FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Costanza, ME Berry, D Henderson, IC Ratain, MJ Wu, K Shapiro, C Duggan, D Kalra, J Berkowitz, I Lyss, AP AF Costanza, ME Berry, D Henderson, IC Ratain, MJ Wu, K Shapiro, C Duggan, D Kalra, J Berkowitz, I Lyss, AP TI Amonafide: An active agent in the treatment of previously untreated advanced breast cancer - A cancer and leukemia group B study (CALGB 8642) SO CLINICAL CANCER RESEARCH LA English DT Article ID ACETYLATOR PHENOTYPE; PHASE-II; DRUG; PHARMACOKINETICS; NSC-308847 AB Amonafide is a new imide derivative of naphthalic acid, The drug had demonstrated significant activity in preclinical studies and some activity in Phase I trials, The drug is extensively metabolized and detected in plasma and urine, Its toxicity has previously been correlated to the formation of an active metabolite, N-acetyl-amonafide. Amonafide was chosen for inclusion in the Cancer and Leukemia Group B (CGLGB) master metastatic breast cancer protocol, CALGB 8642 randomizes previously untreated metastatic breast cancer patients either to one of several Phase LI agents given for up to four cycles and then followed by standard cyclophosphamide-doxorubicin-5-fluorouracil or to immediate treatment with standard cyclophosphamidedoxorubicin-5-fluorouracil. The end point of CALGB 8642 is to assess the difference in survival, toxicity, and overall response when limited exposure to Phase II agents precedes standard chemotherapy. This report deals only with amonafide as a Phase II agent. Comparisons with the cyclophosphamide-doxorubicin-5-fluorouracil arm will not be addressed, Patients had to have histologically documented measurable breast cancer and a performance status of 0-1. Patients could not have had prior chemotherapy for metastatic disease, Prior adjuvant chemotherapy was permitted. Patients could not have visceral crisis, Amonafide was given at 300 mg/m(2)/day i.v. for 5 days, and repeated at 21-day intervals for a maximum of four cycles, Escalation and reduction in dose was mandated dependent on hematotoxicity or lack thereof, Toxicity was primarily hematological and bimodal: 32% had grade 3 or 4 leukopenia and 24% had grade 3 or 4 thrombocytopenia; 22% had no leukopenia and 44% had no thrombocytopenia, The response rate was 18%, including one complete response. When response was analyzed by hematological toxicity, there was a 35.7% response if patients had leukopenia grade 3/4 (versus 8.3%, P = 0.08). There was a 50% response if patients had thrombocytopenia grade 3/4 (versus 7.1%, P = <0.01). We conclude that amonafide is somewhat active in previously untreated breast cancer patients. There may be a steep dose-response curve, based on the significant correlation between myelosuppression and response, Rates of responses in patients adequately dosed (i.e., with significant hematotoxicity) dth amonafide ranged from 35 to 50%. Further studies will incorporate individualized dosing based on pretreatment acetylator phenotyping. C1 CENT MASSACHUSETTS ONCOL GRP, WORCESTER, MA 01655 USA. LEUKEMIA GRP B, STAT OFF, DURHAM, NC 27705 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. UNIV CHICAGO, MED CTR, CHICAGO, IL 60637 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. SUNY HLTH SCI CTR, SYRACUSE, NY 13210 USA. LONG ISL JEWISH MED CTR, NEW HYDE PK, NY 11040 USA. UNIV MARYLAND, CTR CANC, BALTIMORE, MD USA. DELAWARE COMMUNITY CLIN ONCOL PROGRAM, BALTIMORE, MD USA. JEWISH HOSP ST LOUIS, ST LOUIS, MO 63131 USA. FU NCI NIH HHS [CA41287, CA60138, CA33601] NR 23 TC 38 Z9 39 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 1995 VL 1 IS 7 BP 699 EP 704 PG 6 WC Oncology SC Oncology GA TL082 UT WOS:A1995TL08200005 PM 9816035 ER PT J AU ENG, C MULLIGAN, LM SMITH, DP HEALEY, CS FRILLING, A RAUE, F NEUMANN, HPH PONDER, MA PONDER, BAJ AF ENG, C MULLIGAN, LM SMITH, DP HEALEY, CS FRILLING, A RAUE, F NEUMANN, HPH PONDER, MA PONDER, BAJ TI LOW-FREQUENCY OF GERMLINE MUTATIONS IN THE RET PROTOONCOGENE IN PATIENTS WITH APPARENTLY SPORADIC MEDULLARY-THYROID CARCINOMA SO CLINICAL ENDOCRINOLOGY LA English DT Note ID MULTIPLE ENDOCRINE NEOPLASIA; HISTORY AB BACKGROUND AND OBJECTIVES Medullary thyroid carcinoma (MTC) occurs both sporadically and in the autosomal dominantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes. The distinction between true sporadic MTC and a new mutation familial case is important for future clinical managment of both the patient and family. The susceptibility gene for MEN 2 is the RET proto-oncogene. Systematic analysis for germline mutations of the RET proto-oncogene was performed in a series of 67 patients with apparently sporadic MTC to determine whether they were true sporadic cases or unsuspected de novo MEN 2 cases. DESIGN AND PATIENTS Sixty-seven unselected patients with sporadic MTC were randomly ascertained from clinic patients from four centres. The diagnosis of MTC was confirmed by histopathology. Germline DNA was extracted from peripheral blood leucocytes or from paraffin-embedded tissue and subsequently used for polymerase chain reaction amplification. MEASUREMENTS Polymerase chain reaction based RET mutation analysis was performed by direct double-stranded cycle sequencing of exons 10, 11, 13 and 16, within which the majority of MEN2 mutations have been shown to occur. RESULTS In this series, there was one proven case of germline mutation in RET codon 620, which previously has been shown to be responsible for MEN 2, thus indicating heritable disease. No germline mutation in codon 918, typical of MEN 2B, was found. CONCLUSlONS A figure of 1.5% germline mutations in 67 apparently sporadic MTC is lower than the incidence of familial disease reported in previous series involving clinical and biochemical screening. The presence of a germline mutation in the RET proto-oncogene in a patient with MTC indicates heritable disease. The absence of germline RET exon 10, 11, 13 or 16 mutation appears to rule out MEN 2A to a high probability, although the presence of a familial form of MTC other than classical MEN 2A cannot be excluded conclusively. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. UNIV HAMBURG,KRANKENHAUS EPPENDORF,CHIRURG KLIN,W-2000 HAMBURG 20,GERMANY. UNIV HEIDELBERG,MED KLIN & POLIKLIN,HEIDELBERG,GERMANY. UNIV FREIBURG,INNERE MED NEPHROL ABT 4,D-79106 FREIBURG,GERMANY. RP ENG, C (reprint author), UNIV CAMBRIDGE,ADDENBROOKES HOSP,CRC,HUMAN CANC GENET RES GRP,LEVEL 3,LABS BLOCK,BOX 238,CAMBRIDGE CB2 2QQ,ENGLAND. OI Eng, Charis/0000-0002-3693-5145 NR 20 TC 99 Z9 101 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUL PY 1995 VL 43 IS 1 BP 123 EP 127 DI 10.1111/j.1365-2265.1995.tb01903.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RH155 UT WOS:A1995RH15500017 PM 7641404 ER PT J AU KROSNICK, A AF KROSNICK, A TI UNTITLED 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 BELLE MEAD PA 105 RAIDER BLVD, BELLE MEAD, NJ 08502 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD JUL-AUG PY 1995 VL 17 IS 4 BP 586 EP 586 DI 10.1016/0149-2918(95)80035-2 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RV644 UT WOS:A1995RV64400001 ER PT J AU Kollias, N AF Kollias, N TI The physical basis of skin color and its evaluation SO CLINICS IN DERMATOLOGY LA English DT Article ID INDUCED ERYTHEMA; HUMAN MELANIN; INVIVO; REFLECTANCE; QUANTIFICATION; ABSORPTION RP Kollias, N (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 19 TC 49 Z9 52 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD JUL-AUG PY 1995 VL 13 IS 4 BP 361 EP 367 DI 10.1016/0738-081X(95)00075-Q PG 7 WC Dermatology SC Dermatology GA TL996 UT WOS:A1995TL99600009 PM 8665444 ER PT J AU GHAEMI, SN ZARATE, CA POPLI, AP PILLAY, SS COLE, JO AF GHAEMI, SN ZARATE, CA POPLI, AP PILLAY, SS COLE, JO TI IS THERE A RELATIONSHIP BETWEEN CLOZAPINE AND OBSESSIVE-COMPULSIVE DISORDER - A RETROSPECTIVE CHART REVIEW SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID SYMPTOMS AB The emergence of obsessive-compulsive symptoms during clozapine treatment has been reported in recent case studies, yet the incidence and significance of this finding is still unclear pending reliable data from a larger sample of patients. Hospital records of 142 randomly selected inpatients started on clozapine treatment at McLean Hospital before July 1, 1992, were reviewed retrospectively. Based on a limited retrospective chart review, there were no definitive cases of patients who developed obsessive-compulsive disorder (OCD) or whose OCD worsened as a result of clozapine treatment. Although some fluctuation of OCD symptoms may have occurred in two cases, it is unclear whether those symptoms were related to treatment with clozapine (or other psychotropic drugs) or to undulations in the natural history of OCD, No definitive relationship between OCD symptoms and clozapine treatment could be established in this limited study. Further clarification of this matter awaits outcome research using prospective methodologies. C1 MASSACHUSETTS GEN HOSP,MCLEAN HOSP,PSYCHIAT RES LABS,PSYCHOPHARMACOL PROGRAM,BELMONT,MA. MASSACHUSETTS GEN HOSP,MCLEAN HOSP,PSYCHIAT RES LABS,AFFECT DISORDERS PROGRAM,BELMONT,MA. MASSACHUSETTS GEN HOSP,MCLEAN HOSP,BIPOLAR & PSYCHOT DISORDERS PROGRAM,BELMONT,MA. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. RI Ghaemi, Nassir/J-4934-2013 NR 16 TC 58 Z9 63 U1 2 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 1995 VL 36 IS 4 BP 267 EP 270 PG 4 WC Psychiatry SC Psychiatry GA RH856 UT WOS:A1995RH85600004 PM 7554870 ER PT J AU MESSMER, EM FOSTER, CS AF MESSMER, EM FOSTER, CS TI DESTRUCTIVE CORNEAL AND SCLERAL DISEASE-ASSOCIATED WITH RHEUMATOID-ARTHRITIS - MEDICAL AND SURGICAL-MANAGEMENT SO CORNEA LA English DT Article DE RHEUMATOID ARTHRITIS; NECROTIZING SCLERITIS; PERIPHERAL ULCERATIVE KERATITIS; VASCULITIS AB The onset of necrotizing scleritis (NS) and peripheral ulcerative keratitis (PUK) in the clinical course of rheumatoid arthritis (RA) may reflect the presence of systemic, potentially lethal vasculitis. In an effort to better characterize this subset of patients with severe RA-associated corneal and/or scleral inflammation and to analyze the efficacy of therapy, we reviewed our experience in the medical and surgical management of 16 tertiary referral cases (25 eyes) unresponsive to aggressive conventional therapy with topical and systemic steroids as well as with systemic nonsteroidal drugs. Cytotoxic immunosuppressive therapy was instituted in all patients with NS and/or PUK. Cyclophosphamide and methotrexate were the most successful agents used. Cytotoxic immunosuppressive drugs in conjunction with early aggressive surgical treatment halted the relentlessly progressive inflammation and preserved the integrity of the globe in 92% of eyes. Visual acuity could be stabilized or improved in 83% of patients with NS and in 68% of patients with PUK. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,OCULAR IMMUNOL SERV,243 CHARLES ST,BOSTON,MA 02115. NR 0 TC 42 Z9 46 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD JUL PY 1995 VL 14 IS 4 BP 408 EP 417 DI 10.1097/00003226-199507000-00010 PG 10 WC Ophthalmology SC Ophthalmology GA RE243 UT WOS:A1995RE24300010 PM 7671613 ER PT J AU CIULLA, TA MOULTON, R OBEROI, A MILLER, JW AF CIULLA, TA MOULTON, R OBEROI, A MILLER, JW TI RETINAL ARTERY-OCCLUSION IN RABBIT EYES USING HUMAN ATHEROMA SO CURRENT EYE RESEARCH LA English DT Article DE ARTERY; ATHEROMA; EYE; MODEL; RETINA ID TOLERANCE TIME; OBSTRUCTION AB Previous animal models of central retinal artery occlusion using glass or latex embolic material may not simulate human disease. We have developed a rabbit model using human atherosclerotic material, which may be useful in developing embolus specific treatments, including thrombolysis or laser photodisruption. Fresh human atherosclerotic plaque was harvested from atherosclerotic human aorta by mechanical removal and suspension in normal saline. The suspension was agitated vigorously to produce small particles, which were separated into various sizes by filtration through mesh filters with specific pore sizes. The common carotid artery of the anesthetized rabbit was isolated by neck dissection and cannulated using a modified Seldinger technique. Suspensions of human atherosclerotic plaque were injected into the common carotid artery via this cannula. All animals were examined by slit lamp and fluorescein angiography before and after retinal artery occlusion, This model reliably produced retinal artery occlusion using human atherosclerotic plaque. Plaque particles less than 105 microns reliably produced branch retinal artery occlusion, while larger plaque particles less than 149 microns reliably produced central retinal artery occlusion. Sublingual nitroglycerin, at 0.1 mg/kg, intravenous verapamil, from 0.2 mg/kg to 2 mg/kg, and intracarotid urokinase given acutely in standard doses failed to cause reperfusion. This model will be very useful in the study and treatment of retinal vascular disorders as it may more closely simulate human disease over previous models using artificial embolic materials. Embolic specific treatment stategies, such as thrombolysis and laser photodisruption, may be further developed with this model. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,RETINA SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 30 TC 1 Z9 3 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUL PY 1995 VL 14 IS 7 BP 573 EP 578 DI 10.3109/02713689508998404 PG 6 WC Ophthalmology SC Ophthalmology GA RK654 UT WOS:A1995RK65400007 PM 7587303 ER PT J AU GRIESHAMMER, U MCGREW, MJ ROSENTHAL, N AF GRIESHAMMER, U MCGREW, MJ ROSENTHAL, N TI ROLE OF METHYLATION IN MAINTENANCE OF POSITIONALLY RESTRICTED TRANSGENE EXPRESSION IN DEVELOPING MUSCLE SO DEVELOPMENT LA English DT Article DE MUSCLE; DNA METHYLATION; TRANSGENE; ENHANCER; PROMOTER; LMPCR; MOUSE ID LIGATION-MEDIATED PCR; DNA METHYLATION; SKELETAL-MUSCLE; GENE-EXPRESSION; MOUSE EMBRYO; ROSTROCAUDAL POSITION; MYOGENIC LINEAGES; ACTIN GENE; ENHANCER; MULTIPLE AB In transgenic mouse embryos, expression of a muscle-specific reporter, consisting of a chloramphenicol acetyltransferase gene linked to regulatory sequences from the rat myosin light chain 1/3 locus (MLC-CAT), is graded in developing axial muscles along the rostrocaudal axis and in cell cultures derived from these muscles. Here we demonstrate that maintenance of positional differences in MLC-CAT transgene expression cannot be attributed to differences in the transcriptional competence of corresponding muscles. Rather, patterns of transgene expression are reflected in the extent of CpG demethylation of both MLC1 promoter and MLC enhancer sequences. Variations in reporter gene expression can be reconstituted by in vitro methylation of specific CpGs in transfected MLC-CAT DNA. As the MLC-CAT transgene is activated during embryogenesis, demethylation of the MLC1 promoter lags behind that of the downstream MLC enhancer, which appears to be the initial target for epigenetic modification, In developing somites, demethylation of the transgenic MLC enhancer is not graded and therefore does not reflect early regional differences in MLC-CAT transgene expression patterns. These studies implicate selective methylation in the maintenance rather than in the establishment of transcriptional differences in developing muscles. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118. FU NHLBI NIH HHS [HL07501]; NIAMS NIH HHS [R01AR41926] NR 45 TC 18 Z9 18 U1 1 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1995 VL 121 IS 7 BP 2245 EP 2253 PG 9 WC Developmental Biology SC Developmental Biology GA RH141 UT WOS:A1995RH14100027 PM 7635067 ER PT J AU DONAGHUE, VM GIURINI, JM ROSENBLUM, BI WEISSMAN, PN VEVES, A AF DONAGHUE, VM GIURINI, JM ROSENBLUM, BI WEISSMAN, PN VEVES, A TI VARIABILITY IN FUNCTION MEASUREMENTS OF 3 SENSORY FOOT NERVES IN NEUROPATHIC DIABETIC-PATIENTS SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE NEUROPATHY; SENSORY TESTING VARIABILITY ID PERIPHERAL NEUROPATHY; PREVALENCE; POPULATION; THRESHOLDS AB We have examined the variability in function measurements of three sensory foot nerves in neuropathic diabetic patients and have compared them to measurements from healthy non-diabetic subjects. Sixty-six healthy, non-diabetic subjects (30 (45%) males, mean age 56 years (range, 21-84 years)) and 61 age and sex matched diabetic patients (33 (54%) males, mean age 55 years (range, 34-78 years) Type 1 diabetes mellitus (DM), mean duration of DM 24 years (range, 2-48 years)) were tested. Current perception threshold (CPT) at 250 Hz was employed to test the sensory function of three nerves: superficial peroneal, sural and posterior tibial, The vibration perception threshold, (VPT) and the cutaneous perception threshold (CCPT) were also assessed at the great toe. According to the results of the neuropathy disability score (NDS), mild neuropathy was present in 8 (13%) patients, moderate in 33 (54%) and severe in 20 (33%), In both groups the CPT of the posterior tibial nerve was higher than the other two nerves (P < 0.0001) while no difference was found between the superficial peroneal and sural nerves (P = NS). CPT was different between the two feet at the superficial peroneal nerve in 39 (64%) diabetic patients and 34 (52%) controls (P = NS), at the sural nerve in 40 (65%) and 45 (68%) (P = NS), and at the posterior tibial in 36 (59%) and 33 (50%), respectively (P = NS). VPT was different by more than 10% at the great toes in 26 (43%) diabetic subjects and CCPT in 21 (34%). We conclude that although there is variation in sensory nerve function tests in diabetic patients this is similar to that noticed in healthy subjects, The great variability of all quantitative sensory testing indicates that more than one site should be tested. C1 HARVARD UNIV,SCH MED,DEACONESS JOSLIN FOOT CTR,BOSTON,MA 02215. BAPTIST HOSP MIAMI,JOSLIN DIABET CTR,MIAMI,FL. NR 19 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD JUL PY 1995 VL 29 IS 1 BP 37 EP 42 DI 10.1016/0168-8227(95)01107-O PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TC603 UT WOS:A1995TC60300005 PM 8593757 ER PT J AU VEVES, A SARNOW, MR GIURINI, JM ROSENBLUM, BI LYONS, TE CHRZAN, JS HABERSHAW, GM AF VEVES, A SARNOW, MR GIURINI, JM ROSENBLUM, BI LYONS, TE CHRZAN, JS HABERSHAW, GM TI DIFFERENCES IN JOINT MOBILITY AND FOOT PRESSURES BETWEEN BLACK-AND-WHITE DIABETIC-PATIENTS SO DIABETIC MEDICINE LA English DT Article DE RACIAL DIFFERENCES; JOINT MOBILITY; FOOT PRESSURE; AT RISK DIABETIC FOOT AB Limited joint mobility is common in diabetes and is related to high foot pressures and foot ulceration. We have examined the differences in joint mobility and foot pressures in four groups matched for age, sex, and duration of diabetes: 31 white diabetic, 33 white non-diabetic, 24 black diabetic, and 22 non-diabetic black subjects. Joint mobility was assessed using a goniometer at the fifth metacarpal, first metatarsal, and subtalar joints. In-shoe and without shoes foot pressures were measured using an F-Scan system. Neuropathy was evaluated using clinical symptoms (Neuropathy Symptom Score), signs (Neuropathy Disability Score), and Vibration Perception Threshold. There was no difference between white and black diabetic patients in Neuropathy Symptom Score, Neuropathy Disability Score, and Vibration Perception Threshold. Subtalar joint mobility was significantly reduced in white diabetic patients (22 +/- 7 degrees) compared to white controls (26 +/- 4 degrees, black diabetic patients (25 +/- 5 degrees), and black controls (29 +/- 7 degrees), and increased in black controls compared to white controls and black diabetic patients (level of statistical significance p < 0.05). Without shoes foot pressures were higher in white diabetic patients (8.31 +/- 400 kg cm(-2)) compared to white controls (6.81 +/- 2.31 kg cm(a2)), black diabetic patients (6.2 +/- 2.53 kg cm(-2)) and black controls (5.00 +/- 1.24 kg cm(-2)) and lower in black controls compared to white and black diabetic patients (p< 0.05 in all cases). We conclude that racial differences exist in joint mobility and foot pressures between black and white subjects. Thus, in black diabetic patients the joint mobility, although reduced compared to black healthy subjects, is increased when compared to white diabetic patients. This contributes to lower foot pressures, comparable to non-diabetic white subjects and probably reduces the risk of foot ulceration in black diabetic patients. RP VEVES, A (reprint author), HARVARD UNIV,SCH MED,DEACONESS JOSLIN FOOT CTR,185 PILGRIM RD,BOSTON,MA 02215, USA. NR 0 TC 26 Z9 27 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD JUL PY 1995 VL 12 IS 7 BP 585 EP 589 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RJ557 UT WOS:A1995RJ55700005 PM 7554779 ER PT J AU DUMONT, RH JACOBSON, AM COLE, C HAUSER, ST WOLFSDORF, JI WILLETT, JB MILLEY, JE WERTLIEB, D AF DUMONT, RH JACOBSON, AM COLE, C HAUSER, ST WOLFSDORF, JI WILLETT, JB MILLEY, JE WERTLIEB, D TI PSYCHOSOCIAL PREDICTORS OF ACUTE COMPLICATIONS OF DIABETES IN YOUTH SO DIABETIC MEDICINE LA English DT Article DE KETOACIDOSIS; SEVERE HYPOGLYCEMIA; PREDICTORS; PSYCHOSOCIAL FACTORS; FAMILY FUNCTIONING AB In this paper we determine whether individual and family psychosocial functioning predicts the risk for recurrent acute diabetic complications. An onset-cohort of 61 children and adolescents with Type 1 diabetes received conventional diabetes care. Episodes of ketoacidosis and of severe hypoglycemia were recorded for 8 years, and glycaemic control was measured by glycohaemoglobin. Measures of psychosocial functioning of the patient and parents were obtained during the first year. Over 8 years, 28% of subjects had at least one episode of ketoacidosis, and 21% had at least one episode of hypoglycaemia. The odds of observing recurrent hypoglycaemia versus recurrent ketoacidosis was 14 times greater in boys than in girls (Fisher's exact test p<0.05). Girls with recurrent ketoacidosis had more behaviour problems and lower social competence, they reported higher levels of family conflict, and their parents reported lower levels of family cohesion, expressiveness and organization in year one. These relationships were independent of any association with poor glycaemic control. Recurrent hypoglycaemia in boys was generally unrelated to individual and family functioning or glycohaemoglobin. Despite our small sample size, our findings are suggestive of relationships that may lead to early identification of patients who are prone to recurrent ketoacidosis, and to the development of early intervention strategies. C1 JOSLIN DIABET CTR,DEPT PEDIAT,BOSTON,MA. OI Willett, John/0000-0001-7183-350X FU PHS HHS [K05-018, R-01 27845] NR 0 TC 34 Z9 35 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD JUL PY 1995 VL 12 IS 7 BP 612 EP 618 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RJ557 UT WOS:A1995RJ55700010 PM 7554784 ER PT J AU ZERBINI, G ROTH, T PODESTA, F CAGLIERO, E DORIA, A CANESSA, M LORENZI, M AF ZERBINI, G ROTH, T PODESTA, F CAGLIERO, E DORIA, A CANESSA, M LORENZI, M TI ACTIVITY AND EXPRESSION OF THE NA+/H+ EXCHANGER IN HUMAN ENDOTHELIAL-CELLS CULTURED IN HIGH GLUCOSE SO DIABETOLOGIA LA English DT Article DE NA+/H+ EXCHANGER; ENDOTHELIAL CELLS; CELL REPLICATION; FIBRONECTIN; DIABETIC NEPHROPATHY ID DEPENDENT DIABETES-MELLITUS; BASEMENT-MEMBRANE COMPONENTS; SMOOTH-MUSCLE CELLS; GROWTH-FACTOR-BETA; PROTEIN KINASE-C; EXTRACELLULAR-MATRIX; MOLECULAR-CLONING; ELEVATED GLUCOSE; PROLIFERATION; ANTIPORTER AB Establishing whether high ambient glucose affects the plasma membrane Na+/H+ exchanger is relevant to understanding the adverse effects of high glucose on cell replication and the mechanisms of the increased exchanger activity encountered in diabetic patients with nephropathy. In 8 primary and 15 first-passage isolates of human endothelial cells cultured in 30 mmol/l glucose for 8.7 +/- 2.3 and 15.8 +/- 2.3 days, respectively, we determined Na+/H+ exchanger activity and mRNA levels. Activity was determined by measuring Na-22(+) influx in the presence or absence of dimethylamiloride (DMA) after intracellular acidification. We also measured fibronectin mRNA because fibronectin provides signals for cell replication through the Na+/H+ antiporter. Control cells grown in 5 mmol/l glucose showed at morphologic confluency a total Na+ influx (in nmol . mg protein(-1) . min(-1)) of 10.1 +/- 3.2 in primary and 11.7 +/- 2.2 in first subculture, which was reduced to 5.3 +/- 0.3 in the presence of DMA. Paired cultures exposed to 30 mmol/l glucose and exhibiting pHi and cell densities identical to controls showed in both primary and first subculture a reduction in total Naf influx (Delta = -0.98 +/- 0.93 nmol . mg protein(-1) . min(-1) p < 0.005) whereas DMA-resistant Na+ influx was identical to that of control. Neither chronic hypertonicity nor acute exposure to high glucose mimicked the effects of chronic high glucose. The level of the Na+/H+ exchanger isoform 1 (NHE-1) mRNA was unchanged by high glucose whereas fibronectin mRNA levels were increased 1.5-fold. These studies indicate that in endothelial cells exposed to elevated ambient glucose the regulation of the Na+/H+ exchanger is altered at the post-transcriptional level; decreased activity of the antiporter is concomitant with fibronectin overexpression and may contribute to the decreased replication caused by high glucose. C1 SCHEPENS EYE RES INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV ENDOCRINE HYPERTENS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,EPIDEMIOL & GENET SECT,BOSTON,MA 02115. FU NEI NIH HHS [EY09122]; NHLBI NIH HHS [HL35664] NR 38 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUL PY 1995 VL 38 IS 7 BP 785 EP 791 DI 10.1007/s001250050353 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RF733 UT WOS:A1995RF73300006 PM 7556979 ER PT J AU WELCH, K BROWN, G JONAS, V FERRARO, MJ AF WELCH, K BROWN, G JONAS, V FERRARO, MJ TI PERFORMANCE OF THE GEN-PROBE AMPLIFIED MYCOBACTERIUM-TUBERCULOSIS DIRECT TEST IN A LABORATORY THAT INFREQUENTLY ISOLATES MYCOBACTERIUM-TUBERCULOSIS SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Note AB The performance of the Gen-Probe Mycobacterium tuberculosis direct (MTD) test was assessed in a laboratory whose specimens were derived from a population with a low prevalence (1.3%) of tuberculosis. A total of 339 specimens from 113 patients were included in the study. Nine of 10 MTD positive samples were culture positive (smear positive, n = 7; smear negative, n = 1; smear not ordered, n = 2). The 10th MTD-positive sample, which was smear and culture negative, was from a patient whose two other study specimens were smear and culture positive and who had a clinical history consistent with tuberculosis. Prior to and following resolution of discrepant results, the sensitivities and specificities of the MTD test relative to culture were 100 and 99.7% and 100 and 100%, respectively. C1 MASSACHUSETTS GEN HOSP,MICROBIOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. GENPROBE INC,SAN DIEGO,CA. NR 10 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUL PY 1995 VL 22 IS 3 BP 297 EP 299 DI 10.1016/0732-8893(95)00065-I PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA RV449 UT WOS:A1995RV44900009 PM 8565420 ER PT J AU ORLOFF, JJ KATS, Y URENA, P SCHIPANI, E VASAVADA, RC PHILBRICK, WM BEHAL, A ABOUSAMRA, AB SEGRE, GV JUPPNER, H AF ORLOFF, JJ KATS, Y URENA, P SCHIPANI, E VASAVADA, RC PHILBRICK, WM BEHAL, A ABOUSAMRA, AB SEGRE, GV JUPPNER, H TI FURTHER EVIDENCE FOR A NOVEL RECEPTOR FOR AMINO-TERMINAL PARATHYROID HORMONE-RELATED PROTEIN ON KERATINOCYTES AND SQUAMOUS CARCINOMA CELL-LINES SO ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACIDS; PEPTIDE RECEPTOR; COMMON RECEPTOR; BINDING; HYPERCALCEMIA; EXPRESSION; RESPONSES; BONE; DIFFERENTIATION; IDENTIFICATION AB PTH and PTH-related peptides (PTHrPs) interact with a common PTH/PTHrP receptor (type I), which is expressed in many tissues, including bone and kidney. Amino-terminal PTH and PTHrPs also recognize receptors in several nonclassical PTH target tissues, and in some of these, the signaling mechanisms differ qualitatively from those of the classical type I receptor. In normal keratinocytes and squamous carcinoma cell Lines, PTH and PTHrP stimulate a rise in intracellular calcium, but not cAMP, suggesting the existence of an alternate, type II PTH/PTHrP receptor. SqCC/Y1 squamous carcinoma cells stably expressing the type I receptor displayed sensitive intracellular cAMP responses to PTHrP and PTH, indicating that these cells express functional G(s) proteins and that the type I receptor is capable of signaling through adenylyl cyclase in this cell line. Therefore, the endogenous type II receptor in SqCC/Y1 cells differs from the cloned type I receptor. We next examined whether messenger RNA (mRNA) from keratinocytes and squamous cell Lines could hybridize to a human type I PTH/PTHrP receptor complementary DNA [1.9 kilobases (kb)]. No type I receptor mRNA (2.3 kb) was detected in polyadenylated RNA from any of the squamous cell lines. However, squamous cell lines did express several mRNA transcripts that hybridized with the type I receptor probe, yet were smaller (1 and 1.5 kb) or larger (3.5-5 kb) than the cloned receptor mRNA. The predominant mRNA in two squamous carcinoma cell lines and normal keratinocytes was a 1-kb transcript; Northern analysis with five different region-specific probes that span the entire coding region of the human type I receptor was used to map homologous regions within each of the transcripts. Several of the transcripts identified in squamous lines are also present in polyadenylated RNA from SaOS-2 human bone cells, but a unique 1-kb transcript hybridizing to probe 2 (nucleotides 490-870) was observed only in squamous cells. The smaller 1- and 1.5-kb transcripts did not hybridize to probes corresponding to the extreme 5'- and 3'-coding regions of the type I receptor complementary DNA. Ribonuclease protection analysis employing riboprobes that correspond to the five region-specific DNA probes revealed strong RNA signals of the expected size in SaOS-2 cells, but no hybridization with squamous cell RNA. Several smaller, but minor, bands that were unique to squamous cells were observed with riboprobe 2 only, suggesting partial homology of this region with the type I receptor. These studies indicate that 1) the classical type I receptor, when transfected into squamous cells, transduces signals in a manner distinct from the endogenous type II PTH/PTHrP receptor; 2) the squamous cell type II receptor may share some regions of homology with the type I receptor, but the identified transcripts are not completely homologous and could represent products of a distinct gene; and 3) regions of homology between the type I and type II receptors may prove useful in the molecular cloning of this novel type II PTH/PTHrP receptor. C1 W HAVEN VET AFFAIRS MED CTR, DIV ENDOCRINOL & METAB, W HAVEN, CT USA. YALE UNIV, SCH MED, DIV ENDOCRINOL & METAB, NEW HAVEN, CT 06510 USA. MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NCI NIH HHS [CA-62114]; NIDDK NIH HHS [DK-11794, DK-01936] NR 39 TC 89 Z9 89 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 1995 VL 136 IS 7 BP 3016 EP 3023 DI 10.1210/en.136.7.3016 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RE897 UT WOS:A1995RE89700030 PM 7789327 ER PT J AU Jia, GQ GutierrezRamos, JC AF Jia, GQ GutierrezRamos, JC TI Quantitative measurement of mouse cytokine mRNA by polymerase chain reaction SO EUROPEAN CYTOKINE NETWORK LA English DT Article C1 HARVARD UNIV,SCH MED,CTR BLOOD RES INC,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. NR 4 TC 4 Z9 4 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD JUL-DEC PY 1995 VL 6 IS 4 BP 253 EP 255 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA TP115 UT WOS:A1995TP11500008 PM 8789291 ER PT J AU GUARRO, J SOLER, L RINALDI, MG AF GUARRO, J SOLER, L RINALDI, MG TI PATHOGENICITY AND ANTIFUNGAL SUSCEPTIBILITY OF CHAETOMIUM SPECIES SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Note ID GLOBOSUM; ONYCHOMYCOSIS; KUNZE AB Several reports have been published implicating Chaetomium spp, as opportunistic pathogens. A critical review of these cases was made, and the majority of the responsible strains were studied. Chaetomium globosum was the most common species, being isolated in at least nine clinical cases of infection. Some of these clinical isolates and others from environmental sources were tested against six antifungal agents (5-fluorocytosine, fluconazole, amphotericin B, itraconazole, ketoconazole and miconazole). The 23 strains tested were totally resistant to the first two drugs, and none of the other antifungal agents demonstrated fungicidal activity. There were no significant differences between the susceptibility of the clinical strains and the other strains. C1 UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,CTR HLTH SCI,DEPT PATHOL,LAB SERV 113,SAN ANTONIO,TX 78284. RP GUARRO, J (reprint author), UNIV ROVIRA & VIRGILI,FAC MED,UNITAT MICROBIOL,C ST LLORENC 21,E-43201 REUS,SPAIN. OI Guarro, Josep/0000-0002-7839-7568 NR 16 TC 31 Z9 31 U1 1 U2 5 PU FRIEDR VIEWEG SOHN VERLAG GMBH PI WIESBADEN 1 PA PO BOX 5829, W-6200 WIESBADEN 1, GERMANY SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD JUL PY 1995 VL 14 IS 7 BP 613 EP 618 DI 10.1007/BF01690737 PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA RQ617 UT WOS:A1995RQ61700011 PM 7588850 ER PT J AU CRAIG, WA AF CRAIG, WA TI ANTIBIOTIC SELECTION FACTORS AND DESCRIPTION OF A HOSPITAL-BASED OUTPATIENT ANTIBIOTIC-THERAPY PROGRAM IN THE USA SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID PEAK CONCENTRATION; INFECTION MODELS; PENICILLIN-G; EFFICACY; INVITRO; PHARMACODYNAMICS; SUSCEPTIBILITY; ACCUMULATION; RESISTANCE; NETILMICIN AB A variety of pharmacodynamic, pharmacokinetic and drug stability factors can influence the choice of drug, the dosing regimen and the method of drug administration for outpatient parenteral antibiotic therapy (OPAT). Beta-lactam antibiotics exhibit little if any concentration-dependent killing and produce short-term or no persistent effects with most bacterial pathogens. Optimal dosing regimens for these agents should provide serum levels that continually exceed the minimal inhibitory concentration (MIC) of the pathogen. Beta-lactam agents with long half-lives (greater than 2 hours) can provide these levels with intermittent dosing once or twice daily. Beta-lactam agents with shorter half-lives can be administered by programmable pumps or by continuous infusion providing the drug is sufficiently stable to degradation in solution. Imipenem and ampicillin are examples of drugs with short half-lives that are unstable in solution and must be dosed intermittently. Intramuscular administration slows absorption and can also prolong the length of time during which serum levels exceed the MIC of infecting bacteria. Aminoglycosides and fluoroquinolones, on the other hand, exhibit concentration-dependent killing and produce prolonged persistent effects. Optimal dosage regimens of these drugs should maximize serum levels. Once-daily dosing regimens for the aminoglycosides meet this goal and also appear to reduce drug-induced nephrotoxicity. Application of these principles to drug selection and administration in a hospital-based OPAT program has provided efficacious therapy and a low incidence of adverse reactions in an elderly population distributed over a wide geographic area. C1 UNIV WISCONSIN,MADISON,WI 53705. RP CRAIG, WA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT MED,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 27 TC 36 Z9 37 U1 0 U2 0 PU FRIEDR VIEWEG SOHN VERLAG GMBH PI WIESBADEN 1 PA PO BOX 5829, W-6200 WIESBADEN 1, GERMANY SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD JUL PY 1995 VL 14 IS 7 BP 636 EP 642 DI 10.1007/BF01690745 PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA RQ617 UT WOS:A1995RQ61700019 PM 7588857 ER PT J AU JIA, GQ GUTIERREZRAMOS, JC AF JIA, GQ GUTIERREZRAMOS, JC TI ANALYSIS OF INTERLEUKIN RECEPTOR GENE-EXPRESSION IN MOUSE FETAL LIVER BY QUANTITATIVE POLYMERASE CHAIN-REACTION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE INTERLEUKIN RECEPTOR; GENE EXPRESSION; POLYMERASE CHAIN REACTION ID MESSENGER-RNA; GAMMA-CHAIN; MURINE; CDNAS AB We describe a simplified and sensitive polymerase chain reaction (PCR)-based method for the quantification of low-abundance RNA for mouse cytokine receptor genes. Accurate quantification is achieved in a two-step protocol which uses a synthetic RMA as an internal standard. The proper titration of the amount of mRNA molecules is followed by a kinetic analysis which ensures precise measurement. This quantitative PCR method provides a rapid and reliable way to quantify the amount of cytokine receptor mRNA in samples containing as few as 1000 molecules of RNA for a cytokine receptor target gene. We illustrate our approach by quantifying mRNA levels for two families of cytokine receptor genes in the fetal liver and bone marrow of the mouse. Our results reveal early and abundant expression of the genes encoding the signal transducing subunits interleukin-2 receptor gamma and gp130. Their expression seems to precede that of the genes encoding the specific subunits of these interleukin receptor systems. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. FU NHLBI NIH HHS [1POIHL 48675-02] NR 18 TC 8 Z9 8 U1 0 U2 0 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 JUL PY 1995 VL 25 IS 7 BP 2096 EP 2100 DI 10.1002/eji.1830250744 PG 5 WC Immunology SC Immunology GA RH878 UT WOS:A1995RH87800043 PM 7621883 ER PT J AU KURATA, C CALLAHAN, RJ MOLEA, N WILKINSON, R FISCHMAN, AJ STRAUSS, HW AF KURATA, C CALLAHAN, RJ MOLEA, N WILKINSON, R FISCHMAN, AJ STRAUSS, HW TI LOCALIZATION OF [I-125] ENDOTHELIN-1 IN INJURED AORTA OF RABBITS SO EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION LA English DT Article DE ENDOTHELIN-1; ATHEROSCLEROSIS; DEENDOTHELIALIZATION; ATHEROGENIC DIET; (TISSUE DISTRIBUTION) ID VASCULAR SMOOTH-MUSCLE; INCREASED PLASMA-LEVEL; CIRCULATING ENDOTHELIN; CORONARY SPASM; IMMUNOREACTIVITY; ATHEROSCLEROSIS; PROSTACYCLIN; BINDING; ANGINA; CELLS AB Endothelin-1 is a potent vasoconstrictor. This study was performed to determine whether arterial injury, induced by either hypercholesterolemia or mechanical disruption of the endothelium, is associated with increased localization of endothelin-1 in the artery. The blood clearance and tissue distribution of intravenously injected [I-125]endothelin-1 was evaluated in 33 rabbits control animals (n = 7), balloon de-endothelialized animals (n = 12), cholesterol-fed animals (n = 6) and animals that had both balloon de-endothelialization and high cholesterol diet (n = 8). The blood clearance half time was less than 10 min, with slightly slower clearance in the ballooned/cholesterol-fed animals. [I-125]Endothelin-1 localized in the lung (similar to 12% injected dose (ID)/organ) and kidney(similar to 8%ID/organ). [I-125]Endothelin-1 localization in the injured aorta increased from the baseline level of 0.06%kgID/g to its highest level within 5 min of balloon de-endothelialization (0.2%kgID/g) and decreased to 0.11%kgID/g within one week and remained essentially unchanged through 16 weeks. The area with increased binding of [I-125]endothelin-1 corresponded to the zone of arterial injury stained with Evans blue. On the other hand, the binding in the aorta did not increase with the atherogenic diet. These findings suggest that endothelin-1 accumulates in injured vessels, attaining the highest levels immediately after mechanical injury. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. NR 25 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6917 J9 EUR J PHARM-ENVIRON JI Eur. J. Pharmacol.-Environ. Toxicol. Pharmacol. Sect. PD JUL 1 PY 1995 VL 293 IS 2 BP 109 EP 114 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA RL022 UT WOS:A1995RL02200002 PM 7589224 ER PT J AU OBERLEY, TD SCHULTZ, JL LI, N OBERLEY, LW AF OBERLEY, TD SCHULTZ, JL LI, N OBERLEY, LW TI ANTIOXIDANT ENZYME LEVELS AS A FUNCTION OF GROWTH-STATE IN CELL-CULTURE SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE MANGANESE SUPEROXIDE DISMUTASE; CELL CULTURE; DENSITY INHIBITION OF GROWTH; CELL CYCLE; FREE RADICALS ID MANGANESE SUPEROXIDE-DISMUTASE; MOUSE EPIDERMAL-CELLS; PROTEIN KINASE-C; HYDROGEN-PEROXIDE; CU,ZN-SUPEROXIDE DISMUTASE; ORNITHINE DECARBOXYLASE; GLUTATHIONE-PEROXIDASE; INTRACELLULAR PH; OXIDATIVE STRESS; EPITHELIAL-CELLS AB Manganese superoxide dismutase (MnSOD) levels were monitored as a function of time in culture to determine whether these levels were altered at logarithmic growth versus when the cells exhibited density limitation of growth. For comparison, activities of the antioxidant enzymes copper, zinc superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase were also evaluated. Four cell lines were studied, two of which exhibited density limitation of growth and two of which did not. Each cell line showed a unique antioxidant enzyme profile. The two cell lines that showed density limitation of growth also demonstrated induction of MnSOD at the time when the cells stopped proliferating in culture, whereas the other two cell lines did not show induction of MnSOD. There was no strict correlation between density limitation of growth and activities of the other antioxidant enzymes. To determine whether SOD varied with various phases of the cell cycle, NIH/3T3 cells were synchronized using serum starvation, and then SOD activities were measured during quiescence (G(0)) and the phase of DNA synthesis (S-phase). MnSOD was decreased during S-phase compared with G(0), whereas CuZnSOD was increased during S-phase compared with G(0), demonstrating alteration of SOD activities with varying phases of the cell cycle. This study suggests the possibility that increased MnSOD may correlate with decreased cell proliferation and suggests significant alterations in SOD activities during the cell cycle. C1 UNIV WISCONSIN,SCH MED,DEPT PATHOL,MADISON,WI 53706. UNIV IOWA,COLL MED,RADIAT RES LAB,IOWA CITY,IA. RP OBERLEY, TD (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL & LAB MED SERV,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NCI NIH HHS [CA 41267] NR 52 TC 76 Z9 77 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUL PY 1995 VL 19 IS 1 BP 53 EP 65 DI 10.1016/0891-5849(95)00012-M PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA QZ423 UT WOS:A1995QZ42300007 PM 7635359 ER PT J AU MERTZ, H NALIBOFF, B MUNAKATA, J NIAZI, N MAYER, EA AF MERTZ, H NALIBOFF, B MUNAKATA, J NIAZI, N MAYER, EA TI ALTERED RECTAL PERCEPTION IS A BIOLOGICAL MARKER OF PATIENTS WITH IRRITABLE-BOWEL-SYNDROME SO GASTROENTEROLOGY LA English DT Article ID PAIN; NEURONS; NERVES; DISTENSION; MECHANISMS AB Background and Aims: Lowered visceral perception thresholds have been suggested as a biological marker of irritable bowel syndrome (IBS). The current study sought to determine the prevalence of altered rectal visceral perception in patients with IBS and the correlation of altered perception thresholds with subjective symptoms. Methods: Anorectal manometry and rectal perception thresholds to balloon distention were determined in 100 patients with IBS and 15 control subjects. Gastrointestinal and psychological symptoms were assessed by questionnaire. Perception thresholds and symptoms were reassessed after 3 months in 15 patients with IBS. Results: Ninety-four percent of patients showed altered rectal perception in the form of lowered thresholds for aversive sensations (discomfort), increased intensity of sensations, or altered viscerosomatic referral. Hypersensitivity was found only for aversive sensations in response to rapid phasic distention; stool thresholds and thresholds in response to slow ramp distention were normal. Cluster analysis by physiological parameters identified three IBS subgroups with predominant patterns of symptoms. Longitudinal evaluation indicated a correlation between changes in perception thresholds and symptom severity. Conclusions: Because altered rectal perception is present in almost all patients with IBS and perception thresholds correlate with temporal changes in retrospective symptom severity, altered rectal perception represents a reliable biological marker of IBS. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,VET ADM UCLA CURE GASTROENTER BIOL CTR,DEPT MED,NEUROENTER BIOL GRP,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA. VET ADM MED CTR,SEPULVEDA,CA 91343. FU NIDDK NIH HHS [DK40919] NR 42 TC 701 Z9 724 U1 0 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1995 VL 109 IS 1 BP 40 EP 52 DI 10.1016/0016-5085(95)90267-8 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RG191 UT WOS:A1995RG19100005 PM 7797041 ER PT J AU JACOBY, RF MARSHALL, DJ KAILAS, S SCHLACK, S HARMS, B LOVE, R AF JACOBY, RF MARSHALL, DJ KAILAS, S SCHLACK, S HARMS, B LOVE, R TI GENETIC INSTABILITY ASSOCIATED WITH ADENOMA TO CARCINOMA PROGRESSION IN HEREDITARY NONPOLYPOSIS COLON-CANCER SO GASTROENTEROLOGY LA English DT Article ID FAMILIAL COLORECTAL-CANCER; MUTATIONS; LOCUS; DNA; MAP; EVOLUTION; HOMOLOG; GENOME AB Background & Aims: Genetic instability related to defective DNA mismatch repair genes may be involved in the pathogenesis of carcinoma in hereditary nonpolyposis colon cancer (HNPCC). However, nonneoplastic tissues from patients inheriting defects in human MSH2 or human MLH1 do not show significant genetic instability. The aim of this study was to determine whether acquisition of genetic instability at the adenoma stage promotes malignant transformation by studying adenoma-carcinoma progression in HNPCC. Methods: Dinucleotide repeat loci were analyzed by polymerase chain reaction from microdissected adenoma and/or carcinoma stages from formalin-fixed paraffin-embedded HNPCC tumors. Results: Although genetic instability was observed at some loci in almost all cases, the proportion of microsatellite loci altered was significantly less (P < 0.01) in completely benign adenomas (24%) than in benign areas of adenomas with malignancy (54%). Molecular fingerprints indicated intratumor heterogeneity, with evolution of related subclones of neoplastic cells. However, in all cases of tumor progression, at least one subclone from the adenoma stage was closely related to the carcinoma. Conclusions: Some genetic instability develops at the benign adenoma stage in most HNPCC tumors. Adenomas with a greater rate of genetic instability are more likely to progress to carcinoma. Topographic genotyping data provides evidence supporting the hypothesis of adenoma-carcinoma progression in HNPCC. C1 UNIV WISCONSIN,DIV GASTROENTEROL,MADISON,WI. UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI. UNIV WISCONSIN,DEPT SURG,MADISON,WI. UNIV WISCONSIN,DEPT HUMAN ONCOL,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,NJ. FU NCI NIH HHS [U01 CA59352, P30 CA14520] NR 37 TC 92 Z9 93 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1995 VL 109 IS 1 BP 73 EP 82 DI 10.1016/0016-5085(95)90270-8 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RG191 UT WOS:A1995RG19100008 PM 7797042 ER PT J AU MITHOFER, K CASTILLO, CF FRICK, TW LEWANDROWSKI, KB RATTNER, DW WARSHAW, AL AF MITHOFER, K CASTILLO, CF FRICK, TW LEWANDROWSKI, KB RATTNER, DW WARSHAW, AL TI ACUTE HYPERCALCEMIA CAUSES ACUTE-PANCREATITIS AND ECTOPIC TRYPSINOGEN ACTIVATION IN THE RAT SO GASTROENTEROLOGY LA English DT Article ID SECONDARY; SECRETION; ZYMOGENS; CALCIUM; PATIENT; CHOLECYSTOKININ; STIMULATION AB Background & Aims: Clinical and experimental observations have associated acute and chronic hypercalcemia with pancreatitis. The aim of this study was to determine whether acute hypercalcemia can induce acute pancreatitis and, if so, whether the pathogenesis involves premature protease activation. Methods: Rats given bolus infusions of CaCl2 (200 mg/kg; n = 76) were compared with saline-treated controls (n = 40). Serum [Ca2+], serum amylase activity, trypsinogen activation peptide (TAP) concentration in serum and pancreatic tissue, pancreatic wet/dry weight ratio, and histology were assessed for 24 hours. For dose-response analysis, CaCl2 was injected at a dose of 50-200 mg/kg, and the aforementioned indices were assayed for 1 hour (n = 5 each). Results: There were no significant changes in the controls. Calcium infusion increased serum [Ca2+] 3-fold after 5 minutes (P < 0.001). Within 1 hour, serum amylase (2.5-fold) and tissue TAP (3-fold) levels increased along with macroscopic and microscopic edema formation and leukocytic infiltration. The extent of the changes at 1 hour correlated with the calcium dose. Amylase and tissue TAP concentrations remained elevated until 24 hours when serum TAP concentration had increased (P < 0.001) and focal acinar necrosis became evident. Conclusions: Acute experimental hypercalcemia induces dose-dependent morphological alterations characteristic of acute pancreatitis, acute hyperamylasemia, and early ectopic trypsinogen activation. This supports the pathophysiological relevance of excess calcium and offers a possible pathogenetic mechanism for its association with clinical pancreatitis. C1 MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NR 40 TC 76 Z9 78 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1995 VL 109 IS 1 BP 239 EP 246 DI 10.1016/0016-5085(95)90290-2 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RG191 UT WOS:A1995RG19100028 PM 7540999 ER PT J AU SINGARAM, C SWEET, MA GAUMNITZ, EA CAMERON, AJ CAMILLERI, M AF SINGARAM, C SWEET, MA GAUMNITZ, EA CAMERON, AJ CAMILLERI, M TI PEPTIDERGIC AND NITRINERGIC DENERVATION IN CONGENITAL ESOPHAGEAL STENOSIS SO GASTROENTEROLOGY LA English DT Note ID NITRIC-OXIDE SYNTHASE; HIRSCHSPRUNGS-DISEASE AB Congenital esophageal stenosis (CES) is a rare disorder with narrowed esophageal lumen that presents as dysphagia from childhood and that is often associated with tracheobronchial remnants or webs. The pathogenesis of CES is unknown. The aim of this study was to examine the histological and immunohistochemical features of CES. Esophagi from 2 young adults with CES and 3 controls with no motility disorders underwent routine H&E staining, trichrome staining for collagen, and detailed immunocytochemical studies for general neuronal markers (protein gene product 9.5, neuron-specific enolase, and S-100) and neurotransmitters (vasoactive intestinal polypeptide, substance P, and galanin) and nitric oxide synthase by beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and a specific NO synthase antibody. Quantitative experiments compared the numbers of myenteric neurons and amounts of fibers at the circular muscle. CES esophagi showed infiltration of neutrophils in the myenteric plane, without any increase in collagen. NADPH-diaphorase histochemistry showed a significant reduction of myenteric nitrinergic neurons (7 +/- 3.4 vs. 2.7 +/- 1.8 neurons per high-power field) and fibers at the circular muscle. Other peptidergic neurons studied were not significantly reduced in CES. The specific total lack of NO inhibitory innervation may be an important mechanism in the pathogenesis of stenosis and aperistalsis of the esophagus in this disorder. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. MAYO CLIN,DEPT MED,DIV GASTROENTEROL,ROCHESTER,MN. RP SINGARAM, C (reprint author), UNIV WISCONSIN,CTR CLIN SCI,DEPT MED,DIV GASTROENTEROL,ROOM H6-516,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 19 TC 27 Z9 29 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1995 VL 109 IS 1 BP 275 EP 281 DI 10.1016/0016-5085(95)90294-5 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RG191 UT WOS:A1995RG19100032 PM 7541000 ER PT J AU SUMMERGRAD, P HERMAN, JB WEILBURG, JB JELLINEK, MS AF SUMMERGRAD, P HERMAN, JB WEILBURG, JB JELLINEK, MS TI WAGONS HO - FORWARD ON THE MANAGED CARE TRAIL SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID LEVEL AB This paper describes the impact of managed care on an academic medical center department of psychiatry. Like the pioneers before us, academic medical centers have often traveled wilderness paths, training new generations of psychiatrists and providing research about and new understandings of psychiatric illness; under assault from powerful competitive forces, we have all too often circled the wagons in an attempt to survive what we perceive as an onslaught. We describe the ways in which our academic medical center department of psychiatry has responded to managed care forces, in particular, the impact of managed care on residency training, inpatient services, outpatient psychotherapeutic and psychopharmacological care, and faculty morale. We describe how we have worked closely with our medical colleagues, formed new committees, and initiated forays into capitated arrangements. Despite difficult external circumstances, we have been able to survive, regroup, provide leadership, and continue with renewed purpose. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP SUMMERGRAD, P (reprint author), MASSACHUSETTS GEN HOSP,32 FRUIT ST,WARREN 1220,BOSTON,MA 02114, USA. NR 11 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL PY 1995 VL 17 IS 4 BP 251 EP 259 DI 10.1016/0163-8343(95)00048-V PG 9 WC Psychiatry SC Psychiatry GA RL896 UT WOS:A1995RL89600003 PM 7590188 ER PT J AU KOPELOWICZ, A LIBERMAN, RP AF KOPELOWICZ, A LIBERMAN, RP TI BIOBEHAVIORAL TREATMENT AND REHABILITATION OF SCHIZOPHRENIA SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID SEVERELY MENTALLY-ILL; SOCIAL SKILLS; CASE-MANAGEMENT; LONG-TERM; EXPRESSED EMOTION; CONTROLLED TRIAL; FOLLOW-UP; RELAPSE; FAMILY; VULNERABILITY AB The psychopathology and associated disabilities experienced by persons with schizophrenia have only partially responded to conventional pharmacological and psychosocial treatment approaches. Biobehavioral treatment and rehabilitation employs behavioral assessment, social learning principles, skills training, and a focus on the recovery process to amplify the effects of pharmacotherapy. Utilizing the Medline database, we review a selection of English-language studies published from 1970 to 1994 that support the effectiveness of each of the components of biobehavioral therapy such as case management, psychopharmacology with behavioral assessment, psychoeducation, family involvement, and social skills training. An integrated biobehavioral therapy directed toward early detection and treatment of schizophrenic symptoms, collaboration between consumers and caregivers in managing treatment, family and social skills training, and teaching coping skills and self-help techniques has been documented to improve the course and outcome of schizophrenia, as measured by symptom recurrence, social functioning, and quality of life. A case vignette is presented to illustrate the successful integration of biobehavioral therapies into a treatment system that focuses on consumers' attempts to become increasingly responsible for recovering from illness. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,CAMARILLO NEUROPSYCHIAT RES CTR,LOS ANGELES,CA. RP KOPELOWICZ, A (reprint author), SAN FERNANDO MENTAL HLTH CTR,15535 SAN FERNANDO MISSION BLVD,MISSION HILLS,CA 91345, USA. OI kopelowicz, alex/0000-0002-1728-4105 NR 81 TC 27 Z9 27 U1 2 U2 3 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 1995 VL 3 IS 2 BP 55 EP 64 DI 10.3109/10673229509017168 PG 10 WC Psychiatry SC Psychiatry GA RL894 UT WOS:A1995RL89400001 PM 9384930 ER PT J AU HARTMAN, N VORON, SC HERSHMAN, JM AF HARTMAN, N VORON, SC HERSHMAN, JM TI RESOLUTION OF MIGRAINE FOLLOWING BROMOCRIPTINE TREATMENT OF A PROLACTINOMA (PITUITARY MICROADENOMA) SO HEADACHE LA English DT Note DE MIGRAINE; BROMOCRIPTINE; PROLACTIN; HYPERPROLACTINEMIA; PROLACTINOMA; PITUITARY NEOPLASM ID HYPERPROLACTINEMIA AB A 39-year-old male physician with a 27-year history of chronic severe migraine had a prolactin-secreting pituitary microadenoma diagnosed as an incidental finding following an automobile accident. Treatment of the prolactinoma with bromocriptine provided complete and lasting resolution of the migraine as well, suggesting a possible etiologic relationship between these two prevalent conditions, and the possibility of treating st least some cases of migriane with bromocriptine. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA. RP HARTMAN, N (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 6 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC STUDY HEADACHE PI WOODBURY PA 875 KINGS HIGHWAY, STE 200, WOODBURY, NJ 08096 SN 0017-8748 J9 HEADACHE JI Headache PD JUL-AUG PY 1995 VL 35 IS 7 BP 430 EP 431 DI 10.1111/j.1526-4610.1995.hed3507430.x PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA RM335 UT WOS:A1995RM33500011 PM 7672963 ER PT J AU SHAH, DM FREEMAN, DM WEISS, TF AF SHAH, DM FREEMAN, DM WEISS, TF TI THE OSMOTIC RESPONSE OF THE ISOLATED, UNFIXED MOUSE TECTORIAL MEMBRANE TO ISOSMOTIC SOLUTIONS - EFFECT OF NA+, K+, AND CA2+ CONCENTRATION SO HEARING RESEARCH LA English DT Article DE TECTORIAL MEMBRANE; LYMPH COMPOSITION; MOUSE ID GUINEA-PIG COCHLEA; HAIR-CELLS; TRANSDUCER CURRENTS; INNER-EAR; ADAPTATION; ENDOLYMPH; MICROMECHANICS; ORGANIZATION; MOVEMENT; FLUIDS AB Changes in the size, shape, and structure of the isolated tectorial membrane (TM) of the mouse were measured in response to isosmotic changes in the ionic composition of the bathing solution. Substitution of artificial perilymph (AP) for artificial endolymph (AE) caused a small(approximate to 1%) shrinkage of the TM's thickness. This substitution alters not only the predominate cation (from K+ to Na+) but also the Ca2+ concentration(from 20 mu mol/l to 2 mmol/l). When the predominate cation was changed from K+ to Na+, while holding Ca2+ concentration constant, results depended on Ca2+ concentration: there was a small(approximate to 1%) swelling for 20 mu mol/l Ca2+, larger (approximate to 14%) swelling for lower (< 7 mu mol/l) concentrations of Ca2+, and little response for 2 mmol/l Ca2+ or for solutions containing the Ca2+ chelator EGTA. Addition of Ca2+ while holding the predominate cation constant caused shrinkage of the TM; both removal of Ca2+ and addition of the Ca2+ chelator EGTA caused swelling. Swelling responses were largely reversible if the magnitude of the swelling was small. Responses greater than a few percent were only partially reversible and caused long-lasting changes. Changes in ionic composition of the bath affected not only the thickness of the TM but also its other dimensions. Solution changes that increase TM thickness tend to cause radial shearing motions of the surfaces of the TM, which are accompanied by small decreases in width. Little change in length was observed. Although the responses were non-isotropic, increases in thickness were highly correlated with increases in volume. Swelling of the TM was also accompanied by a reduction in prominence of its radially oriented fibrillar structure. These results for the isolated TM of the mouse are qualitatively similar to those obtained previously for the isolated chick TM (Freeman et al., 1994) but different from those obtained for the in vitro mouse TM (Kronester-Frei, 1979a). C1 MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139. MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,BOSTON,MA 02114. JOHNS HOPKINS UNIV,SCH MED,DEPT OTOLARYNGOL HEAD & NECK SURG,BALTIMORE,MD 21203. NR 53 TC 37 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUL PY 1995 VL 87 IS 1-2 BP 187 EP 207 DI 10.1016/0378-5955(95)00089-M PG 21 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA TB396 UT WOS:A1995TB39600020 PM 8567436 ER PT J AU HASSLEN, SR VONANDRIAN, UH BUTCHER, EC NELSON, RD ERLANDSEN, SL AF HASSLEN, SR VONANDRIAN, UH BUTCHER, EC NELSON, RD ERLANDSEN, SL TI SPATIAL-DISTRIBUTION OF L-SELECTIN (CD62L) HUMAN-LYMPHOCYTES AND TRANSFECTED MURINE L1-2 CELLS SO HISTOCHEMICAL JOURNAL LA English DT Article ID NODE HOMING RECEPTOR; ADHESION MOLECULE; LECAM-1; RECOGNITION; NEUTROPHILS; VENULES; DOMAIN; COMMON; ELAM-1 AB We have examined the topographical distribution of L-selectin on surface membrane domains of human lymphocytes and murine L1-2 cells transfected to express human L-selectin. L-selectin was immunolocalized using murine monoclonal DREG 200 Fab antibody and a 12 nm colloidal gold-conjugated secondary antibody. Cell surface morphology and surface distribution of gold-labelled L-selectin were visualized using backscatter electron images obtained by high-resolution, field emission scanning electron microscopy. The topographical morphologies of lymphocytes of both types were complex. The surface of human lymphocytes was composed of both microvilli and ruffles; that of the murine cells was composed of long microvilli and few, if any, ruffles. L-selectin on human lymphocytes was observed primarily as focal clusters on the apical surfaces of ruffles and microvilli. Similarly, on the transfected murine cells, L-selectin was detected predominantly on the apical surface of microvilli. We conclude that L-selectin has a common spatial distribution and clustered organization on all leukocytes examined to-date, and that these features of receptor expression likely facilitate rolling of circulating leukocytes on the endothelial surface. C1 UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. STANFORD UNIV,DEPT PATHOL,STANFORD,CA 94305. UNIV MINNESOTA,DEPT DERMATOL,MINNEAPOLIS,MN 55455. RP HASSLEN, SR (reprint author), UNIV MINNESOTA,DEPT CELL BIOL & NEUROANAT,MINNEAPOLIS,MN 55455, USA. RI von Andrian, Ulrich/A-5775-2008 FU NIAID NIH HHS [AI-19957]; NIDDK NIH HHS [DK-45448]; NIGMS NIH HHS [GM-37734] NR 19 TC 35 Z9 35 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 JUL PY 1995 VL 27 IS 7 BP 547 EP 554 PG 8 WC Cell Biology SC Cell Biology GA RK682 UT WOS:A1995RK68200006 PM 7591847 ER PT J AU BROWN, D KATSURA, T KAWASHIMA, M VERKMAN, AS SABOLIC, I AF BROWN, D KATSURA, T KAWASHIMA, M VERKMAN, AS SABOLIC, I TI CELLULAR-DISTRIBUTION OF THE AQUAPORINS - A FAMILY OF WATER CHANNEL PROTEINS SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Review ID KIDNEY COLLECTING TUBULE; RAT-KIDNEY; ANTIDIURETIC-HORMONE; MEMBRANE-PROTEIN; XENOPUS-OOCYTES; CHIP28 PROTEIN; COATED PITS; VASOPRESSIN; LOCALIZATION; CELLS AB A group of transmembrane proteins that are related to the major intrinsic protein of lens fibers (MIP26) have been named ''aquaporins'' to reflect their role as water channels. These proteins are located at strategic membrane sites in a variety of epithelia, most of which have well-defined physiological functions in fluid absorption or secretion. However, some aquaporins have been localized in cell types where their role is at present unknown. Most of the aquaporins are delivered to the plasma membrane in a non-regulated (constitutive) fashion, but AQP2 enters the regulated exocytotic pathway and its membrane expression is controlled by the action of the antidiuretic hormone, vasopressin. These pathways of constitutive versus regulated delivery to the plasma membrane have been reconstituted in transfected LLC-PK1 epithelial cells, indicating that the information encoded within the protein sequence is sufficient to allow sorting of newly synthesized protein into distinct intracellular vesicles. Finally, different members of the aquaporin family can be targeted to apical, basolateral or both apical and basolateral plasma membrane domains of polarized epithelial cells. This implies that signals for the polarized targeting of these proteins also is located in non-homologous regions of these similar proteins. Thus, future investigations on the aquaporin family of proteins will provide important information not only on the physiology of membrane transport processes in many cell types, but also on the targeting and trafficking signals that allow proteins to enter distinct intracellular vesicular pathways in epithelial cells. In the case of AQP2, the availability of the transfected cell culture system will allow the intracellular signaling pathway, and the accessory molecules that are involved in this pathway, to be dissected and identified. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02129. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02129. UNIV ZAGREB,INST MED RES & OCCUPAT HLTH,ZAGREB 41001,CROATIA. NR 61 TC 64 Z9 64 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-5564 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD JUL PY 1995 VL 104 IS 1 BP 1 EP 9 DI 10.1007/BF01464780 PG 9 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA RM497 UT WOS:A1995RM49700001 PM 7584554 ER PT J AU OCONNELL, JX FANBURG, JC ROSENBERG, AE AF OCONNELL, JX FANBURG, JC ROSENBERG, AE TI GIANT-CELL TUMOR OF TENDON SHEATH AND PIGMENTED VILLONODULAR SYNOVITIS - IMMUNOPHENOTYPE SUGGESTS A SYNOVIAL CELL ORIGIN SO HUMAN PATHOLOGY LA English DT Article DE GIANT CELL TUMOR OF TENDON SHEATH; PIGMENTED VILLONODULAR SYNOVITIS; SYNOVIUM; IMMUNOHISTOCHEMISTRY ID EPITHELIOID SARCOMA; SOFT-TISSUE; EXPRESSION; NEOPLASMS; MARKER; CD34; KP1 AB Giant cell tumor of tendon sheath (GCTS) and pigmented villonodular synovitis (PVNS) are common synovial ''tumors.'' Their immunohistochemical profile, however, has not been well characterized, and uncertainty exists regarding their histogenesis and relationship to fibroma of tendon sheath. In an effort to clarify these uncertainties and to better define the immunohistochemical profile of GCTS/PVNS, we examined formalin fixed tissue from 35 specimens of GCTS, 12 specimens of PVNS, and three cases of reactive synovitis using avidin biotin complex (ABC) and streptavidin immunohistochemical methods. Antibodies to vimentin, CD68, HAM56, cytokeratins, EMA, S100, HMB45, leukocyte common antigen, CD34, desmin, and smooth muscle actin were used in the study. The proliferating mononuclear cells and surface synovial cells in GCTS/PVNS and reactive synovitis: stained positively for CD68, HAM56, and vimentin only. Multinucleated cells stained for CD68, vimentin, and leukocyte common antigen. Ah other stains were negtive. Our results suggest that GCTS/PVNS are tumors of synovial cell origin, and do not support an association between GCTS and fibroma of tendon sheath. Copyright (C) 1995 by W.B. Saunders Company C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP OCONNELL, JX (reprint author), VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,910 W 10TH AVE,VANCOUVER,BC V5Z 1M9,CANADA. NR 22 TC 46 Z9 47 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 1995 VL 26 IS 7 BP 771 EP 775 DI 10.1016/0046-8177(95)90226-0 PG 5 WC Pathology SC Pathology GA RH907 UT WOS:A1995RH90700012 PM 7628850 ER PT J AU BAKA, SG TOTH, TL VEECK, LL JONES, HW MUASHER, SJ LANZENDORF, SE AF BAKA, SG TOTH, TL VEECK, LL JONES, HW MUASHER, SJ LANZENDORF, SE TI EVALUATION OF THE SPINDLE APPARATUS OF IN-VITRO MATURED HUMAN OOCYTES FOLLOWING CRYOPRESERVATION SO HUMAN REPRODUCTION LA English DT Article DE CRYOPRESERVATION; HUMAN OOCYTE; NF; MEIOTIC SPINDLE ID 2ND MEIOTIC SPINDLE; STAGE MOUSE OOCYTES; PARTHENOGENETIC ACTIVATION; MICROTUBULE DYNAMICS; 1,2-PROPANEDIOL; ORGANIZATION; INVITRO; MATURATION; EXPOSURE; EMBRYOS AB The present study was conducted to determine if the cryopreservation of immature human oocytes has a deleterious effect on the meiotic spindle following maturation in vitro. Oocytes were obtained in excess from in-vitro fertilization patients and divided into four groups, Groups 1 (n = 98) and 2 (n = 80) consisted of immature oocytes cryopreserved before or after maturation in vitro respectively, Groups 3 (n = 37) and 4 (n = 9) served as nonfrozen controls and included oocytes matured in vitro and in vivo respectively. The meiotic spindle was identified after incubation in anti-tubulin monoclonal antibody (1 h, 37 degrees C) and fluorescein-conjugated goat anti-mouse immunoglobulin G (IgG) (1 h, RT). Chromosomes were counterstained with 4',6'-diamidino-2-phenylindole. Following cryopreservation, group 1 oocytes demonstrated a 63% survival rate and 68% maturation rate in vitro. In all, 58% of the oocytes in group 2 survived the thaw. The number of oocytes with normal spindles in group 1 (81.0%) was not significantly different from control groups 3 (83.8%) and 4 (88.9%), while the number of group 2 oocytes with normal structures (43.5%) was significantly lower than groups 1 (P = 0.0004), 3 (P = 0.0002), and 4 (P = 0.025). These results suggest that cryopreservation of the prophase I human oocyte does not significantly increase abnormalities in the resulting meiotic spindle. C1 EASTERN VIRGINIA MED SCH,JONES INST REPROD MED,DEPT OBSTET & GYNECOL,NORFOLK,VA 23507. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 30 TC 117 Z9 125 U1 0 U2 2 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 1995 VL 10 IS 7 BP 1816 EP 1820 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA RP657 UT WOS:A1995RP65700041 PM 8582988 ER PT J AU HOLLANDER, GA SIMPSON, SJ MIZOGUCHI, E NICHOGIANNOPOULOU, A SHE, JA GUTIERREZRAMOS, JC BHAN, AK BURAKOFF, SJ WANG, BP TERHORST, C AF HOLLANDER, GA SIMPSON, SJ MIZOGUCHI, E NICHOGIANNOPOULOU, A SHE, JA GUTIERREZRAMOS, JC BHAN, AK BURAKOFF, SJ WANG, BP TERHORST, C TI SEVERE COLITIS IN MICE WITH ABERRANT THYMIC SELECTION SO IMMUNITY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; CD4+ T-CELLS; INDUCE WASTING DISEASE; INTRAEPITHELIAL LYMPHOCYTES; INTESTINAL EPITHELIUM; NEGATIVE SELECTION; SELF-TOLERANCE; RECEPTOR; GUT; EXPRESSION AB Tg epsilon 26 mice display an arrest very early in T cell development that has a profound effect on the architecture of thymic stromal cells. We have recently demonstrated that transplantation of wild-type bone marrow cells restores the thymic microenvironment of fetal but not adult Tg epsilon 26 mice. Here, we report that T cell-reconstituted adult Tg epsilon 26 mice develop a spontaneous wasting syndrome characterized by extensive inflammation of the colon, resembling human ulcerative colitis. Colitis in these animals was marked by substantial infiltration of the colon by activated thymus-derived CD4(+) T cells. Importantly, bone marrow-transplanted Tg epsilon 26 mice previously engrafted with a fetal Tg epsilon 26 thymus did not develop colitis. These results suggest that T cells selected in an aberrant thymic microenvironment contain a population of cells able to induce severe colitis that can be prevented by T cells that have undergone normal thymic development. C1 BETH ISRAEL HOSP,DIV IMMUNOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP HOLLANDER, GA (reprint author), BETH ISRAEL HOSP,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [5 PO1 CA39542-09]; NIDDK NIH HHS [R01 DK47677-01, P30 DK43351] NR 46 TC 171 Z9 174 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 1995 VL 3 IS 1 BP 27 EP 38 DI 10.1016/1074-7613(95)90156-6 PG 12 WC Immunology SC Immunology GA RK868 UT WOS:A1995RK86800005 PM 7621076 ER PT J AU PAHLAVANI, MA HARRIS, MD AF PAHLAVANI, MA HARRIS, MD TI EFFECT OF DEHYDROEPIANDROSTERONE ON MITOGEN-INDUCED LYMPHOCYTE-PROLIFERATION AND CYTOKINE PRODUCTION IN YOUNG AND OLD F344 RATS SO IMMUNOLOGY LETTERS LA English DT Article DE DHEA; IL-2; IFN-GAMMA; AGING; (RAT) ID LYMPHOKINE PRODUCTION INVIVO; AGE-RELATED DECLINE; CD4+ T-CELLS; INTERLEUKIN-2 SYNTHESIS; INTERFERON-GAMMA; IMMUNE FUNCTION; IL-2 PRODUCTION; MICE; EXPRESSION; INHIBITION AB The steroid hormone intermediate, dehydroepiandrosterone (DHEA), has been proposed as a therapeutic agent for the treatment of immunosenescence in mouse model. In the present study, the in vitro effect of DHEA on mitogen-induced lymphocyte proliferation and cytokine production was evaluated in a rat model. Spleen lymphocytes were isolated from young (4-6 months) and old (24-26 months) F344 rats and were incubated with DHEA for 30 min. The induction of lymphocyte proliferation, interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) production by concanavalin A (Con A) was measured in a culture medium supplemented with either fetal calf serum (FCS) or with serum-free medium (Nutridoma-SR, N-SR). The induction of lymphocyte proliferation and IL-2 production by Con A decreased significantly with age, whereas induction of IFN-gamma increased with age. Treatment of lymphocytes with DHEA did not significantly alter Con A-induced proliferation or the production of IL-2 or IFN-gamma by spleen lymphocytes isolated from either young or old rats. These data indicate that in vitro DHEA treatment appears to have no immunomodulatory effect on the age-related changes in mitogen-induced proliferation or cytokine production in rat lymphocytes. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR & GERONTOL,SAN ANTONIO,TX 78284. RP PAHLAVANI, MA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU NIA NIH HHS [AG-01548] NR 49 TC 15 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUL-AUG PY 1995 VL 47 IS 1-2 BP 9 EP 14 DI 10.1016/0165-2478(95)00057-C PG 6 WC Immunology SC Immunology GA RU972 UT WOS:A1995RU97200002 PM 8537107 ER PT J AU IAKOUBOV, L ROKHLIN, O TORCHILIN, V AF IAKOUBOV, L ROKHLIN, O TORCHILIN, V TI ANTINUCLEAR AUTOANTIBODIES OF THE AGED REACTIVE AGAINST THE SURFACE OF TUMOR BUT NOT NORMAL-CELLS SO IMMUNOLOGY LETTERS LA English DT Note DE ANTINUCLEAR AUTOANTIBODY; AGING; TUMOR CELL SURFACE ID ANTINUCLEAR ANTIBODIES; CROSS-REACTIVITY; PROTEINS; MEMBRANE; HISTONES; DISEASE; SLE C1 UNIV IOWA,SCH MED,DEPT PATHOL,IOWA CITY,IA 52242. RP IAKOUBOV, L (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,149 13TH ST,BOSTON,MA 02129, USA. NR 13 TC 37 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD JUL-AUG PY 1995 VL 47 IS 1-2 BP 147 EP 149 DI 10.1016/0165-2478(95)00066-E PG 3 WC Immunology SC Immunology GA RU972 UT WOS:A1995RU97200026 PM 8537094 ER PT J AU BUTTERTON, JR BEATTIE, DT GARDEL, CL CARROLL, PA HYMAN, T KILLEEN, KP MEKALANOS, JJ CALDERWOOD, SB AF BUTTERTON, JR BEATTIE, DT GARDEL, CL CARROLL, PA HYMAN, T KILLEEN, KP MEKALANOS, JJ CALDERWOOD, SB TI HETEROLOGOUS ANTIGEN EXPRESSION IN VIBRIO-CHOLERAE VECTOR STRAINS SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEINS; I B-SUBUNIT; ESCHERICHIA-COLI; TOXIN-I; SYNTHETIC PEPTIDES; SUICIDE VECTOR; SHIGELLA TOXIN; GENE; IMMUNIZATION; CONSTRUCTION AB Live attenuated vector strains of Vibrio cholerae were derived from Peru-2, a Peruvian El Tor Inaba strain deleted for the cholera toxin genetic element and attRS1 sequences, which was developed as a live, oral vaccine strain, A promoterless gene encoding the Shiga-like toxin I B subunit (slt-IB) was inserted in the V. cholerae virulence gene irgA by in vivo marker exchange, such that slt-IB was under transcriptional control of the iron-regulated irgA promoter, slt-IB was also placed under transcriptional control of the V. cholerae heat shock promoter, htpGp, and introduced into either the irgA or lacZ locus, or both loci, on the chromosome of Peru-2, generating JRB10, JRB11, or JRB12, respectively, A new technique was used to perform allelic exchange with lacZ, This method uses plasmid p6891MCS, a pBR327 derivative containing cloned V. cholerae lacZ, to insert markers of interest into the V. cholerae chromosome, Recombinants can be detected by simple color screening and antibiotic selection, In vitro measurements of Slt-IB produced by the vector strains suggested that expression of Slt-IB from the irgA and htpG promoters was synergistic and that two copies of the gene for Slt-IB increased expression over a single copy, The V. cholerae vectors colonized the gastrointestinal mucosa of rabbits after oral immunization, as demonstrated by very high serum antibody responses to V. cholerae antigens. Comparison of the serologic responses to the B subunit of cholera toxin (CtxB) following orogastric inoculation either with the wild-type C6709 or with Peru-10, a strain containing ctxB regulated by htpGp, suggested that both the cholera toxin and heat shock promoters were active in vivo, provoking comparable immunologic responses. Orogastric inoculation of rabbits with vector strains evoked serum immunoglobulin G (IgG) responses to Slt-IB in two of the four strains tested; all four strains produced biliary IgA responses, No correlation was observed between the type of promoter expressing slt-IB and the level of serum IgG or biliary IgA response, but the vector strain containing two copies of the gene for slt-IB evoked greater serum IgG responses than strains containing a single copy, consistent with the increased expression of Slt-IB from this strain observed in vitro. A comparison of the serum and biliary antibody responses to Slt-IB expressed from htpGp versus CtxB expressed from the same promoter suggested that CtxB is a more effective orally delivered immunogen. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. INST VIRUS RES,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NIAID NIH HHS [AI34968] NR 46 TC 38 Z9 38 U1 0 U2 3 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 1995 VL 63 IS 7 BP 2689 EP 2696 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RE842 UT WOS:A1995RE84200042 PM 7790086 ER PT J AU ALONSO, A AF ALONSO, A TI DISCUSSANT COMMENTS FOR SPECIAL SECTION ON ANGER AND AGGRESSION IN GROUPS SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article C1 MASSACHUSETTS GEN HOSP,CTR PSYCHOANALYT STUDIES,BOSTON,MA. FIELDING INST,SANTA BARBARA,CA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU GUILFORD PRESS 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 1995 VL 45 IS 3 BP 331 EP 338 PG 8 WC Psychology, Clinical SC Psychology GA RF824 UT WOS:A1995RF82400006 PM 7649697 ER PT J AU GANS, JS AF GANS, JS TI DISCUSSION OF THERAPIST ANGER IN GROUP-PSYCHOTHERAPY SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 10 TC 1 Z9 1 U1 0 U2 0 PU GUILFORD PRESS 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 1995 VL 45 IS 3 BP 355 EP 362 PG 8 WC Psychology, Clinical SC Psychology GA RF824 UT WOS:A1995RF82400009 ER PT J AU SCULLY, RE AF SCULLY, RE TI EARLY DE-NOVO OVARIAN-CANCER AND CANCER DEVELOPING IN BENIGN OVARIAN LESIONS SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE OVARY; PRECANCER; CARCINOMA; ENDOMETRIOSIS; CARCINOGENESIS ID TUMORS AB Ovarian carcinoma can arise directly from the ovarian surface epithelium or its intraparenchymal inclusions or from pre-existing benign ovarian lesions such as endometriosis and epithelial tumors. RP SCULLY, RE (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114, USA. NR 13 TC 26 Z9 26 U1 0 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD JUL PY 1995 VL 49 SU S BP S9 EP S15 DI 10.1016/0020-7292(95)02404-Z PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RQ523 UT WOS:A1995RQ52300002 PM 7589745 ER PT J AU BORNSTEIN, BA HERMAN, TS HANSEN, JL BUSWELL, L ZOURANJIAN, PS FRASER, SM TEICHER, BA SVENSSON, GK COLEMAN, CN AF BORNSTEIN, BA HERMAN, TS HANSEN, JL BUSWELL, L ZOURANJIAN, PS FRASER, SM TEICHER, BA SVENSSON, GK COLEMAN, CN TI PILOT-STUDY OF LOCAL HYPERTHERMIA, RADIATION-THERAPY, ETANIDAZOLE, AND CISPLATIN FOR ADVANCED SUPERFICIAL TUMORS SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE RADIATION THERAPY; HYPERTHERMIA; CHEMOTHERAPY; ETANIDAZOLE; COMBINED MODALITY ID CELL RADIOSENSITIZER SR-2508; PHASE-I TRIAL; PROGNOSTIC FACTORS; GROWTH DELAY; CIS-DIAMMINEDICHLOROPLATINUM(II); NEUROTOXICITY; MALIGNANCIES; CARCINOMA; TUMORS; CANCER AB Five patients (six hyperthermia sites) with advanced superficial tumours were treated with combined etanidazole, cisplatin, local hyperthermia, and radiation therapy as part of a Phase I pilot study. Treatment was given once weekly and consisted of etanidazole 3 gm/m(2) IV bolus, cisplatin 50 mg/m(2) IV bolus, hyperthermia for 60 min with a target temperature of 43 degrees C, and radiation therapy 500 cGy/fraction (median total dose 3000 cGy) for a total of six weeks. Blood levels of etanidazole were taken during treatment at week 1 and week 4. Etanidazole drug exposure was calculated using the trapezoidal rule and expressed as the area under the curve (AUG) of plasma concentration X time. Five of six treatment sites had received prior irradiation. Prior chemotherapy had been given in three patients and tamoxifen therapy given in the other two patients. The median follow-up time is 34 months; 3/5 patients have died of disease. The most significant toxicity was grade I or II nausea and vomiting associated with 19/32 treatments (59%) and a second degree burn in 2/6 fields. None of the five patients experienced peripheral neuropathy, skin ulceration, or needed surgical repair. In addition, there was mild renal toxicity; pharmacokinetic analysis showed a 28-75% increase in the week 1 to week 4 AUC in three patients, all of whom had a decrease in creatinine clearance over the same time of 15-47%. This pilot study suggests this combined modality therapy can be delivered without major complications and that renal function, determined by creatinine clearance, affects clearance of etanidazole and alters the AUG. Therefore, monitoring renal function is important in patients receiving etanidazole in addition to other nephrotoxic agents such as cisplatin. The impact of etanidazole on the therapeutic index of hyperthermia, radiation therapy and cisplatin may be worthy of study, especially since a positive interaction between these modalities is found in laboratory models. C1 HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02215. DANA FARBER CANC INST,BOSTON,MA 02215. RP BORNSTEIN, BA (reprint author), HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,44 BINNEY ST,BOSTON,MA 02215, USA. FU NCI NIH HHS [CA-31303, CA-42391] NR 24 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD JUL-AUG PY 1995 VL 11 IS 4 BP 489 EP 499 DI 10.3109/02656739509022484 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA RJ559 UT WOS:A1995RJ55900002 PM 7594803 ER PT J AU KUSUMOTO, T HOLDEN, SA ARA, G TEICHER, BA AF KUSUMOTO, T HOLDEN, SA ARA, G TEICHER, BA TI HYPERTHERMIA AND PLATINUM COMPLEXES - TIME BETWEEN TREATMENTS AND SYNERGY IN-VITRO AND IN-VIVO SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE HYPERTHERMIA; CIS-DIAMMINEDICHLOROPLATINUM (II); RHODAMINE-123; THERAPEUTIC SYNERGY ID HAMSTER OVARY CELLS; FIBRO-SARCOMA; CIS-DIAMMINEDICHLOROPLATINUM(II); RADIOSENSITIVITY; ENHANCEMENT; SEQUENCE; SURVIVAL; THERAPY; INVIVO; DYES AB To investigate the greatest therapeutic efficacy, we investigated the effect of scheduling on the cytotoxic interaction between hyperthermia and seven different platinum complexes in vitro and in vivo using the FSaII murine fibrosarcoma cells. Hyperthermia treatment (43 degrees C, 1 h) was administered at various times relative to exposure of the cells to the IC90 (at 37 degrees C, 1 h) of each platinum complex. Greater-than-additive killing of FSaII cells was obtained with cis-diamminedichloroplatinum (II) (CDDP) and hyperthermia when the drug and heat exposure were overlapping or simultaneous. The same cell killing effect with carboplatin and hyperthermia resulted from heat exposure up to 5 h prior to, simultaneous with, or immediately after the drug exposure. D-Tetraplatin and K2PtCl4 were synergistic with hyperthermia only if the drug and heat exposure were simultaneous. PtCl4(Nile Blue)(2) and hyperthermia produced greater than-additive cell killing if the heat and drug exposure occurred in immediate sequence, simultaneously, or with drug exposure up to 5 h prior to heat exposure. PtCl4(Rh-123)(2) and hyperthermia produced greater-than-additive cell killing if the drug and heat occurred in immediate sequence, overlapping, or simultaneously. PtCl4(Fast Black)(2) and hyperthermia were additive over a wide range of scheduling from heat exposure 2 h prior to 5 h after drug exposure. When animals bearing FSaIIC tumours were treated with single doses of CDDP (10 mg/kg), carboplatin/PtCl4(Nile Blue)(2) (50 mg/kg), PtCl4(Rh-123)(2)/PtCl4(Fast Black)(2) (100 mg/kg) under various combined schedules with hyperthermia treatment (43 degrees C, 30 min), similar cytotoxicity patterns were observed. To administer hyperthermia at a time when the drug concentration in the tumour tissue is at peak level, careful scheduling of systemically administered anticancer drugs with hyperthermia is needed. Modelling studies can identify the stringency/flexibility of drug/heat scheduling to achieve synergistic tumour cell killing. C1 DANA FARBER CANC INST,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. FU NCI NIH HHS [R01-CA50174, P01-CA31303] NR 33 TC 18 Z9 19 U1 0 U2 5 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD JUL-AUG PY 1995 VL 11 IS 4 BP 575 EP 586 DI 10.3109/02656739509022491 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA RJ559 UT WOS:A1995RJ55900009 PM 7594810 ER PT J AU SHAH, HN COLLINS, MD OLSEN, I PASTER, BJ DEWHIRST, FE AF SHAH, HN COLLINS, MD OLSEN, I PASTER, BJ DEWHIRST, FE TI RECLASSIFICATION OF BACTEROIDES-LEVII (HOLDEMAN, CATO, AND MOORE) IN THE GENUS PORPHYROMONAS, AS PORPHYROMONAS-LEVII COMB-NOV SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Note ID 3-KETODIHYDROSPHINGOSINE SYNTHETASE; RE-CLASSIFICATION; FATTY-ACID; MELANINOGENICUS; PROPOSAL; ASACCHAROLYTICUS; ENDODONTALIS; PREVOTELLA; GINGIVALIS; MITSUOKA AB The genus Bacteroides was recently redefined to include only the type species Bacteroides fragilis and closely related taxa. Most other species that were previously designated Bacteroides have been reclassified in new genera. The taxonomic position of Bacteroides levii (Holdeman, Cato, and Moore) has remained incertae sedis, On the basis of biochemical, chemical and comparative 16S rRNA sequence analyses, this species shares a high degree of similarity with members of the genus Porphyromonas. We therefore formally propose that Bacteroides levii (Holdeman, Cato, and Moore) be reclassified in the genus Porphyromonas, as Porphyromonas levii comb, nov. C1 INST FOOD RES,DEPT MICROBIOL,READING LAB,READING,BERKS,ENGLAND. UNIV OSLO,FAC DENT,DEPT ORAL BIOL,OSLO,NORWAY. FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02115. RP SHAH, HN (reprint author), UNIV LONDON,EASTMAN DENT INST,DEPT MICROBIOL,256 GRAYS INN RD,LONDON WC1X 8LD,ENGLAND. NR 41 TC 15 Z9 15 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 1995 VL 45 IS 3 BP 586 EP 588 PG 3 WC Microbiology SC Microbiology GA RG937 UT WOS:A1995RG93700028 ER PT J AU ZHANG, X HERNANDEZ, MR YANG, HM ERICSON, K AF ZHANG, X HERNANDEZ, MR YANG, HM ERICSON, K TI EXPRESSION OF MUSCARINIC RECEPTOR SUBTYPE MESSENGER-RNA IN THE HUMAN CILIARY MUSCLE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MESSENGER-RNAS; IRIS SPHINCTER; SMOOTH-MUSCLE; CELLS; ACCOMMODATION; GENES AB Purpose. To investigate the expression of the muscarinic receptor (mAChR) subtypes (m1, m2, m3, m4, and m5) in the human ciliary muscle. Methods. cDNA probes specific for the m1 to m5 subtypes were used to characterize the expression of subtype-specific mRNAs by in situ hybridization and Northern blot analysis on a cell line derived from human ciliary muscle tissue (H7CM), sectioned tissue from four donors, and fresh human ciliary muscle tissue from three donors. Results. Messenger RNA for m2, m3, and m5 was detected by in situ hybridization and Northern blot analysis in the H7CM cell line and in human ciliary muscle tissue from the donors. In human ciliary muscle tissues, the expression of mRNA of the m2 and m3 subtypes was more prominent in the circular portion than in the longitudinal portion. In contrast, mRNA for the m5 subtype was greater in the longitudinal portion than in the circular portion. Additionally, Northern blot analysis showed that m1 and m4 were expressed in ciliary muscle tissue. Conclusion. These studies show that the human ciliary muscle definitely expresses the mRNA of subtypes m2, m3, and m5, and may also express the mRNA of m1 and m4. Although the expression of mRNA for the m2, m3, and m5 subtypes differed between the circular and longitudinal portions of the ciliary muscle, the strong expression of all three subtypes of muscarinic receptors by both portions demonstrates that the differential distribution of muscarinic subtypes probably is not responsible for the dissociation between outflow facility and accommodation that can occur under certain conditions. C1 MASSACHUSETTS EYE & EAR INFIRM,HOWE LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. SCHEPENS EYE RES INST,BOSTON,MA. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL,LOS ANGELES,CA. FU NEI NIH HHS [EYO6416, EYO7321] NR 27 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 1995 VL 36 IS 8 BP 1645 EP 1657 PG 13 WC Ophthalmology SC Ophthalmology GA RG990 UT WOS:A1995RG99000017 PM 7541396 ER PT J AU MORGAN, BJ CRABTREE, DC PALTA, M SKATRUD, JB AF MORGAN, BJ CRABTREE, DC PALTA, M SKATRUD, JB TI COMBINED HYPOXIA AND HYPERCAPNIA EVOKES LONG-LASTING SYMPATHETIC ACTIVATION IN HUMANS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE SYMPATHETIC NERVOUS SYSTEM ID BODY NEGATIVE-PRESSURE; BLOOD-PRESSURE; SLEEP-APNEA; TERM POTENTIATION; EPISODIC HYPOXIA; CARDIAC-OUTPUT; RESPONSES; NOREPINEPHRINE; CARDIOGRAPHY; VENTILATION AB We studied ventilatory and neurocirculatory responses to combined hypoxia (arterial O-2 saturation 80%) and hypercapnia (end-tidal CO2 + 5 Torr) in awake humans. This asphyxic stimulus produced a substantial increase in minute ventilation (6.9 +/- 0.4 to 20.0 +/- 1.5 l/min) that promptly subsided on return to room air breathing. During asphyxia, muscle sympathetic nerve activity (intraneural microelectrodes) increased to 220 +/- 28% of the room air baseline. Approximately two-thirds of this sympathetic activation persisted after return to room air breathing for the duration of our measurements (20 min in 8 subjects, 1 h in 2 subjects). In contrast, neither ventilation nor sympathetic outflow changed during time control experiments. A 20-min exposure to hyperoxic hypercapnia also caused a sustained increase in sympathetic activity, but, unlike the aftereffect of asphyxia, this effect was short lived and coincident with continued hyperpnea. In summary, relatively brief periods of asphyxic stimulation cause substantial increases in sympathetic vasomotor outflow that outlast the chemical stimuli. These findings provide a potential explanation for the chronically elevated sympathetic nervous system activity that accompanies sleep apnea syndrome. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,DEPT PREVENT MED,MADISON,WI 53706. UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,MADISON,WI 53706. RP MORGAN, BJ (reprint author), UNIV WISCONSIN,DEPT KINESIOL,5175 MED SCI CTR,1300 UNIV AVE,MADISON,WI 53706, USA. NR 37 TC 149 Z9 151 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 1995 VL 79 IS 1 BP 205 EP 213 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA RK488 UT WOS:A1995RK48800031 PM 7559221 ER PT J AU LEE, R NEYA, K SVIZZERO, TA VLAHAKES, GJ AF LEE, R NEYA, K SVIZZERO, TA VLAHAKES, GJ TI LIMITATIONS OF THE EFFICACY OF HEMOGLOBIN-BASED OXYGEN-CARRYING SOLUTIONS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE HEMOGLOBIN; METHEMOGLOBIN; HEMODILUTION; BLOOD SUBSTITUTE ID STROMA-FREE HEMOGLOBIN; BOVINE HEMOGLOBIN; INHIBITORY FACTOR; NITRIC-OXIDE; ERYTHROCYTES; RELAXATION; OXIDATION; ACID AB Improvements in hemoglobin-based oxygen-carrying (HBOCs) solutions have overcome the toxicities that plagued earlier efforts. However, Limitations of the efficacy of KBOCs are emerging. The potential Limitations of an HBOC were studied in an ovine model (n = 6) of exchange transfusion. Hemodynamic, oxygen transport, and hemoglobin kinetic parameters were examined during isovolumic blood exchange to a final hematocrit of 3.2 +/- 0.7% and a plasma hemoglobin concentration of 8.1 +/- 0.4 g/dl while sheep were awake and breathing room air. However, the infusion of HBOC was associated with immediate increases in systemic and pulmonary arterial pressures. Despite hemodilution with HBOC, systemic and pulmonary vascular resistance increased 43.9% (P < 0.001) and 204.2% (P < 0.001), respectively, after HBOC infusion. After blood exchange, the plasma hemoglobin level exhibited a circulatory half-life of 52.7 +/- 18.0 h. The formation of methemoglobin was significant, accounting for 33.0 +/- 7.1% of the total circulating plasma hemoglobin at 24 h; the half-life of HBOC capable of carrying oxygen was 30.1 +/- 5.4 h. This relatively short period of oxygen-carrying efficacy and the observed vasoconstriction properties may constrain the potential applications of KBOC solutions. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,CARDIAC SURG UNIT EDW105,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 23 TC 117 Z9 120 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 1995 VL 79 IS 1 BP 236 EP 242 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA RK488 UT WOS:A1995RK48800035 PM 7559226 ER PT J AU SIMON, PM LEEVERS, AM MURTY, JL SKATRUD, JB DEMPSEY, JA AF SIMON, PM LEEVERS, AM MURTY, JL SKATRUD, JB DEMPSEY, JA TI NEUROMECHANICAL REGULATION OF RESPIRATORY MOTOR OUTPUT IN VENTILATOR-DEPENDENT C-1-C-3 QUADRIPLEGICS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE PHRENIC AFFERENTS; CHEST WALL MECHANORECEPTORS; INSPIRATORY INHIBITION; MECHANICAL VENTILATION ID MECHANICAL VENTILATION; AIR HUNGER; INSPIRATORY ACTIVITY; MUSCLE-ACTIVITY; PRESSURE; HUMANS; INHIBITION; AFFERENTS; VOLUME; FREQUENCY AB To evaluate the role of phrenic and sternocleidomastoid afferents as alternate sources of inhibitory feedback. during mechanical ventilation, we studied five C-2-C-3 quadriplegics with sensory denervation of the rib cage and diaphragm, six C-1-C-2 quadriplegics with additional loss of sensory feedback from the neck muscles, and seven normal subjects. We compared the return of inspiratory muscle activity [the recruitment-threshold (PCO2RT)] during mechanical ventilation between subject groups after stepwise increases in end-tidal PCO2 (PET(CO2)) either by increasing the inspired fraction of CO2 (FICO2), decreasing tidal volume (VT; 50 ml/min), or decreasing frequency (f; 1 breath/2 min). Normal subjects were mechanically hyperventilated via a nasal mask until inspiratory activity was undetectable. Efferent input to the sternocleidomastoid was intact at both levels of spinal cord injury, but phasic activity was not evident at the quadriplegics' baseline resting ventilation. The PCO2RT was defined as the level of PET(CO2) at which phasic activity of the diaphragm in normal subjects and of the sternocleidomastoid in C-1-C-2 and C-2-C-3 quadriplegics recurred. The mean PCO2RT (in response to raising PET(CO2) via increased FICO2 while maintaining a high VT and f) was not significantly different (P = 0.6) between normal subjects (43 +/- 3 Torr) and C-2-C-3 quadriplegics (38 +/- 5 Torr). Both subject groups demonstrated a frequency- and volume-related inhibition, as evidenced by a substantially lower PCO2RT when PET(CO2) was raised by reducing either VT or f In contrast to the C-2-C-3 quadriplegics, the C-1-C-2 quadriplegics responded with a similar PCO2RT among the three different mechanical ventilation trials, independent-of whether PET(CO2) was raised with high VT and f, with reduced VT, or with reduced f. We conclude that feedback from at least some part of the chest wall is required to produce a volume- and frequency-dependent inhibition of inspiratory muscle activity observed during mechanical ventilation. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MED RES SERV,MADISON,WI 53705. UNIV WISCONSIN,DEPT MED,JOHN RANKIN LAB PULM MED,MADISON,WI 53706. UNIV WISCONSIN,DEPT PREVENT MED,MADISON,WI 53706. RP SIMON, PM (reprint author), MAYO CLIN & MAYO FDN,DIV PULM & CRIT CARE MED,4-411 ALFRED BLDG,200 1ST ST SW,ROCHESTER,MN 55905, USA. NR 39 TC 10 Z9 10 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 1995 VL 79 IS 1 BP 312 EP 323 PG 12 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA RK488 UT WOS:A1995RK48800045 PM 7559237 ER PT J AU CHEW, FS SMIRNIOTOPOULOS, JG AF CHEW, FS SMIRNIOTOPOULOS, JG TI TEACHING SKELETAL RADIOLOGY WITH USE OF COMPUTER-ASSISTED-INSTRUCTION WITH INTERACTIVE VIDEODISC SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID PATHOLOGY AB We evaluated the effectiveness and logistical practicality of use of a program consisting of computer-assisted instruction with interactive videodisc to teach residents in orthopaedic surgery the radiology of musculoskeletal injuries. Eleven residents (four in the fourth year of postgraduate training, five in the third year, one in the second year, and one whose level of training was not recorded) used the computer-videodisc program in a single session with no supervision. The residents took a pre-test and a post-test and also filled out a questionnaire on the efficacy and usefulness of this program compared with other educational materials. The eleven residents improved their scores from 56 +/- 8.6 per cent correct answers (mean and standard deviation) (range, 44 to 69 per cent correct answers) on the pre-test to 86 +/- 9.2 per cent correct answers (range, 69 to 100 per cent correct answers) on the post-test. All of the residents improved their scores, and the improvements were significant (p < 0.001; effect size, 3.57). The residents thought that the program increased their interest in the subject, and they preferred the computer-videodisc program to the use of actual radiographs, textbooks, videotapes, and slides and audiotapes for individual study. The residents reported no difficulty in using the program or the electronic equipment. C1 ARMED FORCES INST PATHOL,DEPT RADIOL PATHOL,WASHINGTON,DC 20306. RP CHEW, FS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. RI Smirniotopoulos, James/D-3726-2011; OI Chew, Felix/0000-0003-2711-2013 NR 21 TC 11 Z9 12 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 JUL PY 1995 VL 77A IS 7 BP 1080 EP 1086 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA RJ671 UT WOS:A1995RJ67100016 PM 7608232 ER PT J AU YOUNG, JA TALAMO, JH SIEGEL, IM AF YOUNG, JA TALAMO, JH SIEGEL, IM TI CONTOUR RESOLUTION OF THE EYESYS CORNEAL ANALYSIS SYSTEM SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article DE COMPUTERIZED VIDEOKERATOGRAPHY; CONTOUR; CORNEA; RESOLUTION AB We investigated the accuracy of a conventional videokeratography instrument (Corneal Analysis System, EyeSys Laboratories) to measure contour information using specialized software developed by the manufacturer. Seven calibrated spheres were measured and the results tabulated. A contour resolution for all spheres for all reflected rings was found to be +/-0.0047 mm, representing a 95% confidence interval. This level of resolution is high enough to obtain clinical value from using the EyeSys instrument as a contour measuring device. RP YOUNG, JA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,CORNEA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CATARACT REFRACTIVE SURGERY PI FAIRFAX PA 4000 LEGATO RD, SUITE 850, FAIRFAX, VA 22030 SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD JUL PY 1995 VL 21 IS 4 BP 404 EP 406 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA RL316 UT WOS:A1995RL31600013 PM 8523283 ER PT J AU LIU, X WU, H BYRNE, M JEFFREY, J KRANE, S JAENISCH, R AF LIU, X WU, H BYRNE, M JEFFREY, J KRANE, S JAENISCH, R TI A TARGETED MUTATION AT THE KNOWN COLLAGENASE CLEAVAGE SITE IN MOUSE TYPE-I COLLAGEN IMPAIRS TISSUE REMODELING SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HUMAN FIBROBLAST COLLAGENASE; TRANSGENIC MICE; MATRIX METALLOPROTEINASES; OSTEOGENESIS IMPERFECTA; POSTPARTUM INVOLUTION; SEQUENCE-ANALYSIS; MESSENGER-RNA; GENE; CELLS; CARTILAGE AB Degradation of type I collagen, the most abundant collagen, is initiated by collagenase cleavage at a highly conserved site between Gly(775) and Ile(776) of the alpha 1(I) chain. Mutations at or around this site render type I collagen resistant to collagenase digestion in vitro. We show here that mice carrying a collagenase-resistant mutant Colla-1 transgene die late in embryogenesis, ascribable to overexpression of the transgene, since the same mutation introduced into the endogenous Colla-1 gene by gene targeting permitted normal development of mutant mice to young adulthood. With increasing age, animals carrying the targeted mutation developed marked fibrosis of the dermis similar to that in human scleroderma. Postpartum involution of the uterus in the mutant mice was also impaired, with persistence of collagenous nodules in the uterine wall. Although type I collagen from the homozygous mutant mice was resistant to cleavage by human or rat fibroblast collagenases at the helical site, only the rat collagenase cleaved collagen trimers at an additional, novel site in the nonhelical N-telopeptide domain. Our results suggest that cleavage by murine collagenase at the N-telopeptide site could account for resorption of type I collagen during embryonic and early adult life. During intense collagen resorption, however, such as in the immediate postpartum uterus and in the dermis later in life, cleavage at the helical site is essential for normal collagen turnover. Thus, type I collagen is degraded by at least two differentially controlled mechanisms involving collagenases with distinct, but overlapping, substrate specificities. C1 WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA 02142 USA. MIT, DEPT BIOL, CAMBRIDGE, MA 02142 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, MED SERV, ARTHRIT UNIT, BOSTON, MA 02114 USA. ALBANY MED COLL, DEPT PHARMACOL & TOXICOL, ALBANY, NY 12208 USA. FU NIAMS NIH HHS [AR03564, AR07258]; NICHD NIH HHS [HD05291] NR 61 TC 188 Z9 190 U1 0 U2 2 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 JUL PY 1995 VL 130 IS 1 BP 227 EP 237 DI 10.1083/jcb.130.1.227 PG 11 WC Cell Biology SC Cell Biology GA RF986 UT WOS:A1995RF98600020 PM 7790374 ER PT J AU PETERS, LL JOHN, KM LU, FM EICHER, EM HIGGINS, M YIALAMAS, M TURTZO, LC OTSUKA, AJ LUX, SE AF PETERS, LL JOHN, KM LU, FM EICHER, EM HIGGINS, M YIALAMAS, M TURTZO, LC OTSUKA, AJ LUX, SE TI ANK3 (EPITHELIAL ANKYRIN), A WIDELY DISTRIBUTED NEW MEMBER OF THE ANKYRIN GENE FAMILY AND THE MAJOR ANKYRIN IN KIDNEY, IS EXPRESSED IN ALTERNATIVELY SPLICED FORMS, INCLUDING FORMS THAT LACK THE REPEAT DOMAIN SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HUMAN-ERYTHROCYTE ANKYRIN; MEMBRANE CYTOSKELETAL COMPLEX; BINDING-SITES; BRAIN ANKYRIN; CELL-ADHESION; CYTOPLASMIC DOMAIN; REGULATORY DOMAIN; ANION-EXCHANGER; K+-ATPASE; SPECTRIN AB We cloned a novel ankyrin, Ank3, from mouse kidney cDNA. The full-length transcript is predicted to encode a 214-kD protein containing an 89 kD, NH2 terminal ''repeat'' domain; a 65 kD, central ''spectrin-binding'' domain; and a 56 kD, COOH-terminal ''regulatory'' domain. The Ank3 gene maps to mouse Chromosome 10, similar to 36 cM from the centromere, a locus distinct from Ank1 and Ank2. Ank3 is the major kidney ankyrin. Multiple transcripts of approximately 7.5, 6.9, 6.3, 5.7, 5.1, and 4.6 kb are highly expressed in kidney where Ank1 and Ank2 mRNAs are barely detectable. The smaller mRNAs (less than or equal to 6.3 kb) lack the entire repeat domain. These transcripts have a unique 5'untranslated region and NH2-terminal sequence and encode a predicted protein of 121 kD. Two small sequences of 21 and 18 amino acids are alternatively spliced at the junction of the repeat and spectrin-binding domains in the larger (greater than or equal to 6.9 kb) RNAs. Alternative splicing of a 588 bp sequence (corresponding to a 21.5-kD acidic amino acid sequence) within the regulatory domain also occurs. Ank3 is much more widely expressed than previously described ankyrins. By Northern hybridization or immunocytochemistry, it is present in most epithelial cells, in neuronal axons, in muscle cells, and in megakaryocytes/platelets, macrophages, and the interstitial cells of Leydig (testis). On immunoblots, an antibody raised to a unique region of the regulatory domain detects multiple Ank3 isoforms in the kidney (215, 200, 170, 120, 105 kD) and in other tissues. The 215/200 kD and 120/105-kD kidney proteins are close to the sizes predicted for the 7.5/6.9- and 6.3/5.7-kb RNAs (with/without the 588;bp acidic insert). Interestingly, it appears that Ank3 exhibits a polarized distribution only in tissues that express the similar to 7.0-kb isoforms, the only isoforms in the kidney that contain the repeat domain. In tissues where smaller transcripts (less than or equal to 6.3 kb) are expressed, Ank3 is diffusely distributed in some or all cells and may be associated with cytoplasmic structures. We conclude that Ank3 is a broadly distributed epithelial ankyrin and is the major ankyrin in the kidney and other tissues, where it plays an important role in the polarized distribution of many integral membrane proteins. C1 CHILDRENS HOSP, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DEPT PEDIAT, BOSTON, MA 02115 USA. ILLINOIS STATE UNIV, DEPT BIOL SCI, NORMAL, IL 61790 USA. JACKSON LAB, BAR HARBOR, ME 04609 USA. FU NCRR NIH HHS [RR01183]; NHLBI NIH HHS [HL32262]; NIDDK NIH HHS [DK34083] NR 65 TC 115 Z9 116 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 JUL PY 1995 VL 130 IS 2 BP 313 EP 330 DI 10.1083/jcb.130.2.313 PG 18 WC Cell Biology SC Cell Biology GA RK161 UT WOS:A1995RK16100007 PM 7615634 ER PT J AU CHANG, JH GILL, S SETTLEMAN, J PARSONS, SJ AF CHANG, JH GILL, S SETTLEMAN, J PARSONS, SJ TI C-SRC REGULATES THE SIMULTANEOUS REARRANGEMENT OF ACTIN CYTOSKELETON, P190RHOGAP, AND P120RASGAP FOLLOWING EPIDERMAL GROWTH-FACTOR STIMULATION SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; GAP-ASSOCIATED PROTEINS; PP60C-SRC TYROSINE KINASE; FACTOR-I RECEPTOR; BINDING PROTEIN; MITOGENIC RESPONSIVENESS; SIGNAL-TRANSDUCTION; CELLULAR PROTEINS; FOCAL ADHESIONS; PHOSPHORYLATION AB Analysis of C3H10T1/2 murine fibroblasts overexpressing wild type and dominant negative variants of c-Src has demonstrated a requirement for c-Src in EGF-induced mitogenesis. Correlating with the ability of c-Src variants to potentiate or inhibit EGF-dependent DNA synthesis is the phosphotyrosine content of multiple cellular proteins, including p190-RhoGAP, a protein thought to regulate growth factor-induced actin cytoskeleton remodeling by modulating the activity of the small GTP binding protein, Rho. Because the in vivo phosphotyrosine content of p190 varies with the level of active c-Src and not with EGF treatment, p190 is considered to be a preferred substrate of c-Src. To determine whether tyrosyl phosphorylation of p190 (by c-Src) could influence EGF-dependent actin remodeling, we used conventional and confocal immunofluorescence microscopy to examine the intracellular distribution of p190, actin, and p120RasGAP in EGF-stimulated or unstimulated 10T1/2 Neo control cells and cells that stably overexpress wild-type (K+) or kinase-defective (K-) c-Src. We found that in all cell lines, EGF induced a rapid and transient condensation of p190 and RasGAP into cytoplasmic, arclike structures. However, in K+ cells the rate of appearance and number of cells exhibiting arcs increased when compared with control cells, Conversely, K- cells exhibited delayed are formation and a reduction in number of cells forming arcs. EGF-induced actin stress fiber disassembly and reassembly occurred with the same kinetics and frequency as did p190 and RasGAP rearrangements in all three cell lines. These results, together with the documented Rho-GAP activity intrinsic to p190 and the ability of Rho to modulate actin stress fiber formation, suggest that c-Src regulates EGF-dependent actin cytoskeleton reorganization through phosphorylation of p190. C1 UNIV VIRGINIA, HLTH SCI CTR, DEPT MICROBIOL, CHARLOTTESVILLE, VA 22908 USA. UNIV VIRGINIA, HLTH SCI CTR, CTR CANC, CHARLOTTESVILLE, VA 22908 USA. MASSACHUSETTS GEN HOSP, CTR CANC, BOSTON, MA 02129 USA. FU NCI NIH HHS [CA 29243, CA 39438] NR 73 TC 177 Z9 177 U1 0 U2 3 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 JUL PY 1995 VL 130 IS 2 BP 355 EP 368 DI 10.1083/jcb.130.2.355 PG 14 WC Cell Biology SC Cell Biology GA RK161 UT WOS:A1995RK16100010 PM 7542246 ER PT J AU KIRSCHNER, PB HENSHAW, R WEISE, J TRUBETSKOY, V FINKLESTEIN, S SCHULZ, JB BEAL, MF AF KIRSCHNER, PB HENSHAW, R WEISE, J TRUBETSKOY, V FINKLESTEIN, S SCHULZ, JB BEAL, MF TI BASIC FIBROBLAST GROWTH-FACTOR PROTECTS AGAINST EXCITOTOXICITY AND CHEMICAL HYPOXIA IN BOTH NEONATAL AND ADULT-RATS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE BASIC FIBROBLAST GROWTH FACTOR; MALONATE; N-METHYL-D-ASPARTATE; 1-METHYL-4-PHENYLPYRIDINIUM; PARKINSONS DISEASE; STROKE ID CALCIUM HOMEOSTASIS; NEURONS; HIPPOCAMPAL; LESIONS; NEUROTOXICITY; DEGENERATION; GLUTAMATE; ISCHEMIA; INJURY; CELLS AB Basic fibroblast growth factor (bFGF) is a polypeptide growth factor that promotes neuronal survival. We recently found that systemic administration of bFGF protects against both excitotoxicity and hypoxia-ischemia in neonatal animals. In the present study, we examined whether systemically administered bFGF could prevent neuronal death induced by intrastriatal injection of N-methyl-D-aspartate (NMDA) or chemical hypoxia induced by intrastriatal injection of malonate in adult rats and 1-methyl-4-phenylpyridinium (MPP(+)) in neonatal rats. Systemic administration of bFGF (100 mu g/kg) for three doses both before and after intrastriatal injection of either NMDA or malonate in adult rats produced a significant neuroprotective effect. In neonatal rats, bFGF produced dose-dependent significant neuroprotective effects against MPP(+) neurotoxicity, with a maximal protection of similar to 50% seen with either a single dose of bFGF of 300 mu g/kg or three doses of 100 mu g/kg. These results show that systemic administration of bFGF is effective in preventing neuronal injury under circumstances in which the blood-brain barrier may be compromised, raising the possibility that this strategy could be effective in stroke. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CNS GROWTH FACTOR RES LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 FU NIA NIH HHS [AG08207]; NINDS NIH HHS [NS10828, NS16367] NR 27 TC 58 Z9 59 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 1995 VL 15 IS 4 BP 619 EP 623 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA RE749 UT WOS:A1995RE74900009 PM 7790410 ER PT J AU DALKARA, T IRIKURA, K HUANG, Z PANAHIAN, N MOSKOWITZ, MA AF DALKARA, T IRIKURA, K HUANG, Z PANAHIAN, N MOSKOWITZ, MA TI CEREBROVASCULAR RESPONSES UNDER CONTROLLED AND MONITORED PHYSIOLOGICAL CONDITIONS IN THE ANESTHETIZED MOUSE SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE BLOOD GASES AND PH; CEREBRAL BLOOD FLOW; CEREBROVASCULAR AUTOREGULATION; CORTICAL BARREL FIELDS; HYPERCAPNIA; MECHANICAL VENTILATION; MOUSE ID PIAL ARTERIOLES INVIVO; CEREBRAL BLOOD-FLOW; MICE; RATS; AUTOREGULATION; MICROSPHERE; ISCHEMIA; VENULES; MODEL AB Control of physiological parameters such as respiration, blood pressure, and arterial blood gases has been difficult in the mouse due to the lack of technology required to monitor these parameters in small animals. Here we report that anesthetized and artificially ventilated mice can be maintained under physiological control for several hours with apparently normal cerebrovascular reactivity to hypercapnia and mechanical vibrissal stimulation. SV-129 mice were anesthetized with urethane (750 mg/kg i.p.) and alpha-chloralose (50 mg/kg i.p.), intubated, paralyzed, and artificially ventilated. Respiratory control was maintained within physiological range by reducing the inspiratory phase of the respiratory cycle to <0.1 a and by adjusting end-tidal CO2 to give a PCO2 of 35 +/- 3 mm Hg. In these mice, mean arterial pressure (95 +/- 9 mm Hg), heart rate (545 +/- 78 beats/min), and arterial pH (7.27 +/- 0.10) could be maintained for several hours. Body temperature was kept at 36.5-37.5 degrees C. We observed stable regional CBF (rCBF) measurements (as determined by laser-Doppler flowmetry) when systemic arterial blood pressure was varied between 40 and 130 mm Hg. Hypercapnia led to a 38 +/- 15% (5% CO2) and 77 +/- 34% (10% CO2) increase in rCBF. Mechanical stimulation of contralateral vibrissae for 1 min increased rCBF by 14 +/- 4%. Changes in rCBF compare favorably with those observed previously in another rodent species, the Sprague-Dawley rat. After placement of a closed cranial window, cerebrovascular reactivity to hypercapnia and whisker stimulation was intact and well maintained during 2-h superfusion with artificial CSF. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,STROKE RES LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS 26361, NS 10828] NR 26 TC 73 Z9 74 U1 0 U2 3 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 1995 VL 15 IS 4 BP 631 EP 638 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA RE749 UT WOS:A1995RE74900011 PM 7790412 ER PT J AU BIEDERMAN, J SANTANGELO, SL FARAONE, SV KIELY, K GUITE, J MICK, E REED, ED KRAUS, I JELLINEK, M PERRIN, J AF BIEDERMAN, J SANTANGELO, SL FARAONE, SV KIELY, K GUITE, J MICK, E REED, ED KRAUS, I JELLINEK, M PERRIN, J TI CLINICAL CORRELATES OF ENURESIS IN ADHD AND NON-ADHD CHILDREN SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Article DE ATTENTION DEFICIT HYPERACTIVITY DISORDER; ENURESIS; RISK ID DEFICIT HYPERACTIVITY DISORDER; CHILDHOOD ENURESIS; LEARNING-DISABILITIES; PATTERNS; ADOLESCENTS; COMORBIDITY; VALIDITY AB Enuresis and attention deficit hyperactivity disorder (ADHD) are common childhood disorders that often co-occur. Although each has been linked to neurodevelopmental immaturity and increased risk for psychopathology, the clinical correlates of enuresis remain unclear. Subjects were 140 6-17-year-old boys with DSM-III-RADHD and 120 non-ADHD controls. Information on enuresis and psychiatric diagnoses was obtained in a standardized manner blind to the child's clinical status. Our results show that (1) enuresis did not increase the risk for psychopathology in children with or without ADHD; (2) enuresis tvas not associated with psychosocial adversity or developmental immaturity; (3) enuresis was associated with increased risk for learning disability, impaired intellectual functioning, and impaired school achievement in normal control children but not in children with ADHD; and (4) the same pattern of findings was obtained after stratifying children with enuresis by primary versus secondary and by nocturnal versus diurnal subtypes. These results suggest that the clinical implications of enuresis may differ for ADHD and non-ADHD children. C1 HARVARD COMMUNITY HLTH PLAN,BOSTON,MA. 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 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 48 TC 39 Z9 39 U1 6 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD JUL PY 1995 VL 36 IS 5 BP 865 EP 877 DI 10.1111/j.1469-7610.1995.tb01334.x PG 13 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA RG322 UT WOS:A1995RG32200011 PM 7559850 ER PT J AU SPENCER, T BIEDERMAN, J WILENS, T GUITE, J HARDING, M AF SPENCER, T BIEDERMAN, J WILENS, T GUITE, J HARDING, M TI ADHD AND THYROID ABNORMALITIES - A RESEARCH NOTE SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Article DE ADHD; THYROID ID DEFICIT HYPERACTIVITY DISORDER; HYPERTHYROIDISM; RESISTANCE; HORMONE AB Contradictory findings have been reported on associations between ADHD and thyroid abnormalities including the syndrome of generalized resistance to thyroid hormone. We systematically reviewed thyroid function in a large group of children and adolescents with ADHD (N = 132). We failed to find evidence of generalized resistance to thyroid hormone. Although mild laboratory abnormalities in thyroid function were observed in a minority of ADHD subjects, they were not different than rates reported in the literature for normal children. RP SPENCER, T (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,FRUIT ST,BOSTON,MA 02114, USA. NR 14 TC 24 Z9 24 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD JUL PY 1995 VL 36 IS 5 BP 879 EP 885 DI 10.1111/j.1469-7610.1995.tb01335.x PG 7 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA RG322 UT WOS:A1995RG32200012 PM 7559851 ER PT J AU REDDY, SV SINGER, FR ROODMAN, GD AF REDDY, SV SINGER, FR ROODMAN, GD TI BONE-MARROW MONONUCLEAR-CELLS FROM PATIENTS WITH PAGETS-DISEASE CONTAIN MEASLES-VIRUS NUCLEOCAPSID MESSENGER-RIBONUCLEIC-ACID THAT HAS MUTATIONS IN A SPECIFIC REGION OF THE SEQUENCE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; ANTIGENS; RNA; OSTEOCLASTS; INCLUSIONS; POLYMERASE; DNA AB Ultrastructural, immunocytochemical, and in situ hybridization studies have suggested that paramyxoviruses, such as measles virus (MV), are present in Pagetic osteoclasts and may contribute to the abnormality in osteoclast function. However, little additional information is known about potential viruses present in Pagetic osteoclasts. As there are increased numbers of osteoclast precursors among the marrow mononuclear cells of Paget's patients, we used the reverse transcriptase-polymerase chain reaction to amplify the nucleocapsid sequence of MV from freshly isolated bone marrow-derived mononuclear cells to examine the potential role of these viruses in cells in the osteoclast lineage. We detected MV nucleocapsid transcripts in 5 of 6 individual Paget's patients' marrow samples. MV transcripts were not detected in marrow samples from 10 normal subjects. Sequence analysis of the PCR products revealed that 1 patient had the same sequence as the Edmonston strain of MV. The remaining 4 patients had point mutations clustered between position 1360-1371 base pairs. Two of the patients exhibited identical mutations at this region. In total, 3 different point mutations were identified that resulted in amino acid substitutions. These data show that 1) unlike those from normal subjects, marrow mononuclear cells from Pager's patients express MV nucleocapsid messenger ribonucleic acid; and 2) mutations of a specific region of the MV nucleocapsid gene were present in 4 of 5 patients and suggest a persistent MV infection in Pagetic osteoclast precursors. These data further suggest that osteoclasts are infected by fusion with infected precursors. C1 VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX 78284 USA. JOHN WAYNE CANC INST, SANTA MONICA, CA 90404 USA. ST JOHNS HOSP, SANTA MONICA, CA 90404 USA. FU NIADDK NIH HHS [AM-35188]; NIAMS NIH HHS [AR-39539, AR-41336] NR 26 TC 73 Z9 74 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1995 VL 80 IS 7 BP 2108 EP 2111 DI 10.1210/jc.80.7.2108 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RP492 UT WOS:A1995RP49200022 PM 7608263 ER PT J AU BONKOVSKY, HL LIANG, TJ HASEGAWA, K BANNER, B AF BONKOVSKY, HL LIANG, TJ HASEGAWA, K BANNER, B TI CHRONIC LEUKOCYTOCLASTIC VASCULITIS COMPLICATING HBV INFECTION - POSSIBLE ROLE OF MUTANT FORMS OF HBV IN PATHOGENESIS AND PERSISTENCE OF DISEASE SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE HBE-ANTIGEN NEGATIVE HBV; VIRAL HEPATITIS; HEPATITIS B; LEUKOCYTOCLASTIC VASCULITIS; PRECORE MUTANT; INTERFERON; IMMUNODOMINANT EPITOPES ID CHRONIC HEPATITIS-B; VIRUS-INFECTION; C VIRUS; MIXED CRYOGLOBULINEMIA; ANTIGEN; POLYARTERITIS AB A young woman developed arthritis and leukocytoclastic vasculitis, followed by hepatitis due to a precore mutant strain of hepatitis B virus (HBV) incapable of synthesizing HBe antigen. Tests for antibodies to HCV were persistently negative. Treatment of the patient with alpha interferon initially led to a severe exacerbation of hepatitis. Later, higher doses of interferon were tolerated and were associated with reduction of HBV replication and improvement in liver histopathology and serum aminotransferases. After interferon therapy, sequencing of HBV DNA from a repeat liver biopsy showed a cluster of new mutations, which may have led to alterations in immunodominant epitopes of viral proteins. The findings suggest that a ''naturally occurring'' mutant form of HBV was associated with chronic hepatitis and vasculitis in the patient, and that the immunological pressure on HBV produced by therapy with interferon may have led to other mutations in the viral genome with persistence of low-level HBV infection. C1 UNIV MASSACHUSETTS,MED CTR,DEPT MED,WORCESTER,MA. UNIV MASSACHUSETTS,MED CTR,DEPT BIOCHEM MOLEC BIOL,WORCESTER,MA. UNIV MASSACHUSETTS,MED CTR,DEPT PATHOL,WORCESTER,MA. MASSACHUSETTS GEN HOSP,DEPT MED,GASTROENTEROL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA 54524]; NIDDK NIH HHS [DK 01952, DK 38825] NR 27 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JUL PY 1995 VL 21 IS 1 BP 42 EP 47 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RH219 UT WOS:A1995RH21900012 PM 7560833 ER PT J AU NAPOLI, R HIRSHMAN, MF HORTON, ES AF NAPOLI, R HIRSHMAN, MF HORTON, ES TI MECHANISMS AND TIME-COURSE OF IMPAIRED SKELETAL-MUSCLE GLUCOSE-TRANSPORT ACTIVITY IN STREPTOZOCIN DIABETIC RATS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GLUT4; GLUT1; HYPERGLYCEMIA; INTRINSIC ACTIVITY; INSULIN RESISTANCE ID INSULIN-INDUCED TRANSLOCATION; PLASMA-MEMBRANE; 3T3-L1 ADIPOCYTES; INTRINSIC ACTIVITY; SUBCELLULAR-DISTRIBUTION; ADIPOSE-TISSUE; EXPRESSION; RESISTANCE; INVIVO; GLUT4 AB Skeletal muscle glucose transport is altered in diabetes in humans, as well as in rats. To investigate the mechanisms of this abnormality, we measured glucose transport V-max, the total transporter number, their average intrinsic activity, GLUT4 and GLUT1 contents in skeletal muscle plasma membrane vesicles from basal or insulin-stimulated streptozocin diabetic rats with different duration of diabetes, treated or not with phlorizin, The glucose transport V,, progressively decreased with the duration of diabetes, In the basal state, this decrease was primarily associated with the reduction of transporter intrinsic activity, which appeared earlier than any change in transporter number or GLUT4 and GLUT1 content, In the insulin-stimulated state, the decrease of transport was mainly associated with severe defects in transporter translocation, Phlorizin treatment partially increased the insulin-stimulated glucose transport by improving the transporter translocation defects, In conclusion, in streptozocin diabetes (a) reduction of intrinsic activity plays a major and early role in the impairment of basal glucose transport; (b) a defect in transporter translocation is the mechanism responsible for the decrease in insulin-stimulated glucose transport; and (c) hyperglycemia per se affects the insulin-stimulated glucose transport by altering the transporter translocation. RP NAPOLI, R (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,METAB SECT,1 JOSLIN PL,BOSTON,MA 02215, USA. OI NAPOLI, Raffaele/0000-0002-3366-2321 FU NIDDK NIH HHS [R01-DK-26317] NR 73 TC 36 Z9 39 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 PY 1995 VL 96 IS 1 BP 427 EP 437 DI 10.1172/JCI118053 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RH894 UT WOS:A1995RH89400053 PM 7615815 ER PT J AU WESLEY, IV SCHROEDERTUCKER, L BAETZ, AL DEWHIRST, FE PASTER, BJ AF WESLEY, IV SCHROEDERTUCKER, L BAETZ, AL DEWHIRST, FE PASTER, BJ TI ARCOBACTER-SPECIFIC AND ARCOBACTER BUTZLERI-SPECIFIC 16S RIBOSOMAL-RNA-BASED DNA PROBES SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CAMPYLOBACTER-LIKE ORGANISMS; AEROTOLERANT CAMPYLOBACTER; SP-NOV; RIBOSOMAL-RNA; DIARRHEAL ILLNESS; IDENTIFICATION; CRYAEROPHILA; HELICOBACTER; DIFFERENTIATION; SEQUENCES AB The genus Arcobacter encompasses gram-negative, aerotolerant, spiral-shaped bacteria formerly designated Campylobacter cryaerophila. Two genus-specific 16S rRNA-based oligonucleotide DNA probes (23-mer and 27-mer) were developed. The probes hybridized with strains of Arcobacter butzleri (n = 58), Arcobacter cryaerophilus (n = 19), and Arcobacter skirrowii (n = 17). The probes did not cross-react with any of the reference strains of Campylobacter, Helicobacter, including ''Flexispira rappini,'' or Wolinella. The 27-mer hybridized with, 61 Arcobacter spp. field isolates originating from late-term aborted porcine (n = 54) and equine (n = 2) fetuses and humans with enteritis (n = 5). The species of Arcobacter isolates (n = 56) recovered from aborted livestock fetuses were determined by ribotyping and were as follows: A. cryaerophilus group 1A (11 of 56; 20%), A. cryaerophilus group 1B (37 of 56; 66%), A. butzleri (5 of 56; 9%), and unknown (3 of 56; 5%). The five human field strains were identified as A. butzleri. A species-specific DNA probe (24-mer) for A. butzleri was also developed since there is evidence that this organism may be a human pathogen. This probe hybridized with previously characterized strains of A. butzleri (n = 58), with 10 field strains identified as A. butzleri by ribotyping and with 2 strains having an indeterminate ribotype. The A. butzleri-specific probe did not crossreact with strains of A. skirrowii (n = 17) and A. cryaerophilus (n = 19). C1 USDA,NATL VET SERV LABS,ANIM & PLANT HLTH INSPECT SERV,AMES,IA 50010. FORSYTH DENT CTR,BOSTON,MA 02115. RP WESLEY, IV (reprint author), USDA ARS,NATL ANIM DIS CTR,POB 70,AMES,IA 50010, USA. FU NIDCR NIH HHS [DE-08303, DE-10374] NR 53 TC 45 Z9 45 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1995 VL 33 IS 7 BP 1691 EP 1698 PG 8 WC Microbiology SC Microbiology GA RD990 UT WOS:A1995RD99000002 PM 7545177 ER PT J AU WOLFF, AC ETTINGER, DS NEUBERG, D COMIS, RL RUCKDESCHEL, JC BONOMI, PD JOHNSON, DH AF WOLFF, AC ETTINGER, DS NEUBERG, D COMIS, RL RUCKDESCHEL, JC BONOMI, PD JOHNSON, DH TI PHASE-II STUDY OF IFOSFAMIDE, CARBOPLATIN, AND ORAL ETOPOSIDE CHEMOTHERAPY FOR EXTENSIVE-DISEASE SMALL-CELL LUNG-CANCER - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP PILOT-STUDY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED TRIAL; CARCINOMA; CISPLATIN; THERAPY; VP-16-213; CYCLOPHOSPHAMIDE; VINCRISTINE; PHARMACOLOGY; RADIOTHERAPY; TENIPOSIDE AB Purpose: A phase II study of ifosfamide, carboplatin, and prolonged oral administration of etoposide (ICE) in patients with untreated extensive-disease (ED) small-cell lung cancer (SCLC) was conducted to assess toxicities, response, and median survival. Patients and Methods: Between July 1990 and August 1992, 35 patients were treated. ICE doses were ifosfamide 5 g/m(2) by 24-hour continuous intravenous (CIV) infusion with mesna on day 1, carboplatin 300 mg/m(2) intravenously (IV) on day 1, and etoposide 50 mg/m(2) orally on days 1 to 21 every 4 weeks for up to six to eight cycles (schedule I). Because of severe hematologic toxicity in the first 18 patients, the last 17 patients received ifosfamide 3.75 mg/m(2) IV on day 1, carboplatin 300 mg/m(2) IV on day 1, and etoposide 50 mg orally on days 1 to 14 (schedule II). Results: Nine of 18 patients (50%) on schedule I held 13 episodes of severe hematologic toxicity (one death), and only two (11%) received full doses on cycle 2. However, with schedule II, only four of 17 patients (24%) developed severe hematologic toxicity, and eight (47%) received full doses on cycle 2. Objective responses were observed in 29 of 35 patients (83%) (schedule I, 16 of 18 patients [89%]; schedule II, 13 of 17 patients [76%]), There were eight (23%) complete responses (CRs) and 21 (60%) partial responses (PRs). The median survival duration was 8.3 months, and 1- and 2-year survival rates were 37% and 14%, respectively. Conclusion: ICE with oral etoposide has comparable activity with other regimens in ED SCLC, However, the 2-year survival rate may be higher and ICE with the lower doses of schedule II could be given safely with acceptable toxicity. Further studies of ICE compared with standard two-drug regimens are warranted, C1 DANA FARBER CANC INST,BOSTON,MA 02115. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. ALBANY MED COLL,ALBANY,NY. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. VANDERBILT UNIV,NASHVILLE,TN. JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. RI Johnson, David/A-7437-2009; OI Wolff, Antonio/0000-0003-3734-1063 FU NCI NIH HHS [CA 16116, CA 21115, CA 23318] NR 58 TC 30 Z9 30 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 1995 VL 13 IS 7 BP 1615 EP 1622 PG 8 WC Oncology SC Oncology GA RG157 UT WOS:A1995RG15700013 PM 7602350 ER PT J AU PICHERT, G ROY, DC GONIN, R ALYEA, EP BELANGER, R GYGER, M PERREAULT, C BONNY, Y LERRA, I MURRAY, C SOIFFER, RJ RITZ, J AF PICHERT, G ROY, DC GONIN, R ALYEA, EP BELANGER, R GYGER, M PERREAULT, C BONNY, Y LERRA, I MURRAY, C SOIFFER, RJ RITZ, J TI DISTINCT PATTERNS OF MINIMAL RESIDUAL DISEASE-ASSOCIATED WITH GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKEMIA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; CHRONIC MYELOID-LEUKEMIA; CHROMOSOME-POSITIVE CELLS; T-CELL; COMPLETE REMISSION; LYMPHOCYTES-T; CHRONIC PHASE; RELAPSE; IMMUNOTHERAPY; TRANSCRIPTS AB Purpose: Allogeneic bone marrow transplantation (BMT) has been shown to provide effective therapy for chronic myelogenous leukemia (CML), but previous reports have also demonstrated the persistence of bcr-abl-positive cells for months to years after BMT in the majority of patients. To evaluate the biologic significance of persistent bcr-abl-positive cells, we examined the relationship between clinical parameters known to affect the risk of relapse and the ability to detect bcr-abl-positive cells post-BMT. Patients and Methods: We analyzed 480 samples from 92 patients at two transplant centers for the presence of bcr-abl-positive cells by polymerase chain reaction (PCR). two different BMT preparative regimens and protocols for prevention of graft-versus-host disease (GVHD) were used. One center used cyclophosphamide plus total-body irradiation (CY/TBI) and T-cell-depleted marrow; the second center used busulfan plus cyclophosphamide (Bu/CY) and untreated marrow with cyclosporine and methotrexate (Csp/MTX) os GVHD prophylaxis. Results: We first determined the percent of patients at each center with greater than or equal to one PCR-positive (PCR(+)) result at defined intervals post-BMT. Between 0 and 6 months post-BMT, the majority of patients (80% to 83%) in both populations had PCR-detectable bcr-abl-positive cells. Between 6 and 24 months post-BMT, 80% to 83% of patients who received T-cell-depleted marrow remained PCR(+), as compared with 26% to 30% of patients who received unmodified marrow. After 24 months post-BMT, the percentage of PCR(+) patients was not significantly different in the two populations. This pattern of detection of bcr-abl-positive cells post-BMT followed the development of chronic GVHD in patients who received unmodified marrow. All patients were also divided into three groups based on post-BMT PCR results os follows: (1) persistent PCR(+) (n = 29), (2) intermittent PCR-negative ([PCR(-)] n = 40), and (3) persistent PCR(-) (n = 23). These three groups were found to have a low, intermediate, and high probability of maintaining remission and disease-free survival, respectively (P = .0001). Intermittent or persistent PCR(-) results, which reflect levels of minimal residual disease less than or equal to the limit of detection by PCR, were clearly associated with both acute (P = .004) and chronic (P = .000005) GVHD. Nevertheless, 44% of patients without GVHD also had intermittent or persistent PCR(-) assays. Conclusion: The persistence of PCR-detectable bcr-abl-positive cells early post-BMT in more than 80% of patients suggests that neither BMT preparative regimen effectively eradicates CML cells in most patients. Subsequently, acute and/or chronic GVHD are associated with a decreased ability to detect residual bcr-abl-positive cells, which suggests that immunologic mechanisms mediated by donor cells are important for inducing longterm remissions after BMT. The demonstration that 44% of patients without GVHD had either low or undetectable levels of residual leukemia suggests the presence of mechanisms capable of suppression or eradication of CML independent of GVHD. (C) 1995 by American Society of Clinical Oncology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DEPT BIOSTAT,BOSTON,MA 02115. UNIV MONTREAL,HOP MAISON NEUVE ROSEMONT,DEPT MED,UNITE TRANSPLANTAT MOELLE OSSEUSE,MONTREAL,PQ,CANADA. RI Perreault, Claude/A-7220-2008 OI Perreault, Claude/0000-0001-9453-7383 FU NIAID NIH HHS [AI29530] NR 40 TC 29 Z9 29 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 1995 VL 13 IS 7 BP 1704 EP 1713 PG 10 WC Oncology SC Oncology GA RG157 UT WOS:A1995RG15700024 PM 7602361 ER PT J AU WOLFE, JT CHOOBACK, L FINN, DT JAWORSKY, C ROOK, AH LESSIN, SR AF WOLFE, JT CHOOBACK, L FINN, DT JAWORSKY, C ROOK, AH LESSIN, SR TI LARGE-CELL TRANSFORMATION FOLLOWING DETECTION OF MINIMAL RESIDUAL DISEASE IN CUTANEOUS T-CELL LYMPHOMA - MOLECULAR AND IN-SITU ANALYSIS OF A SINGLE NEOPLASTIC T-CELL CLONE EXPRESSING THE IDENTICAL T-CELL RECEPTOR SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; LEUKEMIA AB Purpose: One of the unique characteristics of cutaneous T-cell lymphoma (CTCL) is its ability to undergo cytologic transformation in which the malignant T-cells develop the morphologic appearance of a large-cell lymphoma. Reported to occur in vp to 20% of advanced cases, large-cell transformation (LCT) is associated with an aggressive clinical course, Little is known about the risk factors or the molecular mechanisms of LCT. Before current immunohistochemical and molecular techniques, it was not possible to determine if LCT represented changes of the initial neoplastic T-cell clone or, in fact, was a distinct second malignancy. The goal of this study was to define the clonal evolution of LCT in CTCL. Patients and Method: Polymerase chain reaction (PCR) amplification of T-cell receptor-beta (TCR-beta) gene rearrangements and immunohistochemistry with monoclonol antibodies to TCR-V beta regions were used as markers of T-cell clonality to analyze the skin and peripheral blood of a patient with CTCL and LCT. Results: We first detected the presence of minimal residual disease (MRD) in a CTCL patient with a complete clinical response to biologic response modifiers (BRMs). When clinical relapse occurred and demonstrated LCT, TCR-beta-PCR and in situ immunohistochemistry with a specific TCR-V beta monoclonal antibody identified a single neoplastic T-cell clone that expressed the identical TCR as the original clone. Conclusion: Our results confirm a common clonal origin for CTCL and LCT. We also provide evidence of MRD in CTCL by molecular analysis, implying that residual malignant cells maintain a potential for clinical relapse and possibly LCT, The role of MRD detection remains to be defined in the clinical assessment of CTCL. LCT in CTCL provides a unique model to investigate the molecular events that underlie terminal-stage tumor progression. C1 PHILADELPHIA VET AFFAIRS MED CTR,MOLEC BIOL CORE FACIL,PHILADELPHIA,PA 19104. UNIV PENN,MED CTR,CUTANEOUS LYMPHOMA GRP,PHILADELPHIA,PA 19104. UNIV PENN,MED CTR,DEPT DERMATOL,PHILADELPHIA,PA 19104. FU NCI NIH HHS [R29 CA-55017, R01-CA-58841]; NIAMS NIH HHS [T32 AR07465] NR 17 TC 32 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1995 VL 13 IS 7 BP 1751 EP 1757 PG 7 WC Oncology SC Oncology GA RG157 UT WOS:A1995RG15700030 PM 7602365 ER PT J AU ZIE, SW PICARD, MH WEISSMAN, NJ AF ZIE, SW PICARD, MH WEISSMAN, NJ TI AORTIC DISSECTIONS MASQUERADING AS AORTIC VALVULAR DISEASE SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Note ID DIAGNOSIS; ECHOCARDIOGRAPHY; ANGIOGRAPHY C1 MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. SHANGHAI CHEST HOSP,DIV CARDIOL,SHANGHAI,PEOPLES R CHINA. OI Picard, Michael/0000-0002-9264-3243 NR 12 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD JUL-AUG PY 1995 VL 23 IS 6 BP 382 EP 387 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA RC134 UT WOS:A1995RC13400008 ER PT J AU AMARANTE, MTJ CONSTANTINESCU, MA OCONNOR, D YAREMCHUK, MJ AF AMARANTE, MTJ CONSTANTINESCU, MA OCONNOR, D YAREMCHUK, MJ TI BIOMECHANICAL EVALUATION OF THE CANINE AND PORCINE MODELS FOR EXPERIMENTAL CRANIOFACIAL SURGERY SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE BIOMECHANICAL PROPERTIES; BIOMECHANICAL ANALYSIS; CRANIOFACIAL MODEL AB This investigation compared the variation of the biomechanical properties of canine and porcine craniofacial bones in homotypical (same site in opposite sides of an animal) and heterotypical (same site in different animals) sites. Biomechanical analysis is a reliable method to assess bone healing, because fracture repair correlates closely with the changes in biomechanical properties. Paired bone fragments were harvested in nine dogs and nine minipigs from each side of the skull from three different sites-the frontal bone, the supraorbital rim, and the zygomatic arch-and submitted to torque to failure. Maximum torque, stiffness, and toughness were recorded and comparative analysis performed. A normal range of variation between paired craniofacial bones in two useful animal models is provided. The results showed that the variability between homotypic left and right sides was not significant, whereas the variability between heterotypic sites in separate animals was. Maximum torque was the most reliable of the three parameters considered, because the data fell over a much narrower range. We conclude that the use of the contralateral side is a valid control in experimental procedures that may alter the biomechanical properties of one side. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV PLAST & RECONSTRUCT SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ORTHOPED BIOMECH LAB,BOSTON,MA 02114. NR 9 TC 1 Z9 1 U1 1 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD JUL PY 1995 VL 6 IS 4 BP 288 EP 291 DI 10.1097/00001665-199507000-00005 PG 4 WC Surgery SC Surgery GA RH648 UT WOS:A1995RH64800005 PM 9020703 ER PT J AU CHEN, ZW KOU, ZC LEKUTIS, C SHEN, L ZHOU, DJ HALLORAN, M LI, J SODROSKI, J LEEPARRITZ, D LETVIN, NL AF CHEN, ZW KOU, ZC LEKUTIS, C SHEN, L ZHOU, DJ HALLORAN, M LI, J SODROSKI, J LEEPARRITZ, D LETVIN, NL TI T-CELL RECEPTOR V-BETA REPERTOIRE IN AN ACUTE INFECTION OF RHESUS-MONKEYS WITH SIMIAN IMMUNODEFICIENCY VIRUSES AND A CHIMERIC SIMIAN-HUMAN IMMUNODEFICIENCY VIRUS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; PRIMARY HIV-1 INFECTION; PLASMA; GAG AB Changes in T cell receptor (TCR) V beta repertoire and their correlation with virologic events were investigated in rhesus monkeys after acute infection with the simian immunodeficiency virus (SIV). 11 genetically defined rhesus monkeys were experimentally infected with SIVmac or a chimeric simian-human immunodeficiency virus (SHIV), and their peripheral blood lymphocytes (PBL) and lymph nodes were prospectively assessed for TCR V beta gene expression. PBL and lymph nodes of the acutely infected monkeys demonstrated an expansion of selected V beta-expressing T lymphocyte subpopulations as early as 3 d after infection. These expanded V beta-expressing lymphocyte subpopulations were comprised predominantly of CD8+ cells. Six of seven infected monkeys sharing a single electrophoretically defined major histocompatibility complex class I allele exhibited a similar expansion of V beta 14-expressing PBL. Sequence analyses of V-D-J segments of TCR-beta cDNA indicated that the V beta-expressing T cell subpopulation expansion can be oligoclonal. SIVmac-specific CD8+ cytotoxic T lymphocytes were demonstrated in both PBL and lymph nodes of the infected monkeys at the time expansion of the selected V beta-expressing cell subpopulations was seen. Finally, the expansion of the selected V beta-expressing lymphocytes in PBL coincided with the emergence and clearance of SIV p27 from the plasma of the infected monkeys. These results demonstrate that acute infection of rhesus monkeys with SIVmac or SHIV results in an expansion of CD8+ lymphocyte subpopulations expressing selected V beta gene families. The selectively expanded T lymphocytes may contribute to early viral clearance after acute SIVmac or SHIV infection. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,SOUTHBOROUGH,MA 01772. RP CHEN, ZW (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI01189, AI33832, AI36628] NR 24 TC 82 Z9 82 U1 0 U2 0 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 1995 VL 182 IS 1 BP 21 EP 31 DI 10.1084/jem.182.1.21 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RF296 UT WOS:A1995RF29600004 PM 7540651 ER PT J AU AKHTAR, I GOLD, JP PAN, LY FERRARA, JLM YANG, XD KIM, JI TAN, KN AF AKHTAR, I GOLD, JP PAN, LY FERRARA, JLM YANG, XD KIM, JI TAN, KN TI CD4(+) BETA-ISLET CELL-REACTIVE T-CELL CLONES THAT SUPPRESS AUTOIMMUNE DIABETES IN NONOBESE DIABETIC MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; MIXED-LYMPHOCYTE-REACTION; NECROSIS-FACTOR TNF; NOD MICE; IFN-GAMMA; MONOCLONAL-ANTIBODY; BINDING PROTEIN; REGION GENES; PREVENTION; RECEPTOR AB We report the isolation of a panel of CD4(+) T helper type 1 autoreactive T cell clones from the spleen of unprimed nonobese diabetic mice, a murine model of human insulin-dependent diabetes mellitus. The T cell clones express a diverse repertoire of T cell receptors, three of which recognize beta islet cell autoantigen(s). The islet cell-reactive T cell clones inhibit adoptive transfer of insulin-dependent diabetes mellitus and intraislet lymphocytic infiltration. The protective capacity of the T cell clones correlates with their ability to produce a novel immunoregulatory activity that potently inhibits in vitro allogeneic mixed lymphocyte reaction. The partially purified activity significantly inhibited the adoptive transfer of diabetes. Our work provides evidence in support of the existence of T helper type 1, CD4(+) T cells reactive to beta islet cell autoantigens that have acquired a protective instead of a diabetogenic effector function. These T cells mediate their protective action in part by production of an immunoregulatory activity capable of downregulating immune responses, and they are likely to represent a population of regulatory T cells that normally plays a role in maintaining peripheral tolerance. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV PEDIAT ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA. STANFORD UNIV, MED CTR, DEPT MICROBIOL & IMMUNOL, STANFORD, CA 94305 USA. FU NIAID NIH HHS [R01 AI 30018]; NIDDK NIH HHS [R01 DK-46382] NR 54 TC 67 Z9 67 U1 0 U2 0 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 1995 VL 182 IS 1 BP 87 EP 97 DI 10.1084/jem.182.1.87 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RF296 UT WOS:A1995RF29600011 PM 7790825 ER PT J AU SILVA, JA LEONG, GB WEINSTOCK, R PENNY, G AF SILVA, JA LEONG, GB WEINSTOCK, R PENNY, G TI DANGEROUS DELUSIONS OF MISIDENTIFICATION OF THE SELF SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE PSYCHIATRY; PSYCHOSIS; DELUSIONS; DELUSIONAL MISIDENTIFICATION; AGGRESSION; VIOLENCE; DANGEROUSNESS ID CAPGRAS SYNDROME; SUBJECTIVE DOUBLES AB Delusions of misidentification of the self involve radical misidentification of physical and/or psychological aspects of the self. These delusions have received limited attention from a phenomenological as well as from a forensic psychiatric perspective. In this article we present a series of four cases of dangerous delusional misidentification of the self and discuss important factors that may contribute to their dangerousness. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 27 TC 8 Z9 8 U1 0 U2 1 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 1995 VL 40 IS 4 BP 570 EP 573 PG 4 WC Medicine, Legal SC Legal Medicine GA RL472 UT WOS:A1995RL47200011 PM 7595292 ER PT J AU LISH, JD ZIMMERMAN, M FARBER, NJ LUSH, D KUZMA, MA PLESCIA, G AF LISH, JD ZIMMERMAN, M FARBER, NJ LUSH, D KUZMA, MA PLESCIA, G TI PSYCHIATRIC SCREENING IN GERIATRIC PRIMARY-CARE - SHOULD IT BE FOR DEPRESSION ALONE SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Review ID DIAGNOSTIC INTERVIEW SCHEDULE; ELDERLY MEDICAL INPATIENTS; NORMAL CORONARY-ARTERIES; CATCHMENT-AREA SITES; ATYPICAL CHEST PAIN; AGE CONCERN SURVEY; DSM-III-R; PANIC DISORDER; SOMATIZATION DISORDER; MENTAL-DISORDERS AB Depression in the elderly is highly prevalent, associated with functional disability and increased medical costs, and treatable; however, it is infrequently recognized and treated. The Agency for Health Care Policy and Research has advocated, therefore, increased case-finding efforts for depression in primary geriatric care. Anxiety, substance, and somatoform disorders in the elderly are similarly prevalent, associated with disability and cost, treatable, and also infrequently detected and treated. We believe that psychiatric case-finding in geriatric primary care should attend to these disorders, therefore, as well as to depression. In the present study, we examined whether the association between depressive and nondepressive forms of psychopathology was similar in geriatric and nongeriatric medical patients. We also examined the relationship between each type of pathology and health care utilization and global ratings of physical and mental health. In a VA hospital general medical outpatient clinic, 508 patients completed the SCREENER, which is a brief self-report questionnaire that screens for a range of psychiatric disorders, along with a self-report questionnaire regarding subjective health and medical care utilization. Of these patients, 98% were male, and the median age was 63 years. Patients aged 63 and over were compared to younger patients. In both geriatric and younger adult patients, we found substantial comorbidity between depressive and nondepressive forms of pathology. Moreover, in both age groups, there were significant associations between both depressive and nondepressive symptoms and fair-to-poor self-rated physical and mental health and increased medical care utilization. Approximately half of the cases of nondepressive disorders in the elderly were not comorbid with depression, and thus would not have been detected by screening for depression alone. Therefore, psychiatric case finding in primary care of geriatric males should be directed at anxiety, substance, and somatoform disorders, as well as at depression, for treatment resources to be triaged to maximally decrease morbidity and cost. C1 MED COLL PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19129. MED COLL PENN,DIV GEN MED,PHILADELPHIA,PA 19129. VET AFFAIRS MED CTR,DEPT INTERNAL MED,PHILADELPHIA,PA. NR 129 TC 8 Z9 8 U1 21 U2 21 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, 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 1995 VL 8 IS 3 BP 141 EP 153 PG 13 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA RJ669 UT WOS:A1995RJ66900001 PM 7576037 ER PT J AU BECK, BJ AF BECK, BJ TI NEUROPSYCHIATRIC MANIFESTATIONS OF DIFFUSE LEWY BODY DISEASE SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article ID ELECTRON-MICROSCOPIC IMMUNOCYTOCHEMISTRY; ANTI-UBIQUITIN IMMUNOCYTOCHEMISTRY; PROGRESSIVE SUPRANUCLEAR PALSY; IDIOPATHIC PARKINSONS-DISEASE; ALZHEIMER-TYPE PATHOLOGY; SENILE DEMENTIA; ELECTROCONVULSIVE-THERAPY; NEUROFIBRILLARY TANGLES; CLINICAL-FEATURES; BODIES AB This article reviews the nature and prevalence of Lewy bodies (LBs) found during postmortem examination of demented individuals. Neuropathologic findings associated with diffuse Lewy body disease (DLBD) are contrasted with those of other causes of dementia (e.g., Pick's disease and Alzheimer's disease). A sufficiently specific clinical syndrome is suggested to enhance the antemortem diagnosis of DLBD. Current and speculative clinical management strategies of DLBD are discussed. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CONSULTAT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 70 TC 12 Z9 12 U1 1 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, 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 1995 VL 8 IS 3 BP 189 EP 196 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA RJ669 UT WOS:A1995RJ66900009 PM 7576045 ER PT J AU JENIKE, MA AF JENIKE, MA TI MANAGING DEPRESSION IN THE ELDERLY SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 1 TC 1 Z9 1 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, 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 1995 VL 8 IS 3 BP 197 EP 199 PG 3 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA RJ669 UT WOS:A1995RJ66900010 ER PT J AU WILSON, CC WONG, JT GIRARD, DD MERRILL, DP DYNAN, M AN, DD KALAMS, SA JOHNSON, RP HIRSCH, MS DAQUILA, RT WALKER, BD AF WILSON, CC WONG, JT GIRARD, DD MERRILL, DP DYNAN, M AN, DD KALAMS, SA JOHNSON, RP HIRSCH, MS DAQUILA, RT WALKER, BD TI EX-VIVO EXPANSION OF CD4 LYMPHOCYTES FROM HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED PERSONS IN THE PRESENCE OF COMBINATION ANTIRETROVIRAL AGENTS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BISPECIFIC MONOCLONAL-ANTIBODIES; REVERSE-TRANSCRIPTASE INHIBITORS; BLOOD MONONUCLEAR-CELLS; HIGH-LEVEL RESISTANCE; HIV-INFECTION; T-CELLS; HTLV-I; ZIDOVUDINE; THERAPY; INVITRO AB Expansion of CD4 lymphocytes from human immunodeficiency virus type 1 (HIV-1)-infected persons ex vivo has been limited by enhanced virus replication and cell death. The successful expansion of functional CD4 lymphocytes from HIV-1-infected persons has now been accomplished using a bispecific monoclonal antibody to CD3 and CD8 in combination with three antiretroviral agents. CD4 lymphocytes were polyclonally expanded by a factor of 10(3)-10(7) during 4-8 weeks in culture. Supernatants from most cultures were persistently HIV-1 p24 antigen-negative by day 14 and remained negative despite removal of antiretroviral agents at day 28. In such cultures, HIV-1 could not be recovered by cocultivation, and amounts of HIV-1 DNA declined or remained stable at low levels, eventually becoming undetectable in 2 cases. This approach establishes the feasibility of CD4 lymphocyte expansion in persons with HIV disease and may be useful for immune-based or gene therapies. C1 MASSACHUSETTS GEN HOSP,IMMUNOPATHOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP WILSON, CC (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,GRAY 5,BOSTON,MA 02114, USA. FU NIAID NIH HHS [AI-36550, AI-30914, AI-36611] NR 36 TC 44 Z9 45 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 JUL PY 1995 VL 172 IS 1 BP 88 EP 96 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RF041 UT WOS:A1995RF04100012 PM 7541065 ER PT J AU MILENO, MD MARGOLIS, NH CLARK, BD DINARELLO, CA BURKE, JF GELFAND, JA AF MILENO, MD MARGOLIS, NH CLARK, BD DINARELLO, CA BURKE, JF GELFAND, JA TI COAGULATION OF WHOLE-BLOOD STIMULATES INTERLEUKIN-1-BETA GENE-EXPRESSION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID MECHANISMS; SECRETION; PLATELETS AB To study interleukin (IL)-1 beta gene expression, reverse transcription-polymerase chain reaction was used on 25-mu L whole blood samples from 11 healthy subjects. Coagulated and unclotted whole blood was compared. There was no evidence of IL-1 beta gene expression in any time zero samples (i.e., whole blood from which mRNA was immediately extracted) from 11 subjects, whereas a 388-bp band representing IL-1 beta mRNA was detected in all coagulated samples. No mRNA for IL-1 beta was detected in EDTA-anticoagulated whole blood, although in these samples the addition of lipopolysaccharide as a positive control induced the expression of IL-1 beta. In time course studies on samples allowed to clot, mRNA for IL-1 beta was detectable after 30 min. These findings demonstrate that IL-1 beta gene expression is not present in circulating cells of healthy subjects and that coagulation is a stimulus for IL-1 beta gene expression. This may be a mechanism by which thrombosis produces inflammation and fever. