEUROSURG, BOSTON, MA USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. TOKAI UNIV, SCH MED, DEPT NEUROSURG, KANAGAWA, JAPAN. MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BOSTON, MA 02114 USA. FU PHS HHS [5-PO1-A604953] NR 71 TC 47 Z9 47 U1 1 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUN PY 1996 VL 84 IS 6 BP 972 EP 981 DI 10.3171/jns.1996.84.6.0972 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UM587 UT WOS:A1996UM58700010 PM 8847592 ER PT J AU Matsumae, M Kikinis, R Morocz, IA Lorenzo, AV Sandor, T Albert, MS Black, PL Jolesz, FA AF Matsumae, M Kikinis, R Morocz, IA Lorenzo, AV Sandor, T Albert, MS Black, PL Jolesz, FA TI Age-related changes in intracranial compartment volumes in normal adults assessed by magnetic resonance imaging SO JOURNAL OF NEUROSURGERY LA English DT Article DE cerebrospinal fluid; brain; cerebral ventricles; magnetic resonance imaging; volumetric study ID CEREBROSPINAL-FLUID VOLUMES; VENTRICULAR VOLUME; BRAIN ATROPHY; CSF VOLUME; COMPUTERIZED-TOMOGRAPHY; CEREBRAL ATROPHY; SENILE DEMENTIA; MR IMAGES; WHITE; SCHIZOPHRENIA AB Magnetic resonance (MR) image-based computerized segmentation was used to measure various intracranial compartments in 49 normal volunteers ranging in age from 24 to 80 yeats to determine age-related changes in brain, ventricular, and extraventricular cerebrospinal fluid (CSF) volumes. The total intracranial volume (sum of brain, ventricular, and extraventricular CSF) averaged 1469 +/- 102 cm(3) in men and 1289 +/- 111 cm(3) in women. The difference was attributable primarily to brain volume, which accounted for 88.6% of the respective intracranial volumes in both sexes, but was significantly larger in men (1302 +/- 112 cm(3)) than in women (1143 +/- 105 cm(3)). In both, the cranial CSF volume averaged 11.4%. Total intracranial volume did not change with age, although the normalized brain volume of both men and women began to decrease after the age of 40 years. This decrease was best reflected by expansion of the extraventricular CSF volume which, after the age of 50 years, was more marked in men than in women. The volume of the cranial CSF, as determined by MR image-based computerized segmentation, is considerably larger than traditionally accepted and resides mostly extraventricularly. Expansion of CSF volume with age provides a good index of brain shrinkage although evolving changes and growth of the head with age tend to confound the results. C1 BRIGHAM & WOMENS HOSP, DEPT RADIOL, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DEPT NEUROSURG, BOSTON, MA 02115 USA. HARVARD UNIV, CHILDRENS HOSP, DEPT NEUROSURG, SCH MED, BOSTON, MA USA. TOKAI UNIV, SCH MED, DEPT NEUROSURG, KANAGAWA, JAPAN. MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BOSTON, MA 02114 USA. FU PHS HHS [5-PO1-A604953] NR 60 TC 116 Z9 117 U1 2 U2 6 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUN PY 1996 VL 84 IS 6 BP 982 EP 991 DI 10.3171/jns.1996.84.6.0982 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UM587 UT WOS:A1996UM58700011 PM 8847593 ER PT J AU Dietrich, WD Alonso, O Busto, R Finklestein, SP AF Dietrich, WD Alonso, O Busto, R Finklestein, SP TI Posttreatment with intravenous basic fibroblast growth factor reduces histopathological damage following fluid-percussion brain injury in rats SO JOURNAL OF NEUROTRAUMA LA English DT Article DE basic fibroblast growth factor; traumatic brain injury; fluid-percussion; histopathology ID FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; MODERATE HYPOTHERMIA; HIPPOCAMPAL-NEURONS; FACTOR PROTECTS; FACTOR BFGF; ADULT-RATS; BLOOD-FLOW; EXCITOTOXICITY; DEGENERATION AB The purpose of this study was to determine whether treatment with intravenous basic fibroblast growth factor (bFGF) would protect histopathologically in a rat model of traumatic brain injury (TBI). Twenty-four hours prior to TBI, the fluid-percussion interface was positioned parasagittally over the right cerebral cortex. On the second day, fasted rats were anesthetized with 70% nitrous oxide, 1% halothane, and 30% oxygen. Under controlled physiological conditions and normothermic brain temperature (37-37.5 degrees C), rats were injured with a fluid-percussion pulse ranging from 1.6 to 1.9 atm. Rats were randomized into two groups where either bFGF (45 mu g/kg/h) in vehicle (n = 7) or vehicle alone (n = 7) was infused intravenously for 3 h, beginning 30 min after TBI. Three days later, brains were perfusion-fixed for histopathological assessment and quantitative analysis of contusion volume and numbers of necrotic cortical neurons. In vehicle-treated animals, necrotic neurons were observed throughout the lateral cerebral cortex remote from the impact site. In addition, an intracerebral contusion was present in all rats at the gray-white interface underlying the injured cortical areas. Posttraumatic administration of bFGF significantly reduced the numbers of damaged cortical neuron profiles at several coronal levels and reduced the total number of damaged neurons (696 +/- 148 vs. 1,248 +/- 198, means +/- SEM), p < 0.05, ANOVA). In addition, contusion areas at several coronal levels as well as total contusion volume was significantly reduced (1.13 +/- 0.39 mm(3) vs. 3.18 +/- 0.81 mm(3), p < 0.05). These data demonstrate neuroprotection with intravenous bFGF infusion in the posttraumatic setting. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,CNS GROWTH FACTOR RES LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP Dietrich, WD (reprint author), UNIV MIAMI,SCH MED,DEPT NEUROL D45,NEUROTRAUMA RES CTR,POB 016960,MIAMI,FL 33101, USA. FU NINDS NIH HHS [NS-27127, NS-30291] NR 49 TC 73 Z9 76 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN PY 1996 VL 13 IS 6 BP 309 EP 316 PG 8 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA UZ052 UT WOS:A1996UZ05200003 PM 8835798 ER PT J AU Hunter, GJ Hamberg, LM Alpert, NM Choi, NC Fischman, AJ AF Hunter, GJ Hamberg, LM Alpert, NM Choi, NC Fischman, AJ TI Simplified measurement of deoxyglucose utilization rate SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE fluorine-18-FDG; PET; dose uptake ratio; glucose metabolism; lung cancer; diagnostic imaging ID POSITRON EMISSION TOMOGRAPHY; METASTATIC BREAST-CARCINOMA; F-18 FLUORODEOXYGLUCOSE; GLUCOSE-UTILIZATION; NECK TUMORS; MUSCULOSKELETAL TUMORS; PROLIFERATIVE ACTIVITY; MALIGNANT-LYMPHOMA; FLOW-CYTOMETRY; FDG-PET AB The reliability of the dose uptake ratio (DUR), a widely used index of F-18-fluoro-2-deoxy-D-glucose ((18)FDG) metabolism in a variety of tumors, depends on the overall rate of removal of (18)FDG from the circulation. Correcting for this factor is important if DUR is to be used quantitatively for pre- and post-treatment assessments of tumors. Methods: We developed a simplified kinetic method (SKM), based on measured blood curves from a control group, which requires one venous blood sample. We compared the simplified method to the conventional kinetic method and the widely used DUR index in 13 patients with grade 3 or 4 non-small-cell lung carcinoma. Studies were obtained before and after treatment. In all patients, dynamic PET imaging and blood activity measurement was performed for 80 min. The utilization rate of (18)FDG (MRDGlc) was calculated by using a three-compartment model and correlated with a 55-min measurement of DUR and with the simplified kinetic method. Results: Coefficients of determination (R(2)) between MRDGlc and DUR before and after treatment were 0.53 and 0.71, respectively. Using the SKM, these values improved significantly (p < 0.0001) to 0.96 and 0.94, respectively. The pooled pre- and post-treatment coefficient of determination for DUR versus MRDGlc was 0.81; for SKM, it improved significantly (p < 0.001) to 0.98. Conclusion: These results indicate that the observed tumor tissue uptake of (18)FDG, corrected for blood (18)FDG activity and glucose concentration, can reliably predict glucose metabolic rate from a single static image acquired al between 45 min and 1 hr after injection. This has substantial implications for the quantitative use of (18)FDG PET to diagnose and manage malignancy. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 53 TC 104 Z9 106 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUN PY 1996 VL 37 IS 6 BP 950 EP 955 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UQ516 UT WOS:A1996UQ51600018 PM 8683318 ER PT J AU Morgan, CJ Coutts, AGP McFadyen, MC King, TP Kelly, D AF Morgan, CJ Coutts, AGP McFadyen, MC King, TP Kelly, D TI Characterization of IGF-I receptors in the porcine small intestine during postnatal development SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE IGF-I; receptors; intestine; microvillar; phosphorylation; neonatal ID GROWTH FACTOR-I; RAT GASTROINTESTINAL-TRACT; AFFINITY CROSS-LINKING; SKELETAL-MUSCLE; INSULIN; EXPRESSION; EPITHELIUM; BINDING; PHOSPHORYLATION; DIFFERENTIATION AB Receptors for insulin-like growth factor I were characterized on intestinal membranes of jejunum from newborn, suckling, and weaned pigs. I-125-labelled insulin-like growth factor I (IGF-I) binding was time-dependent, saturable, linearly related to membrane protein, and reversible. Analysis of saturation curve data from membrane homogenates revealed a single class of receptors, with receptor number declining during development. In vitro autoradiography localized receptors to the small intestinal submucosa and mucosa and further immunohistochemical localization identified receptors on the apical (microvillar membrane) and basolateral surfaces of enterocytes. After affinity cross-linking of I-125-labelled IGF-I to microvillar membranes, 135 and 260 kilodalton bands were visualized on polyacrylamide gels under reducing conditions. Parallel incubations with excess unlabeled IGF-I, -II, or insulin demonstrated that these bands correspond to the a subunit and an incompletely reduced dimeric a complex of the IGF-I receptor. Receptor number on microvillar membranes increased dramatically during the suckling period and was negatively correlated with maltase and sucrase activities. The functional activity of receptors on microvillar membranes was demonstrated using an in vitro phosphorylation assay. The expression of functional IGF-I receptors during development on both apical and basolateral membranes suggests a regulatory role for this receptor and its ligands. C1 ROWETT RES INST,BUCKSBURN AB2 9SB,ABERDEEN,SCOTLAND. JOSLIN DIABET CTR,BOSTON,MA 02215. NR 46 TC 25 Z9 30 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD JUN PY 1996 VL 7 IS 6 BP 339 EP 347 DI 10.1016/0955-2863(96)00054-X PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UU729 UT WOS:A1996UU72900005 ER PT J AU Foy, DW Madvig, BT Pynoos, RS Camilleri, AJ AF Foy, DW Madvig, BT Pynoos, RS Camilleri, AJ TI Etiologic factors in the development of posttraumatic stress disorder in children and adolescents SO JOURNAL OF SCHOOL PSYCHOLOGY LA English DT Article ID NATURAL DISASTER; SEXUAL ABUSE; PTSD; SCHOOL; CHILDHOOD; SYMPTOMS; AGE AB This article presents an overview of the literature on potential etiological factors in the development of PTSD in children. An etiological model for PTSD is offered which generates hypotheses for identifying links between exposure to traumatic events and consequent symptoms, as well as testing relationships between expo sure variables and other possible mediating factors. Three possible kinds of interaction between etiologic and mediating variables, leading to different levels of symptoms, are presented. Findings from 25 recent studies examining etiologic factors are considered to form an empirical basis for current knowledge about PTSD in children. Severity of trauma exposure and parental trauma-related distress have consistently produced positive correlations with PTSD symptoms. Length of time since trauma exposure is consistently negatively correlated with PTSD severity. Findings regarding relationships between PTSD risk, age and gender are inconsistent at this time. Other gaps in our current knowledge and understanding are identified, and implications for future clinical and research efforts are discussed. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. FULLER THEOL SEMINARY,PASADENA,CA 91101. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. RP Foy, DW (reprint author), PEPPERDINE UNIV,400 CORP POINTE,CULVER CITY,CA 90230, USA. NR 34 TC 65 Z9 65 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-4405 J9 J SCHOOL PSYCHOL JI J. Sch. Psychol. PD SUM PY 1996 VL 34 IS 2 BP 133 EP 145 DI 10.1016/0022-4405(96)00003-9 PG 13 WC Psychology, Educational SC Psychology GA UL372 UT WOS:A1996UL37200003 ER PT J AU Nozue, M Lee, I Manning, JM Manning, LR Jain, RK AF Nozue, M Lee, I Manning, JM Manning, LR Jain, RK TI Oxygenation in tumors by modified hemoglobins SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE tumor oxygenation; modified hemoglobin; carbogen; Eppendorf ''histograph'' ID FLUOSOL-DA 20-PERCENT; BLOOD-FLOW; CARBOXYMETHYLATED HEMOGLOBIN; RADIOSENSITIZATION; RADIATION; AFFINITY; CANCER; CELL AB The effect of systemic injection of modified hemoglobin (Hb) prepared from bovine, human, or mouse Hb on tumor oxygenation was investigated. Hb was modified by (1) diisothiocyanatobenzenesulfonate (DIBS) to yield cross-linking within a tetramer; (2) glycolaldehyde (Glyal) to yield cross-linking between and within tetramers; (3) carboxymethylation (Cm) to change oxygen affinity; or (4) poly(ethylene glycol) (PEG) to yield attachment between tetramers. HGL9 (human glioma) in nude mice and FSaII (mice fibrosarcoma) in C3H mice were used as tumor models. Dose and time dependency were detected in the oxygenation effect by bovine-PEG-Hb. Internal cross-linkage prolonged the half-life in the circulation, and thus showed a significant effect. Compared to bovine-CmHb, bovine-DIBS-Hb and bovine-DIBS-CmHb were more effective. Decreasing the oxygen affinity by Cm significantly enhanced tumor oxygenation. Human-DIBS-CmHb was more effective than human-DIBS-Hb. These effects were caused by oxygen carrying capacity of modified Hbs as well as hemodynamic factors, and the injection seemed to reduce both perfusion-limited (acute) and diffusion-limited (chronic) hypoxia. (C) 1996 Wiley-Liss, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. UNIV MED & DENT NEW JERSEY,COOPER HOSP,DEPT RADIAT ONCOL,CAMDEN,NJ 08103. ROCKEFELLER UNIV,BIOCHEM LAB,NEW YORK,NY 10021. FU NCI NIH HHS [CA-13311, R35-CA-56591] NR 24 TC 29 Z9 30 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUN PY 1996 VL 62 IS 2 BP 109 EP 114 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA UT221 UT WOS:A1996UT22100007 PM 8649036 ER PT J AU Giurgiu, DIN Karam, JA Madan, AK Roslyn, JJ Abedin, MZ AF Giurgiu, DIN Karam, JA Madan, AK Roslyn, JJ Abedin, MZ TI Apical and basolateral Ca2+ channels modulate cytosolic Ca2+ in gallbladder epithelia SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 08-11, 1995 CL DEARBORN, MI SP Assoc Acad Surg ID CHOLESTEROL GALLSTONE FORMATION; INCREASED BILIARY CALCIUM; ION-TRANSPORT; CELLS; BILE; CA-2+; ABSORPTION; SECRETION; CARRIERS; MEMBRANE AB Gallstone formation is associated with altered gallbladder (GB) ion transport and increased concentration of GB bile Ca2+. Recent studies show that increased cytosolic Ca2+ ([Ca2+](i)) stimulates GB Cl(-)secretion. However, the mechanism by which extracellular Ca2+ ([Ca2+](e)) enters the cytosol remains unclear. We tested the hypothesis that entry of [Ca2+](e) into cytosol occurs via apical and basolateral membrane Ca2+ channels. Prairie dog GBs were mounted in Ussing chambers, standard electrophysiologic parameters were recorded, and unidirectional Cl- fluxes (J, mu Eq . cm(-2). hr(-1)) were measured using Cl-36 at various mucosal Ca2+ in the absence or presence of mucosal lanthanum (La3+), a non-diffusible Ca2+ channel blocker. Serosal [Ca2+](e) was maintained at trace levels, In the absence of mucosal La3+, short circuit current (Isc) showed a positive correlation with mucosal [Ca2+](e) as represented by a second order polynomial equation (y = 4.1 + 2.5x - 0.73x(2), r = 0.68, P < 0.001). In contrast, unidirectional mucosa to serosa Cl- flux (J(ms)(Cl)) was inversely correlated with [Ca2+](e) (y = 47.9 - 8.7x + 0.9x(2), r = 0.51, P < .05) Addition of 1 mM mucosal La3+ blunted the effects of [Ca2+](e) on electrophysiologic parameters and J(ms)(Cl). However, basolateral repletion with 5 mM Ca2+ reverses the blocking effects of La3+ on J(ms)(Cl). These data suggest that [Ca2+](e) enters the cytosol via apical and basolateral Ca2+ channels. We conclude that GB apical Ca2+ channels may represent a pathway for biliary Ca2+ entry into the cell and therefore may represent an important regulatory pathway for GB ion transport during gallstone formation. (C) 1996 Academic Press, Inc. C1 MED COLL PENN & HAHNEMANN UNIV,DEPT SURG,PHILADELPHIA,PA 19129. DEPT VET AFFAIRS MED CTR,RES SERV,PHILADELPHIA,PA 19104. NR 33 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN PY 1996 VL 63 IS 1 BP 179 EP 184 DI 10.1006/jsre.1996.0244 PG 6 WC Surgery SC Surgery GA UU471 UT WOS:A1996UU47100033 PM 8667618 ER PT J AU Espat, NJ Watkins, KT Lind, DS Weis, JK Copeland, EM Souba, WW AF Espat, NJ Watkins, KT Lind, DS Weis, JK Copeland, EM Souba, WW TI Dietary modulation of amino acid transport in rat and human liver SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 08-11, 1995 CL DEARBORN, MI SP Assoc Acad Surg ID TOTAL PARENTERAL-NUTRITION; PLASMA-MEMBRANE VESICLES; GLUTAMINE; ARGININE; ENDOTOXIN AB Specialized diets enriched in the amino acids glutamine and arginine have been shown to benefit surgical patients. In the liver, glutamine supports glutathione biosynthesis, arginine regulates nitric oxide synthesis, and both of these amino acids serve as precursors for ureagenesis, gluconeogenesis, and acute phase protein synthesis. The effects of a diet enriched with glutamine and arginine on hepatic plasma membrane transport activity have not been studied in humans. We hypothesized that feeding supradietary amounts of these nutrients would enhance the activities of the specific carriers which mediate their transmembrane transport in the liver. We fed surgical patients (n = 8) and rats (n = 6) one of three diets: a) a regular diet, b) an enteral liquid diet containing arginine and glutamine, or c) an enteral diet supplemented with pharmacologic amounts of glutamine and arginine. Diets were isocaloric and were administered for 3 days. Hepatic plasma membrane vesicles were prepared from rat liver and from human wedge biopsies obtained at laparotomy. The transport of glutamine and arginine by rat and human vesicles was assayed. Vesicle integrity and functionality were verified by osmolarity plots, enzyme marker enrichments, and time courses. Provision of both a standard enteral liquid diet and one enriched with glutamine and arginine increased the activities of Systems N (glutamine) and y(+) (arginine) in rat and human liver compared to a control diet. The diet supplemented with glutamine and arginine was the most effective in increasing transport activity. We conclude that the liver responds to diets enriched with specific amino acids by increasing membrane transport activity, This adaptive response provides essential precursors for hepatocytes which may enhance hepatic synthetic functions during catabolic states. This study provides insights into the mechanisms by which enteral nutrition regulates nutrient transport at the cellular level and may provide a biochemical rationale for the use of formulas which are enriched with conditionally essential nutrients. (C) 1996 Academic Press, Inc. C1 ABBOTT LABS,ROSS PROD DIV,COLUMBUS,OH. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. RP Espat, NJ (reprint author), UNIV FLORIDA,DEPT SURG,GAINESVILLE,FL 32601, USA. FU NCI NIH HHS [CA57690] NR 28 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN PY 1996 VL 63 IS 1 BP 263 EP 268 DI 10.1006/jsre.1996.0258 PG 6 WC Surgery SC Surgery GA UU471 UT WOS:A1996UU47100047 PM 8661208 ER PT J AU Liberman, MC Puria, S Guinan, JJ AF Liberman, MC Puria, S Guinan, JJ TI The ipsilaterally evoked olivocochlear reflex causes rapid adaptation of the 2f(1)-f(2) distortion product otoacoustic emission SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID AUDITORY-NERVE RESPONSES; GUINEA-PIG COCHLEA; CONTRALATERAL SOUND; ACOUSTIC DISTORTION; ACTION-POTENTIALS; EFFERENT NEURONS; STIMULATION; MECHANICS; SYSTEM; SUPPRESSION AB The onset behavior of the distortion product otoacoustic emission (DPOAE) at 2f(1)-f(2) in anesthetized cats was measured with temporal resolution finer than 70 ms. The amplitude of the DPOAE adapts after onset of the primary tones by as much as 6 dB for monaural stimulation and 10 dB when the primaries are presented binaurally. DPOAE adaptation consists oa large, rapid component, with a time constant of roughly 100 ms, and a small, slower component with a time constant of roughly 1000 ms. The rapid component disappears when only the crossed olivocochlear bundle (OCB) is cut, whereas the slow adaptation persists after complete OCB section. The loss of rapid adaptation upon OC section is accompanied by a concomitant increase in the steady-slate amplitude of the DPOAE, Thus an intact OC reflex can significantly alter DPOAEs obtained during routine measurement. Rapid adaptation of the monaurally evoked 2f(1)-f(2) DPOAE is probably mediated by reflex activity in ipsilaterally responsive OC neurons innervating outer hair cells. The effects of this ipsilateral reflex oil DPOAE amplitudes are typically twice as large as those of the contralateral reflex, presumably because there are twice as many ipsilaterally responsive OC neurons. Tests for the ipsilateral OC reflex based on the phenomenon of rapid adaptation should be both feasible and useful in human subjects. (C) 1996 Acoustical Society of America. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139. RP Liberman, MC (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [R01 DC00188, R01 DC00235, R03 DC02677] NR 40 TC 104 Z9 109 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUN PY 1996 VL 99 IS 6 BP 3572 EP 3584 DI 10.1121/1.414956 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA UQ669 UT WOS:A1996UQ66900030 PM 8655789 ER PT J AU Biederman, J Faraone, S Mick, E Moore, P Lelon, E AF Biederman, J Faraone, S Mick, E Moore, P Lelon, E TI Child behavior checklist findings further support comorbidity between ADHD and major depression in a referred sample SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; Child Behavior Checklist; major depressive disorder ID ATTENTION DEFICIT DISORDER; CO-MORBIDITY; HYPERACTIVITY DISORDER; PSYCHIATRIC DIAGNOSES; RISK-FACTORS; CONDUCT; ANXIETY; SPECIFICITY; ADOLESCENTS; CONVERGENCE AB Objective: To examine the convergence of categorical and empirical diagnostic systems to evaluate whether psychiatric comorbidity of juvenile major depression with attention-deficit hyperactivity disorder (ADHD) is due to assessment bias. Method: Using total predictive value and the odds ratio, the authors evaluated the convergence of Child Behavior Checklist (CBCL) scales with structured interview-derived diagnoses in 94 children with major depression, 97 with ADHD, and 115 normal control children with neither diagnosis. Results: The CBCL Anxious/Depressed scale discriminated depressed from nondepressed children irrespective of comorbidity with ADHD, and the Attention Problems scale discriminated ADHD from non-ADHD children irrespective of comorbidity with major depression. Children with major depression comorbid with ADHD had CBCL correlates of both syndromes. Conclusions: Since the CBCL is an empirically derived taxonomic system, the correspondence between the content-congruent CBCL scales and DSM-III-R categorical diagnoses of major depression and of ADHD indicates that previously reported findings of high overlap between these two disorders using structured diagnostic interview methodology and trained raters were not due to rater biases. C1 MASSACHUSETTS GEN HOSP,JOINT PROGRAM PEDIAT PSYCHOPHARMACOL,BOSTON,MA 02114. MCLEAN HOSP,BELMONT,MA 02178. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP Biederman, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC725,FRUIT ST,BOSTON,MA 02114, USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 38 TC 59 Z9 59 U1 1 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1996 VL 35 IS 6 BP 734 EP 742 DI 10.1097/00004583-199606000-00013 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UN376 UT WOS:A1996UN37600013 PM 8682754 ER PT J AU Wozniak, J Biederman, J AF Wozniak, J Biederman, J TI A pharmacological approach to the quagmire of comorbidity in juvenile mania SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID CHILDHOOD; CHILDREN; ILLNESS RP Wozniak, J (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CHILD PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114, USA. NR 17 TC 31 Z9 31 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1996 VL 35 IS 6 BP 826 EP 828 DI 10.1097/00004583-199606000-00023 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UN376 UT WOS:A1996UN37600023 PM 8682764 ER PT J AU Jette, AM Harris, BA Sleeper, L Lachman, ME Heislein, D Giorgetti, M Levenson, C AF Jette, AM Harris, BA Sleeper, L Lachman, ME Heislein, D Giorgetti, M Levenson, C TI A home-based exercise program for nondisabled older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID SKELETAL-MUSCLE; STRENGTH; WOMEN; LIFE; MEN AB OBJECTIVES: This paper describes a videotaped, home-based, strength training program, titled Strong-for-Life and reports on its effectiveness in improving muscle strength, psychological well-being, and health status in a sample of older persons. DESIGN AND SETTING: We enrolled 102 nondisabled, community-dwelling older people aged 66 to 87, identified from the Medicare beneficiary list, into a randomized, controlled trial. MEASUREMENTS: Effectiveness was based on change in isokinetic upper and lower extremity muscle strength, psychologic well-being, and health status. RESULTS: Results revealed several statistically significant short-term benefits after 12 to 15 weeks of exercise, especially for men. Younger older adults demonstrated a 10% improvement in knee extensor strength relative to control subjects. Older male exercisers achieved significant differences relative to controls in perceived anger, tension, and overall social functioning. Male exercisers, in general, achieved significant improvement in perceived vigor. Women did not report psychological benefits following participation in the program. CONCLUSION: Study results reveal that the Strong for Life program, designed to be widely disseminated to the nondisabled older population, has many short-term positive benefits. C1 BOSTON UNIV,SCH PUBL HLTH,BOSTON,MA. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BRANDEIS UNIV,WALTHAM,MA 02254. BETH ISRAEL HOSP,BOSTON,MA 02215. RP Jette, AM (reprint author), NEW ENGLAND RES INST,9 GALEN ST,WATERTOWN,MA 02172, USA. RI Weaver, Marissa/C-4027-2012 FU NIA NIH HHS [AG11669, AG09715] NR 26 TC 81 Z9 83 U1 0 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 1996 VL 44 IS 6 BP 644 EP 649 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA UP692 UT WOS:A1996UP69200004 PM 8642153 ER PT J AU Warram, JH Gearin, G Laffel, L Krolewski, AS AF Warram, JH Gearin, G Laffel, L Krolewski, AS TI Effect of duration of type I diabetes on the prevalence of stages of diabetic nephropathy defined by urinary albumin/creatinine ratio SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE microalbuminuria; proteinuria; IDDM albumin/creatinine ratio; serum creatinine ID ALBUMIN EXCRETION; DETECT MICROALBUMINURIA; MELLITUS; HYPERTENSION; DETERMINANTS; PROTEINURIA; PREDICTOR; SAMPLES; RISK AB The objective of this study was to determine the prevalence of stages of diabetic nephropathy, defined by the albumin/creatinine ratio (AC ratio) in repeated measurements in random urine samples. Over a 30-month interval, 1613 patients with Type I diabetes (IDDM) (aged 15 to 44 yr, IDDM duration 1 to 39 yr), and 218 healthy control subjects provided multiple urine specimens, AC ratios measured in urine samples taken 5 months apart were highly reproducible (Spearman r = 0.83). A criterion for the boundary between normoalbuminuria and microalbuminuria was obtained by searching for a cutpoint that optimized agreement between serial specimens on individuals. The result was lower in men than women: 17 as compared with 25 mu g/mg. These two values corresponded to the 95th percentiles of the respective distributions of the AC ratio in healthy control subjects. Also these sex-specific cutpoints, when converted to albumin excretion rates, became almost equal: 30 and 31 mu g/min. Microalbuminuria appeared early in the course of IDDM (6% of those with only 1 to 3 yr of diabetes) and then increased rapidly during two intervals, the first and third decades, before leveling off at 52%. By that time the cumulative risk of overt proteinuria had risen to 27%, Determinations of the AC ratio in random urine samples are easily obtained and are reliable indices of elevated urinary albumin excretion (microalbuminuria) in IDDM. The pattern of occurrence of microalbuminuria according to duration of IDDM suggests that there may be two subsets of diabetic nephropathy, one appearing early and the other late. Patients with microalbuminuria and 25 yr of postpubertal IDDM have low risk of progression to advanced diabetic nephropathy. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH PUBL HLTH,DEPT MED,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH PUBL HLTH,DEPT PEDIAT,CAMBRIDGE,MA 02138. RP Warram, JH (reprint author), JOSLIN DIABET CTR,EPIDEMIOL & GENET SECT,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [R01-DK41526] NR 34 TC 204 Z9 210 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 1996 VL 7 IS 6 BP 930 EP 937 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA UT216 UT WOS:A1996UT21600017 PM 8793803 ER PT J AU delaMonte, SM Xu, YY Wands, JR AF delaMonte, SM Xu, YY Wands, JR TI Modulation of neuronal thread protein expression with neuritic sprouting: Relevance to Alzheimer's disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE neuronal thread protein; retinoic acid; primitive neuroectodermal tumor; cell growth and differentiation; gene expression; Alzheimer's disease ID EMBRYONAL CARCINOMA-CELLS; MICROTUBULE-ASSOCIATED PROTEINS; PAIRED HELICAL FILAMENTS; RETINOIC ACID; NEUROFIBRILLARY TANGLES; MONOCLONAL-ANTIBODIES; NEUROBLASTOMA-CELLS; PANCREATIC PROTEIN; SECRETORY PROTEIN; GROWTH CONES AB Widespread proliferation of dystrophic neurites in the cerebral cortex represents an important neuroanatomical correlate of dementia in Alzheimer's disease (AD). Increased CNS expression of the 21-kDa neuronal thread protein (NTP) species is also correlated with dementia in AD. Pilot in vitro experiments provided evidence that high-level NTP expression might be linked to neuritic growth, The present stud!: examines retinoic acid (RA) modulation of NTP expression during neurite outgrowth and neuronal differentiation in SH-Sy5y neuroblastoma and PNET2 CNS-derived cells. In both cell lilies, RA-induced neuronal differentiation resulted in increased synthesis, expression, and phosphorylation of several al NTP species, with high steady-state levels and stepwise hyper-phosphorylation of 21-kDa NTP molecules. With neurite outgrowth, NTP molecules were translocated fi om the perikarya to long, slender, unbranched cell processes (axons) and growth cones. RA-mediated changes in NTP expression were independent oi DNA synthesis. The findings suggest that high-level expression of 21-kDa, and closely related phosphorylated NTP molecules correlates with neuritic growth. Therefore, over-expression of 21-kDa NTP molecules in AD probably reflects the widespread cortical neuritic sprouting associated with dementia. In view of the rapid phosphorylation and cell process translocation of NTP that occurs during neurite outgrowth in vitro, the accumulation of NTP in AD cortical neuronal perikarya suggests a further problem related to post-translational processing and transport of NTP molecules in AD neurodegeneration. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,MGH CANC CTR,ALZHEIMERS DIS RES CTR,DIV NEUROPATH,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,MGH CANC CTR,DEPT MED,BOSTON,MA. FU NCI NIH HHS [CA-35711, CA-49832]; NINDS NIH HHS [NS-29793] NR 61 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUN PY 1996 VL 138 IS 1-2 BP 26 EP 35 DI 10.1016/0022-510X(95)00350-B PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UR405 UT WOS:A1996UR40500004 PM 8791235 ER PT J AU Madsen, JC Sachs, DH Fallon, JT Weissman, NJ AF Madsen, JC Sachs, DH Fallon, JT Weissman, NJ TI Cardiac allograft vasculopathy in partially inbred miniature swine .1. Time course, pathology, and dependence on immune mechanisms SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MODEL; TRANSPLANTATION; ATHEROSCLEROSIS; ANTIGENS AB To assess the role of the immune system in cardiac allograft vasculopathy in large animals, heterotopic heart transplantation was done between partially inbred miniature swine, animals in which transplantation can be done across defined major histocompatibility barriers in a reproducible fashion. Porcine hearts transplanted into untreated recipients across a class I, class II, or full major histocompatibility mismatch were acutely rejected in 6 to 8 days (n = 4). Hearts transplanted into untreated recipients across minor histocompatibility barriers survived for 21 to 44 days (n = 5) and showed no evidence of cardiac allograft vasculopathy. When recipients were treated with a 12-day course of cyclosporine, hearts transplanted across minor histocompatibility barriers survived 42, 64, and 56 days and did not develop vascular lesions. However, hearts transplanted into cyclosporine-treated recipients across a full major histocompatibility disparity survived 20, 22, and 23 days and all three developed biopsy-proven vasculopathy. In one animal, the progression of intimal proliferation was followed in vivo by intracoronary ultrasonography. The degree of intimal thickening documented by ultrasonography correlated well with the intimal proliferation found on tissue histologic samples. These results are the first to show that in large animals, an immune response stimulated by donor major histocompatibility antigens is involved in the induction of cardiac allograft vasculopathy. In addition, these studies point out the utility of a large-animal model of cardiac allograft vasculopathy in which transplantation across defined major histocompatibility barriers can be done reproducibly and in which accurate determinations of the progression or regression of coronary vascular lesions in individual animals can be accurately assessed in vivo. C1 HARVARD UNIV,SCH MED,CARDIAC SURG UNIT,BOSTON,MA 02114. RP Madsen, JC (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT BIOL RES CTR,55 FRUIT ST,BOSTON,MA 02114, USA. NR 29 TC 52 Z9 52 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 1996 VL 111 IS 6 BP 1230 EP 1239 DI 10.1016/S0022-5223(96)70226-X PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA UQ383 UT WOS:A1996UQ38300020 PM 8642825 ER PT J AU Carter, EA Tompkins, RG Babich, JW Correia, JA Fischman, AJ AF Carter, EA Tompkins, RG Babich, JW Correia, JA Fischman, AJ TI Decreased cerebral glucose utilization in rats during the Ebb phase of thermal injury SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; LIPID PEROXIDE LEVELS; HYPERMETABOLIC RESPONSE; HEPATIC-ENCEPHALOPATHY; HUMAN-BRAIN; GLUCOSE-6-PHOSPHATASE; LOCALIZATION; METABOLISM; PROTEIN; TISSUES AB Objective: Thermal injury is associated with the development of encephalopathy. The mechanism(s) for the development of this condition have not been established, In the present study, the effects of thermal injury were determined on rat brain glucose utilization (Rg), using 2-[F-18]fluoro-2-deoxy-D-glucose ((18)FDG). Design: Four types of studies were performed, In one group of rats, the effect of thermal injury on total rat brain glucose utilization (Rg) was determined at 6 hours, 24 hours, and 3 weeks after injury, The brains of thermally injured rats were also assayed for hexokinase and glucose-6-phosphatase activities, since these enzyme activities are responsible for the phosphorylation and dephosphorylation of the (18)FDG, We also measured total body oxygen consumption in the thermally injured rats, We wanted to compare the changes produced by thermal injury on rat brain glucose utilization (Rg) with the effects produced by compounds known to modify energy metabolism and/or rat brain glucose utilization (Rg), For that reason, in a second group of rats, an inflammatory state was produced by lipopolysaccharide injection, and rat brain glucose utilization (Rg) was determined, In the third group of rats, overall metabolism in rats was reduced by pentobarbital injection, followed by hypothermia, and rat brain glucose utilization (Rg) was determined, In the fourth group of rats, overall metabolism in rats was stimulated by 2,4-dinitrophenol injection, and rat brain glucose utilization (Rg) was determined. Materials and Methods: Glucose utilization (Rg) by the brains of these treated rats was determined using (18)FDG, Oxygen consumption in vivo, as well as glucose-6 phosphatase and hexokinase activity in vitro, were measured by standard procedures. Measurements and Main Results: Glucose utilization (Rg) by rat brain was significantly reduced (p < 0.01) at 6 and 24 hours after injury, but returned to normal values 3 weeks after injury, These reductions were associated with decreases in rat brain hexokinase activity, increases in rat brain glucose-6-phosphatase activity, and decreased oxygen consumption by rats in vivo, Pentobarbital injection followed by hypothermia reduced rat brain glucose utilization (Rg) (p < 0.01), while 2,4-dinitrophenol treatment elevated rat brain glucose utilization (Rg) (p < 0.01), In contrast, LPS treatment had no effect on rat brain glucose utilization (Rg). Conclusions: These data indicate that thermal injury decreases glucose utilization (Rg) in rat brain during the hypometabolic phase, This effect can be explained, at least in part, by alterations in hexokinase and glucose-6-phosphatase activities, as well as reductions in oxygen consumption, Thus, the changes in brain glucose utilization (Rg) appear to be associated with the ebb phase of the thermal injury, The present results observed in burned rats may provide evidence to explain the encephalopathy observed in burned patients. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. SHRINERS BURNS INST,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP Carter, EA (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,PEDIAT GASTROINTESTINAL UNIT,BOSTON,MA 02114, USA. NR 48 TC 13 Z9 14 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JUN PY 1996 VL 40 IS 6 BP 930 EP 935 DI 10.1097/00005373-199606000-00011 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA UQ505 UT WOS:A1996UQ50500019 PM 8656479 ER PT J AU Borras, AM Strominger, JL Speck, SH AF Borras, AM Strominger, JL Speck, SH TI Characterization of the ZI domains in the Epstein-Barr virus BZLF1 gene promoter: Role in phorbol ester induction SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL-DNA; C-FOS; PROTEIN; ACTIVATION; CELLS; TRANSCRIPTION; ELEMENTS; EBV; IDENTIFICATION; TRANSACTIVATOR AB Induction of the Epstein-Barr virus lytic cycle is mediated through the immediate-early BZLF1 gene and the coordinately regulated BRLF1 gene, The BZLF1 gene product, Zta, transactivates its own promoter, as well as the promoters of a number of lytic genes, thereby initiating a cascade of viral gene expression. Previous work identified four related elements (ZIA, ZIB, ZIG, and ZID) and a cyclic AMP response element binding-AP-1 element (ZII) that are involved in the induction of the BZLF1 promoter (Zp) by the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) (E. FLemington and S. H. Speck, J. Virol. 64:1217-1226, 1990), Here we report a detailed characterization of TPA induction mediated by the ZI domains. Mutation of individual ZI domains within the context of the intact promoter significantly diminished TPA induction. Cloning of individual ZI domains upstream of a minimal promoter demonstrated that the ZIA, ZIC, and ZID domains, but not the ZIB domain, are TPA responsive. Furthermore, cloning of the ZII domain downstream of the ZI domains significantly augmented TPA induction. The critical regions within the ZIA and ZIC elements involved in binding of cellular factors were identified by using methylation interference and electrophoretic mobility shift analyses of ZI domain mutants. Four specific complexes were observed with the ZIA and ZID domains, all of which could be specifically competed for by either the ZIA or ZID domain. Methylation interference analyses of bound complexes revealed the presence of two overlapping binding sites for cellular factors in the ZIA domain, and functional studies provided evidence that both of these sites are involved in TPA induction. Functional analyses of the ZIC domain revealed that the 5' region of this domain is largely responsible for mediating TPA induction. Binding data correlated well with functional activity and revealed that the ZIC domain binds only a subset of the cellular factors that bind to the ZIA and ZID domains. Analysis of factor binding to the ZIB domain revealed only a single shifted complex, which correlated with the most slowly migrating complex observed with the ZIA and ZID domains, These data provide a direct demonstration of TPA induction mediated by the ZIA, ZIC, and ZID domains and also provide the first evidence that the ZI domains exhibit distinct functional characteristics. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOLEC MICROBIOL,ST LOUIS,MO 63110. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. FU NCI NIH HHS [CA47554, R01 CA52004] NR 37 TC 45 Z9 46 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1996 VL 70 IS 6 BP 3894 EP 3901 PG 8 WC Virology SC Virology GA UL104 UT WOS:A1996UL10400065 PM 8648726 ER PT J AU Silva, P Solomon, RJ Epstein, FH AF Silva, P Solomon, RJ Epstein, FH TI The rectal gland of Squalus acanthias: A model for the transport of chloride SO KIDNEY INTERNATIONAL LA English DT Article ID NATRIURETIC PEPTIDE; VOLUME EXPANSION; CYCLIC-AMP; SECRETION; DOGFISH; SOMATOSTATIN; ELASMOBRANCH; STIMULATION; VIP; INHIBITION AB The rectal gland of the spiny dogfish shark, Squalus acanthias, secretes chloride by a furosemide sensitive process that has been termed ''secondary active.'' Chloride enters the cell across the basolateral cell membrane via the sodium:potassium:2 chloride cotransporter. The energy for this electroneutral uptake step is provided by the electrochemical gradient for sodium directed into the cell. This is maintained by Na-K-ATPase present in the basolateral cell membrane. Present as wall in the basolateral cell membrane is a potassium conductance that permits potassium to exit passively. Chloride leaves the cell across the luminal membrane via a chloride conductance closely similar to CFTR. The rectal gland is thus a model for the mechanism of secondary active chloride transport utilized by various epithelial organs throughout the vertebrate kingdom. This report reviews the humoral agents that regulate the secretion of chloride by the rectal gland and the intracellular mechanisms that mediate it. CNP, released from the heart in response to a volume stimulus, causes the release of VIP from nerves within the gland and together with VIP directly activates the rectal gland cell. C1 MT DESERT ISL BIOL LAB,SALSBURY COVE,ME 04672. NEW ENGLAND DEACONESS HOSP,DIV NEPHROL,BOSTON,MA. BETH ISRAEL HOSP,RENAL UNIT,BOSTON,MA. RP Silva, P (reprint author), JOSLIN DIABET CTR,DIV NEPHROL,BOSTON,MA 02215, USA. NR 50 TC 41 Z9 41 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1996 VL 49 IS 6 BP 1552 EP 1556 DI 10.1038/ki.1996.223 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA UL899 UT WOS:A1996UL89900010 PM 8743453 ER PT J AU Vlassara, H Cohen, JJ Madias, NE Harrington, JT Zusman, CJ Williams, ME Levey, AS Pereira, B Lafayette, R Beasley, D AF Vlassara, H Cohen, JJ Madias, NE Harrington, JT Zusman, CJ Williams, ME Levey, AS Pereira, B Lafayette, R Beasley, D TI Protein glycation in the kidney: Role in diabetes and aging SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID GLYCOSYLATION END-PRODUCTS; GLUCOSE-MODIFIED PROTEINS; MACROPHAGE RECEPTOR; MAILLARD REACTION; PERIPHERAL-NERVE; CROSS-LINKING; GROWTH-FACTOR; NITRIC-OXIDE; AMINOGUANIDINE; RATS C1 TUFTS UNIV NEW ENGLAND MED CTR,DIV NEPHROL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,BOSTON,MA 02111. JOSLIN DIABET CTR,BOSTON,MA 02215. DEACONESS HOSP,BOSTON,MA. RP Vlassara, H (reprint author), PICOWER INST MED RES,LAB DIABET & AGING,MANHASSET,NY 11030, USA. NR 69 TC 68 Z9 71 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1996 VL 49 IS 6 BP 1795 EP 1804 DI 10.1038/ki.1996.270 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA UL899 UT WOS:A1996UL89900057 PM 8743500 ER PT J AU Canellos, GP AF Canellos, GP TI Is ABVD the standard regimen for Hodgkin's disease based on randomized CALGB comparison of MOPP, ABVD and MOPP alternating with ABVD? SO LEUKEMIA LA English DT Editorial Material ID CHEMOTHERAPY RP Canellos, GP (reprint author), DANA FARBER CANC INST,DEPT MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 2 TC 5 Z9 5 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 1996 VL 10 SU 2 BP S68 EP S68 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA UZ467 UT WOS:A1996UZ46700015 PM 8649055 ER PT J AU Urashima, M Chauhan, D Hatziyanni, M Ogata, A Hollenbaugh, D Aruffo, A Anderson, KC AF Urashima, M Chauhan, D Hatziyanni, M Ogata, A Hollenbaugh, D Aruffo, A Anderson, KC TI CD40 ligand triggers interleukin-6 mediated B cell differentiation SO LEUKEMIA RESEARCH LA English DT Article DE B cell; CD40 ligand; interleukin-6 (IL-6); IL-10; IL-4 ID GROWTH-FACTOR-BETA; IN-VITRO; T-CELLS; MULTIPLE-MYELOMA; LYMPHOCYTES-B; SERUM INTERLEUKIN-10; ANTIBODY-PRODUCTION; GENE-EXPRESSION; CROSS-LINKING; IGE SYNTHESIS AB Interleukin-6 (IL-6) is the major cytokine to date mediating antigen (Ag)- or mitogen-driven B cell differentiation. Recently, CD40 ligand (CD40L), with the co-stimulatory cytokines IL-4 and IL-10, has been shown to trigger immunoglobulin (Ig) secretion and class switching. In the present report, we have examined the role of IL-6 in mediating B cell differentiation and Ig secretion triggered with CD40L and/or these cytokines. Culture of splenic B cells with CD40L triggered (1) significant (5.4-fold) increases in IL-6 secretion; (2) differentiation, evidenced by sequential loss of B cell (CD20, CD21) and acquisition of plasma cell (CD38, PCA-1) surface antigens (Ags); and (3) Ig secretion. Interleukin-4 increased both IL-6 and IgG secretion stimulated by CD40L. Interleukin-10+ CD40L triggered 100-fold increments in IgG, IgA and IgM secretion, but IL-10 suppressed IL-6 secretion triggered with CD40L+/-IL-4. Exogenous IL-6 can further increase IgG secretion induced by CD40L + IL-10; moreover, the anti-IL-6 monoclonal antibody partially blocked IgG secretion triggered by CD40L+/-IL-4 or IL-10. Finally, IL-10 suppressed differentiation of B cells induced by CD40L. These studies suggest that CD40L augments Ig secretion in at least two mechanisms: by triggering IL-6 secretion and related differentiation, and by priming B cells for responsiveness to IL-10. Copyright (C) 1996 Elsevier Science Ltd. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. NR 56 TC 39 Z9 39 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JUN PY 1996 VL 20 IS 6 BP 507 EP 515 DI 10.1016/0145-2126(95)00098-4 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA VA110 UT WOS:A1996VA11000009 PM 8709623 ER PT J AU Schweitzer, M Hershey, JC Asch, DA AF Schweitzer, M Hershey, JC Asch, DA TI Individual choice in spending accounts - Can we rely on employees to choose well? SO MEDICAL CARE LA English DT Article DE consumer choice; decision making; employee benefits insurance; medical savings accounts ID SAMPLE SELECTION BIAS; SPECIFICATION ERROR; INSURANCE; DECISIONS; FRAMES AB Flexible spending accounts (FSA) represent a current health care financing tool that may become an important component of incremental health care reform. Because FSAs require employees to make financial contributions based on anticipated health care needs, contribution decisions are likely to be subject to many of the errors made in other insurance decisions. The authors analyzed the benefits selections, benefits forms completion, and FSA contribution levels of approximately 9,500 employees of the University of Pennsylvania from 1987 to 1992. Default and repeat choice trends characterize the completion of benefits forms and the reselection of health insurance options by employees. Despite the economic benefits of contributing to an FSA, only 14% of employees contributed in any one year and 73% never made a contribution. Multivariate models of these contributions fail to demonstrate the importance of what ought to be relevant influences in contribution decisions (for example, age, income, family status, or underlying health insurance). Whereas most FSA decisions are characterized by default contributions of $0, employees who contribute in one year are most likely to contribute exactly the same amount the next year, even when other circumstances change. The pervasiveness of these patterns raises concerns that health care reform plans that rely on financial incentives at the consumer level-for example, proposed medical savings accounts-will be inefficient. C1 UNIV PENN,SCH MED,DIV GEN INTERNAL MED,PHILADELPHIA,PA 19104. UNIV MIAMI,DEPT MANAGEMENT,CORAL GABLES,FL 33124. UNIV PENN,WHARTON SCH,PHILADELPHIA,PA 19104. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. NR 15 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 1996 VL 34 IS 6 BP 583 EP 593 DI 10.1097/00005650-199606000-00008 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA UQ271 UT WOS:A1996UQ27100008 PM 8656724 ER PT J AU Wong, TY Ohara, K Kawashima, M Sober, AJ Nogita, T Mihm, MC AF Wong, TY Ohara, K Kawashima, M Sober, AJ Nogita, T Mihm, MC TI Acral lentiginous melanoma (including in situ melanoma) arising in association with naevocellular naevi SO MELANOMA RESEARCH LA English DT Article DE acral lentiginous melanoma; foot; naevus ID CUTANEOUS MALIGNANT-MELANOMA; NEVI; JAPAN; VOLAR; SOLE AB Acral lentiginous melanoma (ALM) occurring on the sole of the foot is the most common type of malignant melanoma in Asians, African and North American Blacks, but is relatively infrequent in Caucasians. According to the literature ALM is thought less likely to arise in a precursor naevus of any type or be associated with dysplastic naevi elsewhere on the skin, We present five cases of ALM (two invasive and three in situ cases) arising in association with pre-existing naevi on the foot in Asians and Caucasians, All patients were female, aged 35-66 years (mean = 47.8). Clinically, all five tumours demonstrated various shades of tan, brown and black, admired with hypopigmented areas. Histologically, these melanomas showed a lentiginous character of the radial growth phase component with rare foci of pagetoid intra-epidermal spread, Invasive determal components in the form of epithelial and spindle cells were evident in two cases, with a measured depth of 1.7 and 0.85 mm, respectively, Pre-existing naevi, either dermal or junctional, were identified in all tumours, Clinical follow-up in all patients showed no evidence of recurrence or metastasis over a period of 4 months-5 years, These cases appear at variance with the general belief that ALM and ALM in site arise de novo and rarely arise in precursor naevi, To the best of our knowledge, this is the first documented series of ALM in situ arising in association with pre-existing naevi, We conclude that ALM can arise in association with acral naevi. RP Wong, TY (reprint author), MASSACHUSETTS GEN HOSP,DIV DERMATOPATHOL,BOSTON,MA 02114, USA. NR 33 TC 18 Z9 18 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD JUN PY 1996 VL 6 IS 3 BP 241 EP 246 DI 10.1097/00008390-199606000-00007 PG 6 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA UW752 UT WOS:A1996UW75200007 PM 8819127 ER PT J AU Schiff, I AF Schiff, I TI Summing up the Risk: Benefit equation SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,WOMENS CARE DIV,VINCENTS MEM OBSTET & GYNECOL SERV,BOSTON,MA 02114. RP Schiff, I (reprint author), HARVARD UNIV,SCH MED,32 FRUIT ST VBK-113,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SUM PY 1996 VL 3 IS 2 BP 61 EP 64 DI 10.1097/00042192-199603020-00001 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UM133 UT WOS:A1996UM13300001 ER PT J AU Chatzipanteli, K Head, C Megerman, J Axelrod, L AF Chatzipanteli, K Head, C Megerman, J Axelrod, L TI The relationship between plasma insulin level, prostaglandin production by adipose tissue, and blood pressure in normal rats and rats with diabetes mellitus and diabetic ketoacidosis SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID AORTIC ENDOTHELIAL-CELLS; ELEVATED GLUCOSE; PROSTACYCLIN PRODUCTION; ARACHIDONIC-ACID; FAT-CELLS; RELEASE; HYPERINSULINEMIA; FLOW; HYPERTENSION; ADIPOCYTES AB There is a correlation between circulating insulin levels and blood pressure over a wide range of insulin levels and in a variety of clinical conditions. Production of prostaglandin (PG)E(2) (PGE(2)) and prostacyclin (PGI(2)), two potent vasodilators, by adipose tissue is increased in severe insulin deficiency, eg, diabetic ketoacidosis (DKA), explaining the decreased peripheral vascular resistance in DKA. Conversely, decreased production of PGE(2) and PGI(2) may mediate the relationship between hyperinsulinemia and hypertension. Although insulin inhibits PC production in normal rat adipose tissue, PG production in adipose tissue from patients or experimental animals with nonketotic diabetes mellitus (DM) and DKA has not been studied. We examined the effect of plasma insulin levels on blood pressure and on adipose tissue PG production in rats with DM and DKA and normal rats. There was a significant relationship between plasma insulin level and blood pressure in rats with DM and normal controls (P <.021) and in rats with DKA and normal controls (P <.0001). There was an inverse linear correlation between plasma insulin levels and basal 6-keto-PGF(1 alpha), production by a mixture of adipocytes and endothelial cells from epididymal adipose tissue in rats with DKA and normal rats (P <.0252, R(2) =.67). Rates of basal glycerol, PGE(2), and 6-keto-PGF(1 alpha) production by a mixture of adipocytes and endothelial cells from epididymal adipose tissue were significantly higher in rats with DKA than in normal rats. These rates were also higher in rats with DM than in normal rats, but only glycerol values were statistically significant. In rats with DM, PGE(2) production induced by epinephrine 2 x 10(-5) mol/L(but not lower concentrations) was significantly greater than basal production (P <.05); production of 6-keto-PGF(1 alpha) was not stimulated. In rats with DKA, 6-keto-PGF(1 alpha) production induced by epinephrine 2 x 10(-5) mol/L (but not lower concentrations) was significantly greater than basal production (P <.05); production of PGE(2) was not stimulated. We conclude the following: (1) there is a close correlation between circulating insulin level and systemic blood pressure when rats with DM and DKA are compared with controls; (2) in insulin deficiency, PGI(2) and PGE(2) production are increased in adipose tissue versus normal tissue; and (3) the correlation between insulin level and blood pressure may be mediated by the inhibitory effect of insulin on vasodilative PG production by adipose tissue. Copyright (C) 1996 by W.B. Saunders Company. C1 MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. NR 30 TC 6 Z9 6 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUN PY 1996 VL 45 IS 6 BP 691 EP 698 DI 10.1016/S0026-0495(96)90133-X PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UP075 UT WOS:A1996UP07500005 PM 8637442 ER PT J AU Maki, KC Skorodin, MS Jessen, JH Laghi, F AF Maki, KC Skorodin, MS Jessen, JH Laghi, F TI Effects of oral albuterol on serum lipids and carbohydrate metabolism in healthy men SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID HIGH-DENSITY LIPOPROTEINS; BETA-ADRENERGIC AGONISTS; SKELETAL-MUSCLE; INSULIN; SALBUTAMOL; GLUCOSE; CLENBUTEROL; EPINEPHRINE; STIMULATION; STRENGTH AB beta(2)-Selective adrenergic agonists are used in the management of bronchial asthma and preterm labor. Due to their ability to increase muscle strength and size in animal models, new applications for these agents are also being explored for neuromuscular disorders and in rehabilitation. However, the effects of long-term beta(2)-agonist administration on lipoprotein and carbohydrate metabolism are incompletely understood. This investigation evaluated the effects of a beta(2)-agonist, albuterol, on serum lipids and carbohydrate homeostasis in eight healthy nonsmoking men aged 24 to 61 years. Collection of fasting blood samples was completed in duplicate on separate days at baseline, during 14 days of oral albuterol administration (Proventil Repetabs, 8 mg twice daily; Schering Pharmaceuticals, Kenilworth, NJ) and during a 7-day washout period. Carbohydrate homeostasis was evaluated using the minimal model technique at the end of the baseline and albuterol periods. Fasting glucose and insulin, intravenous glucose tolerance, acute insulin response to intravenous glucose (AIRg), insulin sensitivity (Si), and glucose effectiveness (Sg) were not significantly changed during albuterol administration. Significant alterations (P less than or equal to.02) were observed in total cholesterol ([TC] -9.1% +/- 2.5%), low-density lipoprotein cholesterol ([LDL-C] -15.0% +/- 2.9%), and high-density lipoprotein cholesterol ([HDL-C] +10.4% +/- 3.2%) concentrations, as well as the TC/HDL-C (-17.4% +/- 2.6%) and LDL-C/HDL-C (-22.9% +/- 2.4%) ratios. During washout, TC and LDL-C returned to baseline levels, whereas HDL-C remained elevated by 5.8% +/- 2.4% (P <.05). Thus, albuterol administration was associated with favorable changes in the serum lipid profile without marked impairment of glucose tolerance or its physiologic determinants. Copyright (C) 1996 by W.B. Saunders Company. C1 US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,REHABIL RES & DEV CTR,HINES,IL 60141. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,MED SERV,PULM & CRIT CARE SECT,HINES,IL 60141. LOYOLA UNIV,STRITCH SCH MED,DEPT MED,MAYWOOD,IL 60153. NR 37 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUN PY 1996 VL 45 IS 6 BP 712 EP 717 DI 10.1016/S0026-0495(96)90136-5 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UP075 UT WOS:A1996UP07500008 PM 8637445 ER PT J AU Foster, R Hu, KQ Lu, Y Nolan, KM Thissen, J Settleman, J AF Foster, R Hu, KQ Lu, Y Nolan, KM Thissen, J Settleman, J TI Identification of a novel human rho protein with unusual properties: GTPase deficiency and in vivo farnesylation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; P21 TRANSFORMING PROTEIN; MURINE SARCOMA-VIRUS; BIOCHEMICAL-PROPERTIES; ACTIVATING PROTEIN; RAS P21; DOMAIN; SEQUENCE; MECHANISM; BINDING AB We have identified a human Rho family protein, RhoE, which has unusual structural and biochemical properties that suggest a novel mechanism of regulation. Within a region that is highly conserved among small GTPases, RhoE contains amino acid differences specifically at three positions that confer oncogenicity to Ras (12, 59, and 61). As predicted by these substitutions, which impair GTP hydrolysis in Ras, RhoE binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins. Replacing all three positions in RhoE with conventional amino acids completely restores GTPase activity. In vivo, RhoE is found exclusively in the GTP-bound form, suggesting that unlike previously characterized small GTPases, RhoE may be normally maintained in an activated state. Thus, amino acid changes in Ras that are selected during tumorigenesis have evolved naturally in this Rho protein and have similar consequences for catalytic function. All previously described Rho family proteins are modified by geranylgeranylation, a lipid attachment required for proper membrane localization. In contrast, the carboxy-terminal sequence of RhoE predicts that, like Ras proteins, RhoE is normally farnesylated. Indeed, we have found that RhoE is farnesylated in vivo and that this modification is required for association with the plasma membrane and with an unidentified cellular structure that may play a role in adhesion. Thus, two unusual structural features of this novel Rho protein suggest a striking evolutionary divergence from the Rho family of GTPases. C1 MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. DUKE UNIV,MED CTR,DURHAM,NC 27710. FU NCI NIH HHS [CA62142-02] NR 55 TC 193 Z9 200 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1996 VL 16 IS 6 BP 2689 EP 2699 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UL974 UT WOS:A1996UL97400016 PM 8649376 ER PT J AU Mendez, R Myers, MG White, MF Rhoads, RE AF Mendez, R Myers, MG White, MF Rhoads, RE TI Stimulation of protein synthesis, eukaryotic translation initiation factor 4E phosphorylation, and PHAS-I phosphorylation by insulin requires insulin receptor substrate 1 and phosphatidylinositol 3-kinase SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; PHORBOL ESTERS; KINASE-C; CELLS; ACTIVATION; FACTOR-EIF-4E; MODULATION; IRS-1 AB Insulin rapidly stimulates protein synthesis in a wide variety of tissues. This stimulation is associated with phosphorylation of several translational initiation and elongation factors, but little is known about the signaling pathways leading to these events. To study these pathways, we have used a myeloid progenitor cell line (32D) which is dependent on interleukin 3 but insensitive to insulin because of the very low levels of insulin receptor (IR) and the complete lack of insulin receptor substrate (IRS)-signaling proteins (IRS-1 and IRS-2). Expression of more IR permits partial stimulation of mitogen-activated protein kinase by insulin, and expression of IRS-1 alone mediates insulin stimulation of the 70-kDa S6 kinase (pp70(S6K)) by the endogenous LR. However, expression of both IR and IRS-1 is required for stimulation of protein synthesis. Moreover, this effect requires activation of phosphatidylinositol 3-kinase (PI3K), as determined by wortmannin inhibition and the use of an IRS-1 variant lacking all Tyr residues except those which activate PI3K. Stimulation of general protein synthesis does not involve activation by IRS-1 of GRB-2-SOS-p21(ras) or SH-PTP2, since IRS-1 variants lacking the; SH2-binding Tyr residues for these proteins are fully active. Nor does it involve pp70(S6K), since rapamycin, while strongly inhibiting the synthesis of a small subset of growth-regulated proteins, only slightly inhibits total protein synthesis. Recruitment of mRNAs to the ribosome is enhanced by phosphorylation of eIF4E, the cap-binding protein, and PHAS-I, a protein that specifically binds eIF4E. The behavior of cell lines containing IRS-1 variants and inhibition by wortmannin and rapamycin indicate that the phosphorylation of both proteins requires IRS-l-mediated stimulation of PI3K and pp70(S6K) but not mitogen-activated protein kinase or SH-PTP2. C1 LOUISIANA STATE UNIV, MED CTR, DEPT BIOCHEM & MOLEC BIOL, SHREVEPORT, LA 71130 USA. JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. OI Mendez, Raul/0000-0002-1952-6905 FU NIDDK NIH HHS [DK43808]; NIGMS NIH HHS [GM20818] NR 63 TC 188 Z9 191 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 JUN PY 1996 VL 16 IS 6 BP 2857 EP 2864 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UL974 UT WOS:A1996UL97400035 PM 8649395 ER PT J AU Jeyaprakash, A DasGupta, R Kolodner, R AF Jeyaprakash, A DasGupta, R Kolodner, R TI Saccharomyces cerevisiae pms2 mutations are alleles of MLH1, and pms2-2 corresponds to a hereditary nonpolyposis colorectal carcinoma-causing missense mutation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GENE CONVERSION; DNA; HOMOLOG; CANCER; MSH2 AB A number of mutant Saccharomyces cerevisiae strains having phenotypes consistent with defects in DNA mismatch repair have been described, but not all have been extensively characterized. In this study we demonstrated that the pms2-1 and pms2-2 alleles arise from missense mutations in the MLH1 gene which inactivate MLH1. One of these alleles, pms2-2, causes the same amino acid substitution in a highly conserved region of the known MutL homologs as that caused by a proposed missense mutation observed in a Swedish hereditary nonpolyposis colorectal carcinoma kindred. This observation supports the functional significance of missense mutations found in hereditary nonpolyposis colorectal carcinoma kindreds and indicates that in some cases S. cerevisiae can serve as a useful model system for the analysis of such mutations. C1 DANA FARBER CANC INST,CHARLES A DANA DIV HUMAN CANC GENET,BOSTON,MA 02115. UNIV FLORIDA,DEPT ENTOMOL & NEMATOL,GAINESVILLE,FL 32611. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691]; NIGMS NIH HHS [GM50006] NR 23 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1996 VL 16 IS 6 BP 3008 EP 3011 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UL974 UT WOS:A1996UL97400052 PM 8649412 ER PT J AU Torchilin, VP AF Torchilin, VP TI Liposomes as delivery agents for medical imaging SO MOLECULAR MEDICINE TODAY LA English DT Review ID LABELED LIPOSOMES; GD-DTPA; ACCUMULATION; ENHANCEMENT; LIVER; INVIVO; RATS AB Medical imaging requires an appropriate intensity of signal from the area of interest in order to differentiate certain structures from surrounding tissues, regardless of the modality used, In the majority of cases, contrast agents specific for each imaging modality are necessary to achieve a sufficiently intense signal, To facilitate the accumulation of contrast in the required zone, various microparticulates have been suggested as carriers for contrast agents, Among these carriers, liposomes - microscopic artificial phospholipid vesicles - draw special attention because of their easily controlled properties and useful pharmacological characteristics. This review will discuss how the advantages of liposomes have been used so far in the rapidly growing field of diagnostic medical imaging. C1 HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RP Torchilin, VP (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,CHEM PROGRAM,149 13TH ST,CHARLESTOWN,MA 02129, USA. NR 36 TC 71 Z9 73 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD JUN PY 1996 VL 2 IS 6 BP 242 EP 249 DI 10.1016/1357-4310(96)88805-8 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UQ803 UT WOS:A1996UQ80300006 PM 8796897 ER PT J AU Saag, MS Holodniy, M Kuritzkes, DR OBrien, WA Coombs, R Poscher, ME Jacobsen, DM Shaw, GM Richman, DD Volberding, PA AF Saag, MS Holodniy, M Kuritzkes, DR OBrien, WA Coombs, R Poscher, ME Jacobsen, DM Shaw, GM Richman, DD Volberding, PA TI HIV viral load markers in clinical practice SO NATURE MEDICINE LA English DT Editorial Material ID VIRUS; INFECTION; PLASMA C1 STANFORD UNIV,STANFORD,CA 94305. PALO ALTO VET AFFAIRS HLTH CARE SYST,PALO ALTO,CA. UNIV COLORADO,HLTH SCI CTR,BOULDER,CO 80309. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. SAN DIEGO VET AFFAIRS MED CTR,SAN DIEGO,CA. RP Saag, MS (reprint author), UNIV ALABAMA,908 20TH ST S,BIRMINGHAM,AL 35294, USA. NR 33 TC 405 Z9 412 U1 0 U2 8 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 1996 VL 2 IS 6 BP 625 EP 629 DI 10.1038/nm0696-625 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UN691 UT WOS:A1996UN69100022 PM 8640545 ER PT J AU Fink, JK HeimanPatterson, T Bird, T Cambi, F Dube, MP Figlewicz, DA Fink, JK Haines, JL HeimanPatterson, T Hentati, A PericakVance, MA Raskind, W Rouleau, GA Siddique, T AF Fink, JK HeimanPatterson, T Bird, T Cambi, F Dube, MP Figlewicz, DA Fink, JK Haines, JL HeimanPatterson, T Hentati, A PericakVance, MA Raskind, W Rouleau, GA Siddique, T TI Hereditary spastic paraplegia: Advances in genetic research SO NEUROLOGY LA English DT Review ID DUTCH FAMILY; PARAPARESIS; DISEASE; LINKAGE; MOTOR AB Hereditary spastic paraplegia (HSP) is a diverse group of inherited disorders characterized by progressive lower-extremity spasticity and weakness. Insight into the genetic basis of these disorders is expanding rapidly. Uncomplicated autosomal dominant, autosomal recessive, and X-linked HSP are genetically heterogeneous: different genes cause clinically indistinguishable disorders. A locus for autosomal recessive HSP is on chromosome 8q. Loci for autosomal dominant HSP have been identified on chromosomes 2p, 14q, and 15q. One locus (Xq22) has been identified for X-linked, uncomplicated HSP and shown to be due to a proteolipoprotein gene mutation in one family. The existence of HSP families for whom these loci are excluded indicates the existence of additional, as yet unidentified HSP loci. There is marked clinical similarity among HSP families linked to each of these loci, suggesting that gene products from HSP loci may participate in a common biochemical cascade, which, if disturbed, results in axonal degeneration that is maximal at the ends of the longest CNS axons. Identifying the single gene defects that cause HSPs distal axonopathy may provide insight into factors responsible for development and maintenance of axonal integrity. We review clinical, genetic, and pathologic features of HSP and present differential diagnosis and diagnostic criteria of this important group of disorders. We discuss polymorphic microsatellite markers useful for genetic linkage analysis and genetic counseling in HSP. C1 VET AFFAIRS MED CTR,GERIATR RES & EDUC CTR,ANN ARBOR,MI. UNIV MICHIGAN,DEPT NEUROL,ANN ARBOR,MI. THOMAS JEFFERSON UNIV,DEPT NEUROL,PHILADELPHIA,PA 19107. VET ADM MED CTR,DEPT NEUROL,SEATTLE,WA 98108. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA. MONTREAL GEN HOSP,DEPT NEUROL,MONTREAL,PQ H3G 1A4,CANADA. UNIV ROCHESTER,NEUROMUSCULAR DIS CTR,NEW YORK,NY. NORTHWESTERN UNIV,DEPT NEUROL,CHICAGO,IL 60611. DUKE UNIV,MED CTR,DIV NEUROL,DURHAM,NC 27710. RI Haines, Jonathan/C-3374-2012; Dube, Marie-Pierre/B-9364-2008 OI Dube, Marie-Pierre/0000-0001-8442-4393 FU NINDS NIH HHS [1R01 NS33645-01] NR 46 TC 150 Z9 155 U1 0 U2 4 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1996 VL 46 IS 6 BP 1507 EP 1514 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA UQ777 UT WOS:A1996UQ77700002 PM 8649538 ER PT J AU Greenberg, SM Finklestein, SP Schaefer, PW AF Greenberg, SM Finklestein, SP Schaefer, PW TI Petechial hemorrhages accompanying lobar hemorrhage: Detection by gradient-echo MRI SO NEUROLOGY LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY AB Based on the pathologic observation that severe cerebral amyloid angiopathy is often accompanied by multiple petechial hemorrhages, we prospectively obtained gradient-echo MRI on 15 elderly patients with lobar hemorrhage on CT. Nine of the 15 demonstrated accompanying petechial hemorrhages restricted to the cortical or corticosubcortical regions. No similar lesions were present on gradient-echo MRI in 10 elderly control patients. These findings suggest that cerebral amyloid angiopathy might be neuroradiologically diagnosed and staged during life. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV NEURORADIOL,BOSTON,MA 02114. RP Greenberg, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,VINCENT BURNHAM 811,BOSTON,MA 02114, USA. NR 10 TC 160 Z9 174 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1996 VL 46 IS 6 BP 1751 EP 1754 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA UQ777 UT WOS:A1996UQ77700050 PM 8649586 ER PT J AU Cher, L Glass, J Harsh, GR Hochberg, FH AF Cher, L Glass, J Harsh, GR Hochberg, FH TI Therapy of primary CNS lymphoma with methotrexate-based chemotherapy and deferred radiotherapy: Preliminary results SO NEUROLOGY LA English DT Article ID SURVIVAL; BRAIN AB Disease-fi ee survival in primary CNS lymphoma has im proved with the advent of methotrexate-based pre-irradiation chemotherapy. Prolonged response durations have been noted in six of eight patients refusing radiation therapy in two of our prior series. We have treated an additional 11 patients with methotrexate-based chemotherapy without subsequent planned irradiation. Some received maintenance chemotherapy. Most have had durable responses with little or no toxicity. Prolonged responses can be maintained without radiation therapy, thus avoiding potential long-term radiation toxicity. C1 AUSTIN & REPATRIAT MED CTR,MELBOURNE,VIC,AUSTRALIA. NYU,MED CTR,NEW YORK,NY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 10 TC 100 Z9 104 U1 1 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1996 VL 46 IS 6 BP 1757 EP 1759 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA UQ777 UT WOS:A1996UQ77700052 PM 8649588 ER PT J AU Spangler, WJ Cosgrove, GR Ballantine, HT Cassem, EH Rauch, SL Nierenberg, A Price, BH AF Spangler, WJ Cosgrove, GR Ballantine, HT Cassem, EH Rauch, SL Nierenberg, A Price, BH TI Magnetic resonance image-guided stereotactic cingulotomy for intractable psychiatric disease SO NEUROSURGERY LA English DT Article DE cingulate gyrus; cingulotomy; limbic system; major affective disorder; obsessive-compulsive disorder; psychosurgery; stereotactic ID FOLLOW-UP; TRACTOTOMY AB WE DESCRIBE THE modern operative technique of magnetic resonance (MR) image-guided stereotactic cingulotomy and discuss the indications, results, and complications of this procedure. A retrospective analysis of psychiatric outcome was performed for 34 patients with intractable major affective disorder and/or obsessive-compulsive disorder who underwent MR image-guided stereotactic cingulotomy since 1991. Fourteen patients underwent multiple cingulotomies (50 total procedures). Overall, 38% of the patients were classified as responders, 23% as possible responders, and 38% as nonresponders. Of the patients who did not respond to initial cingulotomies and who underwent multiple cingulotomies, 36% became responders, 36% possible responders, and 28% nonresponders. There were no deaths or long-term side effects related to the procedure. The therapeutic results of MR image-guided stereotactic cingulotomy are similar to the results of earlier methods of cingulotomy, and the use of MR imaging offers substantial technical advantages. This procedure also compares favorably with other neurosurgical procedures performed for intractable psychiatric disease with a low rate of undesired side effects. Cingulotomy is safe and well tolerated, with over one-third of the patients demonstrating significant improvement; however, prospective long-term follow-up studies are needed to further define the role of surgery in treating intractable psychiatric disease. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MCLEAN HOSP,DEPT NEUROL,BOSTON,MA. NR 22 TC 38 Z9 39 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 1996 VL 38 IS 6 BP 1071 EP 1076 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UM763 UT WOS:A1996UM76300001 PM 8727135 ER PT J AU Ogilvy, CS Chu, DC Kaplan, S AF Ogilvy, CS Chu, DC Kaplan, S TI Mild hypothermia, hypertension, and mannitol are protective against infarction during experimental intracranial temporary vessel occlusion SO NEUROSURGERY LA English DT Article DE focal ischemia; hypertension; hypothermia; infarction; mannitol ID CEREBRAL BLOOD-FLOW; ISCHEMIC NEURONAL INJURY; PERMANENT FOCAL ISCHEMIA; ARTERY OCCLUSION; MODERATE HYPOTHERMIA; EVOKED-POTENTIALS; BRAIN TEMPERATURE; FOREBRAIN ISCHEMIA; RAT-BRAIN; VISCOSITY AB A RABBIT MODEL of focal temporary ischemia was used to test the protection provided by mild hypothermia, hypertension, mannitol, and the combination of the three methods. Twenty-four New Zealand White rabbits were divided into five groups as follows: a control group, a hypertension group (mean arterial blood pressure increased by 42 mm Hg), a hypothermic group (rectal temperature decreased by 6 degrees C), a mannitol group (1 g/kg of body weight, administered intravenously), and the triple-therapy group. The intracranial internal carotid artery, the middle cerebral artery, and the anterior cerebral artery were clipped for 2 hours and then underwent 4 hours of reperfusion. Blood pressure, rectal and brain temperature, blood glucose level, hematocrit, and arterial blood gases were monitored during the experiment. For measuring the infarction size, the brain was divided into 4-mm slices and stained with 2,3,5-triphenyltetrazolium chloride. The severity of the neuronal damage was also evaluated by conventional histological examination with hematoxylin and eosin staining. The infarct volume was 193.2 +/- 34.8 (standard error of the mean) mm(3) for the control group, 32.3 +/- 22.6 mm(3) for the hypertension group (P < 0.0005 versus control), 40.9 +/- 17.6 mm(3) for the hypothermia group (P < 0.0005), 58.0 +/- 41.0 mm(3) for the mannitol group (P < 0.005), and 0.9 +/- 0.9 mm(3) for the triple-therapy group (P < 0.0001). The infarct volume of the triple-therapy group was smaller than that of the hypertension, hypothermia, and mannitol groups, but the difference was not statistically significant. The combination of hypertension, mild hypothermia, and mannitol to protect against temporary focal ischemia provides a set of manipulations that is readily available for neurovascular procedures. RP Ogilvy, CS (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV VBK710,32 FRUIT ST,BOSTON,MA 02114, USA. NR 76 TC 28 Z9 31 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 1996 VL 38 IS 6 BP 1202 EP 1209 DI 10.1097/00006123-199606000-00030 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UM763 UT WOS:A1996UM76300058 PM 8727152 ER PT J AU Metson, R Gliklich, RE AF Metson, R Gliklich, RE TI Endoscopic treatment of sphenoid sinusitis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID SPHENOETHMOIDECTOMY; SURGERY AB Juxtaposed between the posterior nasal cavity and skull base, the diseased sphenoid sinus presents unique challenges when surgical drainage is required, Endoscopic techniques have gained widespread popularity for the treatment of sphenoid sinusitis, yet the efficacy of such treatment remains largely unknown, Thirty-four patients who underwent endoscopic sphenoidotomy were monitored over a period of 6 months to 5 years. Surgery was performed with the superior turbinate used as the key landmark for identification and enlargement of the natural sphenoid ostium, Surgical access was through either a transnasal or transethmoid approach, depending on whether disease was limited to the sphenoid sinus, Prospective analysis of 26 patients with established outcome measures demonstrated a significant reduction in facial pain, nasal drainage, and congestion 6 months after surgery (p < 0.0001). Medication use was also reduced but to a lesser extent (p < 0.05), Endoscopic sphenoidotomy appears to be a safe technique that effectively reduces patient morbidity associated with sphenoid sinusitis. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOL,BOSTON,MA. NR 16 TC 44 Z9 45 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 1996 VL 114 IS 6 BP 736 EP 744 DI 10.1016/S0194-5998(96)70095-5 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA UR253 UT WOS:A1996UR25300006 PM 8643296 ER PT J AU Sweet, WH AF Sweet, WH TI An analysis of opinions considered adverse to the thesis of the main communication SO PAIN FORUM LA English DT Editorial Material ID SPINAL-CORD STIMULATION; CHRONIC PAIN; RELIEF C1 MASSACHUSETTS GEN HOSP, NEUROSURG SERV, BOSTON, MA 02114 USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1058-9139 J9 PAIN FORUM JI Pain Forum PD SUM PY 1996 VL 5 IS 2 BP 118 EP 120 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UV449 UT WOS:A1996UV44900006 ER PT J AU Shen, OX Zhang, PN Sheen, J Ho, THD AF Shen, OX Zhang, PN Sheen, J Ho, THD TI Potential involvement of PP2C and CaMKII in the signal transduction of ABA action in barley aleurone cells SO PLANT PHYSIOLOGY LA English DT Meeting Abstract C1 WASHINGTON UNIV,DEPT BIOL,DIV BIOL & BIOMED SCI,ST LOUIS,MO 63130. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD JUN PY 1996 VL 111 IS 2 SU S BP 22 EP 22 PG 1 WC Plant Sciences SC Plant Sciences GA UR534 UT WOS:A1996UR53400066 ER PT J AU Fava, M Davidson, KG AF Fava, M Davidson, KG TI Definition and epidemiology of treatment-resistant depression SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID MAJOR DEPRESSION; FOLLOW-UP; DOUBLE-BLIND; DELUSIONAL DEPRESSION; REFRACTORY DEPRESSION; FLUOXETINE; PAROXETINE; DISORDERS; MULTICENTER; OUTPATIENTS AB Although many depressed patients do improve with adequate antidepressant treatment, a significant proportion fails to reach acceptable levels of functioning and well-being. Currently, however, there is no universally accepted definition of treatment resistance in unipolar depression (TRD). This article proposes an operational definition of TRD and discusses partial response, nonresponse, and methodologic issues that emerge in the assessment of resistance. Finally, possible predictors of failure to respond are reviewed, and an attempt is made to estimate the prevalence of TRD. RP Fava, M (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS CLIN & RES PROGRAM,BOSTON,MA 02114, USA. NR 104 TC 427 Z9 439 U1 5 U2 34 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 1996 VL 19 IS 2 BP 179 EP & DI 10.1016/S0193-953X(05)70283-5 PG 23 WC Psychiatry SC Psychiatry GA UP091 UT WOS:A1996UP09100002 PM 8827185 ER PT J AU Sachs, GS AF Sachs, GS TI Treatment-resistant bipolar depression SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID RECURRENT AFFECTIVE-ILLNESS; LOW SERUM LEVELS; AFFECTIVE-DISORDER; DOUBLE-BLIND; PROPHYLACTIC LITHIUM; ANTI-DEPRESSANT; ELECTROCONVULSIVE-THERAPY; UNILATERAL ECT; MANIC SYMPTOMS; IMIPRAMINE AB This article begins with a conceptual overview of treatment-resistant bipolar depression and discusses characteristics of bipolar illness and factors that influence treatment outcome. The literature on treatments for bipolar depression is reviewed, including topics such as antidepressant efficacy and treatment-emergent mania. Strategies are offered to improve clinical treatment outcome. Emphasis is placed on careful clinical assessment and prospective mood charting, and a treatment algorithm that limits the use of standard antidepressant agents is presented. RP Sachs, GS (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,15 PARKMAN ST,SUITE 815,BOSTON,MA 02114, USA. NR 83 TC 73 Z9 74 U1 3 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 1996 VL 19 IS 2 BP 215 EP & DI 10.1016/S0193-953X(05)70285-9 PG 23 WC Psychiatry SC Psychiatry GA UP091 UT WOS:A1996UP09100004 PM 8827187 ER PT J AU Alpert, JE Maddocks, A Nierenberg, AA OSullivan, R Pava, JA Worthington, JJ Biederman, J Rosenbaum, JF Fava, M AF Alpert, JE Maddocks, A Nierenberg, AA OSullivan, R Pava, JA Worthington, JJ Biederman, J Rosenbaum, JF Fava, M TI Attention deficit hyperactivity disorder in childhood among adults with major depression SO PSYCHIATRY RESEARCH LA English DT Article DE antidepressant treatment; mood disorders; comorbidity ID PSYCHIATRIC STATUS; CO-MORBIDITY; RISK-FACTORS; CHILDREN; COMORBIDITY; PREVALENCE; METHYLPHENIDATE; PATTERNS; PARENTS; BOYS AB The prevalence of attention deficit hyperactivity disorder (ADHD) with childhood onset and its relationship to course and treatment outcome of major depressive disorder (MDD) in adults was studied in 116 patients (ages 18-65) consecutively enrolled for treatment of MDD. Sixteen percent of the patients were found to meet full or subthreshold criteria for the DSM-III-R diagnosis of childhood ADHD. Twelve percent endorsed persistence of ADHD symptoms into adulthood, Depressed adults meeting criteria for childhood ADHD did not differ significantly from other depressed adults on any measures related to the chronicity or severity of the mood disorder, Axis I comorbidity, or response to acute antidepressant treatment. Our results are clinically important as they suggest that clinicians need to be aware of the possibility that a substantial proportion of patients with MDD may suffer from comorbid ADHD and that treatments need to include the targeting of possible residual ADHD symptoms in addition to those of depression. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. RP Alpert, JE (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,DEPRESS CLIN & RES PROGRAM,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01-MH48483] NR 41 TC 69 Z9 70 U1 2 U2 6 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 JUN 1 PY 1996 VL 62 IS 3 BP 213 EP 219 DI 10.1016/0165-1781(96)02912-5 PG 7 WC Psychiatry SC Psychiatry GA UU382 UT WOS:A1996UU38200002 PM 8804131 ER PT J AU McDermott, PA Alterman, AI Brown, L Zaballero, A Snider, EC McKay, JR AF McDermott, PA Alterman, AI Brown, L Zaballero, A Snider, EC McKay, JR TI Construct refinement and confirmation for the addiction severity index SO PSYCHOLOGICAL ASSESSMENT LA English DT Article ID SAMPLE-SIZE; RELIABILITY; VALIDITY; PERSONALITY; STABILITY; MODELS AB A series of analyses reconstruct and confirm the validity and reliability of hypothesized scales for the Addiction Severity Index. Using a diverse sample (N = 990 ) of methadone maintenance substance abuse patients, a multistage scaling strategy was applied to identify 7 psychometrically integral addiction problem scales. Exploratory item analyses, confirmatory oblique item clustering, and 2nd-order factor analysis verified that the scales comprised relatively little common variance and that each retained a substantial amount of unique and reliable variance. Concurrent and predictive validity were supported with a sample of 244 methadone patients assessed throughout treatment. The advantages of the new scales are discussed, including provision of computer code for calculating normalized standard scores for use in clinical practice and treatment outcome research. C1 UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. ADDICT RES & TREATMENT CORP,BROOKLYN,NY. RP McDermott, PA (reprint author), UNIV PENN,GRAD SCH EDUC,3700 WALNUT ST,PHILADELPHIA,PA 19104, USA. NR 38 TC 64 Z9 65 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD JUN PY 1996 VL 8 IS 2 BP 182 EP 189 PG 8 WC Psychology, Clinical SC Psychology GA UT983 UT WOS:A1996UT98300010 ER PT J AU Fairclough, DL Cella, DF AF Fairclough, DL Cella, DF TI Functional assessment of cancer therapy (FACT-G): Non-response to individual questions SO QUALITY OF LIFE RESEARCH LA English DT Article DE imputation; missing data; non-response; quality of life ID VALIDATION AB The purpose of this investigation is to examine methods of scoring the FACT-G when there is nonresponse to individual questions. Using completed questionnaires from 350 patients, random and non-random missing responses where simulated. Seven methods of scoring the FACT-G are compared on the basis of accuracy (bias and precision) of both population estimates and prediction of individual scores. Substituting the mean of the completed items in the subscale when more than 50% are completed is generally the most unbiased and precise approach. Case deletion is the worst approach and results in clinically significant bias when the missing responses were non-random and a lack of precision when the rate of non-response was high. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. RP Fairclough, DL (reprint author), HARVARD UNIV,DIV BIOSTAT,DANA FARBER CANC INST,SCH PUBL HLTH,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-23318, CA-51926] NR 15 TC 115 Z9 115 U1 1 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD JUN PY 1996 VL 5 IS 3 BP 321 EP 329 DI 10.1007/BF00433916 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA UV466 UT WOS:A1996UV46600002 PM 8763800 ER PT J AU Stone, ME AF Stone, ME TI Family homeopathy: A practical guide for home treatment - Callinan,P SO RQ LA English DT Book Review RP Stone, ME (reprint author), MASSACHUSETTS GEN HOSP,TREADWELL LIB,REFERENCE SERV,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSN PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 SN 0033-7072 J9 RQ JI RQ PD SUM PY 1996 VL 35 IS 4 BP 557 EP 558 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA VE685 UT WOS:A1996VE68500039 ER PT J AU Demetri, GD AF Demetri, GD TI High-dose ifosfamide in the treatment of sarcomas of tissues and bone SO SEMINARS IN ONCOLOGY LA English DT Article ID SOFT-TISSUE; UNRESECTABLE SARCOMA; CHEMOTHERAPY; CANCER; MESNA C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,SARCOMA PROGRAM,DIV CANC PHARMACOL,BOSTON,MA 02115. RP Demetri, GD (reprint author), DANA FARBER CANC INST,44 BINNEY ST,DANA 1524,BOSTON,MA 02115, USA. NR 19 TC 16 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 1996 VL 23 IS 3 SU 6 BP 22 EP 26 PG 5 WC Oncology SC Oncology GA UW665 UT WOS:A1996UW66500006 PM 8677444 ER PT J AU Hisnanick, JJ Gujral, SS AF Hisnanick, JJ Gujral, SS TI Veterans' health insurance status and their use of VA medical facilities: A joint-choice analysis SO SOCIAL SCIENCE QUARTERLY LA English DT Article ID COMPRESSION; HOSPITALS; MORBIDITY; CARE AB Objective. The aging of the veteran population and proposed changes in how medical care will be (publicly) financed for the elderly, disabled, and poor prompted this study of those factors that most likely influence a veteran to have health insurance and to use a VA facility. Methods. By analyzing data from the third Survey of Veterans (SOV III) under a bivariate probit specification, the joint-choice behavior of the probability of veterans having health insurance and their using a VA facility for care was assessed. Results. A veteran's decision to use a VA facility is largely dependent upon whether the individual has some type of health insurance coverage. A simple simulation high lights the impact of veterans' disability status relative to their household income, in terms of their probabilities of having health insurance and using a VA facility. Conclusions. Dramatic changes are being proposed in how health care is provided to vulnerable populations. Such changes could increase the demand for VA care, given that veterans with low incomes and disabilities have a greater propensity to use VA. The findings from this study could provide a baseline on the potential increased usage of VA. RP Hisnanick, JJ (reprint author), US DEPT VET AFFAIRS,NVCAS 008C13,810 VERMONT AVE NW,WASHINGTON,DC 20420, USA. NR 24 TC 1 Z9 1 U1 3 U2 3 PU UNIV TEXAS PRESS PI AUSTIN PA BOX 7819, AUSTIN, TX 78713-7819 SN 0038-4941 J9 SOC SCI QUART JI Soc. Sci. Q. PD JUN PY 1996 VL 77 IS 2 BP 393 EP 406 PG 14 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA VL357 UT WOS:A1996VL35700014 ER PT J AU Bozon, MV Delgado, JC Turbay, D Salazar, M Granja, CB Alosco, SM Dupont, B Yunis, EJ AF Bozon, MV Delgado, JC Turbay, D Salazar, M Granja, CB Alosco, SM Dupont, B Yunis, EJ TI Comparison of HLA-A antigen typing by serology with two polymerase chain reaction based DNA typing methods: Implications for proficiency testing SO TISSUE ANTIGENS LA English DT Article DE HLA typing; sequence-specific oligonucleotide primer; sequence-specific primer; serology; proficiency testing ID SEQUENCE-SPECIFIC PCR; ALLELES; TRANSPLANTATION; SUBTYPES; LOCUS AB Serology has been routinely used for class I HLA typing for the selection of donors for allotransplantation. However, serology is not adequate for the assignment of all class I specificities especially when testing non-Caucasians subjects and it is necessary to adopt new strategies for routine testing. At the present time the extent of incorrect serologic HLA-A assignments in clinical testing is nor known. The polymerase chain reaction (PCR) based techniques have become useful standard clinical typing methods of HLA class II alleles but most laboratories still use serology for class I typing. In this report we have compared two PCR based techniques, PCR amplification with sequence-specific primers (PCR-SSP) and PCR amplification and subsequent hybridization with sequence-specific oligonucleotide probes (PCR-SSOP), for the assignment of HLA-A specificities in 56 blood samples from patients and families serologically typed for HLA-A. This side-by-side comparison of PCR methods showed 100% correlation between them. However, serology showed 7.1% misassignments and, in an additional panel of 19 cells where serology produced equivocal results, the PCR-SSP and SSOP methods identified the correct HLA-A specificity. Our results emphasize the need to complement routine serologic testing of HLA specificities with a small number of primers designed to test HLA-A34, A36, A43, A66, A74 and A80, that are not detected with high precision by serology. We concluded that the PCR-SSP and -SSOP methods can be used in routine HLA-A typing of patients and donors for transplantation with a greater precision than serology. C1 AMER RED CROSS NEW ENGLAND REG,DEDHAM,MA. SLOAN KETTERING INST CANC RES,NEW YORK,NY. RP Bozon, MV (reprint author), HARVARD UNIV,SCH MED,DIV IMMUNOGENET,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02215, USA. FU NHLBI NIH HHS [HL-29583] NR 20 TC 24 Z9 25 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JUN PY 1996 VL 47 IS 6 BP 512 EP 518 DI 10.1111/j.1399-0039.1996.tb02593.x PG 7 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA UT073 UT WOS:A1996UT07300009 PM 8813740 ER PT J AU Lewis, CB AF Lewis, CB TI Rehabilitation and the quality of one's life - From the editor SO TOPICS IN GERIATRIC REHABILITATION LA English DT Editorial Material C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,WASHINGTON,DC 20052. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. RP Lewis, CB (reprint author), PHYS THERAPY SERV WASHINGTON DC INC,WASHINGTON,DC, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21701 SN 0882-7524 J9 TOP GERIATR REHABIL JI Top. Geriatr. Rehabil. PD JUN PY 1996 VL 11 IS 4 BP R5 EP R6 PG 2 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA UK639 UT WOS:A1996UK63900001 ER PT J AU Surgenor, DM Churchill, WH Wallace, EL Rizzo, RJ Chapman, RH McGurk, S Bertholf, MF Goodnough, LT Kao, KJ Koerner, TAW Olson, JD Woodson, RD AF Surgenor, DM Churchill, WH Wallace, EL Rizzo, RJ Chapman, RH McGurk, S Bertholf, MF Goodnough, LT Kao, KJ Koerner, TAW Olson, JD Woodson, RD TI Determinants of red cell, platelet, plasma, and cryoprecipitate transfusions during coronary artery bypass graft surgery: The Collaborative Hospital Transfusion Study SO TRANSFUSION LA English DT Article ID INTERNAL-MAMMARY-ARTERY; BLOOD; RISK AB Background: Very little is known about the determinants of blood transfusions in patients undergoing coronary artery bypass graft surgery. Study Design and Methods: To identify factors that influenced the transfusion of red cells, platelets, plasma, and cryoprecipitate, statistical methods were used to study 2476 consecutive diagnosis-related group 106 and 107 patients in five teaching hospitals who underwent coronary artery bypass surgery between January 1, 1992, and June 30, 1993. Results: The likelihood of red cell transfusion was significantly associated with 10 preoperative factors: 1) admission hematocrit, 2) the patient's age, 3) the patient's gender, 4) previous coronary artery bypass surgery, 5) active tobacco use, 6) catheterization during the same admission, 7) coagulation defects, 8) insulin-dependent diabetes with renal or circulatory manifestations, 9) first treatment of new episode of transmural myocardial infarction, and 10) severe clinical complications, Platelet and/or plasma transfusions were strongly associated with the dose of red cells transfused. Transfusion requirements and other in-hospital outcomes were associated with patient characteristics, surgical procedure (reoperation vs. primary procedure), and the conduits used for revascularization (venous graft only, venous and internal mammary artery graft, or internal mammary artery graft only). Blood resource use and donor exposures were evaluated with respect to the risk to patients of contracting hepatitis C virus and human immunodeficiency virus infections. Conclusion: The classification of coronary artery bypass graft patients on the basis of attributes known preoperatively and by conduits used yields subsets of patients with distinctly different transfusion requirements and in-hospital outcomes. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT CLIN LABS,DIV HEMATOL ONCOL,BOSTON,MA 02115. CTR MANAGEMENT SYST,SNOWMASS VILLAGE,CO. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. FLORIDA GEORGIA BLOOD ALLIANCE,JACKSONVILLE,FL. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. BARNES HOSP,DIV LAB MED,ST LOUIS,MO 63110. UNIV FLORIDA,SHANDS HOSP,DEPT PATHOL & LAB MED,GAINESVILLE,FL. UNIV IOWA,DEPT PATHOL,IOWA CITY,IA 52242. UNIV WISCONSIN,DEPT MED,HEMATOL SECT,MADISON,WI. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV CARDIAC SURG,BOSTON,MA 02115. UNIV IOWA HOSP & CLIN,DEPT PATHOL,IOWA CITY,IA 52242. UNIV WISCONSIN HOSP & CLIN,HEMATOL SECT,MADISON,WI. RP Surgenor, DM (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL-33774] NR 26 TC 57 Z9 57 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 1996 VL 36 IS 6 BP 521 EP 532 DI 10.1046/j.1537-2995.1996.36696269511.x PG 12 WC Hematology SC Hematology GA UV831 UT WOS:A1996UV83100009 PM 8669084 ER PT J AU Tosa, Y Kollias, N Lee, WPA May, JW AF Tosa, Y Kollias, N Lee, WPA May, JW TI Reduction of ischemia-reperfusion injury by monoclonal antibody to intercellular adhesion molecule-1 SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 4th International Congress of the Asian-Transplantation-Society CY AUG 27-30, 1995 CL SEOUL, SOUTH KOREA SP Asian Transplantat Soc ID LEUKOCYTE ADHESION; SYSTEM; ICAM-1; MODEL C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. RP Tosa, Y (reprint author), MASSACHUSETTS GEN HOSP,WACC 453,DIV PLAST SURG,FRUIT ST,BOSTON,MA 02114, USA. NR 14 TC 9 Z9 9 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1996 VL 28 IS 3 BP 1210 EP 1211 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UR781 UT WOS:A1996UR78100030 PM 8658629 ER PT J AU Nakajima, K Ochiai, T Suzuki, T Gunji, Y Ohta, M Isono, K Sachs, DH AF Nakajima, K Ochiai, T Suzuki, T Gunji, Y Ohta, M Isono, K Sachs, DH TI T-cell restriction patterns in pig bone marrow chimera SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 4th International Congress of the Asian-Transplantation-Society CY AUG 27-30, 1995 CL SEOUL, SOUTH KOREA SP Asian Transplantat Soc ID SELF-RECOGNITION; ANTIGEN RECOGNITION; MINIATURE SWINE; HELPER-CELLS; TRANSPLANTATION; SPECIFICITY; HAPLOTYPE; THYMUS C1 MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA. RP Nakajima, K (reprint author), CHIBA UNIV,SCH MED,DEPT SURG 2,CHUO KU,1-8-1 INOHANA,CHIBA 260,JAPAN. NR 12 TC 0 Z9 0 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1996 VL 28 IS 3 BP 1244 EP 1245 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UR781 UT WOS:A1996UR78100043 PM 8658642 ER PT J AU Shimada, H Emery, DW Shafer, G Germana, S Sachs, DH LeGuern, C AF Shimada, H Emery, DW Shafer, G Germana, S Sachs, DH LeGuern, C TI Miniature swine MHC class II heterodimers expressed through double-copy retroviral vectors SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID GENE; ALLOGRAFTS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. FU NIAID NIH HHS [AI33053] NR 13 TC 1 Z9 1 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1996 VL 28 IS 3 BP 1986 EP 1989 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UR781 UT WOS:A1996UR78100370 PM 8658969 ER PT J AU HannaRose, W Hansen, U AF HannaRose, W Hansen, U TI Active repression mechanisms of eukaryotic transcription repressors SO TRENDS IN GENETICS LA English DT Review ID THYROID-HORMONE RECEPTOR; DROSOPHILA KRUPPEL PROTEIN; DOMAIN; YEAST; PRODUCT AB Regulators of transcription and, in particular, transcriptional repressors, play central roles in vital biological processes, such as development and the regulation of cell growth. A major class of transcriptional repressors consists of DNA-binding proteins that interact with specific promoter elements and repress transcription via small, portable repression 'domains'. Such transcriptional inhibition, first identified only five years ago, has been termed active repression, because it is not mediated simply by steric hindrance mechanisms. It is unknown how interaction(s) between such a repressor and the RNA polymerase II basal or regulatory transcription machinery can derail the formation or competency of a transcription complex at a promoter. However, the recent progress toward identification of molecular targets suggests several specific mechanisms for achieving active repression. C1 HARVARD UNIV,SCH MED,DEPT MOLEC GENET & MICROBIOL,BOSTON,MA 02115. RP HannaRose, W (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOLEC GENET,44 BINNEY ST,BOSTON,MA 02115, USA. NR 46 TC 255 Z9 260 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUN PY 1996 VL 12 IS 6 BP 229 EP 234 DI 10.1016/0168-9525(96)10022-6 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA UN429 UT WOS:A1996UN42900008 PM 8928228 ER EF