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,BOSTON,MA 02111. TUFTS UNIV,SCH MED,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA. FU NIAID NIH HHS [AI-07329, AI-15614]; NIGMS NIH HHS [GM-21700] NR 14 TC 31 Z9 32 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 JUL PY 1995 VL 172 IS 1 BP 308 EP 311 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RF041 UT WOS:A1995RF04100054 PM 7797938 ER PT J AU BENNETT, CL HORNER, RD WEINSTEIN, RA KESSLER, HA DICKINSON, GM PITRAK, DL GILMAN, SC GEORGE, WL COHN, SE SIMBERKOFF, MS JACOBSON, JM DEHOVITZ, JA GOETZ, MB SHAPIRO, MF AF BENNETT, CL HORNER, RD WEINSTEIN, RA KESSLER, HA DICKINSON, GM PITRAK, DL GILMAN, SC GEORGE, WL COHN, SE SIMBERKOFF, MS JACOBSON, JM DEHOVITZ, JA GOETZ, MB SHAPIRO, MF TI EMPIRICALLY TREATED PNEUMOCYSTIS-CARINII PNEUMONIA IN LOS-ANGELES, CHICAGO, AND MIAMI - 1987-1990 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID IN-HOSPITAL MORTALITY; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PNEUMONIA; AIDS; EXPERIENCE AB Many patients infected with the human immunodeficiency virus (HIV) with symptoms suggestive of pneumonia are treated empirically for Pneumocystis carinii pneumonia (PCP), although other bacterial infections (e.g., tuberculosis) and pulmonary Kaposi's sarcoma may cause identical symptoms. Empiric treatment for PCP may result in misdiagnosis and mistreatment. When the outcomes of cytologically confirmed versus empirically treated PCP cases were evaluated, the most important predictors of in-hospital mortality were severity of illness and use of bronchoscopy. Persons who did not undergo bronchoscopy had higher mortality rates than patients negative by bronchoscopy or cytologically confirmed as positive for PCP (22% vs. 11% vs. 14%, P < .01), although severity of illness and timing of anti-PCP medications did not differ significantly. Compared with cytologically confirmed cases persons who did not have bronchoscopy were more likely to die than were bronchoscopy-negative patients (P < .05), after adjusting for severity of illness. Bronchoscopy use may have contributed to better outcomes for persons treated for HIV-related PCP. C1 WESTSIDE VET AFFAIRS MED CTR,CHICAGO,IL. UNIV ILLINOIS,COOK CTY HOSP,MED CTR,CHICAGO,IL 60680. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL. VET AFFAIRS MED CTR,DURHAM,NC 27705. DUKE UNIV,MED CTR,DURHAM,NC. VET AFFAIRS MED CTR,LONG BEACH,CA. UNIV CALIF IRVINE,MED CTR,LONG BEACH,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. VET AFFAIRS MED CTR,BRONX,NY. ALBERT EINSTEIN UNIV,MED CTR,BRONX,NY. SUNY HLTH SCI CTR,BROOKLYN,NY. MANHATTAN VET AFFAIRS MED CTR,NEW YORK,NY. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. VET AFFAIRS MED CTR,MIAMI,FL 33125. UNIV MIAMI,MED CTR,MIAMI,FL. NORTHWESTERN UNIV,MED CTR,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA. NYU MED CTR,NEW YORK,NY. RP BENNETT, CL (reprint author), LAKESIDE VET AFFAIRS MED CTR,DEPT MED,111,333 E HURON ST,CHICAGO,IL 60611, USA. RI Bennett, Charles/C-2050-2008; OI Goetz, Matthew/0000-0003-4542-992X FU AHRQ HHS [IR03-HSO7846-01, IR01-HS06494] NR 12 TC 17 Z9 17 U1 0 U2 3 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 JUL PY 1995 VL 172 IS 1 BP 312 EP 315 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RF041 UT WOS:A1995RF04100055 PM 7797940 ER PT J AU AKASAKA, T VANLEEUWEN, RL YOSHINAGA, IG MIHM, MC BYERS, HR AF AKASAKA, T VANLEEUWEN, RL YOSHINAGA, IG MIHM, MC BYERS, HR TI FOCAL ADHESION KINASE (P125(FAK)) EXPRESSION CORRELATES WITH MOTILITY OF HUMAN-MELANOMA CELL-LINES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE MIGRATION; ACTIN ID PROTEIN-TYROSINE KINASE; EXTRACELLULAR-MATRIX PROTEINS; SIGNAL TRANSDUCTION; INTEGRIN EXPRESSION; BETA-1 INTEGRINS; PHOSPHORYLATION; MIGRATION; METASTASIS; PP125(FAK); MODULATION AB Focal adhesion kinase (p125(PAK)), a recently characterized protein localized within focal adhesion plaques, is believed to play a role in extracellular matrix-integrin-mediated signal transduction involving cytoskeletal proteins, We studied p125(FAK) expression, distribution, and relation to cell migration in six human melanoma cell. lines. Western blot analysis detected differential expression of p125(FAK) among these lines that was directly proportional to the amount of phosphorylated p125(FAK). Time-lapse image analysis of the cell lines exhibited PO-fold differences in the mean migration rates on fibronectin-coated substrates. Regression analysis revealed that p125(FAK) expression correlated significantly with mean migration rate in the six melanoma lines tested; Double immunofluorescent labeling for p125(FAK) and actin in these lines demonstrated p125(FAK) plaques that were localized to actin stress-fiber termination sites in the periphery of cells. The number of p125(FAK) plaques in the melanoma cell lines was heterogeneous, but the cell lines with more p125(FAK) plaques per cell exhibited significantly higher mean migration rates on fibronectin as compared with cell lines with fewer p125(FAK) plaques per cell. The findings support the hypothesis that focal adhesion tyrosine kinase modulates cytoskeletal function during melanoma cell migration on fibronectin. C1 BOSTON UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02118. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. ALBANY MED COLL,DEPT DERMATOL,ALBANY,NY. FU NCI NIH HHS [CA-45587] NR 31 TC 103 Z9 106 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1995 VL 105 IS 1 BP 104 EP 108 DI 10.1111/1523-1747.ep12313396 PG 5 WC Dermatology SC Dermatology GA RJ632 UT WOS:A1995RJ63200020 PM 7615962 ER PT J AU HANAFIN, NM CHEN, TC HEINRICH, G SEGRE, GV HOLICK, MF AF HANAFIN, NM CHEN, TC HEINRICH, G SEGRE, GV HOLICK, MF TI CULTURED HUMAN FIBROBLASTS AND NOT CULTURED HUMAN KERATINOCYTES EXPRESS A PTH/PTHRP RECEPTOR MESSENGER-RNA SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE CAMP; NESTED PCR/3T3 FIBROBLASTS ID HUMAN EPIDERMAL-KERATINOCYTES; POLYMERASE CHAIN-REACTION; HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; BONE-RESORPTION; PROTEIN; CELLS; HYPERCALCEMIA; ACIDS; SKIN AB There is increasing evidence that parathyroid hormone (PTH) and PTH-related peptides (PTHrP) are involved in normal skin cell growth; therefore, we investigated whether the PTH/PTHrP receptor was expressed in cultured human keratinocytes and dermal fibroblasts, Northern analyses of poly (A)(+) RNA isolated from cultured fibroblasts revealed two PTH/PTHrP receptor transcripts with one major band at 2.5 kb and one minor band at 2.3 kb. These transcripts were consistent with those found in human osteosarcoma cells, which are known to express PTH/PTHrP-R mRNAs, In contrast, after repeated Northern analyses no PTH/PTHrP receptor transcripts were found in poly (A)(+) RNA isolated from cultured keratinocytes. Reverse-transcriptase/nested polymerase chain reaction analyses of total RNA isolated from cultured keratinocytes and fibroblasts confirmed the Northern analyses data that the PTH/PTHrP receptor was expressed in cultured fibroblasts but nor in cultured keratinocytes. When cultured fibroblasts and keratinocytes were exposed to 10(-7) M PTH (1-34) there was a twofold increase in cAMP levels in the fibroblasts and no demonstrable increase was noted in keratinocytes. These results suggest that skin fibroblasts possess the classical PTH/PTHrP receptor and are target cells for PTH and PTHrP whereas keratinocytes do not have the receptor and are unresponsive to its N-terminal agonist in the stimulation of cAMP formation. C1 BOSTON UNIV,MED CTR,DEPT MED,VITAMIN D SKIN & BONE RES LAB,ENDOCRINOL SECT,BOSTON,MA 02118. BOSTON UNIV,MED CTR,DEPT MED,MOLEC MED SECT,BOSTON,MA. BOSTON UNIV,MED CTR,DEPT PHYSIOL,ENDOCRINOL SECT,BOSTON,MA. BOSTON UNIV,MED CTR,DEPT PHYSIOL,MOLEC MED SECT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,ENDOCRINE UNIT,BOSTON,MA. FU NCRR NIH HHS [MO1RR00533]; NIDDK NIH HHS [DK43690] NR 26 TC 33 Z9 33 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1995 VL 105 IS 1 BP 133 EP 137 DI 10.1111/1523-1747.ep12313466 PG 5 WC Dermatology SC Dermatology GA RJ632 UT WOS:A1995RJ63200026 PM 7615967 ER PT J AU SCHAEFER, EJ ROBINS, SJ PATTON, GM SANDBERG, MA WEIGELDIFRANCO, CA ROSNER, B BERSON, EL AF SCHAEFER, EJ ROBINS, SJ PATTON, GM SANDBERG, MA WEIGELDIFRANCO, CA ROSNER, B BERSON, EL TI RED-BLOOD-CELL MEMBRANE PHOSPHATIDYLETHANOLAMINE FATTY-ACID CONTENT IN VARIOUS FORMS OF RETINITIS-PIGMENTOSA SO JOURNAL OF LIPID RESEARCH LA English DT Article DE DOCOSAHEXAENOIC ACID; PLASMALOGEN; DIMETHYL ACETAL ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PLASMA-LIPID ABNORMALITIES; ROD-CONE DEGENERATION; DOCOSAHEXAENOIC ACID; PHOSPHOLIPIDS; OMEGA-3-FATTY-ACIDS; ESSENTIALITY; METABOLISM; INFANTS AB In order to test the hypothesis that retinitis pigmentosa (RP) is associated with fatty acid abnormalities within cell membrane phospholipids, red blood cell membrane (RBC) phosphatidylethanolamine (PE) fatty acid content (% of total fatty acids) was measured using high performance liquid chromatography and capillary column gas chromatography in 155 patients from separate families with different genetic types of RP and 101 normal subjects. After controlling for the effects of age and sex, patients with all genetic forms of RP had significantly (P < 0.001) reduced mean RBC PE 22:6 omega 3 (n-3) (docosahexaenoic acid, DHA) content, and significantly (P < 0.001) elevated mean RBC PE dimethyl acetal (DMA) forms of 16:0, 18:0, and 18:1 omega 9 (n-9) as compared with normal subjects. RBC PE content of 22:5 omega 3 (n-3) (a precursor to DHA) and 18:2 omega 6 (n-6) (the major dietary essential fatty acid) were not significantly different in RP than in controls. Analysis by genetic types of RP showed that the mean RBC PE DHA. percentages were significantly reduced by 24%, 14%, 30%, and 17%, respectively, in dominant, recessive, X-linked, and isolate forms of RP. The relative amounts of plasmalogens as indicated by DMA forms of 16:0 and 18:0 were significantly (P < 0.01) increased in dominant (by 33% and 25%), recessive (by 36% and 25%), and isolate cases (by 32% and 26%) of RP as compared with normal subjects. No such differences were seen in X-linked cases versus controls. Our data indicate that RBC PE DHA content is decreased in all genetic types of RP patients as compared to control subjects, and that RBC PE plasmalogens art increased in dominant, recessive, and isolate forms of RP. These data raise the possibility that membrane phospholipid fatty acid abnormalities may contribute to the pathogenesis of RP. C1 BOSTON UNIV,BOSTON VET ADM HOSP,SCH MED,DEPT MED,LIPID METAB LAB,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA. RP SCHAEFER, EJ (reprint author), TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT MED,LIPID RES LAB,711 WASHINGTON ST,BOSTON,MA 02111, USA. FU NEI NIH HHS [R37EY00169] NR 40 TC 38 Z9 38 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 1995 VL 36 IS 7 BP 1427 EP 1433 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RM890 UT WOS:A1995RM89000002 PM 7595066 ER PT J AU GHAEMI, SN STOLL, AL POPE, H AF GHAEMI, SN STOLL, AL POPE, H TI LACK OF INSIGHT IN BIPOLAR DISORDER - THE ACUTE MANIC EPISODE SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article; Proceedings Paper CT 146th Annual Meeting of the American-Psychiatric-Association CY MAY 22-27, 1993 CL SAN FRANCISCO, CA SP Amer Psychiat Assoc ID SCHIZOPHRENIC-PATIENTS; PSYCHOSIS; ILLNESS AB This study examined the clinical correlates of lack of insight in bipolar disorder. In 28 acutely manic patients interviewed upon hospitalization and/or discharge, mean scores on the Insight and Treatment Attitudes Questionnaire (ITAQ) improved only slightly, from 12.0 on admission to 15.5 on discharge (p = .08), despite marked improvement in other psychiatric symptoms. A reciprocal relationship was found between higher ITAQ scores and involuntary hospitalization (r = -.38). Like schizophrenia, bipolar disorder appears to be a condition in which poor insight is a prominent characteristic. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,PSYCHOPHARMACOL UNIT,BOSTON,MA 02115. MCLEAN HOSP,BIOL PSYCHIAT LAB,BELMONT,MA 02178. MCLEAN HOSP,PSYCHIAT RES LABS,BELMONT,MA 02178. RP GHAEMI, SN (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,WACC-815,15 PARKMAN ST,BOSTON,MA 02114, USA. RI Ghaemi, Nassir/J-4934-2013 NR 26 TC 81 Z9 86 U1 1 U2 3 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 1995 VL 183 IS 7 BP 464 EP 467 DI 10.1097/00005053-199507000-00007 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RK479 UT WOS:A1995RK47900007 PM 7623019 ER PT J AU LEVINE, RL TURSKI, PA GRIST, TM AF LEVINE, RL TURSKI, PA GRIST, TM TI BASILAR ARTERY DOLICHOECTASIA - REVIEW OF THE LITERATURE AND 6 PATIENTS STUDIED WITH MAGNETIC-RESONANCE ANGIOGRAPHY SO JOURNAL OF NEUROIMAGING LA English DT Article ID RESOLUTION COMPUTED-TOMOGRAPHY; VERTEBROBASILAR DOLICHOECTASIA; MEGADOLICHOBASILAR ARTERY; ECTASIA AB Six patients for whom computed tomography revealed a curvilinear calcific mass anterior to their brainstem were evaluated and magnetic resonance imaging and magnetic resonance angiography were performed on each. Magnetic resonance studies confirmed the suspicion of basilar artery dolichoectasia, and demonstrated a partial thrombus in the basilar artery in 1 patient. The patients' clinical features were combined with those of basilar artery dolichoectasia patients reported in the literature (n = 122) who had case histories sufficiently detailed enough to determine each person's mode of clinical presentation. Basilar artery dolichoectasia patients were more often men (95/128, 74%) and had a mean age of 59 +/- 11 years. Of the 128 patients studied, there were cranial nerve compressive signs in 74 (58%), especially facial spasm (29/74, 39%) and trigeminal neuralgia (20/74, 27%); vertebral basilar insufficiency or vertebral basilar stroke or both in 61 (48%); hydrocephalus in 40 (31%); compressive brainstem symptoms and signs that progressed clinically in 31 (24%); and arterial hypertension in 31 (24%). Magnetic resonance imaging and magnetic resonance angiography safely diagnose this interesting arterial abnormality. The modes of clinical presentation of this disorder are reviewed. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT NEUROL,MADISON,WI 53705. UNIV WISCONSIN,SCH MED,MADISON,WI 53705. UNIV WISCONSIN,DEPT RADIOL,MADISON,WI 53706. NR 33 TC 21 Z9 27 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 1995 VL 5 IS 3 BP 164 EP 170 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA RJ936 UT WOS:A1995RJ93600006 PM 7626824 ER PT J AU JAGUST, WJ JOHNSON, KA HOLMAN, BL AF JAGUST, WJ JOHNSON, KA HOLMAN, BL TI SPECT PERFUSION IMAGING IN THE DIAGNOSIS OF DEMENTIA SO JOURNAL OF NEUROIMAGING LA English DT Article ID EMISSION COMPUTED-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; MULTIPLE INFARCT DEMENTIA; MOTOR-NEURON DISEASE; TC-99M HM-PAO; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; CLINICAL-DIAGNOSIS; TECHNETIUM-99M-HMPAO SPECT; NEUROPATHOLOGICAL FINDINGS AB Single-photon emission computed tomography (SPECT) imaging has provided the practicing clinician with a method of studying brain function in patients with dementia. A large and growing number of papers report the experiences of a number of laboratories in the use of this technique in the evaluation of demented patients. Studies from several laboratories comparing patients with Alzheimer's disease to control subjects report sensitivity and specificity of SPECT perfusion imaging to be in the 80% vicinity. In addition, a number of studies suggest that the dementias that show the greatest similarities in perfusion patterns to Alzheimer's disease are multi-infarct dementia and dementia associated with Parkinson's disease. Although considerable data exist to guide the physician, a rigorous scientific approach to studying patients in a prospective, unselected clinical sample, with autopsy confirmation of the diagnosis, is needed to define dearly the utility of the technique in diagnosing dementias. C1 UNIV CALIF DAVIS,DEPT NEUROL,DAVIS,CA 95616. UNIV CALIF DAVIS,CTR ALZHEIMERS DIS,DAVIS,CA 95616. UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,CTR FUNCT IMAGING,BERKELEY,CA 94720. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. FU NIA NIH HHS [P30 AG10129, AG07793] NR 57 TC 12 Z9 12 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 1995 VL 5 SU 1 BP S45 EP S52 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA RK853 UT WOS:A1995RK85300007 PM 7626837 ER PT J AU SEGAL, RA POMEROY, SL STILES, CD AF SEGAL, RA POMEROY, SL STILES, CD TI AXONAL GROWTH AND FASCICULATION LINKED TO DIFFERENTIAL EXPRESSION OF BDNF AND NT3 RECEPTORS IN DEVELOPING CEREBELLAR GRANULE CELLS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE CEREBELLUM; GRANULE CELLS; NEUROTROPHINS; AXON OUTGROWTH; FASCICULATION; RECEPTOR TYROSINE KINASE ID CENTRAL-NERVOUS-SYSTEM; NEUROTROPHIC FACTOR; SENSORY NEURONS; MESSENGER-RNA; NGF RECEPTOR; POSTNATAL-DEVELOPMENT; NEURITE OUTGROWTH; TYROSINE KINASE; ADULT-MOUSE; TRK FAMILY AB In the developing cerebellum, young granule neurons in the external germinal layer respond preferentially to BDNF, while mature neurons within the inner portion of the cerebellum respond preferentially to NT3. Here we show that this anatomic distinction reflects a developmentally regulated switch at the level of neurotrophin receptor gene expression. The salient feature of the developmental switch is a change in the ratio of mRNA transcripts encoding functional BDNF and NT3 receptor tyrosine kinases. The ratio of the BDNF receptor trkB to the NT3 receptor trkC reverses from 5:1 in neonatal cerebellum to 1:3 in adult cerebellum. TrkB and TrkC are closely related transmembrane tyrosine protein kinases. However, activation of BDNF and NT3 receptors in cerebellar granule neurons do not give equivalent biological responses. In aggregate cell culture and single cell assays, BDNF enhances axonal outgrowth of early granule cells by influencing neurite elongation. In contrast, NT3 alters the morphology of outgrowth. Collectively, these findings suggest that regulation of neurotrophin receptors during cerebellar development is important for the timing and morphology of axonal growth. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DANA FARBER CANC INST,DEPT CELL & MOLEC BIOL,BOSTON,MA 02115. FU NICHD NIH HHS [HD 24926]; NIGMS NIH HHS [GM 31489]; NINDS NIH HHS [NS27773] NR 68 TC 169 Z9 170 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 PY 1995 VL 15 IS 7 BP 4970 EP 4981 PN 1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA RJ662 UT WOS:A1995RJ66200022 PM 7623126 ER PT J AU LANDWEHRMEYER, GB STANDAERT, DG TESTA, CM PENNEY, JB YOUNG, AB AF LANDWEHRMEYER, GB STANDAERT, DG TESTA, CM PENNEY, JB YOUNG, AB TI NMDA RECEPTOR SUBUNIT MESSENGER-RNA EXPRESSION BY PROJECTION NEURONS AND INTERNEURONS IN RAT STRIATUM SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NMDA; RECEPTOR SUBTYPES; ACETYLCHOLINE; ENKEPHALIN; SOMATOSTATIN; IN SITU HYBRIDIZATION; DOUBLE LABEL; STRIATUM; CEREBRAL CORTEX ID INSITU HYBRIDIZATION HISTOCHEMISTRY; CENTRAL-NERVOUS-SYSTEM; PROTEIN-KINASE-C; QUINOLINIC ACID LESIONS; D-ASPARTATE RECEPTORS; BASAL GANGLIA; HUNTINGTONS-DISEASE; NEUROPEPTIDE-Y; MESSENGER-RNA; CHOLINERGIC NEURONS AB N-Methyl-D-aspartate (NMDA) receptors are enriched in the neostriatum and are thought to mediate several actions of glutamate including neuronal excitability, long-term synaptic plasticity, and excitotoxic injury, NMDA receptors are assembled from several subunits (NMDAR1, NMDAR2A-D) encoded by five genes; alternative splicing gives rise to eight isoforms of subunit NMDAR1, We studied the expression of NMDA receptor subunits in neurochemically identified striatal neurons of adult rats by in situ hybridization histochemistry using a double-labeling technique, Enkephalin-positive projection neurons, somatostatin-positive interneurons, and cholinergic interneurons each have distinct NMDA receptor subunit phenotypes, Both populations of striatal interneurons examined express lower levels of NMDAR1 and NMDAR2B subunit mRNA than enkephalin-positive neurons, The three striatal cell populations differ also in the presence of markers for alternatively spliced regions of NMDAR1, suggesting that interneurons preferentially express NMDAR1 splice forms lacking one (cholinergic neurons) or both (somatostatin-positive neurons) alternatively spliced carboxy-terminal regions, In addition, somatostatin- and cholinergic-, but not enkephalin-positive neurons express NMDAR2D mRNA, Thus, these striatal cell populations express different NMDAR-subunit mRNA phenotypes and therefore are likely to display NMDA channels with distinct pharmacological and physiological properties, Differences in NMDA receptor expression may contribute to the relative resistance of striatal interneurons to the neurotoxic effect of NMDA receptor agonists. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. FU NIA NIH HHS [AG11337]; NIMH NIH HHS [MH10701-01]; NINDS NIH HHS [NS31579] NR 78 TC 240 Z9 243 U1 1 U2 1 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 PY 1995 VL 15 IS 7 BP 5297 EP 5307 PN 2 PG 11 WC Neurosciences SC Neurosciences & Neurology GA RJ666 UT WOS:A1995RJ66600018 PM 7623152 ER PT J AU ALRODHAN, NRF AF ALRODHAN, NRF TI OCCLUSIVE HYPEREMIA REMAINS THE MOST LOGICAL EXPLANATION FOR THE HEMODYNAMIC COMPLICATIONS OF RESECTED INTRACEREBRAL ARTERIOVENOUS-MALFORMATIONS SO JOURNAL OF NEUROSURGICAL ANESTHESIOLOGY LA English DT Editorial Material C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG NEUROSURG,MOLEC NEUROGENET UNIT,BOSTON,MA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0898-4921 J9 J NEUROSURG ANESTH JI J. Neurosurg. Anesthesiol. PD JUL PY 1995 VL 7 IS 3 BP 208 EP 210 DI 10.1097/00008506-199507000-00019 PG 3 WC Anesthesiology; Clinical Neurology; Surgery SC Anesthesiology; Neurosciences & Neurology; Surgery GA RE641 UT WOS:A1995RE64100009 PM 7549373 ER PT J AU TYC, VL MULHERN, RK JAYAWARDENE, D FAIRCLOUGH, D AF TYC, VL MULHERN, RK JAYAWARDENE, D FAIRCLOUGH, D TI CHEMOTHERAPY-INDUCED NAUSEA AND EMESIS IN PEDIATRIC CANCER-PATIENTS - AN ANALYSIS OF COPING STRATEGIES SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE CHEMOTHERAPY; DISTRESS; COPING; NAUSEA; EMESIS; PEDIATRIC ONCOLOGY ID MEDICAL PROCEDURES; BEHAVIORAL INTERVENTIONS; RECEIVING CHEMOTHERAPY; DEVELOPMENTAL-CHANGES; ANTICIPATORY NAUSEA; CHILDREN; ADOLESCENTS; STRESSFUL; DISTRESS; PARENT AB We investigated the preference and perceived efficacy of coping strategies used to manage chemotherapy-induced nausea and emesis in 57 pediatric oncology patients. Over 85% of children preferred ''Wishful Thinking,'' ''Emotional Regulation,'' and ''Distraction'' to cope with nausea and ''Emotional Regulation'' to manage emesis. Stepwise logistic regression analyses revealed that the coping strategy used and its perceived efficacy depended upon patient age and gender; severity of symptom distress, time elapsed from last chemotherapy, experience and whether nausea or emesis was the identified problem. Successful copers, defined as those reporting high coping efficacy and minimal distress, composed only 25% of the sample These children most often used ''Problem Solving'' combined with ''Social Support'' for symptom management. Successful coping was also associated with lower emetogenic potential of chemotherapy. The significance of these results is discussed for identifying high-risk children who may benefit from coping interventions. C1 UNIV TENNESSEE, SCH MED, DEPT PEDIAT, MEMPHIS, TN USA. ST JUDE CHILDRENS RES HOSP, DEPT BIOSTAT, BOSTON, MA USA. DANA FARBER CANC INST, DEPT BIOSTAT, BOSTON, MA USA. RP TYC, VL (reprint author), ST JUDE CHILDRENS RES HOSP, DIV PSYCHOL, 332 N LAUDERDALE, MEMPHIS, TN 38101 USA. FU NCI NIH HHS [CA 23099, CA 21765] NR 32 TC 27 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 1995 VL 10 IS 5 BP 338 EP 347 DI 10.1016/0885-3924(95)00019-U PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA RK911 UT WOS:A1995RK91100003 PM 7673766 ER PT J AU MOSER, AB RASMUSSEN, M NAIDU, S WATKINS, PA MCGUINNESS, M HAJRA, AK CHEN, G RAYMOND, G LIU, A GORDON, D GARNAAS, K WALTON, DS SKJELDAL, OH GUGGENHEIM, MA JACKSON, LG ELIAS, ER MOSER, HW AF MOSER, AB RASMUSSEN, M NAIDU, S WATKINS, PA MCGUINNESS, M HAJRA, AK CHEN, G RAYMOND, G LIU, A GORDON, D GARNAAS, K WALTON, DS SKJELDAL, OH GUGGENHEIM, MA JACKSON, LG ELIAS, ER MOSER, HW TI PHENOTYPE OF PATIENTS WITH PEROXISOMAL DISORDERS SUBDIVIDED INTO 16 COMPLEMENTATION GROUPS SO JOURNAL OF PEDIATRICS LA English DT Article ID CEREBROHEPATORENAL ZELLWEGER SYNDROME; CHAIN FATTY-ACIDS; NEONATAL ADRENOLEUKODYSTROPHY; BETA-OXIDATION; CHONDRODYSPLASIA PUNCTATA; DEFICIENT DISORDERS; PRENATAL-DIAGNOSIS; TARGETING SIGNAL; MEMBRANE-PROTEIN; HETEROGENEITY AB Objective: To use the technique of complementation analysis to help define genotype and classify patients with clinical manifestations consistent with those of the disorders of peroxisome assembly, namely the Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and rhizomelic chondrodysplasia punctata (RCDP). Study design: Clinical findings, peroxisomal function, and complementation groups were examined in 173 patients with the clinical manifestations of these disorders. Results: In 37 patients (21%), peroxisome assembly was intact and isolated deficiencies of one of five peroxisomal enzymes involved in the beta-oxidation of fatty acids or plasmalogen biosynthesis were demonstrated. Ten complementation groups were identified among 93 patients (54%) with impaired peroxisome assembly and one of three phenotypes (ZS, NALD, or IRD) without correlation between complementation group and phenotype. Forty-three patients (25%) had impaired peroxisome assembly associated with the RCDP phenotype and belonged to a single complementation group, Of the 173 patients, 10 had unusually mild clinical manifestations, including survival to the fifth decade or deficits limited to congenital cataracts. Conclusions: At least 16 complementation groups, and hence genotypes, are associated with clinical manifestations of disorders of peroxisome assembly. The range of phenotype is wide, and some patients have mild involvement. C1 JOHNS HOPKINS UNIV, DEPT NEUROL, BALTIMORE, MD 21218 USA. JOHNS HOPKINS UNIV, DEPT PEDIAT, BALTIMORE, MD 21218 USA. UNIV MICHIGAN, NEUROSCI LAB, ANN ARBOR, MI 48104 USA. UNIV MICHIGAN, DEPT NEUROL, ANN ARBOR, MI 48104 USA. MASSACHUSETTS EYE & EAR INFIRM, BOSTON, MA 02114 USA. PEDIAT NEUROL SERV, HELENA, MT USA. THOMAS JEFFERSON UNIV, JEFFERSON MED COLL, DEPT MED GENET, PHILADELPHIA, PA 19107 USA. TUFTS UNIV NEW ENGLAND MED CTR, DIV CLIN GENET, BOSTON, MA 02111 USA. UNIV OSLO, RIKSHOSP, DEPT PEDIAT, N-0027 OSLO, NORWAY. BERG GAARD CENT INST HABILITERING, OSLO, NORWAY. FU NCRR NIH HHS [RR00052, RR00722]; NICHD NIH HHS [HD10981] NR 57 TC 181 Z9 183 U1 3 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 1995 VL 127 IS 1 BP 13 EP 22 DI 10.1016/S0022-3476(95)70250-4 PG 10 WC Pediatrics SC Pediatrics GA RH637 UT WOS:A1995RH63700002 PM 7541833 ER PT J AU CHANG, TKH CHEN, G WAXMAN, DJ AF CHANG, TKH CHEN, G WAXMAN, DJ TI MODULATION OF THIOTEPA ANTITUMOR-ACTIVITY IN-VIVO BY ALTERATION OF LIVER CYTOCHROME P450-CATALYZED DRUG-METABOLISM SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HIGH-DOSE THIOTEPA; PHASE-I; EXPERIMENTAL CHEMOTHERAPY; HUMAN MEDULLOBLASTOMA; ALKYLATING ACTIVITY; OVARIAN-CANCER; N,N',N''-TRIETHYLENETHIOPHOSPHORAMIDE; TEPA; PHARMACOKINETICS; N,N',N''-TRIETHYLENEPHOSPHORAMIDE AB The anticancer drug and alkylating agent thiotepa is metabolized by oxidative desulfuration to yield the alkylating metabolite N,N',N ''-triethylenephosphoramide (TEPA) in a reaction that is catalyzed by specific liver cytochrome P450 (CYP) enzymes, including CYP2B1, the major phenobarbital-inducible P450 of rat liver, and CYP2C11, a constitutively expressed, male-specific form. The present study investigates the potential for modulating the cytotoxicity and antitumor activity of thiotepa by prior treatment of tumor-bearing rats with the CYP2B1 inducer phenobarbital or the CYP2C11 inhibitor 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF-525A) and examines the role of TEPA in the cytotoxicity of thiotepa in vivo. Administration of thiotepa to adult male rats bearing 9L gliosarcoma, grown s.c., resulted in dose-dependent cytotoxicity (ED(90) similar to 12 mg/kg i.v., single dose), as determined by a tumor excision/in vitro colony formation assay carried out 24 hr after drug treatment. Tumor growth delay experiments revealed that thiotepa (5 mg/kg) inhibited 9L tumor growth over a 5- to 7-day period after alkylating agent treatment and this effect was accompanied by moderate body weight loss. Pretreatment with phenobarbital, under conditions in which liver CYP2B1 levels and liver microsomal thiotepa desulfuration to yield TEPA are both markedly increased, did not alter thiotepa's short-term (24-hr) cytotoxicity, as judged by a tumor excision assay, nor did it affect the extent of bone marrow toxicity associated with drug treatment. However, phenobarbital did block the tumor growth delay effect of thiotepa and it also attenuated the body weight loss that occurred during the first 5 days after drug treatment. In contrast, pretreatment with the liver P450 inhibitor 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (40 mg/kg i.p. given 1 hr before thiotepa) inhibited thiotepa elimination in vivo and enhanced the antitumor activity of thiotepa but this was accompanied by increased body weight loss and some lethality. These findings demonstrate that alterations in the in vivo antitumor activity and host toxicity of thiotepa can be achieved by modulation of hepatic CYP-dependent thiotepa metabolism and suggest that thiotepa may be more toxic toward this tumor in vivo than TEPA or other metabolites formed by the oxidative desulfuration pathway. C1 BOSTON UNIV,DEPT BIOL,DIV CELL & MOLEC BIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA-49248] NR 41 TC 32 Z9 34 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1995 VL 274 IS 1 BP 270 EP 275 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RJ364 UT WOS:A1995RJ36400038 PM 7616408 ER PT J AU ATKINSON, SE WILSON, PW AF ATKINSON, SE WILSON, PW TI COMPARING MEAN EFFICIENCY AND PRODUCTIVITY SCORES FROM SMALL SAMPLES - A BOOTSTRAP METHODOLOGY SO JOURNAL OF PRODUCTIVITY ANALYSIS LA English DT Article DE BOOTSTRAP; DATA ENVELOPMENT ANALYSIS; FIXED AND RANDOM EFFECTS; MALMQUIST INDEX; PRODUCTIVITY MEASUREMENT; SMALL SAMPLE; PANEL DATA ID CONFIDENCE-INTERVALS; PANEL DATA AB This paper provides a bootstrap methodology for constructing confidence intervals for means of DEA and econometrically estimated efficiency scores, Malmquist productivity indices, and other similar measures in small samples. The procedure is nonparametric since no distributional assumptions are required. An empirical example is provided. C1 UNIV TEXAS,DEPT ECON,AUSTIN,TX 78712. US DEPT VET AFFAIRS,MANAGEMENT SCI GRP,BEDFORD,MA 01730. RP ATKINSON, SE (reprint author), UNIV GEORGIA,DEPT ECON,ATHENS,GA 30602, USA. NR 25 TC 49 Z9 49 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0895-562X J9 J PROD ANAL JI J. Prod. Anal. PD JUL PY 1995 VL 6 IS 2 BP 137 EP 152 DI 10.1007/BF01073408 PG 16 WC Business; Economics; Social Sciences, Mathematical Methods SC Business & Economics; Mathematical Methods In Social Sciences GA RL083 UT WOS:A1995RL08300003 ER PT J AU TALAMO, JH SIEBERT, K WAGONER, MD YEH, E TELFAIR, W PENDER, P COZEAN, C KENYON, KR MILLER, D FOSTER, CS SPIGELMAN, A ALBERT, W DINGELDEIN, S ISBEY, E UGLAND, D JOINER, S KANE, D SIEPSER, S PIEBENGA, L MATTA, C DEITZ, M TAUBER, J DUDLEY, S ALEXANDER, AD ROWSEY, JJ AF TALAMO, JH SIEBERT, K WAGONER, MD YEH, E TELFAIR, W PENDER, P COZEAN, C KENYON, KR MILLER, D FOSTER, CS SPIGELMAN, A ALBERT, W DINGELDEIN, S ISBEY, E UGLAND, D JOINER, S KANE, D SIEPSER, S PIEBENGA, L MATTA, C DEITZ, M TAUBER, J DUDLEY, S ALEXANDER, AD ROWSEY, JJ TI MULTICENTER STUDY OF PHOTOREFRACTIVE KERATECTOMY FOR MYOPIA OF 6.00 TO 8.00 DIOPTERS SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article ID EXCIMER-LASER; SIGHTED EYES; FOLLOW-UP AB PURPOSE: To summarize the initial results of excimer laser photorefractive keratectomy (PRK) on 89 eyes of 80 patients with moderate myopia (myopia of - 6.00 to - 8.00 diopters [D]; mean - 6.98 +/- 0.90 D) at nine investigational sites. METHODS: All treatments used an argon fluoride excimer laser (VISX, Inc, Santa Clara, Calif) using standard settings. Sixty eyes received single-zone 6.0-millimeter ablations and 29 eyes received two-zone ablations. Follow up ranged from 1 month (n = 89) to 6 months (n = 46). RESULTS: At 3 months, uncorrected visual acuity measured 20/40 or better in 75% and 20/20 or better in 18%; 78% were within +/- 1.00 D of intended correction, 38% were within +/- 0.50 D, and 9% lost two or more lines of spectacle-corrected visual acuity. At 6 months, uncorrected visual acuity measured 20/40 or better in 74% and 20/20 or better in 17%; 67% were within 1.00 D of intended correction, 38% within 0.50 D, and 2% (1/46) lost two lines of spectacle corrected visual acuity. CONCLUSIONS: PRK for moderate myopia with large diameter ablation zones appears safe and more predictable than that done using smaller ablation zone diameters. Longer follow up is needed to better define stability, the effects of postoperative corticosteroids, and the use of single- versus double-zone ablations. C1 CATHOLIC MED CTR,MANCHESTER,NH. SINAI HOSP DETROIT,DETROIT,MI. CAROLINA EXCIMER GRP,GREENSBORO,NC. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,WILLS EYE HOSP,PHILADELPHIA,PA 19107. UNIV MISSOURI,EYE FDN,KANSAS CITY,MO 64110. EYE CLIN FOX VALLEY,OSHKOSH,WI. UNIV S FLORIDA,TAMPA,FL. RP TALAMO, JH (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,KERATOREFRACT SURG UNIT,243 CHARLES ST,BOSTON,MA 02114, USA. NR 16 TC 12 Z9 12 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0883-0444 J9 J REFRACT SURG JI J. Refractive Surg. PD JUL-AUG PY 1995 VL 11 IS 4 BP 238 EP 247 PG 10 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA RK574 UT WOS:A1995RK57400005 PM 7496979 ER PT J AU BOHN, MJ BABOR, TF KRANZLER, HR AF BOHN, MJ BABOR, TF KRANZLER, HR TI THE ALCOHOL-USE DISORDERS IDENTIFICATION TEST (AUDIT) - VALIDATION OF A SCREENING INSTRUMENT FOR USE IN MEDICAL SETTINGS SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID COLLABORATIVE PROJECT; CAGE QUESTIONNAIRE; CONSUMPTION; INDICATORS; DIAGNOSIS; DRINKING; SAMPLE AB Objective: The concurrent, construct, and discriminant validity of the Alcohol Use Disorders Identification Test (AUDIT) were evaluated. AUDIT consists of a 10-item Core questionnaire and an 8-item Clinical procedure. AUDIT was designed to identify hazardous drinkers (whose drinking increases their risk of alcohol-related problems, though alcohol-associated harm has not yet occurred); harmful drinkers (who have had recent physical or mental harm from their drinking, but who are not alcohol-dependent); and people with alcohol dependence. Method: Known alcoholics (n = 65) and general medical patients (n = 187) completed self-report questionnaires and underwent a diagnostic interview, physical examination and laboratory testing. Results: AUDIT scores correlated significantly with scores on the MAST and MacAndrew alcoholism screening tests, and with ALAT, ASAT, GGT and MCV levels, which reflect recent heavy drinking. AUDIT scores were correlated with measures of alcoholism vulnerability (e.g., familial alcoholism and sociopathy), and with somatic and affective consequences of drinking. Receiver operating characteristic and discriminant function analyses indicated that the AUDIT Core and Clinical Instruments were sensitive and specific in discriminating alcoholics from medical patients, most of whom were nonalcoholics. The AUDIT Core was superior to the MAST and the AUDIT Clinical in discriminating hazardous drinkers from nonhazardous drinkers. It was also superior to the AUDIT Clinical in discriminating harmful from nonharmful drinkers. Conclusions: The AUDIT Core Instrument is useful for early detection of hazardous or harmful drinking, while the AUDIT Clinical Instrument is better applied to identification and/or confirmation of cases of alcohol dependence. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. RP BOHN, MJ (reprint author), UNIV WISCONSIN,SCH MED,CTR CLIN SCI,DEPT PSYCHIAT,B6-210,MADISON,WI 53792, USA. FU NIAAA NIH HHS [R29-AA09948, P50-AA03510, T32-AA07290] NR 45 TC 423 Z9 433 U1 3 U2 18 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD JUL PY 1995 VL 56 IS 4 BP 423 EP 432 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA RF318 UT WOS:A1995RF31800009 PM 7674678 ER PT J AU ABCOUWER, SF BODE, BP SOUBA, WW AF ABCOUWER, SF BODE, BP SOUBA, WW TI GLUCOCORTICOIDS REGULATE RAT GLUTAMINE-SYNTHETASE EXPRESSION IN A TISSUE-SPECIFIC MANNER SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 16-19, 1994 CL ALBUQUERQUE, NM SP Assoc Acad Surg ID SKELETAL-MUSCLE; TREATED RATS; METABOLISM; GENE; ENDOTOXEMIA; LUNGS; RNA AB During stress states, organismal glutamine production is augmented secondary to an increase in the activity of glutamine synthetase (GS) in the lung and skeletal muscle. Because glucocorticoids are key regulators of the metabolic response to stress, we undertook a survey of glucocorticoid induction of GS expression in rat organs in response to dexamethasone. Male adult rats were injected with glucocorticoid or vehicle and 4 hr later, 10 organs were assayed for GS messenger RNA and protein contents by Northern and Western blotting. We observed a 20-fold range of GS mRNA levels in organs of control animals. Blotting detected two GS RNA species of approximately 2.8- and 1.4-kb sizes in all tissue except testis, where an additional 2-kb RNA species was observed, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were also assayed and used as a normalization factor. An approximately 10-fold range of GAPDH mRNA levels was observed. Four hours after dexamethasone injection, a nearly a 5-fold increase in glutamine synthetase mRNA levels in lung and muscle, as well as an approximately a-fold increase in heart were observed. Relative to GAPDH mRNA, a significant decrease in GS mRNA levels was observed in the liver. A wide range of glutamine synthetase protein contents were observed in rat organs. Comparison of Northern and Western blotting results revealed a dichotomy in the ratio of relative GS mRNA and protein level in rat organs, suggesting that tissue-specific posttranscriptional processes determine GS protein levels. Four hours after dexamethasone injection, an apparent increase in GS protein was observed in the lung, muscle, and thymus; however, significant induction of GS protein was demonstrated only in lung. The differential response of GS mRNA and protein levels to dexamethasone suggests that GS expression is induced by glucocorticoids in a tissue-specific manner. (C) 1995 Academic Press, Inc. RP ABCOUWER, SF (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114, USA. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NHLBI NIH HHS [R01 HL44986] NR 26 TC 48 Z9 51 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL PY 1995 VL 59 IS 1 BP 59 EP 65 DI 10.1006/jsre.1995.1132 PG 7 WC Surgery SC Surgery GA RM456 UT WOS:A1995RM45600010 PM 7630137 ER PT J AU WOZNIAK, J BIEDERMAN, J KIELY, K ABLON, JS FARONE, SV MUNDY, E MENNIN, D AF WOZNIAK, J BIEDERMAN, J KIELY, K ABLON, JS FARONE, SV MUNDY, E MENNIN, D TI MANIA-LIKE SYMPTOMS SUGGESTIVE OF CHILDHOOD-ONSET BIPOLAR DISORDER IN CLINICALLY REFERRED CHILDREN SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE BIPOLAR DISORDER; ATTENTION-DEFICIT HYPERACTIVITY DISORDER; COMORBIDITY; CHILDREN ID DEFICIT HYPERACTIVITY DISORDER; DEPRESSIVE VARIANT SYNDROME; THERAPEUTIC CONSIDERATIONS; PREPUBERTAL CHILDREN; RISK-FACTORS; ADOLESCENT; ILLNESS; PARENTS; SCHIZOPHRENIA; COMORBIDITY AB Objective: To examine the prevalence, characteristics, and correlates of mania among referred children aged 12 or younger. Many case reports challenge the widely accepted belief that childhood-onset mania is rare. Sources of diagnostic confusion include the variable developmental expression of mania and its symptomatic overlap with attention-deficit hyperactivity disorder (ADHD). Method: The authors compared 43 children aged 12 years or younger who satisfied criteria for mania, 164 ADHD children without mania, and 84 non-ADHD control children. Results: The clinical picture was fully compatible with the DSM-III-R diagnosis of mania in 16% (n = 43) of referred children. All but one of the children meeting criteria for mania also met criteria for ADHD. Compared with ADHD children without mania, manic children had significantly higher rates of major depression, psychosis, multiple anxiety disorders, conduct disorder, and oppositional defiant disorder as well as evidence of significantly more impaired psychosocial functioning. In addition, 21% (n = 9) of manic children had had at least one previous psychiatric hospitalization. Conclusions: Mania may be relatively common among psychiatrically referred children. The clinical picture of childhood-onset mania is very severe and frequently comorbid with ADHD and other psychiatric disorders. Because of the high comorbidity with ADHD, more work is needed to clarify whether these children have ADHD, bipolar disorder, or both. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. RP WOZNIAK, J (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,ACC 725,FRUIT ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07, R01 MH50657-02] NR 51 TC 482 Z9 488 U1 1 U2 19 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 1995 VL 34 IS 7 BP 867 EP 876 DI 10.1097/00004583-199507000-00010 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RG091 UT WOS:A1995RG09100010 PM 7649957 ER PT J AU ARBISER, JL AF ARBISER, JL TI GENETIC IMMUNODEFICIENCIES - CUTANEOUS MANIFESTATIONS AND RECENT PROGRESS SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID CHRONIC GRANULOMATOUS-DISEASE; X-CHROMOSOME INACTIVATION; CHEDIAK-HIGASHI-SYNDROME; WISKOTT-ALDRICH SYNDROME; HYPER-IGM SYNDROME; LIGASE-I GENE; ATAXIA-TELANGIECTASIA; MYELOPEROXIDASE DEFICIENCY; CD40 LIGAND; INTERFERON-GAMMA AB In recent years, remarkable progress has been made in elucidating the pathophysiology of genetic immunodeficiency disorders. Dermatologic manifestations are prominent in these conditions; because of advances in diagnosis and therapy, patients are living longer, increasing the likelihood that dermatologists will encounter patients with these diseases. The genes of many of these disorders have been cloned, including chronic granulomatous disease, X-linked immunodeficiencies, and myeloperoxidase deficiency. Understanding the regulation and function of these genes will not only affect patients with these rare disorders, but may provide an insight into common dermatologic conditions, such as eczema and cutaneous infection. Diagnosis, dermatologic manifestations, and therapy are discussed. C1 HARVARD UNIV,SCH MED,BOSTON,MA. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA. RP ARBISER, JL (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,ACC 489,BOSTON,MA 02114, USA. NR 73 TC 16 Z9 18 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 1995 VL 33 IS 1 BP 82 EP 89 DI 10.1016/0190-9622(95)90016-0 PG 8 WC Dermatology SC Dermatology GA RG223 UT WOS:A1995RG22300014 PM 7601952 ER PT J AU MCDOUGAL, WS AF MCDOUGAL, WS TI THE VESICAL BLOOD-URINE BARRIER - A RELEVANT AND DYNAMIC INTERFACE BETWEEN RENAL-FUNCTION AND NERVOUS BLADDER CONTROL - COMMENT SO JOURNAL OF UROLOGY LA English DT Note RP MCDOUGAL, WS (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,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 1995 VL 154 IS 1 BP 15 EP 15 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RB819 UT WOS:A1995RB81900003 ER PT J AU CAYROL, C FLEMINGTON, EK AF CAYROL, C FLEMINGTON, EK TI IDENTIFICATION OF CELLULAR TARGET GENES OF THE EPSTEIN-BARR-VIRUS TRANSACTIVATOR ZTA - ACTIVATION OF TRANSFORMING GROWTH-FACTOR BETA-IGH3 (TGF-BETA-IGH3) AND TGF-BETA-1 SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-BINDING SPECIFICITY; ORAL HAIRY LEUKOPLAKIA; FACTOR-BETA; BZLF1 PROTEIN; DIMERIZATION DOMAIN; FACTOR-BETA-1 GENE; IMMUNOGLOBULIN-A; LEUCINE ZIPPER; LYMPHOID-CELLS; C-FOS AB The lytic switch transactivator Zta initiates the ordered cascade of Epstein-Barr virus gene expression that culminates in virus production, Zta is a sequence-specific DNA-binding protein that transactivates early viral promoters via cis-acting sequences. Activation of some of these genes is mediated through binding to consensus AP-1 promoter elements. This observation suggests that Zta may also regulate the expression of cellular genes. While many targets of Zta have been identified in the Epstein-Barr virus genome, putative host cell targets remain largely unknown. To address this issue, a tetracycline-regulated Zta expression system was generated, and differential hybridization screening was used to isolate Zta-responsive cellular genes, The major target identified by this analysis is a gene encoding a fasciclin-like secreted factor, transforming growth factor beta igh3 (TGF beta igh3), that was originally identified as a gene that is responsive to the potent immunosuppressor TGF-beta 1. Northern (RNA) blot analysis demonstrated that induction of Zta expression results in a 10-fold increase in TGF-beta igh3 mRNA levels. Zta was also found to increase TGF-beta 1 mRNA levels as well as the amount of active TGF-beta 1 secreted into the medium, Interestingly, alpha 1-collagen IV, which has been shown to potentiate the effects of TGF-beta 1, is also a cellular target of Zta, These results suggest that Zta could play a role in modulating the host cell environment through activating the expression of secreted factors. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. RI CAYROL, Corinne/C-2106-2011 FU NCI NIH HHS [CA 47554]; NIGMS NIH HHS [R29 GM48045] NR 56 TC 73 Z9 75 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 JUL PY 1995 VL 69 IS 7 BP 4206 EP 4212 PG 7 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600032 PM 7769680 ER PT J AU SULLIVAN, N SUN, Y LI, J HOFMANN, W SODROSKI, J AF SULLIVAN, N SUN, Y LI, J HOFMANN, W SODROSKI, J TI REPLICATIVE FUNCTION AND NEUTRALIZATION SENSITIVITY OF ENVELOPE GLYCOPROTEINS FROM PRIMARY AND T-CELL LINE-PASSAGED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; HUMAN MONOCLONAL-ANTIBODY; SOLUBLE CD4; MOLECULAR CHARACTERIZATION; GP120-CD4 BINDING; PLASMA VIREMIA; SYNDROME AIDS; INFECTION; HIV-1; IDENTIFICATION AB The structure, replicative properties, and sensitivity to neutralization by soluble CD4 and monoclonal antibodies were examined for molecularly cloned envelope glycoproteins derived from human immunodeficiency virus type 1 (HIV-1) viruses either isolated directly from patients or passaged in T-cell lines. Complementation of virus entry into peripheral blood mononuclear cell targets by primary patient envelope glycoproteins exhibited efficiencies ranging from that observed for the HXBc2 envelope glycoproteins, which are derived from a T-cell line-passaged virus, to approximately fivefold-lower values. The ability of the envelope glycoproteins to complement virus entry roughly correlated,vith sensitivity to neutralization by soluble CD4. Laboratory adapted viruses were sensitive to neutralization by monoclonal antibodies directed against the CD4-binding site and the third variable (V3) loop of the gp120 glycoprotein. By comparison, viruses with envelope glycoproteins from primary patient isolates exhibited decreased sensitivity to neutralization by these monoclonal antibodies; for these viruses, neutralization sensitivity correlated with replicative ability. Subinhibitory concentrations of soluble CD4 and a CD4-binding site-directed antibody significantly enhanced the entry of viruses containing envelope glycoproteins from some primary patient isolates. The sensitivity of viruses containing the different envelope glycoproteins to neutralization by soluble CD4 or monoclonal antibodies could be predicted by assays dependent on the binding of the inhibitory molecule to the oligomeric envelope glycoprotein complex but less well by assays measuring binding to the monomeric gp120 glycoprotein. These results indicate that the intrinsic structure of the oligomeric envelope glycoprotein complex of primary HIV-1 isolates, while often less than optimal with respect to the mediation of early events in virus replication, allows a relative degree of resistance to neutralizing antibodies. The interplay of selective forces for higher virus replication efficiency and resistance to neutralizing antibodies could explain the temporal course described for the in vivo emergence of HIV-1 isolates with differing phenotypes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,JIMMY FUND 824,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. NR 67 TC 270 Z9 271 U1 0 U2 1 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 JUL PY 1995 VL 69 IS 7 BP 4413 EP 4422 PG 10 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600057 PM 7769703 ER PT J AU LETVIN, NL LI, J HALLORAN, M CRANAGE, MP RUD, EW SODROSKI, J AF LETVIN, NL LI, J HALLORAN, M CRANAGE, MP RUD, EW SODROSKI, J TI PRIOR INFECTION WITH A NONPATHOGENIC CHIMERIC SIMIAN-HUMAN IMMUNODEFICIENCY VIRUS DOES NOT EFFICIENTLY PROTECT MACAQUES AGAINST CHALLENGE WITH SIMIAN IMMUNODEFICIENCY VIRUS SO JOURNAL OF VIROLOGY LA English DT Note AB Prior infection with a nef-deleted simian immunodeficiency virus (SIV) protects macaques not only against a homologous pathogenic SIV challenge but also against challenge with a chimeric SIV expressing a human immunodeficiency virus type 1 env gene (SHIV). Since this SHIV is itself nonpathogenic, we sought to explore the use of a nonpathogenic SHIV as a live, attenuated AIDS virus vaccine. Four cynomolgus monkeys infected for greater than 600 days with a chimeric virus composed of SIVmac 239 expressing the human immunodeficiency virus type 1 HXBc2 env, tat, and rev genes were challenged intravenously with 100 animal infectious doses of the J5 clone of SIVmac 32H, an isolate derived by in vivo passage of SIVmac 251. Three of the four monkeys became infected with SIVmac. This observation underlines the difficulty, even with a live virus vaccine, in protecting against an AIDS virus infection. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. CTR APPL MICROBIOL & RES,SALISBURY,WILTS,ENGLAND. LAB CTR DIS CONTROL,OTTAWA,ON K1A 0L2,CANADA. RP LETVIN, NL (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,330 BROOKLINE AVE,BOSTON,MA 02215, USA. RI Rud, Erling/P-5359-2016 OI Rud, Erling/0000-0001-8615-0277 FU NIAID NIH HHS [AI-29333, AI-33832, AI-35478] NR 9 TC 30 Z9 30 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 JUL PY 1995 VL 69 IS 7 BP 4569 EP 4571 PG 3 WC Virology SC Virology GA RC226 UT WOS:A1995RC22600081 PM 7769725 ER PT J AU SEEMAN, TE BERKMAN, LF CHARPENTIER, PA BLAZER, DG ALBERT, MS TINETTI, ME AF SEEMAN, TE BERKMAN, LF CHARPENTIER, PA BLAZER, DG ALBERT, MS TINETTI, ME TI BEHAVIORAL AND PSYCHOSOCIAL PREDICTORS OF PHYSICAL PERFORMANCE - MACARTHUR STUDIES OF SUCCESSFUL AGING SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID ELDERLY POPULATION; COLLEGE ALUMNI; OLDER MEN; MORTALITY; DISEASE; WOMEN; INDEX; LIFE AB Background Performance-based measures of physical performance are examined for an other cohort of relatively high-functioning men and women. The influences of baseline behavioral, social, and psychological characteristics on patterns of change in performance over 2.5 years are examined. Methods. A cohort of relatively high-functioning men and women, aged 70-79, identified in 1988 by subsampling from three community-based studies on the basis of physical and cognitive function. Baseline assessments included physical performance, sociodemographic characteristics, health status, and behavioral, social, and psychological characteristics. A summary measure of physical performance was developed from tests of balance, gait, lower body strength and coordination, and manual dexterity. In-home assessments were repeated at follow-up in 1991. Results. Linear regression models were used to identify significant behavioral, social, and psychological predictors of better performance at follow-up, controlling for known sociodemographic and health status predictors. Significant, independent associations with better performance were found for participation in moderate and/or strenuous exercise activity and greater frequency of emotional support from social networks, particularly among those reporting low frequency of instrumental support. These effects remained significant independent of incident health conditions during follow-up. None of the psychological characteristics was a significant predictor. Conclusions. Maintenance of better physical performance within a high-functioning cohort is influenced by prior exercise behavior and social network emotional support. Observed patterns of both decline and improvement in performance suggest that older age is not uniformly associated with declines. Predictors of better performance identified here may offer potential for effective interventions to promote more successful aging. C1 YALE UNIV,SCH MED,DEPT INTERNAL MED,NEW HAVEN,CT 06510. DUKE UNIV,DURHAM,NC. MASSACHUSETTS GEN HOSP,BOSTON,MA. RP SEEMAN, TE (reprint author), YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,60 COLL ST,NEW HAVEN,CT 06510, USA. FU NIA NIH HHS [AG-00586] NR 30 TC 159 Z9 160 U1 2 U2 14 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 1995 VL 50 IS 4 BP M177 EP M183 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RY604 UT WOS:A1995RY60400010 PM 7614238 ER PT J AU KINASHI, T SPRINGER, TA AF KINASHI, T SPRINGER, TA TI REGULATION OF CELL-MATRIX ADHESION BY RECEPTOR TYROSINE KINASES SO LEUKEMIA & LYMPHOMA LA English DT Review DE REGULATION CELL MATRIX-ADHESION RECEPTOR AB Cell -cell and cell-matrix adhesive interactions mediated by integrins play crucial roles in leukocyte migration to inflamed tissues, and also in cell migration during embryogenesis, Much remains to be learned about the molecular mechanisms of regulation of adhesion mediated by integrins. Recently we found that steel factor and c-kit induce adhesion to fibronectin by VLA-5 in mast cells.(1) Activation of adhesiveness is transient, and occurs at concentrations of steel factor 100-fold lower than required for growth stimulation. This suggests that regulation of adhesion is an important biological function of steel factor and c-kit. Other receptor tyrosine kinases such as the PDGF receptor can substitute for c-kit, Signaling through receptor tyrosine kinases may offer a general mechanism for the regulation of integrin avidity. C1 CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 15 Z9 15 U1 1 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUL PY 1995 VL 18 IS 3-4 BP 203 EP 208 DI 10.3109/10428199509059608 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA RU512 UT WOS:A1995RU51200002 PM 8535183 ER PT J AU HUANG, MJ OSBORN, L SVAHN, J SCHIFFER, SB ELISEO, L ZHOU, LJ RHYNHART, K BENJAMIN, CD FREEDMAN, AS AF HUANG, MJ OSBORN, L SVAHN, J SCHIFFER, SB ELISEO, L ZHOU, LJ RHYNHART, K BENJAMIN, CD FREEDMAN, AS TI EXPRESSION OF VASCULAR CELL-ADHESION MOLECULE-1 BY FOLLICULAR DENDRITIC CELLS SO LEUKEMIA & LYMPHOMA LA English DT Article AB Follicular dendritic cells are the major supporting cell of the germinal center microenvironment. The major function of follicular dendritic cells is to present antigen to B cells in secondary lymphoid tissues. Through cell-cell interactions, FDCs are hypothesized to be central to the regulation of normal B cell growth and differentiation. The major receptor-ligand pair which mediates B cell-FDC adhesion is the beta 1 integrin VLA-4, present on B cells and VCAM-1 expressed on FDCs. Follicular non-Hodgkin's lymphomas similarly employ this mechanism to bind to neoplastic germinal centers. The VCAM-1 molecule can exist as a 6 or 7 immunoglobulin domain form. The major form of VCAM-1 on activated endothelium is the 7 domain form. In this report we have determined by polymerase chain reaction of purified FDCs that they express predominantly mRNA for 7 domain VCAM-1. It is likely that the two forms of VCAM-1 are associated with distinct functions, therefore the expression of 7 domain VCAM-1 may be important in normal and neoplastic B celI-FDC interactions. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,BOSTON,MA 02115. FU NCI NIH HHS [CA55207] NR 0 TC 6 Z9 7 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUL PY 1995 VL 18 IS 3-4 BP 259 EP 264 DI 10.3109/10428199509059616 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA RU512 UT WOS:A1995RU51200010 PM 8535191 ER PT J AU BOXERMAN, JL BANDETTINI, PA KWONG, KK BAKER, JR DAVIS, TL ROSEN, BR WEISSKOFF, RM AF BOXERMAN, JL BANDETTINI, PA KWONG, KK BAKER, JR DAVIS, TL ROSEN, BR WEISSKOFF, RM TI THE INTRAVASCULAR CONTRIBUTION TO FMRI SIGNAL CHANGE - MONTE-CARLO MODELING AND DIFFUSION-WEIGHTED STUDIES IN-VIVO SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE DIFFUSION-WEIGHTED FUNCTIONAL MRI; MONTE CARLO MODELING; SUSCEPTIBILITY CONTRAST; INTRAVASCULAR BOLD CONTRAST ID CEREBRAL BLOOD-FLOW; HUMAN-BRAIN; FUNCTIONAL MRI; CONTRAST; OXYGENATION; CORTEX; WATER; TIME; SUSCEPTIBILITY; ACTIVATION AB Understanding the relationship between fMRI signal changes and activated cortex is paramount to successful mapping of neuronal activity. To this end, the relative extravascular and intravascular contribution to fMRI signal change from capillaries (localized), venules (less localized) and macrovessels (remote, draining veins) must be determined, In this work, the authors assessed both the extravascular and intravascular contribution to blood oxygenation level-dependent gradient echo signal change at 1.5 T by using a Monte Carlo model for susceptibility-based contrast in conjunction with a physiological model for neuronal activation-induced changes in oxygenation and vascular volume fraction, The authors compared our Model results with experimental fMRI signal changes with and without velocity sensitization via bipolar gradients to null the intravascular signal. The model and experimental results are in agreement and suggest that the intravascular spins account for the majority of fMRI signal change on T-2*-weighted images at 1.5 T. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. HARVARD MIT DIV HLTH SCI & TECHNOL,BOSTON,MA. RP BOXERMAN, JL (reprint author), MASSACHUSETTS GEN HOSP,CTR NMR,DEPT RADIOL,BLDG 149 2301,13TH ST,BOSTON,MA 02129, USA. RI Bandettini, Peter/F-5871-2012 FU NHLBI NIH HHS [R01-HL39810]; PHS HHS [P01 48729] NR 38 TC 410 Z9 414 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 1995 VL 34 IS 1 BP 4 EP 10 DI 10.1002/mrm.1910340103 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RF768 UT WOS:A1995RF76800002 PM 7674897 ER PT J AU MELDER, RJ SALEHI, HA JAIN, RK AF MELDER, RJ SALEHI, HA JAIN, RK TI INTERACTION OF ACTIVATED NATURAL-KILLER-CELLS WITH NORMAL AND TUMOR VESSELS IN CRANIAL WINDOWS IN MICE SO MICROVASCULAR RESEARCH LA English DT Article ID ADOPTIVE IMMUNOTHERAPY; INTERLEUKIN-2; LYMPHOCYTES; FLOW AB A mammary carcinoma, MCa IV, was grown in syngeneic C3H mice in a cranial window preparation which permitted the in vivo observation of the growth and microcirculation of the tumors. Fluorescently labeled activated natural killer (A-NK) cells were injected into the external carotid artery and their interactions with normal and tumor vessels were quantified by video microscopy. Cells which entered the tumor vessels adhered heterogeneously to these vessels, regardless of vessel size or blood flow rates and bound with an efficiency ranging from 0 to 82% of the incoming cell flux. Normal brain tissue showed significantly fewer binding cells per microscopic field (9 +/- 5 vs 85 +/- 27 cells/1.3 mm(2)) and the few cells which were retained by the normal tissue were highly deformed, suggesting mechanical rather than adhesive entrapment. These studies indicate that A-NK cells bind in high numbers to segments of the vessels of mammary tumors growing in an intracranial site when administered through an arterial route; however, some tumor vessels may escape recognition by these cells. These findings suggest that A-NK cells may be used as carriers of genes for anti-cancer agents. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP MELDER, RJ (reprint author), HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. NR 22 TC 35 Z9 35 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD JUL PY 1995 VL 50 IS 1 BP 35 EP 44 DI 10.1006/mvre.1995.1036 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RJ781 UT WOS:A1995RJ78100004 PM 7476578 ER PT J AU FRUMAN, DA PAI, SY BURAKOFF, SJ BIERER, BE AF FRUMAN, DA PAI, SY BURAKOFF, SJ BIERER, BE TI CHARACTERIZATION OF A MUTANT CALCINEURIN A-ALPHA GENE EXPRESSED BY EL4 LYMPHOMA-CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DEPENDENT PROTEIN PHOSPHATASE; CATALYTIC SUBUNIT; MOLECULAR-CLONING; CYCLOSPORINE-A; GROWTH-FACTOR; T-CELLS; ACTIVATION; IDENTIFICATION; INTERLEUKIN-2; DOMAIN AB The calmodulin-stimulated phosphatase calcineurin plays a critical role in calcium-dependent T-lymphocyte activation pathways. Here, we report the identification of a missense mutation in the calcineurin A alpha gene expressed by EL4 T-lymphoma cells. This mutation changes an evolutionarily conserved aspartic acid to asparagine within the autoinhibitory domain of the calcineurin A alpha protein. A comparison of wild-type and mutant autoinhibitory peptides indicates that this amino acid substitution greatly reduces inhibition of calcineurin phosphatase activity. Additional peptide inhibition studies support a pseudosubstrate model of autoinhibitory function, in which the conserved aspartic acid residue may serve as a molecular mimic of either phosphoserine or phosphothreonine. Expression of the mutant calcineurin appears to affect cellular signal transduction pathways, as EL4 cells can be activated by suboptimal concentrations of calcium ionophore in the presence of phorbol esters. Moreover, this phenotype can be transferred to Jurkat T cells by transfection of the mutated calcineurin gene. These findings implicate a conserved aspartic acid in the mechanism of calcineurin autoinhibition and suggest that mutation of this residue is associated with aberrant calcium-dependent signaling in vivo. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV MED SCI,COMM IMMUNOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI 32514] NR 35 TC 35 Z9 36 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 1995 VL 15 IS 7 BP 3857 EP 3863 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RE030 UT WOS:A1995RE03000044 PM 7791792 ER PT J AU KHAZAK, V SADHALE, PP WOYCHIK, NA BRENT, R GOLEMIS, EA AF KHAZAK, V SADHALE, PP WOYCHIK, NA BRENT, R GOLEMIS, EA TI HUMAN RNA-POLYMERASE-II SUBUNIT HSRPB7 FUNCTIONS IN YEAST AND INFLUENCES STRESS SURVIVAL AND CELL MORPHOLOGY SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID 2 DISSOCIABLE SUBUNITS; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; PROTEIN PHOSPHATASE; FILAMENTOUS GROWTH; RAPID METHOD; DNA-BINDING; GENE; SEQUENCE; PHASE AB Using a screen to identify human genes that promote pseudohyphal conversion in Saccharomyces cerevisiae, we obtained a cDNA encoding hsRPB7, a human homologue of the seventh largest subunit of yeast RNA polymerase II (RPB7). Overexpression of yeast RPB7 in a comparable strain background caused more pronounced cell elongation than overexpression of hsRPB7. hsRPB7 sequence and function are strongly conserved with its yeast counterpart because its expression can rescue deletion of the essential RPB7 gene at moderate temperatures. Further, immuno-precipitation of RNA polymerase II from yeast cells containing hsRPB7 revealed that the hsRPB7 assembles the complete set of 11 other yeast subunits. However, at temperature extremes and during maintenance at stationary phase, hsRPB7-containing yeast cells lose viability rapidly, stress-sensitive phenotypes reminiscent of those associated with deletion of the RPB4 subunit with which RPB7 normally complexes. Two-hybrid analysis revealed that although hsRPB7 and RPB4 interact, the association is of lower affinity than the RPB4-RPB7 interaction, providing a probable mechanism for the failure of hsRPB7 to fully function in yeast cells at high and low temperatures. Finally, surprisingly, hsRPB7 RNA In human cells is expressed in a tissue-specific pattern that differs from that of the RNA polymerase II largest subunit, implying a potential regulatory role for hsRPB7. Taken together, these results suggest that some RPB7 functions may be analogous to those possessed by the stress-specific prokaryotic sigma factor rpoS. C1 FOX CHASE CANC CTR, INST CANC RES, PHILADELPHIA, PA 19111 USA. ROCHE INST MOLEC BIOL, NUTLEY, NJ 07110 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA. RI Sadhale, PArag/A-7799-2009 FU NCI NIH HHS [R29-CA63366] NR 63 TC 59 Z9 60 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 1995 VL 6 IS 7 BP 759 EP 775 PG 17 WC Cell Biology SC Cell Biology GA RH687 UT WOS:A1995RH68700002 PM 7579693 ER PT J AU PARHAMISEREN, B LYNCH, M WHITE, HD REED, GL AF PARHAMISEREN, B LYNCH, M WHITE, HD REED, GL TI MAPPING THE ANTIGENIC REGIONS OF STREPTOKINASE IN HUMANS BEFORE AND AFTER STREPTOKINASE THERAPY SO MOLECULAR IMMUNOLOGY LA English DT Article DE STREPTOKINASE (SK); HUMAN ANTISTREPTOKINASE ANTIBODIES (HU ANTI-SK ABS); MURINE MONOCLONAL ANTISTREPTOKINASE ANTIBODIES (ANTI-SK MABS); RECOMBINANT STREPTOKINASE TRUNCATED FRAGMENTS ID ACUTE MYOCARDIAL-INFARCTION; INTRAVENOUS STREPTOKINASE; ANTISTREPTOKINASE ANTIBODY; NEUTRALIZATION TITERS; SERUM-SICKNESS; ANISTREPLASE; SEQUENCE; CELLS AB Streptokinase saves lives in patients suffering a myocardial infarction. However, because nearly all humans tested show antibodies against streptokinase, allergic reactions to streptokinase are common and may be severe. In this report we have analysed antibodies purified from normal blood donors and patients, before and after streptokinase therapy, to identify antigenic regions of the streptokinase molecule. Antibody to streptokinase was seen in all subjects, but there were 20-30-fold differences between individuals in the antibody titer. These individual differences in titer persisted after SK treatment, though the titer for all patients rose an average of 7-fold 1 week after streptokinase therapy. To identify the regions of streptokinase to which the antibody bound, we employed a panel of well-characterized murine monoclonal antibodies and recombinant streptokinase truncated fragments. Antibodies to three discrete regions of streptokinase could be detected in all patients. Antibodies to two other regions, at the amino terminal and carboxyl terminus of the molecule, were found in many but not in all patients. However, antibodies to a sixth region of streptokinase were uncommon and of very low titer. Interestingly, individuals receiving streptokinase tended to show the same pattern of immunoreactivity after treatment as they had prior to streptokinase. We conclude that although individual differences exist in the titers of streptokinase antibody, certain regions of streptokinase appear to be more antigenic or immunodominant. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. GEN HOSP,LUNG IMMUNOBIOCHEM RES LAB,BIRMINGHAM B4 6NH,W MIDLANDS,ENGLAND. GREEN LANE HOSP,CARDIOVASC RES UNIT,AUCKLAND 3,NEW ZEALAND. 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 [HL02348]; NIAID NIH HHS [R29 AI33175-02] NR 27 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUL PY 1995 VL 32 IS 10 BP 717 EP 724 DI 10.1016/0161-5890(95)00041-C PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA RR823 UT WOS:A1995RR82300004 PM 7659098 ER PT J AU PEGUES, DA HANTMAN, MJ BEHLAU, I MILLER, SI AF PEGUES, DA HANTMAN, MJ BEHLAU, I MILLER, SI TI PHOP/PHOQ TRANSCRIPTIONAL REPRESSION OF SALMONELLA-TYPHIMURIUM INVASION GENES - EVIDENCE FOR A ROLE IN PROTEIN SECRETION SO MOLECULAR MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; LOW-CALCIUM-RESPONSE; SHIGELLA-FLEXNERI; EPITHELIAL-CELLS; YERSINIA-ENTEROCOLITICA; PLASMID ANTIGENS; YOP PROTEINS; GEL-ELECTROPHORESIS; ESCHERICHIA-COLI; IPA INVASINS AB Previously, the PhoP-repressed locus prgH was identified as important for signalling epithelial cells to endocytose Salmonella typhimurium. Characterization of prgH revealed that it is an operon of four genes encoding polypeptides of 392 (prgH), 80 (prgI), 101 (prgJ) and 252 amino acid residues (prgK). Synthesis of the 2.6 kb prgHIJK transcript was repressed in bacteria that activate PhoP/PhoQ, indicating that PhoP/PhoQ regulates prgHIJK by transcriptional repression. The prgI, prgJ and prgK predicted gene products were similar to Shigella flexneri and Yersinia enterocolitica proteins required for secretion of Ipa and Yop virulence factors. Analysis of the culture supernatants from wild-type S. typhimurium demonstrated that at least 25 polypeptides larger than 14 kDa could be detected. In contrast, prgH1::TnphoA, phoP-constitutive and hil-deletion mutants had significant defects in their supernatant protein profiles. The invasion and supernatant protein profile defects of the prgH1::TnphoA mutant were both complemented by a 5.1 kb plasmid that included prgHIJK. These results suggest that PhoP/PhoQ regulates extracellular transport of proteins by transcriptional repression of secretion determinants and that secreted proteins may be involved in signalling epithelial cells to endocytose bacteria. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIAID NIH HHS [AI34504, AI08280, AI08873] NR 66 TC 152 Z9 160 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 1995 VL 17 IS 1 BP 169 EP 181 DI 10.1111/j.1365-2958.1995.mmi_17010169.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA RN224 UT WOS:A1995RN22400015 PM 7476203 ER PT J AU FALO, LD KOVACSOVICSBANKOWSKI, M THOMPSON, K ROCK, KL AF FALO, LD KOVACSOVICSBANKOWSKI, M THOMPSON, K ROCK, KL TI TARGETING ANTIGEN INTO THE PHAGOCYTIC PATHWAY IN-VIVO INDUCES PROTECTIVE TUMOR-IMMUNITY SO NATURE MEDICINE LA English DT Article ID INFILTRATING LYMPHOCYTES; SOLUBLE-PROTEIN; T-CELLS; INVIVO; ASSOCIATION; MELANOMA; SURVIVAL AB Cytotoxic T lymphocytes (CTLs) kill neoplastic or virally infected cells after recognizing on their surface antigenic peptides bound to major histocompatibility complex class molecules. These peptides are derived from antigens that are degraded in the cytosol of the affected cell. Because exogenous proteins cannot enter the cytosol, immunizations with killed pathogens or their proteins do not generally elicit CTLs. However, antigens that are internalized into phagocytic cells can enter the cytosol and be processed for class presentation. Here we show that immunization with a purified antigen on an avidly phagocytized particle primes CTLs, which in turn protect animals from subsequent challenge with tumours transfected with the antigen gene. Interestingly, these animals also become immune to other antigens expressed by the tumour. This approach could be exploited to develop tumour and viral vaccines. C1 UNIV PITTSBURGH,SCH MED,PITTSBURGH CANC INST,PITTSBURGH,PA 15213. DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP FALO, LD (reprint author), UNIV PITTSBURGH,SCH MED,DEPT DERMATOL,190 LOTHROP ST,PITTSBURGH,PA 15213, USA. FU NIAID NIH HHS [AI 20248, AI 31337]; PHS HHS [R01-1884] NR 26 TC 201 Z9 203 U1 0 U2 7 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 JUL PY 1995 VL 1 IS 7 BP 649 EP 653 DI 10.1038/nm0795-649 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RQ066 UT WOS:A1995RQ06600038 PM 7585145 ER PT J AU CORDER, EH SAUNDERS, AM STRITTMATTER, WJ SCHMECHEL, DE GASKELL, PC RIMMLER, JB LOCKE, PA CONNEALLY, PM SCHMADER, KE TANZI, RE GUSELLA, JF SMALL, GW ROSES, AD PERICAKVANCE, MA HAINES, JL AF CORDER, EH SAUNDERS, AM STRITTMATTER, WJ SCHMECHEL, DE GASKELL, PC RIMMLER, JB LOCKE, PA CONNEALLY, PM SCHMADER, KE TANZI, RE GUSELLA, JF SMALL, GW ROSES, AD PERICAKVANCE, MA HAINES, JL TI APOLIPOPROTEIN-E, SURVIVAL IN ALZHEIMERS-DISEASE PATIENTS, AND THE COMPETING RISKS OF DEATH AND ALZHEIMERS-DISEASE SO NEUROLOGY LA English DT Article ID E POLYMORPHISM; TYPE-4 ALLELE; EPSILON-4; ATHEROSCLEROSIS; FREQUENCY; DIAGNOSIS; AGE AB The apolipoprotein E (APOE) epsilon 4 allele carries an increased risk of a patient developing Alzheimer's disease (AD) while the epsilon 2 allele carries a decreased risk. We compared survival from the onset of AD in subjects with different numbers of epsilon 4 alleles and evaluated changes in genotypic frequencies with age. Two subject groups were investigated: unrelated AD case and control subjects, and affected and unaffected members from 74 multiplex AD families. In both subject groups, survival from onset decreased with increasing onset age, was longer in women and was unrelated to epsilon 4 gene dose. The epsilon 2/epsilon 3 genotype became more common with age (p = 0.004). The epsilon 4 allele decreased in frequency with age in all patient groups but, unexpectedly, remained unchanged in control subjects. We conclude that the progression of AD is not strongly related to epsilon 4 gene dose, that the higher prevalence of AD in women may involve the longer survival of affected women, and that AD and death are competing risks involving APOE that change over time. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. DUKE UNIV,MED CTR,DIV NEUROL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DIV NEUROBIOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DURHAM,NC 27710. DURHAM VA MED CTR,GRECC,DURHAM,NC. DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27710. INDIANA UNIV,MED CTR,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN. UNIV CALIF LOS ANGELES,CTR HLTH SCI,NEUROPSYCHIAT INST & HOSP,LOS ANGELES,CA 90024. RI Haines, Jonathan/C-3374-2012 FU NIA NIH HHS [U24 AG021886, AG05128]; NINDS NIH HHS [NS26630, NS531153] NR 41 TC 152 Z9 153 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 JUL PY 1995 VL 45 IS 7 BP 1323 EP 1328 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA RJ279 UT WOS:A1995RJ27900017 PM 7617191 ER PT J AU LEVINE, JD SAUMAN, I IMBALZANO, M REPPERT, SM JACKSON, FR AF LEVINE, JD SAUMAN, I IMBALZANO, M REPPERT, SM JACKSON, FR TI PERIOD PROTEIN FROM THE GIANT SILKMOTH ANTHERAEA-PERNYI FUNCTIONS AS A CIRCADIAN CLOCK ELEMENT IN DROSOPHILA-MELANOGASTER SO NEURON LA English DT Article ID MESSENGER-RNA LEVELS; GENE-PRODUCT; BEHAVIORAL RHYTHMS; VISUAL-SYSTEM; DARK CYCLES; MUTANTS; CAMP; TRANSFORMATION; MUTATIONS; PHASE AB Homologs of the Drosophila clock gene per have recently bt!en cloned in Lepidopteran and Blattarian insect species. To assess the extent to which clock mechanisms are conserved among phylogenetically distant species, we determined whether PER protein from the silkmoth Antheraea pernyi can function in the Drosophila circadian timing system. When expressed in transgenic Drosophila, the silkmoth PER protein is detected in the expected neural cell types, with diu mal changes in abundance that are similar to those observed in wild-type fruitflies. Behavioral analysis demonstrates that the silkmoth protein can serve as a molecular element of the Drosophila clock system; expression of the protein shortens circadian period in a dose-dependent manner and restores pacemaker functions to arrhythmic per(0) mutants. This comparative study also suggests that the involvement of PER in different aspects of circadian timing, such as period determination, strength of rhythmicity, and clock output, requires distinct molecular interactions. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEV CHRONOBIOL LAB,BOSTON,MA 02114. ACAD SCI CZECH REPUBL,INST ENTOMOL,PRAGUE,CZECH REPUBLIC. RP LEVINE, JD (reprint author), WORCESTER FDN EXPTL BIOL INC,NEUROBIOL GRP,222 MAPLE AVE,SHREWSBURY,MA 01545, USA. RI Sauman, Ivo/H-2071-2014 FU NCRR NIH HHS [RR09767]; NIDDK NIH HHS [DK42125]; NINDS NIH HHS [NS30386] NR 50 TC 52 Z9 52 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD JUL PY 1995 VL 15 IS 1 BP 147 EP 157 DI 10.1016/0896-6273(95)90072-1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA RL756 UT WOS:A1995RL75600017 PM 7619519 ER PT J AU GAUMNITZ, E SWEET, MA SENGUPTA, A SINGARAM, C AF GAUMNITZ, E SWEET, MA SENGUPTA, A SINGARAM, C TI NITRINERGIC AND PEPTIDERGIC INNERVATIONS AND THEIR INTERRELATIONSHIPS IN HUMAN COLON SO NEUROPEPTIDES LA English DT Article ID NITRIC-OXIDE SYNTHASE; NEURONAL NADPH DIAPHORASE; SMOOTH-MUSCLE; HUMAN GUT; INVOLVEMENT; IMMUNOREACTIVITY; INTESTINE; VIP AB The distribution and colocalization of nitrinergic and peptidergic nerves were examined in six human colons. The tissues were fixed, cryosectioned, and standard immunohistochemistry was performed for several known neuropeptides. The same sections were stained for NADPH-diaphorase to denote nitric oxide synthase. NADPH-diaphorase-positive myenteric neurons were counted and colocalization noted for each peptide, as well as for peptide terminations. Galanin was the only neuropeptide that colocalized to a significant extent (23.0 +/- 7.21%) with NADPH-diaphorase-positive myenteric neurons. Many neuropeptide-containing nerve fibers had extensive terminations onto NADPH-diaphorase-positive neurons. Vasoactive intestinal peptide was the only neuropeptide that colocalized with NADPH-diaphorase to any extent in nerve fibers within circular muscle (59.5 +/- 9.3%). Fiber distribution in the longitudinal muscles showed a similar, but less dense pattern. These observations provide morphological evidence for the presence of nitric oxide, a candidate nonadrenergic noncholinergic neurotransmitter in the human colon. C1 UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,DEPT MED,DIV GASTROENTEROL,MADISON,WI. BOSTON UNIV,SCH MED,DIV PEDIAT GASTROENTEROL & NUTR,BOSTON,MA. NR 24 TC 18 Z9 19 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD JUL PY 1995 VL 29 IS 1 BP 1 EP 9 DI 10.1016/0143-4179(95)90050-0 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA RH553 UT WOS:A1995RH55300001 PM 7566507 ER PT J AU LAFLECHE, G ALBERT, MS AF LAFLECHE, G ALBERT, MS TI EXECUTIVE FUNCTION DEFICITS IN MILD ALZHEIMERS-DISEASE SO NEUROPSYCHOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; PRESENILE-DEMENTIA; SENILE DEMENTIA; SYNAPSE LOSS; NUCLEUS BASALIS; WORKING MEMORY; TEMPORAL-LOBE; ATTENTION; CORTEX; ABNORMALITIES AB Twenty mildly impaired patients with Alzheimer's disease (AD; Mini-Mental State Examination; [MMSE] = 25.1) and 20 controls (MMSE = 29.4) were administered 7 tests to assess executive function. Tests of memory, naming, and copying were included. The executive function tests were the Self-Ordering Test, Controlled Oral Word Association Test (FAS), Trail Making Test, Hukok Logical Matrices, the Proverb Interpretation Test, the Similarities subtest of the Wechsler Adult Intelligence Scale-Revised, and the Cued Reaction Time Test. AD patients differed significantly from controls on 4 executive function tests (the Self-Ordering, Hukok, Trail Making, and FAS) and on the memory test. The executive function tasks on which the AD patients were impaired in comparison with controls primarily required concurrent manipulation of information. Tests of simple concept formation, cue-directed behavior, attention, naming, or figure copying did not differentiate the groups. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. NR 54 TC 162 Z9 165 U1 3 U2 14 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 1995 VL 9 IS 3 BP 313 EP 320 DI 10.1037/0894-4105.9.3.313 PG 8 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA RH692 UT WOS:A1995RH69200005 ER PT J AU ZHANG, D SUCHER, NJ LIPTON, SA AF ZHANG, D SUCHER, NJ LIPTON, SA TI COEXPRESSION OF AMPA/KAINATE RECEPTOR-OPERATED CHANNELS WITH HIGH AND LOW CA2+ PERMEABILITY IN SINGLE-RAT RETINAL GANGLION-CELLS SO NEUROSCIENCE LA English DT Article ID AMINO-ACID RECEPTORS; SELECTIVE GLUTAMATE RECEPTORS; KAINATE RECEPTOR; SUBUNIT IMMUNOREACTIVITY; STRUCTURAL DETERMINANTS; MONOCLONAL-ANTIBODY; STRIATAL NEURONS; NERVOUS-SYSTEM; ION FLOW; AMPA AB The patch-clamp technique was used to record whole-cell currents induced by alpha-amino-3-hydroxyl-5-methyl-isoxazol-4-propionic acid (AMPA) or kainate in solitary rat retinal ganglion cells (n = 125) in vitro. Two groups of retinal ganglion cells could be distinguished according to their responses to kainate or AMPA in extracellular solutions with Ca2+ as the only permeant cation. The ratio of the steady-state currents evoked by a given concentration of AMPA compared to kainate was low (0.08) in the first group and high (0.61) in the second group of retinal ganglion cells. The Ca2+ permeability through AMPA/kainate receptor-operated channels was low (P-Ca2+/P-Cs+ < 0.1) in the first group (n = 74, 59%) and moderate (P-Ca2+/P-Cs+ = 0.53) in the second group (n = 51, 41%) of retinal ganglion cells. The fraction of the total current induced by stimulation of non-N-methyl-D-aspartate receptors that is flowing through Ca2+ permeable AMPA/kainate channels in single cells with high Ca2+ permeability was estimated by comparing the current-voltage relationship in extracellular solutions with either Ca2+ or Na+ as the sole charge carrier. The contribution of Ca2+-permeable channels to the non-N-methyl-D-aspartate receptor induced whole-cell current in single Ca2+ permeable cells (n = 12) ranged from 40 to 70%, correlating with the intermediate level of Ca2+ permeability (P-Ca2+/P-Cs+ = 0.22-0.80) measured by an independent method in these cells. Thus, single Ca2+-permeable cells appear to express at least two types of AMPA/kainate receptor-operated channels with high or low Ca2+ permeability. Using the polymerase chain reaction, transcripts for the glutamate receptor subunits 1-4, including their ''flip'' and ''flop'' versions, were identified in retinal ganglion cells. Together, these findings suggest that among rat retinal ganglion cells there are differences in the pattern of expression of AMPA/kainate receptor-operated channels. Moreover, individual cells co-express multiple heterologous non-N-methyl-D-aspartate receptors with distinct functional properties. The functional diversity of these receptors may play an important role in controlling Ca2+ entry into neurons. We speculate that the low Ca2+ permeability and the preference for kainate in one group of retinal ganglion cells may be due to the predominant expression of non-N-methyl-D-aspartate receptors containing the edited form of the glutamate receptor subunit 2 flop splice variant. C1 CHILDRENS HOSP,CELLULAR & MOLEC NEUROSCI LAB,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. OI Sucher, Nikolaus/0000-0001-6233-1612 FU NEI NIH HHS [R01 EY09024, R01 EY05477]; NICHD NIH HHS [P01 HD29587] NR 54 TC 52 Z9 52 U1 0 U2 0 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 1995 VL 67 IS 1 BP 177 EP 188 DI 10.1016/0306-4522(94)00627-H PG 12 WC Neurosciences SC Neurosciences & Neurology GA RC355 UT WOS:A1995RC35500017 PM 7477898 ER PT J AU TATTER, SB CROWELL, RM OGILVY, CS AF TATTER, SB CROWELL, RM OGILVY, CS TI ANEURYSMAL AND MICROANEURYSMAL ANGIOGRAM-NEGATIVE SUBARACHNOID HEMORRHAGE SO NEUROSURGERY LA English DT Article DE CEREBRAL ANEURYSM; CEREBRAL ANGIOGRAPHY; COMPUTED TOMOGRAPHY; PERIMESENCEPHALIC SUBARACHNOID HEMORRHAGE; RADIOGRAPHICALLY OCCULT; SUBARACHNOID HEMORRHAGE OF UNKNOWN CAUSE ID UNKNOWN ETIOLOGY; INTRACRANIAL ANEURYSMS; ARTERY; ARACHNOIDITIS; PATTERN; ORIGIN AB THE SOURCE OF bleeding remains obscure in most cases of subarachnoid hemorrhage (SAH) with a negative angiogram. From January 1, 1989, to July 1, 1993, 40 patients were admitted to the Massachusetts General Hospital with angiogram-negative SAH; 9 of these patients underwent surgical exploration. In seven of these explorations, an arterial source of the hemorrhage was discovered. These arterial sources included three anterior communicating artery complex lesions, two middle cerebral artery lesions, one internal carotid artery aneurysm arising at the origin of the posterior communicating artery, and one vertebral/posterior inferior cerebellar artery aneurysm. Three of these seven lesions had small aneurysmal sacs, but the other four were microaneurysms too small to accept a surgical clip. No source of hemorrhage could be found during surgery on one patient with a perimesencephalic pattern of blood. Two of the four patients with a microaneurysmal source of hemorrhage had two episodes of SAH. We propose that microaneurysms are the source of a significant percentage of nonperimesencephalic angiogram-negative SAH and suggest that these lesions may represent a forme fruste of saccular aneurysms. These findings lead us to propose a protocol for the management of angiogram-negative SAH based on the distribution of blood as seen on the patient's first computed tomogram. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. NR 35 TC 74 Z9 77 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUL PY 1995 VL 37 IS 1 BP 48 EP 55 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA RE545 UT WOS:A1995RE54500021 PM 8587690 ER PT J AU CARROLL, RS ZHANG, JP DASHNER, K BLACK, PM AF CARROLL, RS ZHANG, JP DASHNER, K BLACK, PM TI PROGESTERONE AND GLUCOCORTICOID RECEPTOR ACTIVATION IN MENINGIOMAS SO NEUROSURGERY LA English DT Article DE GLUCOCORTICOID RECEPTOR; MENINGIOMAS; PROGESTERONE RECEPTOR; PROGESTERONE RESPONSIVE ELEMENT; TRANSFECTIONS ID STEROID-RECEPTORS; ESTROGEN-RECEPTORS; RESPONSE ELEMENTS; PRIMARY BRAIN; BINDING; GENE; TRANSCRIPTION; MIFEPRISTONE; MANIPULATION; FRAGMENTS AB THE POSSIBILITY THAT the female sex steroid progesterone plays a role in meningioma proliferation has been suggested by a number of investigators, and it has been shown that many meningiomas have high-affinity progesterone binding sites. There has been a long-standing debate in the literature as to whether the progesterone receptors that are present in meningiomas are functional. We recently showed, by the use of immunohistochemistry, that the progesterone receptor in meningiomas is localized to the nucleus, suggesting that the receptor is in a location to be activated. In this study, eight meningioma cell cultures were transiently transfected with a construct that contains two palindromic progesterone/glucocorticoid response elements in front of the thymidine kinase promoter and the chloramphenicol acetyl sequence of the tyrosine aminotransferase gene. In all meningioma cell cultures, an increase in the transcription of the progesterone response element construct was observed in the presence of dexamethasome, suggesting that the glucocorticoid receptor in meningiomas is functional. An increase in transcription was observed with the addition of promegestone (R5020), a progesterone agonist, only in meningioma cell cultures that were expressing the progesterone receptor. These data show that both the progesterone and the glucocorticoid receptor in meningiomas are functional and support the concept that progestins and glucocorticoids may play an important role in meningioma growth. C1 BRIGHAM & WOMENS HOSP,CTR BRAIN TUMOR,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP CARROLL, RS (reprint author), BRIGHAM & WOMENS HOSP,NEUROSURG LABS,221 LONGWOOD AVE,ROOM 121,BOSTON,MA 02115, USA. NR 41 TC 30 Z9 33 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 1995 VL 37 IS 1 BP 92 EP 97 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA RE545 UT WOS:A1995RE54500043 PM 8587697 ER PT J AU BABICH, JW GRAHAM, W BARROW, SA FISCHMAN, AJ AF BABICH, JW GRAHAM, W BARROW, SA FISCHMAN, AJ TI COMPARISON OF THE INFECTION IMAGING PROPERTIES OF A TC-99M LABELED CHEMOTACTIC PEPTIDE WITH IN-111 IGG SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID ACUTE BACTERIAL-INFECTION; WHITE BLOOD-CELLS; FOCAL SITES; IMMUNOGLOBULIN-G; POLYCLONAL IGG; INFLAMMATION; LEUKOCYTES; ANALOGS; RATS; BONE AB The biodistribution and infection imaging properties of a Te-99m labeled hydrazino nicotinamide (HYNIC) derivatized chemotactic peptide analog (For-Met-Leu-Phe-Lys-HYNIC) and In-111-DTPA-IgG were compared in rabbits with Escherichia coli infection. Six New Zealand white rabbits were injected in the left posterior thigh with a suspension of E. coli. Twenty four hours later, the animals were injected with: 1.0 mCi of Tc-99m labeled peptide plus 0.1 mCi of In-111-DTPA-IgG. At 2-3 and 16-18 h, dual photon scintigrams were acquired and the images were corrected for crossover between the two windows. After recording the final images, the animals were sacrificed and biodistribution was determined. At both imaging times the biodistributions of the two reagents were markedly different. The highest concentrations of In-111-DTPA-IgG were detected in blood pool structures, liver and kidney. In contrast localization of Tc-99m labeled peptide was greatest in spleen, lung and liver (consistent with binding to leukocytes). In general, the sites of infection were better visualized with the radiolabeled peptide and TIE ratios increased with time (P < 0.01). At both times, the T/Bs for Tc-99m- peptide were higher (P < 0.01); 3.54 +/- 0.47 vs 2.52 +/- 0.38 at 2-3 h and 6.88 +/- 0.79 vs 3.78 +/- 0.36 at 16-18 h. These results indicate that although both radiopharmaceuticals localize at sites of infection, the radiolabeled peptide are superior reagents for the rapid detection of focal sites of infection. However, since the mechanisms of localization are different the combined use of both agents could have value in the general evaluation of infection/inflammation. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. NR 23 TC 48 Z9 48 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JUL PY 1995 VL 22 IS 5 BP 643 EP 648 DI 10.1016/0969-8051(94)00138-A PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RL991 UT WOS:A1995RL99100014 PM 7581175 ER PT J AU CHI, TSK BERRIOS, RR NETLAND, PA AF CHI, TSK BERRIOS, RR NETLAND, PA TI HOLMIUM LASER SCLEROSTOMY VIA CORNEAL APPROACH WITH TRANSCONJUNCTIVAL MITOMYCIN-C IN RABBITS SO OPHTHALMIC SURGERY AND LASERS LA English DT Article ID GLAUCOMA FILTRATION SURGERY; CONJUNCTIVAL INCISION; SUBCONJUNCTIVAL THC; YAG LASER; FOLLOW-UP; TRABECULECTOMY; ABINTERNO; SCLERECTOMY; ABEXTERNO AB We studied the use of the holmium laser for sclerostomy through a small lamellar corneal incision and the effects of transconjunctival mitomycin-C on the outcome of filtration surgery without conjunctival incision. The holmium laser, equipped with a straight-firing probe, was used to create sclerostomies in seven New Zealand white rabbits through a corneal lamellar incision. One eye in each rabbit was treated with transconjunctival mitomycin-C (0.4 mu g/mL for 5 minutes), and the fellow eye underwent sclerostomy without pretreatment with mitomycin-C as a control. The reduction in intraocular pressure was greater and persisted significantly longer in the eyes pretreated with mitomycin-C than in the controls. All control eyes had flat blebs by day 7 to 12, while the treated eyes maintained a bleb throughout the study. Microscopic examination showed that sclerostomies created by the straight-firing probe induced significantly less thermal damage than those created by the stationary side-firing probe. These results demonstrate that successful transcorneal sclerostomy without conjunctival incision can be created using the straight-firing holmium laser probe, with enhancement of filtration by pretreatment with transconjunctival mitomycin-C. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,GLAUCOMA CONSULTAT SERV,BOSTON,MA 02114. NR 28 TC 4 Z9 4 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0022-023X J9 OPHTHALMIC SURG LAS JI Ophthalmic Surg. Lasers PD JUL-AUG PY 1995 VL 26 IS 4 BP 353 EP 357 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA RL232 UT WOS:A1995RL23200020 PM 8532290 ER PT J AU BOUMA, B TEARNEY, GJ BOPPART, SA HEE, MR BREZINSKI, ME FUJIMOTO, JG AF BOUMA, B TEARNEY, GJ BOPPART, SA HEE, MR BREZINSKI, ME FUJIMOTO, JG TI HIGH-RESOLUTION OPTICAL COHERENCE TOMOGRAPHIC IMAGING USING A MODE-LOCKED TI-AL2O3 LASER SOURCE SO OPTICS LETTERS LA English DT Article ID TI-SAPPHIRE LASER; DOMAIN REFLECTOMETRY; EYE-LENGTH; INTERFEROMETRY; GENERATION; DEVICES; LIGHT AB A Kerr-lens made-locked Ti:Al2O3 oscillator, optimized for minimal coherence length, is demonstrated as a high-power source for high-resolution optical coherence tomographic imaging. Dispersion compensation and heterodyne noise rejection are demonstrated to yield in situ images of biological tissues with 3.7-mu m resolution and 93-dB dynamic range. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02144. HARVARD UNIV,SCH MED,BOSTON,MA 02144. RP BOUMA, B (reprint author), MIT,DEPT ELECT ENGN & COMP SCI,ELECTR RES LAB,CAMBRIDGE,MA 02139, USA. RI Boppart, Stephen/C-7338-2009 NR 19 TC 213 Z9 218 U1 1 U2 9 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JUL 1 PY 1995 VL 20 IS 13 BP 1486 EP 1488 DI 10.1364/OL.20.001486 PG 3 WC Optics SC Optics GA RE245 UT WOS:A1995RE24500012 PM 19862057 ER PT J AU SONIS, AL WABER, DP SALLAN, S TARBELL, NJ AF SONIS, AL WABER, DP SALLAN, S TARBELL, NJ TI THE ORAL HEALTH OF LONG-TERM SURVIVORS OF ACUTE LYMPHOBLASTIC-LEUKEMIA - A COMPARISON OF 3 TREATMENT MODALITIES SO ORAL ONCOLOGY-EUROPEAN JOURNAL OF CANCER PART B LA English DT Article DE ACUTE LYMPHOBLASTIC LEUKEMIA; CRANIAL IRRADIATION; ORAL HEALTH; DENTAL CARIES; GINGIVITIS ID NERVOUS-SYSTEM PROPHYLAXIS; CRANIAL IRRADIATION; LEUKEMIA; METHOTREXATE; CHILDREN AB Sixty-eight children who were diagnosed with acute lymphoblastic leukaemia (ALL) prior to age 5 years and treated with chemotherapy alone, chemotherapy plus 1800 cGy cranial irradiation (RT), or chemotherapy plus 2400 cGy RT were assessed clinically for overall dental health. All patients were at least 60 months in continuous remission. Dental caries were assessed by NIDR diagnostic criteria, oral hygiene was assessed by the modified Oral Hygiene Index, and gingival health was assessed by the modified gingival index of Loe and Silness. There was no significant difference in caries experience between the three groups nor with the normal population. Those patients that received 2400 cGy RT had significantly higher plaque and periodontal index scores than patients in the other treatment groups. The results of this study suggest that: (1) children with ALL treated with any of the described modalities are at no greater risk of developing dental caries than the normal population; and (2) patients receiving 2400 cGy prior to age 5 years are at greater risk of developing periodontal disease than patients treated with other central nervous system prophylaxis regimens examined in this study. C1 HARVARD UNIV,SCH DENT MED,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP SONIS, AL (reprint author), HARVARD UNIV,CHILDRENS HOSP,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 21 TC 8 Z9 8 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0964-1955 J9 ORAL ONCOL JI Oral Oncol.-Eur. J. Cancer Pt. B PD JUL PY 1995 VL 31B IS 4 BP 250 EP 252 PG 3 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA RW741 UT WOS:A1995RW74100008 ER PT J AU GLIKLICH, RE METSON, R AF GLIKLICH, RE METSON, R TI THE HEALTH IMPACT OF CHRONIC SINUSITIS IN PATIENTS SEEKING OTOLARYNGOLOGIC CARE SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 18-21, 1994 CL SAN DIEGO, CA SP Amer Acad Otolaryngol Head & Neck Surg ID SURVEY QUESTIONNAIRE; OUTCOME MEASURE; SF-36 AB Although chronic sinusitis Is an increasingly common diagnosis in the United States, the health burden of this disorder relative to the general population and to other chronic diseases has not been previously evaluated. One hundred fifty-eight patients with chronic sinusitis and no prior surgery underwent cross-sectional evaluation by use of the Medical Outcome Study Short-form 36-item Health Survey. These patients were all referred for otolaryngologic care, and more than 80% subsequently underwent sinus surgery. Mean scores were compared from the eight subscales of general health assessment with similarly derived data for the United States general population. Significant differences (p < 0.05) were seen in several domains, including bodily pain, general health, vitality, and social functioning, Comparisons with other chronic diseases revealed significantly lower scores (p < 0.05) in measures of bodily pain and social functioning for sinusitis patients than in patients with congestive heart failure, angina, chronic obstructive pulmonary disease, and back pain. These findings suggest that the national health impact of chronic sinusitis is far greater than is currently appreciated. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,CLIN OUTCOMES RES UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. NR 19 TC 346 Z9 359 U1 0 U2 5 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 1995 VL 113 IS 1 BP 104 EP 109 DI 10.1016/S0194-5998(95)70152-4 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA RH255 UT WOS:A1995RH25500016 PM 7603703 ER PT J AU MATSUBARA, O TAMURA, A OHDAMA, S MARK, EJ AF MATSUBARA, O TAMURA, A OHDAMA, S MARK, EJ TI ALVEOLAR BASEMENT-MEMBRANE BREAKS DOWN IN DIFFUSE ALVEOLAR DAMAGE - AN IMMUNOHISTOCHEMICAL STUDY SO PATHOLOGY INTERNATIONAL LA English DT Article DE ADULT RESPIRATORY DISTRESS SYNDROME; ALVEOLAR BASEMENT MEMBRANE; DIFFUSE ALVEOLAR DAMAGE; MICROTHROMBUS; LAMININ; 7S COLLAGEN; TYPE IV COLLAGEN; THROMBOMODULIN ID RESPIRATORY-DISTRESS SYNDROME; PULMONARY SURFACTANT APOPROTEINS; IV COLLAGEN; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; HUMAN-PLACENTA; HUMAN LUNGS; FIBROSIS; ORGANIZATION AB Sequential structural changes of the alveoli in diffuse alveolar damage (DAD) were examined by immunohistochemical methods. Lung specimens obtained at autopsy from 52 patients with DAD were stained with antibodies to laminin, 7S collagen (7S) and type IV collagen (type IV) for alveolar basement membrane, to von Willebrand factor, CD-31 and thrombomodulin (TM) for the alveolar capillary endothelial cell, and to epithelial membrane antigen and surfactant apoprotein (PE-IO) for the alveolar epithelium. Forty-two of the patients had the exudative form of DAD; 10 of the patients had the proliferative form of DAD, The results were summarized as follows: (i) laminin was most easily impaired both in the epithelial and capillary basement membrane in the early exudative stage; (ii) following laminin, 7S and type IV in the capillary basement membrane were also injured in the early exudative stage, and recovered in the proliferative stage; (iii) subsequently, 7S and type IV in the epithelial basement membrane were also impaired in the late exudative stage, and remained impaired even in the proliferative stage; and (iv) alveolar epithelium regenerated almost completely in the late exudative stage, but staining for TM in the alveolar capillary recovered in the proliferative stage. Because the alveolar basement membrane must govern the homeostasis of alveolar tissue architecture, it was concluded that its preservation is necessary to avoid the abnormal remodeling of the alveoli in the reparative stage of DAD, if the patient survives the acute episodes of the disease. C1 TOKYO MED & DENT UNIV,SCH MED,DEPT INTERNAL MED,TOKYO 113,JAPAN. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP MATSUBARA, O (reprint author), TOKYO MED & DENT UNIV,SCH MED,DEPT PATHOL,BUNKYO KU,1-5-45 YUSHIMA,TOKYO 113,JAPAN. NR 56 TC 18 Z9 18 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL AUSTR PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON 3053, AUSTRALIA SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD JUL PY 1995 VL 45 IS 7 BP 473 EP 482 DI 10.1111/j.1440-1827.1995.tb03488.x PG 10 WC Pathology SC Pathology GA RK534 UT WOS:A1995RK53400002 PM 7551006 ER PT J AU GARCIA, RDJ BAKER, AS CUNNINGHAM, MJ WEBER, AL AF GARCIA, RDJ BAKER, AS CUNNINGHAM, MJ WEBER, AL TI LATERAL SINUS THROMBOSIS ASSOCIATED WITH OTITIS-MEDIA AND MASTOIDITIS IN CHILDREN SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Review DE LATERAL SINUS THROMBOSIS; OTITIS MEDIA; MASTOIDITIS; OTITIC HYDROCEPHALUS ID CEREBRAL VENOUS THROMBOSIS; INTRACRANIAL COMPLICATIONS; PROBLEM STILL; DURAL SINUS; DIAGNOSIS; DISEASE; EAR; HYDROCEPHALUS; US AB Lateral sinus thrombosis (LST) is an infrequent complication of otitis media and mastoiditis in the antibiotic era.(1) A recent case of LST in a 7-year-old boy, the third such case at our institutions in the past 5 years,(2,3) prompted a review of the modern day English literature concerning LST in pediatric patients. Our goal was to highlight the clinical findings suggestive of LST in the antibiotic era as well as to analyze retrospectively the diagnostic and therapeutic modalities of greatest benefit based on the outcomes reported in the reviewed studies. C1 MASSACHUSETTS GEN HOSP,INFECT DIS SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT OTOLARYNGOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 35 TC 47 Z9 51 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUL PY 1995 VL 14 IS 7 BP 617 EP 623 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA RH936 UT WOS:A1995RH93600013 PM 7567293 ER PT J AU BURNS, JC WRIGHT, JD NEWBURGER, JW SCHNEEBERGER, EE MIERAU, GW SMITH, LE AF BURNS, JC WRIGHT, JD NEWBURGER, JW SCHNEEBERGER, EE MIERAU, GW SMITH, LE TI CONJUNCTIVAL BIOPSY IN PATIENTS WITH KAWASAKI-DISEASE SO PEDIATRIC PATHOLOGY & LABORATORY MEDICINE LA English DT Article DE CONJUNCTIVAL BIOPSY; DIAGNOSTIC TEST; KAWASAKI DISEASE ID LYMPH-NODE SYNDROME AB Kawasaki disease (KD) is an acute vasculitis of infants and young children that is associated with bilateral nonexudative conjunctivitis dun;ng the acute illness. Epidemiologic evidence has suggested an infectious cause but the etiology of KD remains unknown. We examined conjunctival biopsy specimens from seven patients with typical KD to characterize the pathologic changes during the acute disease. Light microscopic examination revealed nonspecific, mild inflammatory changes that included vascular dilatation, infiltration with scattered lymphocytes, increased numbers of plasma cells in the conjunctival stroma, and increased prominence of goblet cells in the epithelium. No pathogens were identified by special stains for bacteria and rickettsiae, nor were viral particles seen by electron microscopy. We conclude that the conjunctivitis of acute KD is characterized by vascular dilatation with a mild mononuclear cell response with no pathognomonic features. The conjunctiva can be readily sampled in these patients and biopsy may prove useful in selected patients to exclude other clinical entities in the differential diagnosis. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CARDIOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,ELECTRON MICROSCOPY UNIT,BOSTON,MA 02114. CHILDRENS HOSP,DEPT PATHOL,DENVER,CO 80218. RI Burns, Jane/J-6167-2015 FU NHLBI NIH HHS [HL-01855, HL-34545] NR 15 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1077-1042 J9 PEDIATR PATHOL LAB M JI Pediatr. Pathol. Lab. Med. PD JUL-AUG PY 1995 VL 15 IS 4 BP 547 EP 553 PG 7 WC Pathology; Pediatrics SC Pathology; Pediatrics GA RK590 UT WOS:A1995RK59000002 PM 8597841 ER PT J AU CASTILLO, L DEROJASWALKER, T YU, YM SANCHEZ, M CHAPMAN, TE SHANNON, D TANNENBAUM, S BURKE, JF YOUNG, VR AF CASTILLO, L DEROJASWALKER, T YU, YM SANCHEZ, M CHAPMAN, TE SHANNON, D TANNENBAUM, S BURKE, JF YOUNG, VR TI WHOLE-BODY ARGININE METABOLISM AND NITRIC-OXIDE SYNTHESIS IN NEWBORNS WITH PERSISTENT PULMONARY-HYPERTENSION SO PEDIATRIC RESEARCH LA English DT Article ID RELAXING FACTOR; ENDOTHELIAL DYSFUNCTION; DIETARY ARGININE; RELAXATION; LUNG; CIRCULATION; MECHANISMS; EXPRESSION; PATHWAY; NITRATE AB Despite the potential relevance of the L-arginine-nitric oxide (NO) pathway in the pathophysiology of pulmonary hypertension, no in vivo studies of the kinetics of arginine and NO have been conducted previously in this population. The terminal guanidino N-atom of L-arginine is the precursor for NO, which is oxidized to the stable inorganic nitrogen oxides, nitrite (NO2-) and nitrate (NO3-). Thus, synthesized NO is detected in serum or urine as NO2- and NO3-. The purpose of this investigation was to compare studies of whole body arginine metabolism twice in nine patients with persistent pulmonary hypertension of the newborn (PPHN), using a primed constant i.v. infusion of L- [guanidino-N-15(2),5,5(2)H(2)] arginine and L-[5,5,5(2)H(3)]leucine, first during acute pulmonary vasoconstriction and again during convalescence, and thereby to characterize quantitative aspects of whole body arginine kinetics and NO production, as estimated from the rate of transfer of the N-15-guanidino-label of arginine to urinary nitrate ((NO3-)-N-15). Arginine flux rates were 84.1 +/- 8.6 mu mol . kg .(-1)h(-1) (mean +/- SEM) during acute pulmonary hypertension and increased to 125 +/- 13.2 (p < 0.05) during convalescence, whereas leucine fluxes were unchanged (168.5 +/- 15 versus 178.8 +/- 10.2 mu mol . kg .(-1)h(-1)), and comparable to those reported in healthy newborns. During convalescence total urinary nitrate excreted increased by 66% (p < 0.05), urinary (NO3-)-N-15, increased from 0.29 +/- 0.07 to 0.74 +/- 0.15 mu mol . d(-1) (p < 0.05), and the rate of plasma arginine conversion to NO increased from 10.3 +/- 2.2 to 45.6 +/- 13 mu mol . d(-1) (p < 0.05). This study indicates a decreased plasma arginine utilization for whole body NO synthesis during the acute vasoconstrictive state of PPHN and suggests that arginine availability may become an important factor in NO formation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,NEONATAL INTENS CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,CHILDRENS SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PULM CARE,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. MIT,DIV TOXICOL,BOSTON,MA 02139. SHRINERS BURN INST,BOSTON,MA 02114. MIT,CLIN RES CTR,HUMAN NUTR LAB,BOSTON,MA 02139. RP CASTILLO, L (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,PEDIAT INTENS CARE UNIT,ELLISON 317,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-26731]; NCRR NIH HHS [RR88]; NIDDK NIH HHS [DK 15856] NR 48 TC 57 Z9 58 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JUL PY 1995 VL 38 IS 1 BP 17 EP 24 DI 10.1203/00006450-199507000-00004 PG 8 WC Pediatrics SC Pediatrics GA RF130 UT WOS:A1995RF13000004 PM 7478791 ER PT J AU COLDITZ, GA BERKEY, CS MOSTELLER, F BREWER, TF WILSON, ME BURDICK, E FINEBERG, HV AF COLDITZ, GA BERKEY, CS MOSTELLER, F BREWER, TF WILSON, ME BURDICK, E FINEBERG, HV TI THE EFFICACY OF BACILLUS-CALMETTE-GUERIN VACCINATION OF NEWBORNS AND INFANTS IN THE PREVENTION OF TUBERCULOSIS - METAANALYSES OF THE PUBLISHED LITERATURE SO PEDIATRICS LA English DT Article DE BACILLUS CALMETTE-GUERIN VACCINATION; TUBERCULOSIS; INFANTS; METAANALYSIS ID BCG VACCINATION; CONSUMPTION; INDIANS; TRIALS; CANCER; LIFE; RISK AB Objective. To quantify the efficacy of vaccination of infants with bacillus Calmette-Guerin (BCG) against tuberculosis. Data sources. MEDLINE with index terms BCG vaccine, tuberculosis, and human; lists of all known studies provided by experts at the Centers for Disease Control and Prevention, the World Health Organization, and other organizations. Study selection. A total of 1264 articles and abstracts were reviewed for details on BCG vaccination, the availability of concurrent vaccinated and unvaccinated groups, and a tuberculosis outcome. Seventy articles were reviewed in depth for method of vaccine allocation used to create comparable groups, age at vaccination of study participants, comparability of surveillance and follow-up of recipient and concurrent control groups in trials, an appropriately defined control group in case-control studies, and outcome measures (tuberculosis cases and/or deaths). Five prospective trials and eleven case-control studies of vaccination during infancy were included in the present analyses. Data extraction. We recorded study design, age range of study population, number of patients enrolled, efficacy of vaccine, location of the study, and a series of items to assess the potential for bias in study design, follow-up, and diagnosis. We extracted or computed vaccine efficacy by years since vaccination wherever possible. At least two readers independently extracted data and evaluated data validity. Data synthesis. The relative risk (RR) or odds ratio (OR) for tuberculosis in vaccinated versus unvaccinated infants was the measure of vaccine efficacy analyzed. A random-effects method estimated a weighted average RR or OR from data extracted from the trials and case-control studies. The protective effect was then computed by 1-RR or 1-OR, Overall, the protective effect of vaccination against cases of tuberculosis was 0.74 (95% confidence interval [95% CI], 0.62 to 0.83) when estimated from four randomized controlled trials, and 0.52 (95% CI, 0.38 to 0.64) when estimated from nine case-control studies. Five trials reporting deaths from tuberculosis showed a BCG protective effect of 0.65 (95% CI, 0.12 to 0.86), five studies reporting on meningitis showed a protective effect of 0.64 (95% CI, 0.30 to 0.82), and three studies of disseminated tuberculosis showed a protective effect of 0.78 (95% CI, 0.58 to 0.88). Three case-control studies included separate results for laboratory-confirmed cases of tuberculosis. These studies documented a protective effect of 0.83 (95% CI, 0.58 to 0.93). In a random-effects regression model of the nine case-control studies, study validity score explained 15% of the heterogeneity among study-estimated protective effects, suggesting that better studies reported greater efficacy. Three trials and six case-control studies provided some age-specific information that allowed us to examine the duration of BCG efficacy. Most of this evidence suggested that BCG efficacy may persist through 10 years after infant vaccination. Conclusion. BCG vaccination of newborns and infants significantly reduces the risk of tuberculosis-by over 50%, on average. Protection has been observed across many populations, study designs, and forms of tuberculosis. Rates of protection against cases that are confirmed by laboratory tests, reflecting reduced error in disease classification and consequently more accurate estimates of BCG efficacy, are highest at 83%. C1 BRIGHAM & WOMENS HOSP,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA. MT AUBURN HOSP,INFECT DIS UNIT,CAMBRIDGE,MA. RP COLDITZ, GA (reprint author), HARVARD UNIV,SCH PUBL HLTH,TECHNOL ASSESSMENT GRP,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 42 TC 446 Z9 460 U1 1 U2 14 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 1995 VL 96 IS 1 BP 29 EP 35 PN 1 PG 7 WC Pediatrics SC Pediatrics GA RH182 UT WOS:A1995RH18200006 PM 7596718 ER PT J AU HWANG, IW GOODMAN, HM AF HWANG, IW GOODMAN, HM TI AN ARABIDOPSIS-THALIANA ROOT-SPECIFIC KINASE HOMOLOG IS INDUCED BY DEHYDRATION, ABA, AND NACL SO PLANT JOURNAL LA English DT Article ID RECEPTOR PROTEIN-KINASE; HORMONE ABSCISIC-ACID; WATER-STRESS; SIGNAL TRANSDUCTION; PLANT-CELLS; RICE GENE; EXPRESSION; PHOSPHORYLATION; TYROSINE; TOLERANCE AB Genomic and cDNA clones have been isolated for an Arabidopsis thaliana gene, ARSK1, that encodes a protein with structural similarities to serine/threonine kinases. Expression of ARSK1 is root specific and is induced by exposing roots to air during growth or by treatment of roots with ABA or NaCl. ARSK1 gene expression in transgenic plants is confined to cells in the tissues of the root as measured by beta-glucuronidase (GUS) expression from an ARSK1 gene promoter-GUS gene construct. Transverse sections of the stained roots further defined the tissue-specificity; high levels of expression in the epidermal, endoepidermal and cortex regions, but no or very little expression in the vascular system. Another feature of the expression pattern of the ARSK1 gene was a gradual increase in the expression level along the root with the highest level of expression in the region closest to the root meristem. These studies suggest that ARSK1 may have a role in the signal transduction pathway of osmotic stress. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 48 TC 59 Z9 64 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7412 J9 PLANT J JI Plant J. PD JUL PY 1995 VL 8 IS 1 BP 37 EP 43 DI 10.1046/j.1365-313X.1995.08010037.x PG 7 WC Plant Sciences SC Plant Sciences GA RJ580 UT WOS:A1995RJ58000004 PM 7655506 ER PT J AU ASAHINA, A HOSOI, J MURPHY, GF GRANSTEIN, RD AF ASAHINA, A HOSOI, J MURPHY, GF GRANSTEIN, RD TI CALCITONIN-GENE-RELATED PEPTIDE MODULATES LANGERHANS CELL ANTIGEN-PRESENTING FUNCTION SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article ID NERVE-FIBERS; HUMAN-SKIN; CAPSAICIN; IMMUNOREACTIVITY; INNERVATION; RATS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,HARVARD CUTANEOUS BIOL RES CTR,SCH MED,DEPT DERMATOL,BOSTON,MA 02129. UNIV PENN,PHILADELPHIA,PA. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,PHILADELPHIA,PA. FU NIAMS NIH HHS [AR40667, AR42429] NR 18 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE 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 1995 VL 107 IS 2 BP 242 EP 244 PG 3 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA TF498 UT WOS:A1995TF49800011 PM 8624859 ER PT J AU STREIM, JE AF STREIM, JE TI OBRA REGULATIONS AND PSYCHIATRIC-CARE IN THE NURSING-HOME SO PSYCHIATRIC ANNALS LA English DT Article ID FACILITIES; RESTRAINTS; IMPACT C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP STREIM, JE (reprint author), UNIV PENN,DEPT PSYCHIAT,GERIATR PSYCHIAT SECT,RALSTON PENN CTR,3615 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. NR 29 TC 10 Z9 10 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 1995 VL 25 IS 7 BP 413 EP 418 PG 6 WC Psychiatry SC Psychiatry GA RH497 UT WOS:A1995RH49700006 ER PT J AU KUNIN, HM PATENAUDE, AF GRIER, HE AF KUNIN, HM PATENAUDE, AF GRIER, HE TI SUICIDE RISK IN PEDIATRIC CANCER-PATIENTS - AN EXPLORATORY-STUDY SO PSYCHO-ONCOLOGY LA English DT Article AB This descriptive, retrospective study was undertaken to identify suicide histories in children and adolescents at a pediatric cancer center and to identify potential suicide risk factors in this population. Physicians, nurse practitioners, psychologists and social workers at the Dana-Farber Cancer Institute were surveyed to identify patients known to have made suicide attempts, successful or not. Medical and psychosocial histories, including specifics of the event, were obtained from a semi-structured interview with the respondent and a review of the medical chart, and evaluated for psychosocial risk factors. Thirty-eight clinicians identified 10 patients with suicidal events between 1974 and 1991: two successful suicides, four unsuccessful attempts, two deaths under nuclear circumstances and two instances of self-destructive behavior with unclear intent. Subjects ranged in age from 10 to 27 years at the time of the event (median age 16.34 years) and diagnoses included Hodgkin's disease (4), leukemia (2), Ewing's sarcoma, osteosarcoma, soft tissue sarcoma and neuroblastoma. Psychosocial risk factors or stresses of the current medical situation were present in nine out of the 10 patients (median score, 4 factors). Depression or hopelessness was present in eight patients, and stressful familial events (in addition to patient's illness) such as parental divorce, additional familial illness or financial pressures were present in seven patients. Current medical factors, such as advanced illness/poor prognosis and pain management issues, were present in three and two patients, respectively. Six out of the 10 subjects were off medical treatment at the time of their attempts. Suicide or suicide attempts in this sample indicated that medical factors alone are not adequate to explain the emotional states which may give rise to self-destructive behavior. Psychosocial stressors from non-medical sources appear to contribute to increased suicide risk for pediatric cancer patients. The finding that six out of 10 suicide attempts occurred in cancer survivors raises concers about the special risk to this population. These findings suggest more extensive study is needed of suicidal behavior among pediatric cancer patients and, particularly, survivors of pediatric cancer. In addition to further identification of specific medical and psychosocial factors, the interrelationship between these factors needs to be better understood for its potential to contribute to suicidality in this population. The cumulative effect of chronic stress from medical factors also deserves further investigation. C1 CHILDRENS HOSP MED CTR,DIV HEMATOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DIV ONCOL & PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP KUNIN, HM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 18 TC 6 Z9 6 U1 3 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JUL PY 1995 VL 4 IS 2 BP 149 EP 155 DI 10.1002/pon.2960040209 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA RM403 UT WOS:A1995RM40300046 ER PT J AU KUNIN, H AF KUNIN, H TI HOW WE DIE - REFLECTIONS ON LIFES FINAL CHAPTER - NULAND,SB SO PSYCHO-ONCOLOGY LA English DT Book Review RP KUNIN, H (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JUL PY 1995 VL 4 IS 2 BP 163 EP 163 DI 10.1002/pon.2960040211 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA RM403 UT WOS:A1995RM40300047 ER PT J AU CALABRESE, LV STERN, TA AF CALABRESE, LV STERN, TA TI NEUROPSYCHIATRIC MANIFESTATIONS OF SYSTEMIC LUPUS-ERYTHEMATOSUS SO PSYCHOSOMATICS LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; POSITRON EMISSION TOMOGRAPHY; MAGNETIC-RESONANCE; LYMPHOCYTOTOXIC ANTIBODIES; NEURONAL ANTIBODIES; CHOROID-PLEXUS; CNS LUPUS; INVOLVEMENT; DISEASE; ASSOCIATION AB The authors critically review the literature describing the varied neuropsychiatric syndromes associated with systemic lupus erythematosus (SLE). Factors that have complicated the identification and treatment of affective, behavioral, and cognitive disturbances in these patents are identified, and the utility of various diagnostic interventions is examined. Finally, the authors outline the role of the consultation-liaison psychiatrist in the clinical management of the SLE patient with neuropsychiatric disturbances. C1 MASSACHUSETTS GEN HOSP,AVERY D WEISMAN PSYCHIAT CONSULTAT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. NR 109 TC 24 Z9 24 U1 3 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 1995 VL 36 IS 4 BP 344 EP 359 PG 16 WC Psychiatry; Psychology SC Psychiatry; Psychology GA RG587 UT WOS:A1995RG58700005 PM 7652137 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI STRESS, CATECHOLAMINES, AND CARDIOVASCULAR-DISEASE - GOLDSTEIN,DS SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP GREENBERG, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 1995 VL 36 IS 4 BP 412 EP 413 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA RG587 UT WOS:A1995RG58700013 ER PT J AU PETEET, JR AF PETEET, JR TI SURVIVING TRANSPLANTATION - A PERSONAL GUIDE FOR ORGAN TRANSPLANT PATIENTS, THEIR FAMILIES, FRIENDS AND CAREGIVERS - CRAVEN,J, FARROW,S SO PSYCHOSOMATICS LA English DT Book Review RP PETEET, JR (reprint author), BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 1995 VL 36 IS 4 BP 413 EP 414 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA RG587 UT WOS:A1995RG58700014 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI MEDICAL-PSYCHIATRIC PRACTICE, VOL 3 - STOUDEMIRE,A, FOGEL,BS SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP GREENBERG, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 1995 VL 36 IS 4 BP 414 EP 415 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA RG587 UT WOS:A1995RG58700015 ER PT J AU ZAMBUTO, D BRAMSON, RT BLICKMAN, JG AF ZAMBUTO, D BRAMSON, RT BLICKMAN, JG TI INTRACOLONIC PRESSURE MEASUREMENTS DURING HYDROSTATIC AND AIR CONTRAST BARIUM ENEMA STUDIES IN CHILDREN SO RADIOLOGY LA English DT Article DE BARIUM ENEMA EXAMINATION; BARIUM ENEMA EXAMINATION, IN INFANTS AND CHILDREN; INTUSSUSCEPTION ID INTUSSUSCEPTION; PERFORATION AB PURPOSE: To prospectively evaluate intraluminal pressure changes in the colon of children undergoing conventional hydrostatic (barium and water-soluble contrast material) and air contrast barium enema studies. MATERIALS AND METHODS: Dynamic intracolonic pressure was measured in 26 children undergoing hydrostatic barium (23% wt/vol) enema studies, air contrast barium enema studies, or water-soluble contrast material enema examinations. Measurements were obtained with a measuring device capable of recording rapid changes in pressure. Pressure measurements were obtained with the contrast reservoir system open (contrast material was free to run through the tubing into the patient's colon) and closed (tube was clamped). RESULTS: The colonic pressures during the filling phase with liquid contrast material were equal to those elsewhere at the same level with the hydrostatic system. Mean pressure ranged from 30 to 50 mm Hg with peaks of more than 100 mm Hg during Valsalva maneuvers. During air contrast barium enema studies, sharp pressure increases and rapid swings in the intracolonic pressure occurred during and after manual insufflation of air. CONCLUSION: During conventional hydrostatic barium enema studies, intracolonic pressures remain low. During air insufflation, there were intermittent high, sharp pressure peaks. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,PEDIAT IMAGING SECT,BOSTON,MA 02114. NR 11 TC 21 Z9 23 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 1995 VL 196 IS 1 BP 55 EP 58 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RE308 UT WOS:A1995RE30800015 PM 7784589 ER PT J AU GUPTA, H WEISSLEDER, R BOGDANOV, AA BRADY, TJ AF GUPTA, H WEISSLEDER, R BOGDANOV, AA BRADY, TJ TI EXPERIMENTAL GASTROINTESTINAL HEMORRHAGE - DETECTION WITH CONTRAST-ENHANCED MR-IMAGING AND SCINTIGRAPHY SO RADIOLOGY LA English DT Article DE CONTRAST MEDIA, COMPARATIVE STUDIES; GASTROINTESTINAL TRACT, HEMORRHAGE; GASTROINTESTINAL TRACT RADIONUCLIDE STUDIES; MAGNETIC RESONANCE (MR), CONTRAST ENHANCEMENT; MAGNETIC RESONANCE (MR), VASCULAR STUDIES AB PURPOSE: To examine the use of O-methoxy poly(ethylene)glycol-O'succinyl-N-epsilon-poly(L-lysyl) gadblinium diethylenetriaminepentaacetic acid (MPEG-PL-Gd-DTPA) as a potential magnetic resonance (MR) angiographic contrast agent for the detection of gastrointestinal (GI) bleeding. MATERIALS AND METHODS: MPEG-PL-Gd-DTPA was used for blood pool enhancement, and MPEG-PL-technetium-99m DTPA was used for planar nuclear imaging studies. GI bleeding was tested in rats by controlled injection of contrast material-doped blood through a jejunostomy catheter. MR imaging was performed at 1.5 T. RESULTS: Ideal flip angle, used with a spoiled gradient-echo pulse sequence, was 40 degrees. The smallest amount of hemorrhage detected at MR imaging was 0.05 mL; at nuclear imaging it was 0.02 mL. With the superior spatial resolution of MR imaging, individual loops of contrast material-filled bowel were identified and bleeding points were pinpointed. CONCLUSION: GI hemorrhage can be easily detected at MR imaging if a long circulating macromolecular contrast agent is used to decrease the T1 of extravasated blood. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 14 TC 14 Z9 14 U1 0 U2 1 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 1995 VL 196 IS 1 BP 239 EP 244 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RE308 UT WOS:A1995RE30800043 PM 7784574 ER PT J AU ACKMAN, JB ROSENTHAL, DI AF ACKMAN, JB ROSENTHAL, DI TI GENERALIZED PERIARTICULAR MYOSITIS-OSSIFICANS AS A COMPLICATION OF PHARMACOLOGICALLY INDUCED PARALYSIS SO SKELETAL RADIOLOGY LA English DT Note C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JUL PY 1995 VL 24 IS 5 BP 395 EP 397 PG 3 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA RJ199 UT WOS:A1995RJ19900020 PM 7570166 ER PT J AU KEARSE, LA LOPEZBRESNAHAN, M MCPECK, K ZASLAVSKY, A AF KEARSE, LA LOPEZBRESNAHAN, M MCPECK, K ZASLAVSKY, A TI PREOPERATIVE CEREBROVASCULAR SYMPTOMS AND ELECTROENCEPHALOGRAPHIC ABNORMALITIES DO NOT PREDICT CEREBRAL-ISCHEMIA DURING CAROTID ENDARTERECTOMY SO STROKE LA English DT Article DE ANESTHESIA; CAROTID ENDARTERECTOMY; CEREBRAL ISCHEMIA; ELECTROENCEPHALOGRAPHY ID BLOOD-FLOW; SPECTRAL-ANALYSIS; EEG FREQUENCY; INFARCTION; DISEASE; HEALTHY; OLD AB Background and Purpose The purpose of this prospective study was to establish (1) whether patients with neurological symptoms scheduled for carotid endarterectomy had an increased incidence of electroencephalographic (EEG) abnormalities during awake baseline recordings, (2) whether these symptoms and EEG abnormalities predicted ischemic EEG pattern changes at carotid artery cross-clamp, and (3) whether there was an association between age, presence of EEG baseline abnormalities, and ischemic pattern changes at carotid artery cross-clamp. Methods We reviewed the medical record of each patient scheduled to undergo carotid endarterectomy and recorded the patient's age and history of previous neurological symptoms. We then continuously monitored and analyzed 16 channels of anteroposterior bipolar EEG and two of referential derivations from at least 5 minutes before induction of anesthesia and throughout the operation. Results We completed 394 consecutive studies. Preoperative neurological symptoms were related to EEG abnormalities in awake patients (P<.001) and to EEG asymmetries in anesthetized patients (P<.001). Abnormal awake EEG findings were associated with asymmetries after anesthesia (P<.0001). Twenty-eight percent of both symptomatic (70/249) and asymptomatic (41/145) patients had EEG ischemic pattern changes at carotid artery cross-clamp. Neither neurological symptoms nor EEG abnormalities were associated with age or the development of EEG ischemic pattern changes at carotid artery cross-clamp. Conclusions Despite the strong association between a history of cerebral ischemic symptoms and preoperative EEG abnormalities in patients undergoing carotid endarterectomy, patients who have suffered strokes or transient ischemic events are at no greater risk of having EEG evidence of cerebral ischemia during carotid artery cross-clamp than patients without symptoms and with normal baseline EEGs. We conclude that preoperative EEG abnormalities in symptomatic patients are not due to age or to insufficiency of regional cerebral blood flow. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & NEUROL,BOSTON,MA 02114. HARVARD UNIV,DEPT STAT,CAMBRIDGE,MA 02138. RP KEARSE, LA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 23 TC 10 Z9 10 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 1995 VL 26 IS 7 BP 1210 EP 1214 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA RG251 UT WOS:A1995RG25100014 PM 7604416 ER PT J AU GRABOWSKI, EF LAM, FP AF GRABOWSKI, EF LAM, FP TI ENDOTHELIAL-CELL FUNCTION, INCLUDING TISSUE FACTOR EXPRESSION, UNDER FLOW CONDITIONS SO THROMBOSIS AND HAEMOSTASIS LA English DT Article; Proceedings Paper CT XVth Congress of the International-Society-on-Thrombosis-and-Haemostasis CY JUN 12-15, 1995 CL JERUSALEM, ISRAEL SP Int Soc Thrombosis & Haemostasis ID FLUID SHEAR-STRESS; FIBROBLAST GROWTH-FACTOR; TUMOR NECROSIS FACTOR; PROTEIN-KINASE-C; VASCULAR ENDOTHELIUM; ATHEROSCLEROTIC LESIONS; SUBENDOTHELIAL MATRIX; MESSENGER-RNA; SURFACE; THROMBOPLASTIN C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NHLBI NIH HHS [HL33095] NR 50 TC 42 Z9 44 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUL PY 1995 VL 74 IS 1 BP 123 EP 128 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RP386 UT WOS:A1995RP38600021 PM 8578444 ER PT J AU Horstman, DH Ball, BA Brown, J Gerrity, T Folinsbee, LJ AF Horstman, DH Ball, BA Brown, J Gerrity, T Folinsbee, LJ TI Comparison of pulmonary responses of asthmatic and nonasthmatic subjects performing light exercise while exposed to a low level of ozone SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE asthma; light exercise; ozone; prolonged exposure; pulmonary function ID HOSPITAL ADMISSIONS; AIR-POLLUTION; MODERATE EXERCISE; SOUTHERN ONTARIO; UNITED-STATES; 0.12 PPM; HEALTHY AB To determine if asthmatic subjects (ASTH, n = 17) experience greater O-3-induced pulmonary decrements than nonasthmatic subjects (NONA, n = 13), both groups were exposed for 7.6 h to both clean air and 0.16 ppm O-3. Exposures consisted of seven 50-min periods of light exercise (V-E = 14.2 and 15.3 l/min/m(2) for ASTH and NONA, respectively), each followed by 10 min rest. A 35-min lunch period followed the third exercise. Following O-3 exposure, decrements in forced expiratory volume in one second (FEV(1)) and FEV(1) divided by forced viral capacity (FVC), corrected for air exposure, for ASTH (-19.4 +/- 3.1 % and 6.2 +/- 2%, respectively) were significantly greater (p = 0.04 and 0.02) than for NONA (-9.8 +/- 1.9% and -1 +/- 1%, respectively). There was no difference (p = 0.33) for decrements in FVC between ASTH (-11.8 +/- 1.9%) and NONA (-8.8 +/- 2.1%). Nine of 17 ASTH experienced wheezing with O-3, while only one experienced wheezing with air (p = 0.004); no NONA experienced wheezing. Six of 17 ASTH requested inhaled P-agonist bronchodilator prior to and/or during O-3 exposure and experienced some temporary alleviation of decrements. At end exposure, however, ASTH who were medicated had greater Os-induced decrements than those who were not medicated. ASTH who had the larger Os-induced decrements had lower baseline FEV(1)/FVC and lower baseline %predicted FEV(1). These data indicate that in ASTH, unlike NONA, some portion of O-3-induced pulmonary decrements experienced was related to bronchoconstriction, and that O-3-responsiveness for ASTH depended upon baseline airway status. C1 UNIV N CAROLINA,CTR ENVIRONM MED & LUNG BIOL,CHAPEL HILL,NC. US DEPT VET AFFAIRS,MED RES SERV,WASHINGTON,DC. RP Horstman, DH (reprint author), US EPA,NATL HLTH & ENVIRONM EFFECTS RES LAB,DIV HUMAN STUDIES,CLIN RES BRANCH MD58B,RES TRIANGLE PK,NC 27711, USA. NR 24 TC 35 Z9 36 U1 1 U2 3 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-AUG PY 1995 VL 11 IS 4 BP 369 EP 385 PG 17 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA TK629 UT WOS:A1995TK62900001 PM 8748419 ER PT J AU POPOVSKY, MA BENSON, K GLASSMAN, AB HUME, H OBERMAN, HA PISCIOTTO, PT ANDERSON, KC AF POPOVSKY, MA BENSON, K GLASSMAN, AB HUME, H OBERMAN, HA PISCIOTTO, PT ANDERSON, KC TI TRANSFUSION PRACTICES IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS SO TRANSFUSION LA English DT Article ID HOMOLOGOUS BLOOD-TRANSFUSIONS; POSTOPERATIVE INFECTION; PREVENTION; SURVIVAL; SURGERY; COLON; RECURRENCE; LEUKOCYTES; PROGRAMS; CANCER AB Background: The reported immunomodulatory effects of transfusion raise concern about the potential for virus activation and tumor growth in human immunodeficiency virus (HIV)-infected patients. In the absence of ''standards'' of transfusion practice for such patients, a survey of transfusion policies among institutions specializing in the care of HIV-infected patients was performed to delineate current practices. Study Design and Methods: A survey developed by the Transfusion Practices Committee of the American Association of Blood Banks was sent to 47 AIDS clinical trial units and 14 regional hemophilia centers in North America, Results: Forty-three percent of centers completed the survey. Most centers observed more than 200 HIV-infected patients each. The key findings were that 1) 81 percent of centers used identical red cell transfusion criteria for HIV-infected and noninfected patients; 2) 52 percent used recombinant human erythropoietin as initial treatment for zidovudine-induced anemia, while 46 percent used recombinant human erythropoietin for anemia not associated with zidovudine; 3) 35 percent of centers used white cell-reduced blood components in lieu of cytomegalovirus (CMV)-seronegative components when administering transfusion(s) to CMV-seronegative patients; 4) 27 percent gamma-radiated cellular components, but no case of graft-versus-host disease had been observed; 5) >85 percent of centers used monoclonal factor VIII for pediatric and adult hemophiliacs infected with HIV; 6) approximately one-third of centers routinely white cell-reduced cellular components; and 7) the most common reasons for white cell reduction included reduction of febrile reactions and CMV risk, reduction of platelet alloimmunization, and delay of immunomodulatory consequences of transfusion. Conclusion: There is marked heterogeneity in transfusion practice for HIV-infected patients, Modification of cellular components to achieve different objectives is routine in many centers. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV S FLORIDA,COLL MED,DEPT LAB MED & PATHOL,TAMPA,FL. H LEE MOFFIT CANC CTR & RES INST,BLOOD BANK,TAMPA,FL. H LEE MOFFIT CANC CTR & RES INST,HLA LABS,TAMPA,FL. UNIV TEXAS,MD ANDERSON CANCER CTR,DIV LAB MED,HOUSTON,TX 77030. UNIV MONTREAL,HOP ST JUSTINE,MONTREAL,PQ H3T 1C5,CANADA. UNIV MICHIGAN HOSP,DEPT PATHOL,ANN ARBOR,MI 48109. UNIV MICHIGAN HOSP,BLOOD BANK,ANN ARBOR,MI 48109. UNIV MICHIGAN HOSP,TRANSFUS SERV,ANN ARBOR,MI 48109. UNIV CONNECTICUT,CTR HLTH,DEPT LAB MED,FARMINGTON,CT. UNIV CONNECTICUT,CTR HLTH,BLOOD BANK,FARMINGTON,CT. UNIV CONNECTICUT,CTR HLTH,HEMATOL LABS,FARMINGTON,CT. DANA FARBER CANC INST,BLOOD BANK,BOSTON,MA 02115. RP POPOVSKY, MA (reprint author), AMER RED CROSS,BLOOD SERV,180 RUSTCRAFT RD,DEDHAM,MA 02026, USA. NR 35 TC 23 Z9 23 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 JUL PY 1995 VL 35 IS 7 BP 612 EP 616 DI 10.1046/j.1537-2995.1995.35795357887.x PG 5 WC Hematology SC Hematology GA RJ261 UT WOS:A1995RJ26100016 PM 7631396 ER PT J AU BALERCIA, G BHAN, AK DICKERSIN, GR AF BALERCIA, G BHAN, AK DICKERSIN, GR TI SARCOMATOID CARCINOMA - AN ULTRASTRUCTURAL-STUDY WITH LIGHT-MICROSCOPIC AND IMMUNOHISTOCHEMICAL CORRELATION OF 10 CASES FROM VARIOUS ANATOMIC SITES SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Ultrastructural-Pathology (UltraPath VII) on Diagnostic Electron Microscopy of Tumors CY AUG, 1994 CL STEAMBOAT SPRINGS, CO SP Soc Ultrastruct Pathol DE CARCINOSARCOMA; ELECTRON MICROSCOPY; SARCOMATOID CARCINOMA; ULTRASTRUCTURE ID SPINDLE-CELL-CARCINOMA; MIXED MULLERIAN TUMORS; FEMALE GENITAL-TRACT; URINARY-BLADDER; RENAL PELVIS; HEPATOCELLULAR-CARCINOMA; INTERMEDIATE FILAMENTS; CYTOKERATIN EXPRESSION; METAPLASTIC CARCINOMA; AERODIGESTIVE TRACT AB The histogenesis of sarcomatoid carcinoma has been an intriguing topic for pathologists for many years, and considerable evidence has accumulated in the fields of tissue culture, electron microscopy, and immunohistochemistry to support the concept that the sarcomatous cells derive by way of ''divergent differentiation'' (metaplasia) from the carcinomatous elements. We have studied a group of 10 cases of these tumors from various organs, using detailed ultrastructural analysis as well as light microscopic and immunohistochemical correlation. We found that there is an ultrastructural spectrum of differentiation from epithelial to mesenchymal type features and that the malignant spindle cells may be purely epithelial (3 cases), purely mesenchymal (3 cases), or a mixture of both (4 cases). Furthermore, individual cells may show biphasia, having desmosomes and tonofibriis as well as well developed rough endoplasmic reticulum and filaments with dense bodies. Electron microscopic and immunohistochemical results do not always correlate, illustrating the prudence of using several keratin antibodies, including wide-spectrum ones, and of performing electron microscopic examination on these tumors. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. UNIV VERONA,DEPT ANAT,I-37100 VERONA,ITALY. HARVARD UNIV,SCH MED,BOSTON,MA. NR 78 TC 39 Z9 40 U1 1 U2 2 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD JUL-AUG PY 1995 VL 19 IS 4 BP 249 EP 263 PG 15 WC Microscopy; Pathology SC Microscopy; Pathology GA RJ314 UT WOS:A1995RJ31400004 PM 7571082 ER PT J AU BARRY, MJ FLEMING, C COLEY, CM WASSON, JH FAHS, MC OESTERLING, JE AF BARRY, MJ FLEMING, C COLEY, CM WASSON, JH FAHS, MC OESTERLING, JE TI SHOULD MEDICARE PROVIDE REIMBURSEMENT FOR PROSTATE-SPECIFIC ANTIGEN TESTING FOR EARLY DETECTION OF PROSTATE-CANCER .1. FRAMING THE DEBATE SO UROLOGY LA English DT Review ID UNITED-STATES MEN; RADICAL PROSTATECTOMY; CLINICAL STAGE; DIETARY-FAT; TUMOR VOLUME; FOLLOW-UP; ADENOCARCINOMA; CARCINOMA; RISK; VASECTOMY C1 HLTH OUTCOMES ASSOCIATES,VANCOUVER,WA. DARTMOUTH COLL,SCH MED,CTR EVALUAT CLIN SCI,HANOVER,NH 03755. MT SINAI SCH MED,DEPT COMMUNITY MED,DIV HLTH ECON,NEW YORK,NY. MT SINAI SCH MED,US INT LONGEV CTR,NEW YORK,NY. UNIV MICHIGAN,ANN ARBOR,MI 48109. RP BARRY, MJ (reprint author), MASSACHUSETTS GEN HOSP,MED PRACTICES EVALUAT CTR,BOSTON,MA 02114, USA. FU AHRQ HHS [HS 06336, HS 08397] NR 130 TC 28 Z9 28 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUL PY 1995 VL 46 IS 1 BP 2 EP 13 DI 10.1016/S0090-4295(99)80151-4 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA RG401 UT WOS:A1995RG40100002 PM 7541583 ER PT J AU FILLEY, CM KLEINSCHMIDTDEMASTERS, BK AF FILLEY, CM KLEINSCHMIDTDEMASTERS, BK TI NEUROBEHAVIORAL PRESENTATIONS OF BRAIN NEOPLASMS SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID TEMPORAL-LOBE; BEHAVIOR; DISORDER; DISEASE AB We studied 8 patients with frontal or temporolimbic neoplasms who had psychiatric presentations to clarify diagnostic criteria for distinguishing psychiatric disease from structural brain lesions and to examine brain-behavior relationships associated with cerebral neoplasms using modern neuroimaging techniques. Medical records were retrospectively reviewed for evidence of neurobehavioral and neurologic manifestations, tumor histologic features, and the results of treatment. Clinical presentations were correlated with tumor location as determined by computed tomography and magnetic resonance imaging. Patients with frontal lobe tumors presented with abulia, personality change, or depression, whereas those with temporolimbic tumors had auditory and visual hallucinations, mania, panic attacks, or amnesia. After treatment, neurobehavioral syndromes abated or resolved in 7 of 8 patients. We recommend that any patient 40 years of age or older with a change in mental state, cognitive or emotional, should have neuroimaging of the brain. Any patient with a psychiatric presentation who has specific neurobehavioral or neurologic findings or an unexpectedly poor response to psychopharmacologic treatment should also have brain imaging. These case reports extend and update observations on the importance of frontal and temporolimbic systems in the pathogenesis of neurobehavioral disorders. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PATHOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. DENVER VET AFFAIRS MED CTR,DENVER,CO. RP FILLEY, CM (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT NEUROL,BEHAV NEUROL SECT,4200 E 9TH AVE,DENVER,CO 80262, USA. NR 22 TC 41 Z9 43 U1 0 U2 1 PU CALIF MEDICAL ASSN PI SAN FRANCISCO PA 221 MAIN STREET, SAN FRANCISCO, CA 94105 SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD JUL PY 1995 VL 163 IS 1 BP 19 EP 25 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RL563 UT WOS:A1995RL56300001 PM 7667978 ER PT J AU WILLIAMS, JW AF WILLIAMS, JW TI SINUSITIS - BEGINNING A NEW-AGE OF ENLIGHTENMENT SO WESTERN JOURNAL OF MEDICINE LA English DT Editorial Material C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP WILLIAMS, JW (reprint author), UNIV TEXAS,HLTH SCI CTR,DIV GEN INTERNAL MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 4 TC 4 Z9 4 U1 0 U2 0 PU CALIF MEDICAL ASSN PI SAN FRANCISCO PA 221 MAIN STREET, SAN FRANCISCO, CA 94105 SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD JUL PY 1995 VL 163 IS 1 BP 80 EP 82 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA RL563 UT WOS:A1995RL56300021 PM 7667997 ER PT J AU AOKI, Y KIM, YT STILLWELL, R KIM, TJ PILLAI, S AF AOKI, Y KIM, YT STILLWELL, R KIM, TJ PILLAI, S TI THE SH2 DOMAINS OF SRC FAMILY KINASES ASSOCIATE WITH SYK SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ANTIGEN RECEPTOR; PROTEIN-TYROSINE KINASE; X-LINKED AGAMMAGLOBULINEMIA; LYMPHOCYTES-B; ZETA-CHAIN; STIMULATION; EXPRESSION; GENE; PHOSPHORYLATION; ACTIVATION AB Src family kinases (Lyn, Fyn, Lck, and Blk) and Syk, a tandem SH2 domain containing tyrosine kinase, have been demonstrated to be associated with the antigen receptor in B cells. Both of these categories of tyrosine kinases are presumed to be critical players in the process of antigen-mediated signal transduction. Cross linking of membrane immunoglobulin on the surface of B cells leads to the activation of Lyn, Fyn, and Blk, which presumably associate with the cytoplasmic tails of the membrane immunoglobulin-associated Ig alpha/beta heterodimer. Receptor ligation also leads to the tyrosine phosphorylation and catalytic activation of Syk, but the mechanism of association of this kinase with the antigen receptor remains to be established, A number of phosphoproteins that can associate with the SH2 domains of Blk, Lyn, and Fyn have been described in activated B cells. We demonstrate here that Syk is one of the proteins in the lysates of activated B cells which bind to the SH2 domains of Src family kinases. Syk binds directly to the SH2 domain of Blk and complexes in vivo with Lyn and Blk in activated B cells. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02139. RI Kim, Tae Jin/D-6544-2011 OI Kim, Tae Jin/0000-0001-9802-0568 FU NIAID NIH HHS [AI-27835, AI-33507] NR 40 TC 29 Z9 29 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 30 PY 1995 VL 270 IS 26 BP 15658 EP 15663 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RG538 UT WOS:A1995RG53800036 PM 7797565 ER PT J AU LI, SW OKAMOTO, T CHUN, MY SARGIACOMO, M CASANOVA, JE HANSEN, SH NISHIMOTO, I LISANTI, MP AF LI, SW OKAMOTO, T CHUN, MY SARGIACOMO, M CASANOVA, JE HANSEN, SH NISHIMOTO, I LISANTI, MP TI EVIDENCE FOR A REGULATED INTERACTION BETWEEN HETEROTRIMERIC G-PROTEINS AND CAVEOLIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH FACTOR-II; TRANS-GOLGI-NETWORK; ALPHA-SUBUNIT; GTP-BINDING; GUANINE-NUCLEOTIDES; EPITHELIAL-CELLS; MEMBRANE-PROTEIN; PLASMA-MEMBRANE; RECEPTOR; INSULIN AB Caveolae are flash-shaped plasma membrane specializations, A 22-kDa protein, caveolin, is a principal component of caveolar membranes in vivo, As recent evidence suggests that caveolae may participate in G protein-coupled signaling events, we have investigated the potential interaction of caveolin with heterotrimeric G proteins, Using cell fractionation techniques, we found that mutational or pharmacologic activation of G(s alpha) prevents its co-fractionation with caveolin, In a second independent approach, we directly examined the interaction of G proteins with caveolin, For this purpose, we recombinantly expressed caveolin as a glutathione S-transferase fusion protein, Using an in vitro binding assay, we found that caveolin interacts with G protein alpha subunits (G(s), G(o), and G(i)). Mutational or pharmacologic activation (with guanosine 5'-O-(thiotriphosphate)) of G(alpha) subunits prevents this interaction, indicating that the inactive GDP-bound form of G(alpha) subunits preferentially interacts with caveolin, This G protein binding activity is located within a 41-amino acid region of caveolin's cytoplasmic N-terminal. domain (residues 61-101), Further functional analysis shows that a polypeptide derived from this region of caveolin (residues 82-101) effectively suppresses the basal activity of purified G proteins, apparently by inhibiting GDP/GTP exchange, This caveolin sequence is homologous to a region of the Rab GDP dissociation inhibitor, a known inhibitor of GDP/GTP exchange for Rab proteins, These data suggest that caveolin could function to negatively regulate the activation state of heterotrimeric G proteins. C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP EAST,DEPT PEDIAT GASTROENTEROL,DIV MUCOSAL IMMUNOL,BOSTON,MA 02129. RI Lisanti, Michael/C-6866-2013 FU NIAID NIH HHS [AI-32991]; NIGMS NIH HHS [GM-50443] NR 62 TC 520 Z9 529 U1 2 U2 9 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 30 PY 1995 VL 270 IS 26 BP 15693 EP 15701 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RG538 UT WOS:A1995RG53800041 PM 7797570 ER PT J AU PEMBERTON, PA WONG, DT GIBSON, HL KIEFER, MC FITZPATRICK, PA SAGER, R BARR, PJ AF PEMBERTON, PA WONG, DT GIBSON, HL KIEFER, MC FITZPATRICK, PA SAGER, R BARR, PJ TI THE TUMOR-SUPPRESSOR MASPIN DOES NOT UNDERGO THE STRESSED TO RELAXED TRANSITION OR INHIBIT TRYPSIN-LIKE SERINE PROTEASES - EVIDENCE THAT MASPIN IS NOT A PROTEASE INHIBITORY SERPIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR; CONFORMATIONAL CHANGE; ALPHA-1-ANTITRYPSIN; YEAST AB The role of tumor suppressor proteins in the development of malignancy has made the understanding of their molecular mechanisms of action of great importance. Maspin is a tumor suppressor produced by a number of cell types of epithelial origin, Exogenous recombinant maspin has been shown to block the growth, motility, and invasiveness of breast tumor cell lines in vitro and in vivo. Although belonging to the the serine proteinase inhibitor (serpin) superfamily of proteins, the molecular mechanism of maspin is currently unknown, Here we show that the reactive site loop of maspin exists in an exposed conformation that does not require activation by cofactors. The reactive site loop of maspin, however, does not act as an inhibitor of proteinases such as chymotrypsin, elastase, plasmin, thrombin, and trypsin but rather as a substrate. Maspin is also unable to inhibit tissue and urokinase type plasminogen activators. Stability studies show that maspin cannot undergo the stressed-relaxed transition typical of proteinase-inhibitory serpins, and the protein is capable of spontaneous polymerization induced by changes in pH. It is likely, therefore, that maspin is structurally more closely related to ovalbumin and angiotensinogen, and its tumor suppressor activity is independent of a latent or intrinsic trypsin-like serine proteinase-inhibitory activity. C1 DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. RP PEMBERTON, PA (reprint author), LXR BIOTECHNOL,1401 MARINA WAY S,RICHMOND,CA 94804, USA. NR 36 TC 118 Z9 120 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 30 PY 1995 VL 270 IS 26 BP 15832 EP 15837 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RG538 UT WOS:A1995RG53800060 PM 7797587 ER PT J AU RAHME, LG STEVENS, EJ WOLFORT, SF SHAO, J TOMPKINS, RG AUSUBEL, FM AF RAHME, LG STEVENS, EJ WOLFORT, SF SHAO, J TOMPKINS, RG AUSUBEL, FM TI COMMON VIRULENCE FACTORS FOR BACTERIAL PATHOGENICITY IN PLANTS AND ANIMALS SO SCIENCE LA English DT Article ID PSEUDOMONAS-AERUGINOSA; ARABIDOPSIS-THALIANA; ESCHERICHIA-COLI; IDENTIFICATION; DETERMINANTS; RESISTANCE; SECRETION; CLONING; REGION; GENES AB A Pseudomonas aeruginosa strain (UCBPP-PA14) is infectious both in an Arabidopsis thaliana leaf infiltration model and in a mouse full-thickness skin burn model. UCBPP-PA14 exhibits ecotype specificity for Arabidqosis, causing a range of symptoms from none to severe in four different ecotypes. In the mouse model, UCBPP-PA14 is as lethal as other well-studied P. aeruginosa strains. Mutations in the UCBPP-PA14 toxA, plcS, and gacA genes resulted in a significant reduction in pathogenicity in both hosts, indicating that these genes encode virulence factors required for the full expression of pathogenicity in both plants and animals. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. NR 33 TC 681 Z9 704 U1 7 U2 91 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 30 PY 1995 VL 268 IS 5219 BP 1899 EP 1902 DI 10.1126/science.7604262 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF990 UT WOS:A1995RF99000038 PM 7604262 ER PT J AU BUSH, AI MOIR, RD ROSENKRANZ, KM TANZI, RE AF BUSH, AI MOIR, RD ROSENKRANZ, KM TANZI, RE TI ZINC AND ALZHEIMERS-DISEASE - RESPONSE SO SCIENCE LA English DT Article ID ALUMINUM; PROTEIN; PEPTIDE C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02129. RP BUSH, AI (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GENET & AGING UNIT,BLDG 149,13TH ST,BOSTON,MA 02129, USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 14 TC 55 Z9 57 U1 0 U2 5 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 30 PY 1995 VL 268 IS 5219 BP 1921 EP 1923 DI 10.1126/science.268.5219.1921 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF990 UT WOS:A1995RF99000047 PM 17797535 ER PT J AU KIM, K AF KIM, K TI A BIVARIATE CUMULATIVE PROBIT REGRESSION-MODEL FOR ORDERED CATEGORICAL-DATA SO STATISTICS IN MEDICINE LA English DT Article ID GENERALIZED LINEAR-MODELS; OPHTHALMOLOGY; ADJUSTMENT; TABLES; EYES AB This paper proposes a latent variable regression model for bivariate ordered categorical data and develops the necessary numerical procedure for parameter estimation. The proposed model is an extension of the standard bivariate probit model for dichotomous data to ordered categorical data with more than two categories for each margin. In addition, the proposed model allows for different covariates for the margins, which is characteristic of data from typical ophthalmological studies. It utilizes the stochastic ordering implicit in the data and the correlation coefficient of the bivariate normal distribution in expressing intra-subject dependency. Illustration of the proposed model uses data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy for identifying risk factors for diabetic retinopathy among younger-onset diabetics. The proposed regression model also applies to other clinical or epidemiological studies that involve paired organs. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP KIM, K (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,44 BINNEY ST,MAYER 4,BOSTON,MA 02115, USA. FU NEI NIH HHS [R01 EY09252] NR 20 TC 23 Z9 23 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1995 VL 14 IS 12 BP 1341 EP 1352 DI 10.1002/sim.4780141207 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA RG428 UT WOS:A1995RG42800006 PM 7569492 ER PT J AU SHERRINGTON, R ROGAEV, EI LIANG, Y ROGAEVA, EA LEVESQUE, G IKEDA, M CHI, H LIN, C LI, G HOLMAN, K TSUDA, T MAR, L FONCIN, JF BRUNI, AC MONTESI, MP SORBI, S RAINERO, I PINESSI, L NEE, L CHUMAKOV, I POLLEN, D BROOKES, A SANSEAU, P POLINSKY, RJ WASCO, W DASILVA, HAR HAINES, JL PERICAKVANCE, MA TANZI, RE ROSES, AD FRASER, PE ROMMENS, JM STGEORGEHYSLOP, PH AF SHERRINGTON, R ROGAEV, EI LIANG, Y ROGAEVA, EA LEVESQUE, G IKEDA, M CHI, H LIN, C LI, G HOLMAN, K TSUDA, T MAR, L FONCIN, JF BRUNI, AC MONTESI, MP SORBI, S RAINERO, I PINESSI, L NEE, L CHUMAKOV, I POLLEN, D BROOKES, A SANSEAU, P POLINSKY, RJ WASCO, W DASILVA, HAR HAINES, JL PERICAKVANCE, MA TANZI, RE ROSES, AD FRASER, PE ROMMENS, JM STGEORGEHYSLOP, PH TI CLONING OF A GENE BEARING MISSENSE MUTATIONS IN EARLY-ONSET FAMILIAL ALZHEIMERS-DISEASE SO NATURE LA English DT Article ID PRECURSOR PROTEIN GENE; CAENORHABDITIS-ELEGANS; HUMAN GENOME; APOLIPOPROTEIN-E; CHROMOSOME-14; IDENTIFICATION; LINKAGE; LIBRARY; ALLELE; CLONES AB Some cases of Alzheimer's disease are inherited as an autosomal dominant trait. Genetic linkage studies have mapped a locus (AD3) associated with susceptibility to a very aggressive form of Alzheimer's disease to chromosome 14q24.3. We have defined a minimal cosegregating region containing the AD3 gene, and isolated at least 19 different transcripts encoded within this region. One of these transcripts (S182) corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein. Five different missense mutations have been found that cosegregate with early-onset familial Alzheimer's disease. Because these changes occurred In conserved domains of this gene, and are not present in normal controls, they are likely to be causative of AD3. C1 UNIV TORONTO,DEPT MED NEUROL,CTR RES NEURODEGENERAT DIS,TORONTO,ON,CANADA. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO,ON,CANADA. UNIV TORONTO,DEPT MED,DIV NEUROL,TORONTO,ON M5S 1A8,CANADA. UNIV TORONTO,HOSP SICK CHILDREN,RES INST,TORONTO,ON M5S 1A8,CANADA. UNIV TORONTO,DEPT MED & MOLEC GENET,TORONTO,ON M5S 1A8,CANADA. ECOLE PRAT HAUTES ETUD,NEUROHIST LAB,F-75651 PARIS 13,FRANCE. INSERM LA SALPETRIERE,U106,F-75651 PARIS 13,FRANCE. USL 6,I-88046 LAMEZIA TERME,ITALY. CNR,UO,I-88046 LAMEZIA TERME,ITALY. UNIV FLORENCE,DEPT NEUROL & PSYCHIAT,FLORENCE,ITALY. UNIV TURIN,DEPT NEUROL,I-10126 TURIN,ITALY. NINCDS,CLIN NEUROPHARMACOL SECT,BETHESDA,MD 20892. CTR ETUD POLYMORPHISME HUMAIN,F-75010 PARIS,FRANCE. UNIV MASSACHUSETTS,MED CTR,DEPT NEUROL,WORCESTER,MA 01655. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC NEUROGENET LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,GENET & AGING LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. DUKE UNIV,MED CTR,BRYAN ALZHEIMERS DIS RES CTR,DURHAM,NC 27710. GLAXO GRP RES LTD,RES & DEV,MOLEC PATHOL,GREENFORD UB6 0HE,MIDDX,ENGLAND. SANDOZ PHARMACEUT CORP,SANDOZ RES INST,E HANOVER,NJ 07936. WESTERN GEN HOSP,MRC,HUMAN GENET UNIT,EDINBURGH,MIDLOTHIAN,SCOTLAND. RI de Silva, Rohan/C-1734-2008; Haines, Jonathan/C-3374-2012; OI de Silva, Rohan/0000-0002-5052-5775; sorbi, sandro/0000-0002-0380-6670 FU Canadian Institutes of Health Research [64309]; Telethon [E.0010] NR 50 TC 2824 Z9 2903 U1 11 U2 118 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 29 PY 1995 VL 375 IS 6534 BP 754 EP 760 DI 10.1038/375754a0 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF989 UT WOS:A1995RF98900069 PM 7596406 ER PT J AU LIPSHULTZ, SE LIPSITZ, SR MONE, SM GOORIN, AM SALLAN, SE SANDERS, SP ORAV, EJ GELBER, RD COLAN, SD AF LIPSHULTZ, SE LIPSITZ, SR MONE, SM GOORIN, AM SALLAN, SE SANDERS, SP ORAV, EJ GELBER, RD COLAN, SD TI FEMALE SEX AND HIGHER DRUG DOSE AS RISK-FACTORS FOR LATE CARDIOTOXIC EFFECTS OF DOXORUBICIN THERAPY FOR CHILDHOOD-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CONGESTIVE HEART-FAILURE; RADIONUCLIDE ANGIOGRAPHY; OSTEO-SARCOMA; FREE SURVIVAL; GENDER; ANTHRACYCLINES; CHILDREN; ECHOCARDIOGRAPHY; CARDIOMYOPATHY AB Background. Late cardiotoxic effects of doxorubicin are increasingly a problem for patients who survive childhood cancer. Cardiotoxicity is often progressive, and some patients have disabling symptoms. Our objective was to identify risk factors for late cardiotoxicity. Methods. We examined echocardiograms from 120 children and adults who had received cumulative doses of 244 to 550 mg of doxorubicin per square meter of body-surface area for the treatment of acute lymphoblastic leukemia or osteogenic sarcoma in childhood, a mean of 8.1 years earlier. Measurements of blood pressure and left ventricular function, contractility (measured as the stress-velocity index), end-diastolic posterior-wall thickness, end-diastolic dimension, mass, and afterload (measured as end-systolic wall stress) were compared with sex-specific values from a cohort of 296 normal subjects. Results. All echocardiographic measurements were abnormal at follow-up a minimum of two years after the end of therapy, with more frequent and severe abnormalities in female patients. In a multivariate analysis, female sex and a higher cumulative dose of doxorubicin were associated with depressed contractility (P less than or equal to 0.001), and there was an interaction between these two variables. independent and significant associations were found between a higher rate of administration of doxorubicin and increased afterload (P less than or equal to 0.001), left ventricular dilatation, and depressed left ventricular function; between a higher cumulative dose and depressed left ventricular function (P less than or equal to 0.001); between a younger age at diagnosis and reduced left-ventricular-wall thickness and mass and increased afterload; and between a longer time since the completion of doxorubicin therapy and reduced left-ventricular-wall thickness and increased afterload (P less than or equal to 0.001). Conclusions. Female sex and a higher rate of administration of doxorubicin were independent risk factors for cardiac abnormalities after treatment with doxorubicin for childhood cancer; the prevalence and severity of abnormalities increased with longer follow-up. C1 CHILDRENS HOSP,DEPT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. RP LIPSHULTZ, SE (reprint author), CHILDRENS HOSP,DEPT CARDIOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. OI Sanders, Stephen/0000-0003-3521-4044 FU NCI NIH HHS [CA06516, CA34183, CA55576] NR 41 TC 409 Z9 413 U1 0 U2 4 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 29 PY 1995 VL 332 IS 26 BP 1738 EP 1743 DI 10.1056/NEJM199506293322602 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA RE667 UT WOS:A1995RE66700002 PM 7760889 ER PT J AU RISKIND, PN RICHARDSON, EP BUCHBINDER, BR IRIZARRY, MC AF RISKIND, PN RICHARDSON, EP BUCHBINDER, BR IRIZARRY, MC TI A 66-YEAR-OLD MAN WITH A HISTORY OF RHEUMATOID-ARTHRITIS TREATED WITH ADRENOCORTICOSTEROIDS, WITH THE DEVELOPMENT OF APHASIA AND RIGHT-SIDED WEAKNESS - PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID SYSTEMIC LUPUS-ERYTHEMATOSUS; NON-HODGKINS-LYMPHOMAS; GLIOMATOSIS CEREBRI; CYTARABINE; VIRUS; AIDS; BRAIN; HYBRIDIZATION; INVOLVEMENT; DIAGNOSIS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP RISKIND, PN (reprint author), MASSACHUSETTS GEN HOSP,NEUROIMMUNOL UNIT,BOSTON,MA 02114, USA. NR 36 TC 9 Z9 9 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 29 PY 1995 VL 332 IS 26 BP 1773 EP 1780 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA RE667 UT WOS:A1995RE66700009 ER PT J AU SZPIR, MR WRIGHT, DD RYUGO, DK AF SZPIR, MR WRIGHT, DD RYUGO, DK TI NEURONAL ORGANIZATION OF THE COCHLEAR NUCLEI IN ALLIGATOR LIZARDS - A LIGHT AND ELECTRON-MICROSCOPIC INVESTIGATION SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE CYTOLOGY; HEARING; REPTILE; SYNAPSE; ULTRASTRUCTURE ID STEM AUDITORY NUCLEI; SYNAPTIC CONNECTIONS; RESPONSE PROPERTIES; FINE-STRUCTURE; NERVE-FIBERS; HAIR-CELLS; BARN OWL; CAT; PROJECTIONS; MAGNOCELLULARIS AB The organization of neurons and fibers in the cochlear nuclei of the alligator lizard (Gerrhonotus multicarinatus) was examined with light and electron microscopy. In this species, much is known about the anatomy and physiology of the inner ear including the cochlear nerve, but little is known about the synaptic connections of cochlear fibers on second-order neurons. These data will help to develop general principles addressing the cellular organization of the vertebrate auditory system. Subdivisions of the cochlear nuclei were defined on the basis of their histologic appearance and neuronal composition. Neuron classes were proposed from their light microscopic and ultrastructural features. Nucleus magnocellularis medialis consists of a homogeneous population of neurons called ''lesser ovoid'' cells. Nucleus magnocellularis lateralis consists of ''greater ovoid'' and ''small'' cells. Nucleus angularis lateralis consists of ''spindle'' cells. Lastly, nucleus angularis medialis contains a population of large neurons called ''duckhead'' and ''multipolar'' cells, and a population of smaller neurons called ''bulb'' and ''agranular'' cells. These neuron populations are differentially innervated by tectorial and free-standing cochlear fibers that are associated with separate frequency ranges. All neuronal populations except agranular cells were observed to receive synaptic input from cochlear nerve fibers. In nucleus magnocellularis medialis and nucleus angularis medialis, primary afferents form both chemical and electrical synapses with resident neurons. These observations imply that acoustic information is synaptically processed in fundamentally distinct ways in the cochlear nuclei of alligator lizards and distributed along separate neural circuits. Thus, the characteristic structural and functional dichotomy of the alligator lizard inner ear is extended to central auditory pathways by way of cochlear nerve projections. (C) 1995 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT OTOLARYNGOL HEAD & NECK SURG,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAT & CELLULAR BIOL,BOSTON,MA 02115. FU NIDCD NIH HHS [DC00232, DC00119] NR 73 TC 8 Z9 9 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 26 PY 1995 VL 357 IS 2 BP 217 EP 241 DI 10.1002/cne.903570204 PG 25 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA RC961 UT WOS:A1995RC96100003 PM 7665726 ER PT J AU SONGYANG, Z MARGOLIS, B CHAUDHURI, M SHOELSON, SE CANTLEY, LC AF SONGYANG, Z MARGOLIS, B CHAUDHURI, M SHOELSON, SE CANTLEY, LC TI THE PHOSPHOTYROSINE INTERACTION DOMAIN OF SHC RECOGNIZES TYROSINE-PHOSPHORYLATED NPXY MOTIF SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; SRC HOMOLOGY-2 DOMAIN; BINDING-SITE; ACTIVATION; MOLECULES; P56(LCK); PEPTIDE AB Reversible assembly of intracellular signaling complexes is, in some cases, mediated by direct binding of a Src homology 2 (SH2) domain of one protein to a phosphotyrosine moiety of another protein (Cantley, L. C., Auger, K. R., Carpenter, C. L., Duckworth, B., Graziani, A., Kapeller, R., and Soltoff, S. (1991) Cell 64, 281-302). Using a degenerate phosphotyrosine-containing peptide library, we showed that individual SH2 domains recognize phosphotyrosine in a specific sequence context to provide fidelity in signaling (Songyang, Z., Shoelson, S. E., Chaudhuri, M., Gish, G., Pawson, T., Haser, W. G., King, F., Roberts, T., Ratnofsky, S., Lechleider, R. J., Neel, B. G., Birge, R. B., Fajardo, J. E., Chou, M. M., Hanafusa, H., Schaffhausen, B., and Cantley, L. C. (1993) Cell 72, 767-778). Recently a second type of phosphotyrosine interaction domain (PID) or phosphotyrosine-binding domain (PTB) was discovered in the amino terminus of the SHC proto-oncoprotein (Kavanaugh, W. Ri., and Williams, L. (1994) Science 266, 1862-1865; Blaikie, P., Immanuel, D., Wu, J., Li, N., Yajnik, V., and Margolis, B. (1994) J. Biol. Chem. 269, 32031-32034). Here we demonstrate, using a phosphotyrosine peptide library, that the SHC PID domain preferentially binds to the sequence Asn-Pro-Xaa-phosphotyrosine. This motif is in agreement with sequences at sites implicated in in vivo SHC binding. These results indicate that while SH2 domains predominantly interact with specific residues carboxyl-terminal of phosphotyrosine, the PID domain has high specificity for residues amino-terminal of phosphotyrosine. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02111. NYU,SCH MED,DEPT PHARMACOL,NEW YORK,NY 10016. BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 26 TC 119 Z9 120 U1 0 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 23 PY 1995 VL 270 IS 25 BP 14863 EP 14866 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RE666 UT WOS:A1995RE66600006 PM 7541030 ER PT J AU NOJIMA, Y MORINO, N MIMURA, T HAMASAKI, K FURUYA, H SAKAI, R SATO, T TACHIBANA, K MORIMOTO, C YAZAKI, Y HIRAI, H AF NOJIMA, Y MORINO, N MIMURA, T HAMASAKI, K FURUYA, H SAKAI, R SATO, T TACHIBANA, K MORIMOTO, C YAZAKI, Y HIRAI, H TI INTEGRIN-MEDIATED CELL-ADHESION PROMOTES TYROSINE PHOSPHORYLATION OF P130(CAS), A SRC HOMOLOGY 3-CONTAINING MOLECULE HAVING MULTIPLE SRC HOMOLOGY 2-BINDING MOTIFS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXTRACELLULAR-MATRIX; SIGNAL TRANSDUCTION; PROTEIN; KINASE; FIBRONECTIN AB p130(Cas) (Cas) has been recently identified as a 130-kDa protein that is highly phosphorylated on tyrosine residues and is stably associated with p47(v-crk) (v-Crk) and p60(v-src) (v-Src) oncogene products in cells transformed by the respective genes. Cas is a novel signaling molecule having a single Src homology (SH) 3 domain and a cluster of multiple SH2-binding motifs. While the tight association of Cas with v-Crk and v-Src is strongly suggestive of a significant role in regulating cellular transformation, the function of Cas in normal untransformed cells is totally unknown. We report here that cell adhesion to fibronectin rapidly promotes tyrosine phosphorylation of Cas in human and rat fibroblast cell lines. The response was equally induced by cell adhesion to plates coated with vitronectin, laminin, and collagen but not by cell attachment to nonspecific substrate poly-L-lysine. The kinetic profile of Cas phosphorylation was almost identical with that of tyrosine phosphorylation of focal adhesion kinase pp125(FAK) (Fak), which is well known to be activated subsequent to integrin-mediated cell adhesion. Adhesion-dependent Cas phosphorylation was completely inhibited by treating cells with cytochalasin D, an agent that disrupts polymerization of actin stress fibers. These results suggest that tyrosine phosphorylation of Cas is stimulated by normal cell adhesion in close association with Fak phosphorylation and the formation of actin stress fibers. In v-Src- or v-Crk-transformed cells, however, the tyrosine phosphorylation of Cas is markedly increased in an adhesion-independent manner that is insensitive to treatment with cytochalasin D. Thus, Cas plays a role in signaling pathways mediated by cell adhesion as well as by transformation. We propose that Cas may amplify and propagate integrin-mediated signals by interacting with SH2-containing molecule(s). C1 JICHI MED SCH,DIV MOLEC BIOL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. RP NOJIMA, Y (reprint author), UNIV TOKYO,FAC MED,DEPT INTERNAL MED 3,BUNKYO KU,7-3-1 HONGO,TOKYO 113,JAPAN. NR 26 TC 279 Z9 279 U1 0 U2 3 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 23 PY 1995 VL 270 IS 25 BP 15398 EP 15402 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RE666 UT WOS:A1995RE66600082 PM 7541040 ER PT J AU FRANCIS, JW HOSLER, BA BROWN, RH FISHMAN, PS AF FRANCIS, JW HOSLER, BA BROWN, RH FISHMAN, PS TI CUZN SUPEROXIDE-DISMUTASE (SOD-1)-TETANUS TOXIN FRAGMENT-C HYBRID PROTEIN FOR TARGETED DELIVERY OF SOD-1 TO NEURONAL CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH-LEVEL EXPRESSION; AMYOTROPHIC-LATERAL-SCLEROSIS; RETROGRADE AXONAL-TRANSPORT; TETANUS TOXIN; ESCHERICHIA-COLI; TRANSGENIC MICE; HIGH-AFFINITY; OXIDATIVE STRESS; CULTURED NEURONS; BRAIN MEMBRANES AB Increased levels of CuZn superoxide dismutase (SOD-1) are cytoprotective in experimental models of neurological disorders associated with free radical toxicity (e.g. stroke, trauma). Targeted delivery of SOD-1 to central nervous system neurons may therefore be therapeutic in such diseases. The nontoxic C-fragment of tetanus toxin (TTC) possesses the nerve cell binding/transport properties of tetanus holotoxin and has been used as a vector to enhance the neuronal uptake of proteins including enzymes. We have now produced a recombinant, hybrid protein in Escherichia coli tandemly joining human SOD-1 to TTC. The expressed hybrid protein (SOD:Tet451) has a subunit molecular mass of 68 kDa and is recognized by both anti-SOD-1 and anti-TTC antibodies. Calculated per mol, SOD:Tet451 has approximately 60% of the expected SOD-1 enzymatic activity. Analysis of the hybrid protein's interaction with the neuron-like cell line, N18-RE-105, and cultured hippocampal neurons by enzyme immunoassay for human SOD-1 revealed that SOD:Tet451 association with cells was neuron-specific and dose-dependent. The hybrid protein was also internalized, but there was substantial loss of internalized hybrid protein over the first 24 h. Hybrid protein associated with cells remained enzymatically active. These results suggest that human SOD-1 and TTC retain their respective functional properties when expressed together as a single peptide. SOD: Tet451 may prove to be a useful agent for the targeted delivery of SOD-1 to neurons. C1 UNIV MARYLAND, SCH MED, DEPT ANAT, BALTIMORE, MD 21201 USA. MASSACHUSETTS GEN HOSP, CECIL B DAY LAB NEUROMUSCULAR RES, BOSTON, MA 02129 USA. UNIV MARYLAND, SCH MED, VET ADM MED CTR, NEUROL SERV, BALTIMORE, MD 21201 USA. UNIV MARYLAND, SCH MED, DEPT NEUROL, BALTIMORE, MD 21201 USA. FU NINDS NIH HHS [NS31248-01, 1P01NS31248] NR 69 TC 61 Z9 64 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 23 PY 1995 VL 270 IS 25 BP 15434 EP 15442 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RE666 UT WOS:A1995RE66600087 PM 7797532 ER PT J AU XIAO, ZX CHEN, JD LEVINE, AJ MODJTAHEDI, N XING, J SELLERS, WR LIVINGSTON, DM AF XIAO, ZX CHEN, JD LEVINE, AJ MODJTAHEDI, N XING, J SELLERS, WR LIVINGSTON, DM TI INTERACTION BETWEEN THE RETINOBLASTOMA PROTEIN AND THE ONCOPROTEIN MDM2 SO NATURE LA English DT Article ID GENE-PRODUCT; TRANSCRIPTION FACTOR; GROWTH SUPPRESSION; COMPLEX-FORMATION; P53; TRANSACTIVATION; IDENTIFICATION; AMPLIFICATION; EXPRESSION; REPRESSION AB INACTIVATION of tumour-suppressor genes leads to deregulated cell proliferation and is a key factor in human tumorigenesis. Both p53 and retinoblastoma genes are frequently mutated in human cancers(1,2), and the simultaneous inactivation of RB and p53 is frequently observed in a variety of naturally occurring human tumours(3). Furthermore, three distinct DNA tumour virus groups papovaviruses, adenoviruses and human papillomaviruses-transform cells by targeting and inactivating certain functions of both the p53 and retinoblastoma proteins(1,2). The cellular oncoprotein, Mdm2, binds to and downmodulates p53 function(4-6); its human homologue, MDM2, is amplified in certain human tumours, including sarcomas(7-9) and gliomas(10). Overproduction of Mdm2 is both tumorigenic(4) and capable of immortalizing primary rat embryo fibroblasts(11). Here we show that MDM2 interacts physically and functionally with pRB and, as with p53, inhibits pRB growth regulatory function. Therefore, both pRB and p53 can be subjected to negative regulation by the product of a single cellular proto-oncogene. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544. RP XIAO, ZX (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 30 TC 513 Z9 530 U1 0 U2 11 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 22 PY 1995 VL 375 IS 6533 BP 694 EP 698 DI 10.1038/375694a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RE576 UT WOS:A1995RE57600064 PM 7791904 ER PT J AU STONE, RM BERG, DT GEORGE, SL DODGE, RK PACIUCCI, PA SCHULMAN, P LEE, EJ MOORE, JO POWELL, BL SCHIFFER, CA AF STONE, RM BERG, DT GEORGE, SL DODGE, RK PACIUCCI, PA SCHULMAN, P LEE, EJ MOORE, JO POWELL, BL SCHIFFER, CA TI GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AFTER INITIAL CHEMOTHERAPY FOR ELDERLY PATIENTS WITH PRIMARY ACUTE MYELOGENOUS LEUKEMIA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; CLINICAL-TRIALS; INDUCTION CHEMOTHERAPY; INTENSIVE CHEMOTHERAPY; REMISSION-INDUCTION; DOSE CYTARABINE; GROWTH-FACTORS; GM-CSF AB Background. Elderly patients with primary acute myelogenous leukemia (AML) are less likely to enter remission than younger adults, in part because of a higher mortality rate related to severe myelosuppression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to shorten the duration of neutropenia and decrease infectious complications when administered after chemotherapy to patients with lymphomas and solid tumors. Methods. We randomly assigned 388 patients 60 years of age or older who had newly diagnosed primary AML to receive placebo or GM-CSF (5 mu g per kilogram of body weight per day intravenously) in a double-blind manner, beginning the day after the completion of three days of daunorubicin and seven days of cytarabine. If leukemic cells persisted in the marrow three weeks after the initiation of chemotherapy, further daunorubicin (two days) and cytarabine (five days) were administered. GM-CSF or placebo was given daily until the neutrophil count was at least 1000 per cubic millimeter, there was evidence of the regrowth of leukemia, or severe toxic effects attributable to the study infusion occurred. Patients who had a complete remission were then randomly assigned to receive one of two intensification regimens. Results. Of 388 patients (median age, 69 years), 193 were randomly assigned to receive GM-CSF and 195 to receive placebo. The rate of complete remission was 51 percent (95 percent confidence interval, 44 to 59 percent) among those assigned to GM-CSF and 54 percent (95 percent confidence interval, 47 to 61 percent) among those assigned to placebo (P = 0.61). The reasons for failure (early death, death during marrow hypoplasia, and persistent leukemia), the incidence of severe or lethal infection, and the incidence of the regrowth of leukemia (2 percent overall) were similar in the two groups. The median duration of neutropenia was slightly shorter (P = 0.02) in the patients who received GM-CSF (15 days) than in those who received placebo (17 days), but the clinical importance of this result was minimal because the growth factor failed to lower the treatment-related mortality rate or improve the rate of complete remission. Conclusions. GM-CSF, in the dose and schedule we used, does not stimulate the regrowth of leukemia, but it also does not decrease the severe myelosuppressive consequences of initial chemotherapy or improve the response rate in patients 60 years of age or older with primary AML. It should not be recommended for use in such patients. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. DUKE UNIV,MED CTR,DURHAM,NC. N SHORE UNIV HOSP,MANHASSET,NY. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. BOWMAN GRAY SCH MED,WINSTON SALEM,NC. RP STONE, RM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA31946, CA33601, CA37055] NR 42 TC 334 Z9 340 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 22 PY 1995 VL 332 IS 25 BP 1671 EP 1677 DI 10.1056/NEJM199506223322503 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RD996 UT WOS:A1995RD99600003 PM 7760868 ER PT J AU SYSTROM, DM MARK, EJ BHALLA, M DEMIRJIAN, ZN KAZEMI, H AF SYSTROM, DM MARK, EJ BHALLA, M DEMIRJIAN, ZN KAZEMI, H TI A 55-YEAR-OLD WOMAN WITH ACUTE RESPIRATORY-FAILURE AND RADIOGRAPHICALLY CLEAR LUNGS - PULMONARY EMBOLIC AND LYMPHANGITIC CARCINOMATOSIS OF BREAST ORIGIN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID ANGIOPATHIC HEMOLYTIC-ANEMIA; ALVEOLAR SEPTAL CAPILLARIES; SUBACUTE COR-PULMONALE; TUMOR EMBOLISM; DIAGNOSIS; HYPERTENSION; PERFUSION; DISEASE; CANCER; OCCULT C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SYSTROM, DM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 40 TC 11 Z9 11 U1 0 U2 1 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 22 PY 1995 VL 332 IS 25 BP 1700 EP 1707 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA RD996 UT WOS:A1995RD99600008 ER PT J AU WEIR, GC AF WEIR, GC TI WHICH COMES FIRST IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS - INSULIN-RESISTANCE OR BETA-CELL FAILURE - BOTH COME FIRST SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 HARVARD UNIV,DEACONESS HOSP,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NR 6 TC 21 Z9 21 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 21 PY 1995 VL 273 IS 23 BP 1878 EP 1879 DI 10.1001/jama.273.23.1878 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RD116 UT WOS:A1995RD11600034 PM 7776508 ER PT J AU JOUNG, I KIM, TU STOLZ, LA PAYNE, G WINKLER, DG WALSH, CT STROMINGER, JL SHIN, J AF JOUNG, I KIM, TU STOLZ, LA PAYNE, G WINKLER, DG WALSH, CT STROMINGER, JL SHIN, J TI MODIFICATION OF SER(59) IN THE UNIQUE N-TERMINAL REGION OF TYROSINE KINASE P56(LCK) REGULATES SPECIFICITY OF ITS SRC HOMOLOGY 2 DOMAIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TYROSINE PHOSPHORYLATION; GLUTATHIONE S-TRANSFERASE FUSION PROTEIN; SURFACE PLASMON RESONANCE ID PHOSPHORYLATED PEPTIDES; SIGNAL TRANSDUCTION; MAP KINASE; BINDING; TRANSFORMATION; RECOGNITION; PROTEIN; CELLS; SITE; LCK AB During T-cell activation, Ser(59) in the unique N-terminal region of p56(lck) is phosphorylated. Mutation of Ser(59) to Glu(59) mimics Ser(59) phosphorylation, and upon CD4 crosslinking, this mutant p56(lck) induces tyrosine phosphorylation of intracellular proteins distinct from those induced by wild-type p56(lck). Mutant and wild-type p56(lck) have similar affinities for CD4 and similar kinase activities, In glutathione S-transferase fusion proteins, the p56(lck) Src homology 2 (SH2) domain with the SH3 domain and the unique N-terminal region (including Ser(59)) has a different binding specificity for phosphotyrosyl proteins than the SH2 domain alone, Either deletion of the unique N-terminal region or mutation of Ser(59) to Glu(59) in the fusion protein reverts the phosphotyrosyl protein binding specificity back to that of the SH2 domain alone. These results suggest that phosphorylation of Ser(59) regulates the function of p56(lck) by controlling binding specificity of its SH2 domain. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP JOUNG, I (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA47554]; NIGMS NIH HHS [GM20011, GM48961] NR 29 TC 45 Z9 46 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 20 PY 1995 VL 92 IS 13 BP 5778 EP 5782 DI 10.1073/pnas.92.13.5778 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF050 UT WOS:A1995RF05000005 PM 7597029 ER PT J AU GROSS, J FARINELLI, W SADOW, P ANDERSON, R BRUNS, R AF GROSS, J FARINELLI, W SADOW, P ANDERSON, R BRUNS, R TI ON THE MECHANISM OF SKIN WOUND CONTRACTION - A GRANULATION-TISSUE KNOCKOUT WITH A NORMAL PHENOTYPE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE WOUND REPAIR; CLOSURE; SURGICAL EXCISION; PIG ID FIBROBLAST TRACTION; COLLAGEN; FIBRONECTIN; MATRIX; MODEL; MORPHOGENESIS; EXPRESSION; CLOSURE; ACTIN AB This report explores the mechanism of spontaneous closure of full-thickness skin wounds. The domestic pig, often used as a human analogue for skin wound repair studies, closes these wounds with kinetics similar to those in the guinea pig (mobile skin), even though the porcine dermis on the back is thick and nearly immobile. In the domestic pig, as in the guinea pig, daily full-thickness excisions of the central granulation tissue up to but not including the wound edges in both back and flank wounds do not alter the rate or completeness of wound closure or the final pattern of the scar. A purse-string mechanism of closure was precluded by showing that surgical interruption of wound edge continuity does not alter closure kinetics or wound shape. We conclude that ''tightness'' of skin is not a key factor nor is the central granulation tissue required for normal wound closure. These data imply that in vitro models such as contraction of isolated granulation tissue or of the cell-populated collagen lattice may not be relevant for understanding the cell biology of in viv wound closure. Implications for the mechanism for mound closure are discussed. C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. RP GROSS, J (reprint author), MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129, USA. NR 43 TC 62 Z9 62 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 20 PY 1995 VL 92 IS 13 BP 5982 EP 5986 DI 10.1073/pnas.92.13.5982 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF050 UT WOS:A1995RF05000047 PM 7597065 ER PT J AU KHARBANDA, S SALEEM, A YUAN, ZM EMOTO, Y PRASAD, KVS KUFE, D AF KHARBANDA, S SALEEM, A YUAN, ZM EMOTO, Y PRASAD, KVS KUFE, D TI STIMULATION OF HUMAN MONOCYTES WITH MACROPHAGE-COLONY-STIMULATING FACTOR INDUCES A GRB2-MEDIATED ASSOCIATION OF THE FOCAL ADHESION KINASE PP125(FAK) AND DYNAMIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FACTOR-I RECEPTOR; PROTEIN TYROSINE KINASE; SIGNAL-TRANSDUCTION; SH3 DOMAINS; PHOSPHATIDYLINOSITOL-3 KINASE; RAS; PHOSPHORYLATION; IDENTIFICATION; ACTIVATION; CSF-1 AB Macrophage colony-stimulating factor (M-CSF) is required for the growth and differentiation of mononuclear phagocytes, In the present studies using human monocytes, we show that M-CSF induces interaction of the Grb2 adaptor protein with the focal adhesion kinase pp125(FAK). The results demonstrate that tyrosine-phosphorylated pp125(FAK) directly interacts with the SH2 domain of Grb2. The findings indicate that a pYENV site at Tyr-925 in pp125(FAK) is responsible for this interaction. We also demonstrate that the Grb2-FAK complex associates with the GTPase dynamin. Dynamin interacts with the SH3 domains of Grb2 and exhibits M-CSF-dependent tyrosine phosphorylation in association with pp125(FAK). These findings suggest that M-CSF-induced signaling involves independent Grb2-mediated pathways, one leading to Ras activation and another involving pp125(FAK) and a GTPase implicated in receptor internalization. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. RP KHARBANDA, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA42802, CA34183] NR 38 TC 71 Z9 72 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 20 PY 1995 VL 92 IS 13 BP 6132 EP 6136 DI 10.1073/pnas.92.13.6132 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RF050 UT WOS:A1995RF05000077 PM 7597091 ER PT J AU BROWN, MC LIU, TS AF BROWN, MC LIU, TS TI FOS-LIKE IMMUNOREACTIVITY IN CENTRAL AUDITORY NEURONS OF THE MOUSE SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE C-FOS; COCHLEAR NUCLEUS; INFERIOR COLLICULUS; SUPERIOR OLIVE; GENE EXPRESSION ID DORSAL COCHLEAR NUCLEUS; SUPERIOR OLIVARY COMPLEX; SINGLE-UNIT RESPONSES; NERVE GROWTH-FACTOR; INFERIOR COLLICULUS; C-FOS; TONOTOPIC ORGANIZATION; MESSENGER-RNA; BRAIN-STEM; DESCENDING PROJECTIONS AB Fos-like immunoreactivity was used to study sound-induced activation of neurons in the auditory brainstem. Immunoreactivity was assayed with a polyclonal antibody to Fos. In response to 6-kHz tone bursts, the pattern of staining was a band of immunoreactive neurons positioned at the tonotopically appropriate position within the cochlear nucleus and the inferior colliculus. The band was narrow at low sound pressure levels but wider along the tonotopic axis at higher sound levels. In response to noise bursts, the pattern was broader and often extended throughout the auditory nuclei. Often within this broad pattern were ''sub-bands'' of immunostained neurons, interspersed with bands of unstained neurons. With increasing sound pressure levels above 35-55 dB, the number of Fos-like immunoreactive neurons increased for the cochlear nucleus, superior olivary complex, and inferior colliculus. In the cochlear nucleus and inferior colliculus, the stained cells were small, and hence their activity would be difficult to sample in electrophysiological studies. In the medial nucleus of the trapezoid body, the stained neurons had larger somata and other characteristics of principal cells. Anesthesia with Nembutal or Avertin, but not with ketamine or urethane, decreased the number of Fos-like immunoreactive neurons in the cochlear nucleus. The different anesthetics produced more variable results in the inferior colliculus. In anesthetized, monaurally stimulated animals, the presence of staining in the contralateral cochlear nucleus indicates that some Fos-like immunoreactivity may be mediated by descending or commissural systems. These observations indicate that Fos assays are useful for studying the pattern of neuronal activation in the auditory system and may also be useful in studying the descending auditory pathways. (C) 1995 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HARVARD MIT DIV HLTH SCI & TECHNOL,BOSTON,MA 02115. RP BROWN, MC (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC00119, DC01089] NR 85 TC 45 Z9 45 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 19 PY 1995 VL 357 IS 1 BP 85 EP 97 DI 10.1002/cne.903570109 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA RC942 UT WOS:A1995RC94200008 PM 7673470 ER PT J AU SCHIFFER, SG HEMLER, ME LOBB, RR TIZARD, R OSBORN, L AF SCHIFFER, SG HEMLER, ME LOBB, RR TIZARD, R OSBORN, L TI MOLECULAR MAPPING OF FUNCTIONAL ANTIBODY-BINDING SITES OF ALPHA-4 INTEGRIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID CELL-ADHESION MOLECULE-1; PLATELET INTEGRIN; OVERLAP EXTENSION; I-DOMAIN; VLA-4; RECEPTOR; FIBRONECTIN; MURINE; IDENTIFICATION; DISTINCT AB Integrin (alpha 4 beta 1 is a leukocyte receptor for fibronectin and vascular cell adhesion molecule-1 (VCAM-1). It is important in inflammatory recruitment of leukocytes, lymphopoiesis, and a number of developmental events. Here we have mapped a panel of functional monoclonal antibodies (mAbs) recognizing the integrin alpha 4 chain, using murine/human chimeric constructs expressed in COS7 cells. We find that: 1) mAbs that induce homotypic aggregation (epitope A mAbs) map to the most N-terminal 100 amino acids of the human alpha 4 chain; 2) mAbs that block adhesion of alpha 4 beta 1 to VCAM-1 and fibronectin (epitope B mAbs) map to a 52-amino-acid region between residues 152 and 203 of human alpha 4; 3) epitope B mAbs that do or do not induce aggregation (epitope B2 and B1 mAbs, respectively) map to the same regions and are therefore indistinguishable by this analysis; 4) mAbs that neither induce homotypic aggregation nor block adhesion (epitope C mAbs) map to a distinct region of the molecule comprising amino acids 422-606. The N-terminal region of the alpha 4 chain identified by functional A and B epitope mAbs does not correspond to ligand binding sites identified in other alpha subunits, such as cation binding sites or the ''I-domain,'' which alpha 4 lacks, and thus represents a novel site for epitope functionality among the integrins. C1 BIOGEN INC,CAMBRIDGE,MA 02142. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NIGMS NIH HHS [GM38903] NR 43 TC 48 Z9 49 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 16 PY 1995 VL 270 IS 24 BP 14270 EP 14273 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RD455 UT WOS:A1995RD45500008 PM 7782282 ER PT J AU ARGETSINGER, LS HSU, GW MYERS, MG BILLESTRUP, N WHITE, MF CARTERSU, C AF ARGETSINGER, LS HSU, GW MYERS, MG BILLESTRUP, N WHITE, MF CARTERSU, C TI GROWTH-HORMONE, INTERFERON-GAMMA, AND LEUKEMIA INHIBITORY FACTOR PROMOTED TYROSYL PHOSPHORYLATION OF INSULIN-RECEPTOR SUBSTRATE-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; PHOSPHATIDYLINOSITOL 3'-KINASE; FACTOR-I; GLUCOSE TRANSPORTERS; BINDING-PROTEIN; MESSENGER-RNA; KINASE; EXPRESSION; CELLS AB The identification of JAK2 as a growth hormone (G:H) receptor-associated, GH-activated tyrosine kinase has established tyrosyl phosphorylation as a signaling mechanism for GH. In the present study, GH is shown to stimulate tyrosyl phosphorylation of insulin receptor substrate 1 (IRS-1), the principle substrate of the insulin receptor. Tyrosyl phosphorylation if IRS-1 is a critical step in insulin signaling and provides binding sites for proteins with the appropriate Src homology 2 domains, including the 85-kDa regulatory subunit of phosphatidylinositol (PI) 3'-kinase. In 3T3-F442A fibroblasts, GH-dependent tyrosyl phosphorylation of IRS-1 was detected by I min and at GH concentrations as low as 5 ng/ml (0.23 nM). Tyrosyl phosphorylation of IRS-1 was transient, with maximal stimulation detected at 30 rain and diminished signal detected at 60 min. The ability of GH receptor (GHR) to transduce the signal for IRS-1 tyrosyl phosphorylation is mediated by the intracellular region of GHR between amino acids 295 and 380 by a mechanism not involving the two tyrosines in this region. This region of GHR is required for GH-dependent JAK2 association and activation (VanderKuur, J. A., Wang, X., Zhang,L., Campbell, G. S., Allevato, G., Billestrup, N., Norstedt, G., and Carter-Su, C. (1994:) J. Biol. Chem. 269, 21709-21717). When other cytokines that activate JAK2 were tested for the ability to stimulate the tyrosyl phosphorylation of IRS-1, stimulation was detected with interferon-gamma and leukemia inhibitory factor. The correlation between JAK2 tyrosyl phosphorylation and IRS-1 tyrosyl phosphorylation in response to GH, interferon-gamma, and leukemia inhibitory factor rind in cells expressing different GHR mutants, provides evidence that IRS-1 may interact with JAK2 or an auxiliary molecule that binds to JAK2. GH is also shown to stimulate binding of IRS-1 to the 85-kDa regulatory subunit of PI 3'-kinase. The ability of GH to stimulate tyrosyl phosphorylation of IRS-1 and its association with PI 3'-kinase provides a biochemical basis for responses shared by insulin and GH including the well characterized insulin-like metabolic effects of GH observed in a variety of cell types. C1 UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,ANN ARBOR,MI 48109. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. HAGEDORN RES LAB,DK-2820 GENTOFTE,DENMARK. OI Billestrup, Nils/0000-0002-4968-8067 FU NIDDK NIH HHS [DK 43808, DK36836, R01 DK034171, R01 DK043808, R01-DK34171] NR 81 TC 213 Z9 215 U1 0 U2 2 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 16 PY 1995 VL 270 IS 24 BP 14685 EP 14692 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RD455 UT WOS:A1995RD45500068 PM 7782332 ER PT J AU MULROW, CD WILLIAMS, JW GERETY, MB RAMIREZ, G MONTIEL, OM KERBER, C AF MULROW, CD WILLIAMS, JW GERETY, MB RAMIREZ, G MONTIEL, OM KERBER, C TI CASE-FINDING INSTRUMENTS FOR DEPRESSION IN PRIMARY-CARE SETTINGS SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE DEPRESSION; PRIMARY HEALTH CARE; MASS SCREENING; PHYSICIANS, FAMILY; SENSITIVITY AND SPECIFICITY ID DIAGNOSTIC INTERVIEW SCHEDULE; GENERAL HEALTH QUESTIONNAIRE; PRIMARY MEDICAL-CARE; MENTAL-ILLNESS; RECOGNITION; PHYSICIANS; PREVALENCE; MANAGEMENT; DISORDERS; ANXIETY AB Objective: To evaluate the usefulness of case-finding instruments for identifying patients with major depression in primary care settings. Data Sources: A MEDLINE search of the English-language medical literature; bibliographies of selected papers; and experts. Study Selection: Studies that were done in primary care settings with unselected patients and that compared case-finding instruments with accepted diagnostic criterion standards for major depression were selected. Data Synthesis: 9 case-finding instruments were assessed in 18 studies. More than 15000 patients received screening with a case-finding instrument; approximately 5300 of these received criterion standard assessment. Case-finding instruments ranged in length from 2 to 28 questions. Average administration times ranged from less than 2 minutes to 6 minutes. Sensitivities and specificities for detecting major depression ranged from 67% to 99% and from 40% to 95%, respectively. No significant differences between instruments were found. Overall sensitivity was 84% (95% CI, 79% to 89%); overall specificity was 72% (CI, 67% to 77%). If a case-finding instrument were administered to 100 primary care patients with a 5% prevalence of major depression, the clinician could expect that 31 patients would screen positive, that 4 of the 31 would have major depression, and that 1 patient with major depression would not be identified. Conclusions: Several instruments with reasonable operating characteristics are available to help primary care clinicians identify patients with major depression. Because the operating characteristics of these instruments are similar, selection of a particular instrument should depend on issues such as feasibility, administration and scoring times, and the instruments' ability to serve additional purposes, such as monitoring severity or response to therapy. RP MULROW, CD (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,11C6,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 64 TC 337 Z9 340 U1 5 U2 7 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 1995 VL 122 IS 12 BP 913 EP 921 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA RC270 UT WOS:A1995RC27000004 PM 7755226 ER PT J AU VANHOFF, J GRIER, HE DOUGLASS, EC GREEN, DM AF VANHOFF, J GRIER, HE DOUGLASS, EC GREEN, DM TI ETOPOSIDE, IFOSFAMIDE, AND CISPLATIN THERAPY FOR REFRACTORY CHILDHOOD SOLID TUMORS - RESPONSE AND TOXICITY SO CANCER LA English DT Article DE PEDIATRIC ONCOLOGY; SARCOMA; WILMS TUMOR; HEPATOBLASTOMA; CHEMOTHERAPY; IFOSFAMIDE; ETOPOSIDE; CISPLATIN ID PHASE-II TRIAL; GERM-CELL CANCER; SALVAGE THERAPY; PLUS CISPLATIN; ONCOLOGY GROUP; CHILDREN; CHEMOTHERAPY; SARCOMA; REGIMEN AB Background. Etoposide, ifosfamide, and cisplatin (VIP) are each active in treating pediatric solid tumors, and this combination has been shown to be effective in treating adult germ cell tumors. Etoposide, ifosfamide, and cisplatin therapy was used to treat 11 patients, with ages ranging from 14 months to 22 years, with relapsed sarcoma, Wilms' tumor, and hepatoblastoma. Methods. Etoposide, ifosfamide, and cisplatin therapy was administered daily for 3 days in doses of cisplatin 20 mg/m(2) with mannitol 10 g/m(2) for 1 hour, etoposide 100 mg/m(2), and ifosfamide 1.5 g/m(2) with MESNA 360 mg/m(2) X 3 doses. A total of 65 courses (range, 3-10/patient) were administered, with 86% of the courses administered at full dose. Hematopoietic growth factors were not used. Results. All 10 evaluable patients responded. Six patients had a complete response (CR) by computed tomographic or magnetic resonance imaging scan after one to three courses. The remaining four patients had a partial response (PR) (>50% decrease in disease). One PR was converted to a CR by resection of the residual lesions. The major toxicity was myelosuppression. The median nadirs after full doses were as follows: leukocyte count of 900/mm(3), absolute neutrophil count (ANC) of 156/mm(3), platelet count of 61,000/mm(3), and hemoglobin count of 8.6 g/dl; 75% of full dose courses led to an ANC of less than 500. Fever and neutropenia were observed after 8/55 (15%) full dose courses. Two episodes of bacteremia were noted, one with Staphylococcus epidermidis after full recovery of counts. The median time to hematologic recovery was 21 days (range, 14-29 days). No patient developed a decreased creatinine clearance level during therapy. Significant renal salute losses were observed in two patients, both of whom had been pretreated heavily with ifosfamide and had losses before VIP therapy. Conclusions. Etoposide, ifosfamide, and cisplatin appear to be active in treating childhood solid tumors. This therapy has predictable and tolerable myelotoxicity, and nephrotoxicity does not appear to be more severe than that observed after treatment with ifosfamide alone. C1 DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. ST CHRISTOPHERS HOSP CHILDREN,PHILADELPHIA,PA 19133. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,BUFFALO,NY 14263. RP VANHOFF, J (reprint author), YALE UNIV,SCH MED,DEPT PEDIAT,333 CEDAR ST,NEW HAVEN,CT 06520, USA. NR 23 TC 13 Z9 13 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 15 PY 1995 VL 75 IS 12 BP 2966 EP 2970 DI 10.1002/1097-0142(19950615)75:12<2966::AID-CNCR2820751226>3.0.CO;2-W PG 5 WC Oncology SC Oncology GA RC116 UT WOS:A1995RC11600025 PM 7773949 ER PT J AU SERRAPAGES, C KEDERSHA, NL FAZIKAS, L MEDLEY, Q DEBANT, A STREULI, M AF SERRAPAGES, C KEDERSHA, NL FAZIKAS, L MEDLEY, Q DEBANT, A STREULI, M TI THE LAR TRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASE AND A COILED-COIL LAR-INTERACTING PROTEIN CO-LOCALIZE AT FOCAL ADHESIONS SO EMBO JOURNAL LA English DT Article DE COILED-COIL DOMAIN; FOCAL ADHESIONS; PROTEIN TYROSINE PHOSPHORYLATION ID EXTRACELLULAR-MATRIX; IMMUNOGLOBULIN SUPERFAMILY; CELL-ADHESION; PHOSPHOTYROSINE PHOSPHATASE; TRANSFORMED-CELLS; NERVOUS-SYSTEM; PHOSPHORYLATION; KINASE; EXPRESSION; JUNCTIONS AB Focal adhesions are sites of cell-extracellular matrix interactions that function in anchoring stress fibers to the plasma membrane and in adhesion-mediated signal transduction. Both focal adhesion structure and signaling ability involve protein tyrosine phosphorylation. LAR is a broadly expressed transmembrane protein tyrosine phosphatase comprised of a cell adhesion-like ectodomain and two intracellular protein tyrosine phosphatase domains, We have identified a novel cytoplasmic 160 kDa phosphoserine protein termed LAB-interacting protein 1 (LIP.1), which binds to the LAR membrane-distal D2 protein tyrosine phosphatase domain and appears to localize LAR to focal adhesions, Both LAR and LIP.1 decorate the ends of focal adhesions most proximal to the cell nucleus and are excluded from the distal ends of focal adhesions, thus localizing to regions of focal adhesions presumably undergoing disassembly. We propose that LAR and LIP.1 may regulate the disassembly of focal adhesions and thus help orchestrate cell-matrix interactions. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. IMMUNOGEN INC,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. FU NCI NIH HHS [CA55547] NR 63 TC 239 Z9 241 U1 0 U2 3 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 15 PY 1995 VL 14 IS 12 BP 2827 EP 2838 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RF900 UT WOS:A1995RF90000014 PM 7796809 ER PT J AU DURONIO, RJ OFARRELL, PH XIE, JE BROOK, A DYSON, N AF DURONIO, RJ OFARRELL, PH XIE, JE BROOK, A DYSON, N TI THE TRANSCRIPTION FACTOR E2F IS REQUIRED FOR S-PHASE DURING DROSOPHILA EMBRYOGENESIS SO GENES & DEVELOPMENT LA English DT Article DE DROSOPHILA; E2F; S PHASE; CELL CYCLE; EMBRYOGENESIS ID CELL-CYCLE; DNA-REPLICATION; RETINOBLASTOMA PROTEIN; BINDING PROTEIN; GENE; EXPRESSION; MELANOGASTER; PATTERNS; EMBRYOS; CLONING AB Overexpression of the E2F-1 cDNA in mammalian cells disrupts normal control of the cell cycle and drives cells into S phase. Whereas eliminating E2F activity would test its inferred involvement in the G(1)-S transition, elimination is complicated by the existence of gene families encoding mammalian E2F. Here we identify mutations in a single essential Drosophila gene, dE2F, that encodes a homolog of the mammalian E2F gene family. Embryos homozygous for null mutations of dE2F complete early cell cycles, presumably using maternal contributions of gene products, but DNA synthesis falls to virtually undetectable levels in cycle 17. Mutant embryos also lack the pulses of coordinate transcription of genes encoding replication functions that usually accompany each transition from quiescence to S phase. We conclude that in most cells dE2F is essential for a G(1)-S transcriptional program and for G(1)-S progression. C1 MASSACHUSETTS GEN HOSP,MOLEC ONCOL LAB,BOSTON,MA 02129. RP DURONIO, RJ (reprint author), UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143, USA. OI O'Farrell, Patrick/0000-0003-0011-2734 FU NIGMS NIH HHS [R01 GM037193] NR 59 TC 198 Z9 200 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 JUN 15 PY 1995 VL 9 IS 12 BP 1445 EP 1455 DI 10.1101/gad.9.12.1445 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA RG643 UT WOS:A1995RG64300002 PM 7601349 ER PT J AU GERWECK, LE HETZEL, FW AF GERWECK, LE HETZEL, FW TI PO-2 IN IRRADIATED VERSUS NONIRRADIATED TUMORS OF MICE BREATHING OXYGEN AT NORMAL AND ELEVATED PRESSURE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE TUMOR HYPOXIA; OXYGEN BREATHING; RADIATION; HYPERBARIC OXYGEN ID RADIATION; MOUSE AB Purpose: To determine if prior tumor irradiation influences tumor pO(2) changes in mice breathing oxygen (100%) at normal and elevated pressure. Methods and Materials: Single-point pO(2) measurements were performed in nonirradiated and previously irradiated (72 h) isotransplanted MCaIV tumors in C3H/Sed mice, Continuous recordings were performed at the same tumor locus under air breathing, followed by 100% oxygen and oxygen at three atmospheres pressure. Following decompression and induction of pentobarbital anesthesia, the procedure was repeated at the same locus. Six nonirradiated and five irradiated tumors were evaluated under the three gas breathing conditions +/- anesthesia. Results: The mean, median, and range of pO(2) values did not differ under air-breathing conditions in the nonirradiated vs, previously irradiated tumors, However, prior irradiation substantially enhanced the tumor PO2 increase when the inspired gas phase was switched from air to 100% oxygen at 1 or 3 atmospheres pressure, In four of six nonirradiated tumors, 100% oxygen breathing resulted in a pO(2) increase of < 4 mmHg; in the irradiated tumors, the minimum increase was 16 mmHg, Pentobarbital anesthesia did not significantly influence the results obtained. Conclusion: These data indicate that the efficacy of oxygen breathing increases during tumor treatment, and suggests that oxygen breathing is a simple nontoxic method for reducing or eliminating radiobiologic hypoxia during therapy. C1 OFF RES & DEV HLTH 1,DENVER,CO. RP GERWECK, LE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-22860] NR 21 TC 5 Z9 5 U1 0 U2 1 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 15 PY 1995 VL 32 IS 3 BP 695 EP 701 DI 10.1016/0360-3016(94)00609-O PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA RE533 UT WOS:A1995RE53300016 PM 7790256 ER PT J AU WANG, CC AF WANG, CC TI ACCELERATED FRACTIONATION - THE DOS AND DONTS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material RP WANG, CC (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 4 TC 6 Z9 6 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 15 PY 1995 VL 32 IS 3 BP 889 EP 890 DI 10.1016/0360-3016(95)00188-5 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA RE533 UT WOS:A1995RE53300039 PM 7790278 ER PT J AU ISRAEL, EJ PATEL, VK TAYLOR, SF MARSHAKROTHSTEIN, A SIMISTER, N AF ISRAEL, EJ PATEL, VK TAYLOR, SF MARSHAKROTHSTEIN, A SIMISTER, N TI REQUIREMENT FOR A BETA(2)-MICROGLOBULIN-ASSOCIATED FC RECEPTOR FOR ACQUISITION OF MATERNAL IGG BY FETAL AND NEONATAL MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STEM-CELLS; BETA-2-MICROGLOBULIN; MOUSE; RAT; IMMUNOGLOBULIN; TRANSMISSION; ANTIBODIES; PROTEINS; ONTOGENY; VIRUS AB There is considerable evidence to suggest that an FcR similar in structure to class I MHC Ags, neonatal Fc receptor (FcRn), transports IgG across the intestinal epithelium of suckling mice. However, this has not previously been shown definitively, nor has it been shown whether FcRn is the only, or even the major, IgG transporter in the neonatal mouse gut. We report here that neonatal mice homozygous for a targeted disruption of the beta(2)microglobulin (beta(2)m) gene, which encodes one subunit of FcRn, had reduced FcRn alpha-chain at the lumenal plasma membrane of intestinal cells. These mice had strikingly lower serum Ige levels during the First month after birth than littermates that possessed functional FcRn. Furthermore, we found by fostering mice on mothers with a different IgG allotype that all of the IgG in sera of beta(2)m(-/-) mice was endogenous, and that none was obtained from milk. We conclude that FcRn is the only transporter of IgG from mother to young in the mouse. The onset of IgG synthesis in mice that received no milk IgG lagged behind that in siblings with normal Ige transport, suggesting that maternal IgG stimulates Ab production in the neonate. We noted no difference between the IgG concentrations in the milk of beta(2)m(-/-) and beta(2)m(+/-) mice, indicating that FcRn is not involved in the secretion of IgG into milk. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114. BOSTON UNIV,SCH MED,DEPT MICROBIOL,BOSTON,MA 02118. BRANDEIS UNIV,DEPT BIOL,WALTHAM,MA 02254. BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,WALTHAM,MA 02254. FU NICHD NIH HHS [HD00938, HD12437, HD27691] NR 37 TC 139 Z9 142 U1 0 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 15 PY 1995 VL 154 IS 12 BP 6246 EP 6251 PG 6 WC Immunology SC Immunology GA RC610 UT WOS:A1995RC61000004 PM 7759862 ER PT J AU CUENOUD, B SZOSTAK, JW AF CUENOUD, B SZOSTAK, JW TI A DNA METALLOENZYME WITH DNA-LIGASE ACTIVITY SO NATURE LA English DT Article ID HUMAN THROMBIN; RNA; BINDING; APTAMER; SELECTION; MOLECULES; INVITRO AB SINGLE-STRANDED DNA can fold into well-defined sequence-dependent tertiary structures that specifically bind a variety of target molecules(1-10), raising the possibility that some folded single-stranded DNAs might exhibit catalytic activities similar to those of ribozymes and protein enzymes. Derivatives of the hammerhead ribozyme that contain a majority of deoxyribonucleotides retain the ability to cleave RNA(11), and a 'deoxyribozyme' was generated by leaving all essential ribonucleotides of the hammerhead on the RNA 'substrate'(12). Recently in vitro selection has been used to isolate a DNA sequence that shows Pb2+-dependent RNA-cleaving activity(13). Here we report the isolation by in vitro selection(14-17) of a small single-stranded DNA that is a Zn2+/Cu2+-dependent metalloenzyme. The enzyme catalyses the formation of a new phosphodiester bond by the condensation of the 5'-hydroxyl of one oligodeoxynucleotide and a 3'-phosphorimidazolide on another oligodeoxynucleotide, and shows multiple turnover ligation. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 30 TC 270 Z9 275 U1 8 U2 50 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 15 PY 1995 VL 375 IS 6532 BP 611 EP 614 DI 10.1038/375611a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RD287 UT WOS:A1995RD28700057 PM 7791880 ER PT J AU FULLER, AF FLEISCHHACKER, DS BOLAND, GWL SCULLY, RE HEDBERG, PS FIDIAS, PM AF FULLER, AF FLEISCHHACKER, DS BOLAND, GWL SCULLY, RE HEDBERG, PS FIDIAS, PM TI A 59-YEAR-OLD WOMAN WITH AN APPLE CORE LESION OF THE SIGMOID COLON, A PELVIC MASS, AND A PULMONARY NODULE - SQUAMOUS-CELL CARCINOMA ARISING IN A DERMOID CYST OF THE OVARY, WITH INVASION OF THE MUSCULARIS OF THE RECTOSIGMOID COLON - SMALL-CELL CARCINOMA OF THE LUNG SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID TERATOMA C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP FULLER, AF (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 17 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 15 PY 1995 VL 332 IS 24 BP 1631 EP 1636 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA RC192 UT WOS:A1995RC19200008 ER PT J AU CARRERA, AC BORLADO, LR GONZALEZGARCIA, A ROBERTS, TM MARTINEZA, C AF CARRERA, AC BORLADO, LR GONZALEZGARCIA, A ROBERTS, TM MARTINEZA, C TI ROLE OF THE AUTOPHOSPHORYLATION SITE ON THE BIOLOGICAL FUNCTION OF PP56(LCK) SO ONCOGENE LA English DT Article DE AUTOPHOSPHORYLATION; KINASES; FUNCTION ID CELL ANTIGEN RECEPTOR; GTPASE-ACTIVATING PROTEIN; TYROSINE KINASE P56LCK; T-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; THYMOCYTE DEVELOPMENT; SIGNAL TRANSDUCTION; NUCLEAR FACTOR; EXPRESSION; GENE AB Src-family tyrosine kinases act as signaling molecules in a aide array of cellular activation processes. The existence of the various src-family members reflects the requirement for different cell-surface receptors to transmit cell-type specific intracellular signals. The structural basis for the functional specificity of src-kinases is being actively investigated. In the present report we have analysed the contribution of the area surrounding the autophosphorylation site (located at subdomain VII of the catalytic domain) in determining src-kinases activity and functional specificity. To this end we analysed the kinase activities of the lymphoid src-kinase pp56(lck) and a mutant of pp56(lck) in which this region has been exchanged for the corresponding area of the serine/threonine kinase c-Raf. Our studies indicate that the change at subdomain VII affected the ability of pp56(lck) to phosphorylate physiological substrates. Furthermore, when analysed in T cells, the mutant at subdomain VII failed to induce interleukin-2 production, a specific biological function of pp56(lck). Thus, the area surrounding the autophosphorylation site of pp56(lck) plays a critical role in mediating its specific biological function. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MOLEC & CELLULAR BIOL,BOSTON,MA 02115. RP CARRERA, AC (reprint author), UNIV AUTONOMA MADRID,CSIC,CTR NACL BIOTECNOL,CAMPUS CANTOBLANCO,E-28049 MADRID,SPAIN. RI Gonzalez-Garcia, Ana/D-9736-2014; OI Carrera, Ana/0000-0002-3999-5434 FU NCI NIH HHS [CA 43803] NR 51 TC 7 Z9 7 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 15 PY 1995 VL 10 IS 12 BP 2379 EP 2386 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RE543 UT WOS:A1995RE54300013 PM 7784086 ER PT J AU CHEN, H THALMANN, I ADAMS, JC AVRAHAM, KB COPELAND, NG JENKINS, NA BEIER, DR COREY, DP THALMANN, R DUYK, GM AF CHEN, H THALMANN, I ADAMS, JC AVRAHAM, KB COPELAND, NG JENKINS, NA BEIER, DR COREY, DP THALMANN, R DUYK, GM TI CDNA CLONING, TISSUE DISTRIBUTION, AND CHROMOSOMAL LOCALIZATION OF OCP2 A GENE ENCODING A PUTATIVE TRANSCRIPTION-ASSOCIATED FACTOR PREDOMINANTLY EXPRESSED IN THE AUDITORY ORGANS SO GENOMICS LA English DT Article ID RECOMBINANT INBRED STRAINS; MOUSE CHROMOSOME-4; LINKAGE MAP; FACTOR-SIII; PROTEINS; CORTI; REDUCTASE; SEQUENCES AB We report the cloning of the Ocp2 gene encoding OCP-II from a guinea pig organ-of-Corti cDNA library. The predicted open reading frame encodes a protein of 163 amino acids with an estimated molecular mass of 18.6 kDa. A homology search revealed that Ocp2 shares significant sequence similarity with p15, a subunit of transcription factor SIII that regulates the activity of the RNA polymerase II elongation complex. The Ocp2 messenger RNA is expressed abundantly in the cochlea while not significantly in any other tissues examined, including brain, eye, heart, intestine, kidney, liver, lung, thigh muscle, and testis, demonstrating that the expression of this gene may be restricted to auditory organs. A polyclonal antiserum was raised against the N-terminal region of OCP-II. Immunohistochemical staining of paraffin-embedded sections of the cochlea showed that OCP-II is localized abundantly in nonsensory cells in the organ of Corti; in addition, it was also detected, at a lower concentration, in vestibular sensory organs, as well as auditory and vestibular brain stem nuclei. The Ocp2 gene was mapped to mouse chromosome 4 as well as 11. Our results suggest that OCP-II may be involved in transcription regulation for the development or maintenance of specialized functions of the inner ear. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. WASHINGTON UNIV,DEPT OTOLARYNGOL,ST LOUIS,MO 63110. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. OI Corey, David/0000-0003-4497-6016 FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [5F32GM15909-02]; PHS HHS [R01 00269] NR 40 TC 42 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 10 PY 1995 VL 27 IS 3 BP 389 EP 398 DI 10.1006/geno.1995.1068 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RG981 UT WOS:A1995RG98100001 PM 7558018 ER PT J AU XU, L STERNER, C MAHESHWAR, MM WILSON, PJ NELLIST, M SHORT, PM HAINES, JL SAMPSON, JR RAMESH, V AF XU, L STERNER, C MAHESHWAR, MM WILSON, PJ NELLIST, M SHORT, PM HAINES, JL SAMPSON, JR RAMESH, V TI ALTERNATIVE SPLICING OF THE TUBEROUS SCLEROSIS-2 (TSC2) GENE IN HUMAN AND MOUSE-TISSUES SO GENOMICS LA English DT Article ID HETEROGENEITY; CHROMOSOME-9; LOCUS; LINKAGE; MARKER; RNA; MAP AB The recently isolated gene for tuberous sclerosis 2 (TSC2) encodes a 5.5-kb transcript that is widely expressed. The TSC2 gene product, named tuberin, is a 1784-amino-acid protein that shows a small stretch of homology to the GTPase activating protein rap1GAP. We have detected a novel variant of the TSC2 mRNA lacking 129 nucleotides, predicting an in-frame deletion of 43 amino acids spanning codons 946-988 of tuberin. This 129-bp deletion precisely corresponds to exon 25 of the TSC2 gene suggesting that alternative splicing leads to production of two forms of transcripts designated isoforms 1 and 2. Further molecular analysis revealed a third isoform exhibiting a deletion of 44 amino acids spanning codons 946-989 of tuberin. Amino acid 989 is a Ser residue encoded by the first codon of exon 26. The two isoforms also exist in newborn and adult mouse tissues, reinforcing the potential functional importance of these alternatively spliced products. These alternative isoforms should have implications for efforts aimed at identifying mutations in TSC patients. The distinct polypeptides encoded by the TSC2 gene may have different targets as well as functions involved in the regulation of cell growth. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP EAST, MOLEC NEUROGENET UNIT, BOSTON, MA 02129 USA. UNIV WALES COLL MED, INST MED GENET, CARDIFF CF4 4XN, S GLAM, WALES. RI Haines, Jonathan/C-3374-2012 FU NINDS NIH HHS [NS24279] NR 26 TC 51 Z9 52 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD JUN 10 PY 1995 VL 27 IS 3 BP 475 EP 480 DI 10.1006/geno.1995.1079 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RG981 UT WOS:A1995RG98100012 PM 7558029 ER PT J AU BLOCH, KD WOLFRAM, JR BROWN, DM ROBERTS, JD ZAPOL, DG LEPORE, JJ FILIPPOV, G THOMA, JE JACOB, HJ BLOCH, DB AF BLOCH, KD WOLFRAM, JR BROWN, DM ROBERTS, JD ZAPOL, DG LEPORE, JJ FILIPPOV, G THOMA, JE JACOB, HJ BLOCH, DB TI 3 MEMBERS OF THE NITRIC-OXIDE SYNTHASE-II GENE FAMILY (NOS2A, NOS2B, AND NOS2C) COLOCALIZE TO HUMAN-CHROMOSOME-17 SO GENOMICS LA English DT Note ID EXPRESSION; CLONING; LOCALIZATION; HEPATOCYTES AB Nitric oxide synthases (NOSs) are a family of enzymes responsible for the synthesis of nitric oxide from L-arginine and molecular oxygen. Three human NOS enzymes (I, II, and III) with differing cellular distribution and regulatory mechanisms have been identified. To determine whether additional NOSs are encoded in the human genome, a bovine NOS II-related cDNA was used to screen two human genomic Libraries. Clones containing three independent genes were isolated. One clone encoded the previously identified NOS II gene (NOS2A). The two other genes specified amino acids homologous, but not identical, to human NOS II (NOS2B and NOS2C). Southern blot hybridization demonstrated that all three genes are present in the human genome. DNA from human-mouse somatic cell hybrids were used to determine the chromosomal location of the NOS II-related genes. Ah three NOS II-related genes colocalized to human chromosome 17 between bands p13.1 and q25. These observations suggest that there is more than one NOS II-related gene in the human genome, This finding may have important implications for the design of NOS isoform-specific inhibitors. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,ARTHRIT UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NHLBI NIH HHS [K08 HL004237, HL45895]; NIAMS NIH HHS [AR01866] NR 18 TC 30 Z9 32 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 10 PY 1995 VL 27 IS 3 BP 526 EP 530 DI 10.1006/geno.1995.1086 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RG981 UT WOS:A1995RG98100019 PM 7558036 ER PT J AU CUMMINGS, JL AF CUMMINGS, JL TI DEMENTIA - THE FAILING BRAIN SO LANCET LA English DT Article C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,BEHAV NEUROSCI SECT,LOS ANGELES,CA 90073. RP CUMMINGS, JL (reprint author), UNIV CALIF LOS ANGELES,SCH MED,REED NEUROL RES CTR,DEPT NEUROL,710 WESTWOOD PLAZA,LOS ANGELES,CA 90024, USA. FU NIA NIH HHS [AG 10123] NR 0 TC 25 Z9 26 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD JUN 10 PY 1995 VL 345 IS 8963 BP 1481 EP 1484 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA RC189 UT WOS:A1995RC18900011 PM 7769904 ER PT J AU MATSUDA, M PETERSSON, M LENKEI, R TAUPIN, JL MAGNUSSON, I MELLSTEDT, H ANDERSON, P KIESSLING, R AF MATSUDA, M PETERSSON, M LENKEI, R TAUPIN, JL MAGNUSSON, I MELLSTEDT, H ANDERSON, P KIESSLING, R TI ALTERATIONS IN THE SIGNAL-TRANSDUCING MOLECULES OF T-CELLS AND NK CELLS IN COLORECTAL TUMOR-INFILTRATING, GUT MUCOSAL AND PERIPHERAL LYMPHOCYTES - CORRELATION WITH THE STAGE OF THE DISEASE SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NATURAL-KILLER-CELLS; RECEPTOR ZETA-CHAIN; FC-EPSILON-RI; ANTIGEN RECEPTOR; GAMMA-CHAIN; ETA-CHAIN; ACTIVATION; EXPRESSION; CARCINOMA; INDUCTION AB T cells from mice bearing an experimental colon carcinoma, and from patients with colorectal and renal carcinomas, have atypical T-cell receptors (TCR). In the present study, further characterization of modulations in CD3- and CD16-associated zeta chain in peripheral blood lymphocytes (PBL) and tumorinfiltrating lymphocytes (TIL) from colorectal carcinomas was performed. Relative to PBL, the percentage of natural killer (NK) cells among fresh TIL was reduced, while a higher proportion of T cells expressing HLA-DR was found. As previously reported, we found significantly reduced levels of the CD3- and CD16-associated zeta chain in TIL and, to a lesser extent, also in patients' PBL. Levels of zeta chain in T and NK cells from non-cancerous colorectal tissue from patients were lower than in PBL but higher than in TIL, with a direct relationship between levels of this signal-transducing molecule and the distance from the tumor. In addition, zeta levels correlated with the Dukes' stage of the disease, since PBL from patients with lymph-node involvement or distant organ metastases (Dukes' stages C and D) had significantly less CD3 zeta than patients with localized disease (stages A and B). Patients' T cells also had decreased levels of cell-surface and cytoplasmic CD3 epsilon. We also observed reduced levels of the TCR accessory molecules CD4 and CD8, mainly on TIL but to a lesser extent also on patients' PBL. Biochemical analysis of anti-CD3 epsilon-immunoprecipitated TCR complexes demonstrated that the CD3 complex was not associated with the zeta chain, either on TIL or on PBL or on lymphocytes from non-cancerous colon tissue, suggesting a defect in the assembly of the TCR complex. Following several days of in vitro culture with recombinant interleukin-2 and phytohemagglutinin, anti-CD3 or anti-CD2 monoclonal antibodies (MAbs), levels of CD3 zeta chain as well as of cell surface CD3 epsilon were normalized. Our findings suggest an abnormal expression as well as assembly of several different signal-transducing molecules of T cells and NK cells, which correlate with the stage of the disease in patients with colorectal carcinomas. (C) 1995 Wiley-Liss, Inc. C1 KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. YAMANASHI MED COLL,DEPT SURG,YAMANASHI 40938,JAPAN. CALEB MED LABS,STOCKHOLM,SWEDEN. DANA FARBER CANC INST,BOSTON,MA. SODER SJUKHUSET,DEPT SURG,STOCKHOLM,SWEDEN. KAROLINSKA SJUKHUSET,RADIUMHEMMET,STOCKHOLM,SWEDEN. NR 29 TC 190 Z9 193 U1 0 U2 4 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 9 PY 1995 VL 61 IS 6 BP 765 EP 772 DI 10.1002/ijc.2910610605 PG 8 WC Oncology SC Oncology GA RG107 UT WOS:A1995RG10700004 PM 7790109 ER PT J AU FESCHENKO, MS SWEADNER, KJ AF FESCHENKO, MS SWEADNER, KJ TI STRUCTURAL BASIS FOR SPECIES-SPECIFIC DIFFERENCES IN THE PHOSPHORYLATION OF NA,K-ATPASE BY PROTEIN-KINASE-C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID (NA+ + K+)-ATPASE; CATALYTIC SUBUNIT; NA+/K+-ATPASE; MAMMALIAN KIDNEY; ALPHA-SUBUNIT; NA+,K+-ATPASE; ISOZYME; ENZYME; PURIFICATION; STIMULATION AB There is considerable evidence that protein kinases play a role in regulation of the activity of the Na,K-ATPase, but the characteristics of direct kinase phosphorylation of Na,K-ATPase subunits are still not well understood. There are 36 sites that could qualify as protein kinase C motifs in rat alpha 1. Here we have used protein fragmentation with trypsin to localize the site of phosphorylation of the rat Na,K-ATPase alpha 1 subunit to within the first 32 amino acids of the N terminus and then used direct sequencing of the phosphorylated protein to determine which of two candidate serine residues was modified. The result was that at most 25% of the P-32 was found on Ser-11, a site that is well conserved in Na,K-ATPase alpha 1 subunits. The remaining 75% or more of the P-32 was found on Ser-18, a site that is absent in many Na,K-ATPase alpha subunit sequences. This accounts for the observation that dog and pig alpha 1 subunits can be phosphorylated by protein kinase C only to much lower levels than can rat alpha 1. It is also likely to be relevant to other known species specific effects of protein kinase C on Na,K-ATPase. C1 MASSACHUSETTS GEN HOSP, CTR NEUROSCI, MEMBRANE BIOL LAB, BOSTON, MA 02114 USA. FU NINDS NIH HHS [NS 27653] NR 37 TC 112 Z9 113 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 9 PY 1995 VL 270 IS 23 BP 14072 EP 14077 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RC448 UT WOS:A1995RC44800071 PM 7775468 ER PT J AU DUKECOHAN, JS MORIMOTO, C ROCKER, JA SCHLOSSMAN, SF AF DUKECOHAN, JS MORIMOTO, C ROCKER, JA SCHLOSSMAN, SF TI A NOVEL FORM OF DIPEPTIDYLPEPTIDASE-IV FOUND IN HUMAN SERUM - ISOLATION, CHARACTERIZATION, AND COMPARISON WITH T-LYMPHOCYTE MEMBRANE DIPEPTIDYLPEPTIDASE-IV (CD26) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ACTIVATION ANTIGEN; PEPTIDASE-IV; ADENOSINE-DEAMINASE; MONOCLONAL-ANTIBODIES; AMINOPEPTIDASE-IV; SURFACE; PURIFICATION; EXPRESSION; MOLECULE; PROTEIN AB Human CD26, a Type II membrane glycoprotein with intrinsic dipeptidylpeptidase TV (DPPIV) activity and ability to bind adenosine deaminase type I (ADA-1), is expressed on epithelial cells constitutively, but on T lymphocytes its expression is regulated, A soluble form of CD26/DPPIV has been described in plasma and related to immunological status, but it has been defined by the presence of DPPIV activity rather than by isolation. Using nondenaturing chromatographic techniques followed by nondenaturing native preparative electrophoresis, we obtained a homogeneous preparation of soluble serum DPPIV and compared it with a recombinant soluble CD26/DPPIV (rsCD26). We show that serum DPPIV is a monomer of 175 kDa in contrast to rsCD26 of 105-110 kDa, that it exists as a trimer, and that it is probably a serine proteinase. Deglycosylation removed N-linked sugar hom both serum DPPIV and rsCD26; no O-linked glycosylation was observed, revealing a protein core of 130 kDa for serum DPPIV. The large serum form expresses functional DPPIV activity with substrate and inhibitor specificities and pH activity profile similar to those of rsCD26, Epitope analysis showed that monoclonal antibodies against five epitopes expressed by rsCD26 also bound, but more weakly, with serum DPPIV. Analysis of peptides after limiting proteolysis and N-terminal sequences reveals no homology with rsCD26 but some identity with other peptidases. Unlike rsCD26, the serum form does not bind ADA-1 and has no ADA-1 already associated with it. Similarly to rsCD26, serum DPPIV is a potent T cell costimulator. We conclude that the serum form of DPPIV is unique and is not a breakdown product of membrane CD26, The conservation of DPPIV activity and five epitopes specific to rsCD26 suggest, however, a significant structural similarity. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP DUKECOHAN, JS (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Duke-Cohan, Jonathan/A-5812-2010 OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU NCI NIH HHS [CA55601]; NIAID NIH HHS [AI12069, AI23360-08] NR 40 TC 106 Z9 110 U1 0 U2 6 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 9 PY 1995 VL 270 IS 23 BP 14107 EP 14114 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RC448 UT WOS:A1995RC44800076 PM 7539799 ER PT J AU KOH, J ENDERS, GH DYNLACHT, BD HARLOW, E AF KOH, J ENDERS, GH DYNLACHT, BD HARLOW, E TI TUMOR-DERIVED P16 ALLELES ENCODING PROTEINS DEFECTIVE IN CELL-CYCLE INHIBITION SO NATURE LA English DT Article ID RETINOBLASTOMA PROTEIN AB THE cyclin-dependent kinase inhibitor p16 is a candidate tumour-suppressor protein that maps to a genomic locus strongly associated with familial melanoma and other tumour types(1-3). Screening of primary tumours and linkage analysis of familial melanoma pedigrees have identified many potential mutations in p16, but the functional significance of these sequence variants has remained unclear(1,3-9). We report here that p16 can act as a potent and specific inhibitor of progression through the G1 phase of the cell cycle, and we demonstrate that several tumour-derived alleles of p16 encode functionally compromised proteins. The ability of p16 to arrest cell-cycle progression generally correlates with inhibition of cyclin D1/Cdk4 kinase activity irt vitro, with two exceptions among the alleles tested. In vivo, the presence of functional retinoblastoma protein appears to be necessary but may not be sufficient to confer full sensitivity to p16-mediated growth arrest. Our results provide support for the notion that p16 is an important cell-cycle regulator whose inactivation contributes to the outgrowth of human tumours. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. RP KOH, J (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 27 TC 497 Z9 508 U1 0 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUN 8 PY 1995 VL 375 IS 6531 BP 506 EP 510 DI 10.1038/375506a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RC188 UT WOS:A1995RC18800053 PM 7777061 ER PT J AU HALES, CA MARK, EJ MILLER, SW AF HALES, CA MARK, EJ MILLER, SW TI AN 81-YEAR-OLD WOMAN WITH MITRAL REGURGITATION AND A LEFT-UPPER-LOBE PULMONARY INFILTRATE - PULMONARY HEMORRHAGE, HEMOSIDEROSIS, AND CONGESTIVE VASCULOPATHY DUE TO MITRAL REGURGITATION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID STRESS FAILURE; CAPILLARIES C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP HALES, CA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 25 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 8 PY 1995 VL 332 IS 23 BP 1566 EP 1572 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RB196 UT WOS:A1995RB19600008 ER PT J AU RABB, H MENDIOLA, CC SABA, SR DIETZ, JR SMITH, CW BONVENTRE, JV RAMIREZ, G AF RABB, H MENDIOLA, CC SABA, SR DIETZ, JR SMITH, CW BONVENTRE, JV RAMIREZ, G TI ANTIBODIES TO ICAM-1 PROTECT KIDNEYS IN SEVERE ISCHEMIC REPERFUSION INJURY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ACUTE-RENAL-FAILURE; INTERCELLULAR-ADHESION MOLECULE-1; RAT; NEUTROPHIL AB ICAM-1 has been implicated in the pathophysiology of ischemic-reperfusion injury in a number of organs, but its role in mediating severe ischemic-reperfusion injury in the kidney has not been extensively studied. Uninephrectomized Sprague Dawley rats were pretreated with either control monoclonal antibody (mAb) or mAb to ICAM-1 and subjected to 60 min of renal artery occlusion. The serum creatinine, complete blood count and kidney histo-pathological damage scores (PDS) (Scale:0-4) were assessed prior to and 24 hours after ischemia. Mean serum creatinine (mg/dl) 24 hours after ischemia was significantly decreased in the anti-ICAM-1 group (1.38 +/- 0.23, p<0.001) compared to control (2.87 +/- 0.34). PDS was also reduced in anti-ICAM-1 (2.55 +/- 0.20, p<0.05) group compared to control (3.35 +/- 0.30). These data demonstrate that blocking ICAM-1 significantly mitigates severe ischemic acute renal failure, findings which may lead to improved therapy for this condition. (C) 1995 Academic Press, Inc. C1 UNIV S FLORIDA,DEPT INTERNAL MED,TAMPA,FL 33612. UNIV S FLORIDA,DEPT PATHOL,TAMPA,FL 33612. UNIV S FLORIDA,DEPT PHYSIOL,TAMPA,FL 33612. JAMES A HALEY VET HOSP,TAMPA,FL 33612. BAYLOR COLL MED,HOUSTON,TX 77030. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02129. NR 17 TC 110 Z9 116 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 6 PY 1995 VL 211 IS 1 BP 67 EP 73 DI 10.1006/bbrc.1995.1779 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RB850 UT WOS:A1995RB85000011 PM 7779111 ER PT J AU FEIGIN, AM TEETER, JH BRAND, JG AF FEIGIN, AM TEETER, JH BRAND, JG TI THE INFLUENCE OF STEROLS ON THE SENSITIVITY OF LIPID BILAYERS TO MELITTIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CHOLESTEROL; MEMBRANES; CHANNELS; PERMEABILITY; CONDUCTANCE; VESICLES AB The sensitivity of planar lipid bilayers to the permeabalizing effect of melittin was evaluated when sterols of varying structure were incorporated into the membrane. The addition of increasing amount,of cholesterol (0-50 mole %) decreased the sensitivity of membranes formed from negatively charged phospholipids to melittin but did not (in amount of up to 66 mole %) change the sensitivity of membranes formed from zwitterionic lipids. 7-Dehydrocholesterol, stigmasterol and ergosterol had the same ability as that of cholesterol to decrease the membrane sensitivity to melittin, while lanosterol had no effect on the sensitivity of membranes to melittin, The results suggest that the effect of sterols is complex and cannot be explained only by a direct interaction of melittin with cholesterol, by a decrease of membrane fluidity, or by changes in distribution of surface charge. (C) 1995 Academic Press, Inc. C1 UNIV PENN,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. RP FEIGIN, AM (reprint author), MONELL CHEM SENSES CTR,3500 MARKET ST,PHILADELPHIA,PA 19104, USA. NR 23 TC 14 Z9 14 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 6 PY 1995 VL 211 IS 1 BP 312 EP 317 DI 10.1006/bbrc.1995.1812 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RB850 UT WOS:A1995RB85000044 PM 7779101 ER PT J AU MISSERO, C CALAUTTI, E ECKNER, R CHIN, J TSAI, LH LIVINGSTON, DM DOTTO, GP AF MISSERO, C CALAUTTI, E ECKNER, R CHIN, J TSAI, LH LIVINGSTON, DM DOTTO, GP TI INVOLVEMENT OF THE CELL-CYCLE INHIBITOR CIP1/WAF1 AND THE E1A-ASSOCIATED P300 PROTEIN IN TERMINAL DIFFERENTIATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DEPENDENT KINASES; EPIDERMAL-CELLS; GROWTH; GENE; P53; MUSCLE; P21; GAP AB The mechanism of cell cycle withdrawal during terminal differentiation is poorly understood. We report here that the cyclin-dependent kinase (CDK) inhibitor p21(Cip1/WAF1) is induced at early times of both keratinocyte and myoblast differentiation. p21(Cip1/WAF1) induction is accompanied by a drastic inhibition of total Cdk2, as well as p21(Cip1/WAF1)-associated CDK kinase activities, p21(Cip1/WAF1) has been implicated in p53-mediated G(1) arrest and apoptosis, In keratinocyte differentiation, Cip1/WAF1 induction is observed even in cells derived from p53-null mice, Similarly, keratinocyte differentiation is associated with induction of Cip1/WAF1 promoter activity in both wild-type and p53-negative keratinocytes, Induction of the Cip1/WAF1 promoter upon differentiation is abolished by expression of an adenovirus EIA oncoprotein (d1922/947), which is unable to bind p105-Rb, p107, or cyclin ii but which still binds the nuclear phosphoprotein p300, Overexpression of p300 can suppress the E1A effect, independent of its direct binding to E1A, Thus, terminal differentiation-induced growth arrest in both keratinocyte and myoblast systems is associated with induction of Cip1/WAF1 expression, During keratinocyte differentiation, Cip1/WAF1 induction does not require p53 but depends on the transcriptional modulator p300. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP MISSERO, C (reprint author), MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129, USA. OI CALAUTTI, Vincenzo/0000-0002-4439-9709 FU NCI NIH HHS [CA16038]; NIAMS NIH HHS [AR39190] NR 35 TC 308 Z9 309 U1 0 U2 1 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 6 PY 1995 VL 92 IS 12 BP 5451 EP 5455 DI 10.1073/pnas.92.12.5451 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400040 PM 7777529 ER PT J AU LI, CJ WANG, CL FRIEDMAN, DJ PARDEE, AB AF LI, CJ WANG, CL FRIEDMAN, DJ PARDEE, AB TI RECIPROCAL MODULATIONS BETWEEN P53 AND TAT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONG TERMINAL REPEAT; KAPOSIS-SARCOMA; TRANSGENIC MICE; TUMOR-ANTIGEN; PROTEIN; CELLS; GENE; TRANSCRIPTION; EXPRESSION; WILD-TYPE-P53 AB Infection by human immunodeficiency virus type 1 (HIV-1) causes acquired immunodeficiency syndrome (AIDS) after a long clinical latency. This disease is associated with a spectrum of cancers. Here we report that wild-type p53 is a potent suppressor of Tat, a major transactivator of HIV-1. Reciprocally, Tat inhibits the transcription of p53. Downregulation of p53 by upregulated tat may be important for the establishment of productive viral infection in a cell and also may be involved in the development of AIDS-related malignancies. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP LI, CJ (reprint author), DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI 35576] NR 30 TC 86 Z9 87 U1 0 U2 3 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 6 PY 1995 VL 92 IS 12 BP 5461 EP 5464 DI 10.1073/pnas.92.12.5461 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400042 PM 7777531 ER PT J AU WENG, QP ANDRABI, K KLIPPEL, A KOZLOWSKI, MT WILLIAMS, LT AVRUCH, J AF WENG, QP ANDRABI, K KLIPPEL, A KOZLOWSKI, MT WILLIAMS, LT AVRUCH, J TI PHOSPHATIDYLINOSITOL 3-KINASE SIGNALS ACTIVATION OF P70 S6 KINASE IN-SITU THROUGH SITE-SPECIFIC P70 PHOSPHORYLATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR TYROSINE KINASES; PROTEIN-KINASE; CATALYTIC SUBUNIT; EXPRESSION; CLONING; PI3-KINASE; P70(S6K); DOMAINS AB The p70 S6 kinase is activated by insulin and mitogens through multisite phosphorylation of the enzyme. One set of activating phosphorylations occurs in a putative autoinhibitory domain in the noncatalytic carboxyl-terminal tail. Deletion of this tail yields a variant (p70 Delta CT104) that nevertheless continues to be mitogen regulated, Coexpression with a recombinant constitutively active phosphatidylinositol (PI) 3-kinase (EC 2.7.1.137) gives substantial activation of both full-length p70 and p70 Delta CT104 but not Rsk. Activation of p70 Delta CT104 by PI 3-kinase and inhibition by wortmannin are each accompanied by parallel and selective changes in the phosphorylation of p70 Thr-252. A Thr or Ser at this site, in subdomain VIII of the catalytic domain just amino-terminal to the APE motif, is necessary for p70 40S kinase activity, The inactive ATP-binding site mutant K123M p70 Delta CT104 undergoes phosphorylation of Thr-252 in sial but does not undergo direct phosphorylation by the active PI 3-kinase in vitro. PI 3-kinase provide; a signal necessary for the mitogen activation of the p70 S6 kinase, which directs the site-specific phosphorylation of Thr-252 in the p70 catalytic domain, through a distinctive signal transduction pathway. C1 MASSACHUSETTS GEN HOSP,DIABET RES LABS,DIABET UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DIABET RES LABS,MED SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DAIICHI RES CTR,SAN FRANCISCO,CA 94143. FU NIDDK NIH HHS [DK17776] NR 37 TC 199 Z9 199 U1 0 U2 1 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 6 PY 1995 VL 92 IS 12 BP 5744 EP 5748 DI 10.1073/pnas.92.12.5744 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RB804 UT WOS:A1995RB80400101 PM 7777579 ER PT J AU MITCHISON, HM ORAWE, AM LERNER, TJ TASCHNER, PEM SCHLUMPF, K DARIGO, K DEVOS, N GORMALLY, E PHILLIPS, HA THOMPSON, AD HAINES, JL HART, YM ANDERMANN, E CALLEN, DF BREUNING, MH GARDINER, RM MOLE, SE AF MITCHISON, HM ORAWE, AM LERNER, TJ TASCHNER, PEM SCHLUMPF, K DARIGO, K DEVOS, N GORMALLY, E PHILLIPS, HA THOMPSON, AD HAINES, JL HART, YM ANDERMANN, E CALLEN, DF BREUNING, MH GARDINER, RM MOLE, SE TI REFINED LOCALIZATION OF THE BATTEN-DISEASE GENE (CLN3) BY HAPLOTYPE AND LINKAGE DISEQUILIBRIUM MAPPING TO D16S288-D16S383 AND EXCLUSION FROM THIS REGION OF A VARIANT FORM OF BATTEN-DISEASE WITH GRANULAR OSMIOPHILIC DEPOSITS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 5th International Conference on Neuronal Ceroid-Lipofuscinoses - Ceroid-Lipofuscinoses: Batten Disease and Allied Disorders CY MAY 19-21, 1994 CL STATEN ISLAND, NY SP NEW YORK STATE INST BASIC RES DEV DISABIL DE BATTEN DISEASE; GRANULAR OSMIOPHILIC DEPOSITS; LINKAGE DISEQUILIBRIUM; HAPLOTYPE; GENETIC MAPPING; EXCLUSION; CHROMOSOME 16 AB Haplotype analysis in a collaborative collection of 143 families with juvenile-onset neuronal ceroid lipofuscinosis (JNCL) or Batten (Spielmeyer-Vogt-Sjogren) disease has permitted refined localization of the disease gene, CLN3, which was assigned to chromosome 16 in 1989, Recombination events in four maternal meioses delimit new flanking genetic markers for CLN3 which localize the gene to the chromosome interval 16p12.1-11.2 between microsatellite markers D16S288 and D16S383, This narrows the position of CLN3 to a region of 2.1 cM, a significant reduction from the previous best interval, Using haplotypes, analysis of the strong linkage disequilibrium that exists between genetic markers within the D16S288-D16S383 interval and CLN3 shows that CLN3 is in closest proximity to loci D16S299 and D16S298, Analysis of markers across the D16S288-D16S383 region in four families with a variant form of JNCL characterized histologically by cytosomal granular osmiophilic deposits (GROD) has excluded linkage of the gene locus to the CLN3 region of chromosome 16, suggesting that JNCL with GROD is not an allelic form of JNCL. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. LEIDEN UNIV,DEPT HUMAN GENET,2300 RA LEIDEN,NETHERLANDS. WOMENS & CHILDRENS HOSP,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA,AUSTRALIA. MCGILL UNIV,MONTREAL NEUROL HOSP & INST,MONTREAL,PQ,CANADA. MCGILL UNIV,CTR HUMAN GENET,MONTREAL,PQ,CANADA. RP MITCHISON, HM (reprint author), UNIV LONDON UNIV COLL,SCH MED,RAYNE INST,DEPT PAEDIAT,5 UNIV ST,LONDON WC1E 6JJ,ENGLAND. RI Mole, Sara/C-2024-2008; Haines, Jonathan/C-3374-2012; Callen, David/G-1975-2012; Taschner, Peter/J-8853-2014; OI Taschner, Peter/0000-0001-9621-465X; Callen, David/0000-0002-6189-9991; Mole, Sara/0000-0003-4385-4957 FU Wellcome Trust NR 8 TC 18 Z9 18 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUN 5 PY 1995 VL 57 IS 2 BP 312 EP 315 DI 10.1002/ajmg.1320570241 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA RA820 UT WOS:A1995RA82000040 PM 7668353 ER PT J AU JARVELA, IE MITCHISON, HM CALLEN, DF LERNER, TJ DOGGETT, NA TASCHNER, PEM GARDINER, RM MOLE, SE AF JARVELA, IE MITCHISON, HM CALLEN, DF LERNER, TJ DOGGETT, NA TASCHNER, PEM GARDINER, RM MOLE, SE TI PHYSICAL MAP OF THE REGION CONTAINING THE GENE FOR BATTEN-DISEASE (CLN3) SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 5th International Conference on Neuronal Ceroid-Lipofuscinoses - Ceroid-Lipofuscinoses: Batten Disease and Allied Disorders CY MAY 19-21, 1994 CL STATEN ISLAND, NY SP NEW YORK STATE INST BASIC RES DEV DISABIL DE BATTEN DISEASE; CLN3; JUVENILE ONSET NEURONAL CEROID LIPOFUSCINOSIS; NCL; 16P12 ID HUMAN CHROMOSOME-16; MOUSE CHROMOSOME-7; LOCALIZATION; FRAGMENTS; DNA AB CLN3 has been mapped genetically to 16p12, to the interval between D16S288 and D16S383, a sex-averaged genetic distance of 2.1 cM, Analysis of disease haplotypes for four microsatellite markers in this interval, D16S288, D16S299, D16S298, and SPN, has shown significant allelic association between one allele at each of these loci and CLN3. Ah four of the associated markers were used as nucleation sites in the isolation of genomic clones (YACs), A contig was assembled which contains 3 of the 4 associated markers and which confirmed the relative order of these markers, Marker D16S272 has been located on the physical map between D16S288 and D16S299. Restriction mapping has demonstrated the location of possible CpG islands. One gene, STP, has been localised on the YAC contig proximal to D16S298 and is therefore a candidate for CLN3, Other genes, including IL4R, SGLT2, and UQCRC2, have been excluded from this region. (C) 1995 Wiley-Liss,Inc. C1 UNIV LONDON UNIV COLL,RAYNE INST,DEPT PAEDIAT,LONDON WC1E 6JJ,ENGLAND. WOMENS & CHILDRENS HOSP,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA,AUSTRALIA. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA. LOS ALAMOS NATL LAB,DIV LIFE SCI,LOS ALAMOS,NM. LOS ALAMOS NATL LAB,CTR HUMAN GENOME STUDIES,LOS ALAMOS,NM 87545. LEIDEN UNIV,DEPT HUMAN GENET,SYLVIUS LAB,LEIDEN,NETHERLANDS. RI Mole, Sara/C-2024-2008; Callen, David/G-1975-2012; Taschner, Peter/J-8853-2014; Jarvela, Irma/L-5836-2013; OI Taschner, Peter/0000-0001-9621-465X; Callen, David/0000-0002-6189-9991; Mole, Sara/0000-0003-4385-4957 FU Wellcome Trust NR 12 TC 8 Z9 8 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUN 5 PY 1995 VL 57 IS 2 BP 316 EP 319 DI 10.1002/ajmg.1320570242 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA RA820 UT WOS:A1995RA82000041 PM 7668354 ER PT J AU LERNER, TJ DARIGO, KL HAINES, JL DOGGETT, NA TASCHNER, PEM DEVOS, N BUCKLER, AJ AF LERNER, TJ DARIGO, KL HAINES, JL DOGGETT, NA TASCHNER, PEM DEVOS, N BUCKLER, AJ TI ISOLATION OF GENES FROM THE BATTEN CANDIDATE REGION USING EXON AMPLIFICATION SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 5th International Conference on Neuronal Ceroid-Lipofuscinoses - Ceroid-Lipofuscinoses: Batten Disease and Allied Disorders CY MAY 19-21, 1994 CL STATEN ISLAND, NY SP NEW YORK STATE INST BASIC RES DEV DISABIL DE EXON AMPLIFICATION; BATTEN DISEASE; CANDIDATE GENES ID NEURONAL CEROID-LIPOFUSCINOSIS; LATE-INFANTILE; DISEASE; CHROMOSOME-16; JUVENILE; MAPS; FORM AB In order to identify genes originating from the Batten disease candidate region, we have used the technique of exon amplification to identify transcribed sequences, This procedure produces trapped exon clones, which can represent single exons or multiple exons spliced together and is an efficient method for obtaining probes for physical mapping and for screening cDNA libraries, The source of DNA for these experiments was a collection of chromosome 16 cosmid contigs isolated by the direct subcloning of region-specific yeast artificial chromosomes (YACs) and hybridization of inter-alu PCR products from these YACs to the flow-sorted Los Alamos chromosome 16 cosmid library. We are now using the resulting exon probes to screen retina and brain cDNA libraries for candidate JNCL genes. (C) 1995 Wiley-Liss, Inc. C1 HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02115 USA. LOS ALAMOS NATL LAB, DIV LIFE SCI, LOS ALAMOS, NM USA. LEIDEN UNIV, DEPT GENET, LEIDEN, NETHERLANDS. UCL, SCH MED, RM GARDINER LABS, LONDON W1N 8AA, ENGLAND. ADELAIDE CHILDRENS HOSP INC, ADELAIDE, SA, AUSTRALIA. SW FDN BIOMED RES, SAN ANTONIO, TX 78284 USA. RP LERNER, TJ (reprint author), MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET UNIT, BLDG 149, 13TH ST, BOSTON, MA 02129 USA. RI Haines, Jonathan/C-3374-2012; Taschner, Peter/J-8853-2014 OI Taschner, Peter/0000-0001-9621-465X FU NINDS NIH HHS [NS30152, NS32099] NR 23 TC 4 Z9 4 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUN 5 PY 1995 VL 57 IS 2 BP 320 EP 323 DI 10.1002/ajmg.1320570243 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA RA820 UT WOS:A1995RA82000042 PM 7668355 ER PT J AU HAINES, JL BOUSTANY, RMN WORSTER, T TERMINASSIAN, M JONDRO, P LERNER, TJ AF HAINES, JL BOUSTANY, RMN WORSTER, T TERMINASSIAN, M JONDRO, P LERNER, TJ TI GENOME-WIDE SEARCH FOR CLN2, THE GENE CAUSING LATE-INFANTILE NEURONAL CEROID-LIPOFUSCINOSIS (LNCL) SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 5th International Conference on Neuronal Ceroid-Lipofuscinoses - Ceroid-Lipofuscinoses: Batten Disease and Allied Disorders CY MAY 19-21, 1994 CL STATEN ISLAND, NY SP NEW YORK STATE INST BASIC RES DEV DISABIL DE GENETIC LINKAGE; LATE-INFANTILE NEURONAL CEROID LIPOFUSCINOSIS; EXCLUSION ID JUVENILE; DISEASE; LINKAGE; CHROMOSOME-16; MAPS; FORM AB The loci for the juvenile (CLN3) and infantile (CLN1) neuronal ceroid lipofuscinosis (NCL) types have been mapped by genetic linkage analysis to chromosome arms 16p and 1p, respectively, The late-infantile defect CLN2 has not yet been mapped, although linkage analysis with tightly linked markers excludes it from both the JNCL and INCL loci, We have initiated a genome-wide search for the LNCL gene, taking advantage of the large collection of highly polymorphic markers that has been developed through the Human Genome Initiative. The high degree of heterozygosity of these markers makes it feasible to carry out successful linkage analysis in small nuclear families, such as found in LNCL, Our current collection of LNCL pedigrees includes 19 US families and 11 Costa Rican families. To date, we have completed typing with over 50 markers on chromosomes 2, 9, 13, and 18-22. The results of this analysis formally exclude about 10% of the human genome as the location of the LNCL gene. (C) 1995 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. DUKE UNIV,MED CTR,DIV PEDIAT NEUROL,DURHAM,NC. RP HAINES, JL (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BLDG 149 13TH ST,BOSTON,MA 02129, USA. RI Haines, Jonathan/C-3374-2012 FU NINDS NIH HHS [NS24279, NS32099] NR 14 TC 1 Z9 1 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUN 5 PY 1995 VL 57 IS 2 BP 344 EP 347 DI 10.1002/ajmg.1320570248 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA RA820 UT WOS:A1995RA82000047 PM 7668360 ER PT J AU SHIVDASANI, RA ROSENBLATT, MF ZUCKERFRANKLIN, D JACKSON, CW HUNT, P SARIS, CJM ORKIN, SH AF SHIVDASANI, RA ROSENBLATT, MF ZUCKERFRANKLIN, D JACKSON, CW HUNT, P SARIS, CJM ORKIN, SH TI TRANSCRIPTION FACTOR NF-E2 IS REQUIRED FOR PLATELET FORMATION INDEPENDENT OF THE ACTIONS OF THROMBOPOIETIN/MGDF IN MEGAKARYOCYTE DEVELOPMENT SO CELL LA English DT Article ID DOMINANT CONTROL REGION; TARGETED MUTATION; BINDING PROTEINS; GENE; EXPRESSION; CELLS; MOUSE; LINEAGES; MARROW; GROWTH AB Despite the importance of blood platelets in health and disease, the mechanisms regulating their formation within megakaryocytes are unknown. We generated mice lacking the hematopoietic subunit (p45) of the heterodimeric erythroid transcription factor NF-E2. Unexpectedly, NF-E2(-/-) mice lack circulating platelets and die of hemorrhage; their megakaryocytes show no cytoplasmic platelet formation. Though platelets are absent, serum levels of the growth factor thrombopoietin/MGDF are not elevated above controls. Nonetheless, NF-E2(-/-) megakaryocytes proliferate in vivo in response to thrombopoietin administration. Thus, as an essential factor for megakaryocyte maturation and platelet production, NF-ES must regulate critical target genes independent of the action of thrombopoietin. These findings provide insight into the genetic analysis of megakaryocyte maturation and thrombopoiesis. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. CHILDRENS HOSP, HOWARD HUGHES MED INST, BOSTON, MA USA. CHILDRENS HOSP, DIV HEMATOL ONCOL, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA. NYU, MED CTR, DEPT MED, NEW YORK, NY 10016 USA. ST JUDE CHILDRENS RES HOSP, DIV EXPTL HEMATOL, MEMPHIS, TN 38105 USA. AMGEN INC, AMGEN CTR, THOUSAND OAKS, CA 91320 USA. RP SHIVDASANI, RA (reprint author), DANA FARBER CANC INST, DIV MED ONCOL, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [HL42103, HL51290] NR 65 TC 529 Z9 537 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JUN 2 PY 1995 VL 81 IS 5 BP 695 EP 704 DI 10.1016/0092-8674(95)90531-6 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RB961 UT WOS:A1995RB96100008 PM 7774011 ER PT J AU CASASNOVAS, JM SPRINGER, TA AF CASASNOVAS, JM SPRINGER, TA TI KINETICS AND THERMODYNAMICS OF VIRUS BINDING TO RECEPTOR - STUDIES WITH RHINOVIRUS, INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1), AND SURFACE-PLASMON RESONANCE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SOLUBLE FORMS; NEUTRALIZATION; ANTIBODY; CELLS; IMMUNOGLOBULIN; EXPRESSION; VARIANTS; CANYON; LFA-1 AB We have studied the kinetics and thermodynamics of a virus interacting with its receptor using human rhinovirus serotype 3 (HRV3), soluble intercellular adhesion molecule-1 (ICAM-1, CD54) containing Ig superfamily domains 1-5 (sICAM-1), and surface plasmon resonance. There were two classes of binding sites for sICAM-1 on HRV3, each comprising about 50% of the total sites, with association rate constants of 2450 +/- 300 and 134 +/- 11 M(-1) s(-1). These rates are low, consistent with binding to a relatively inaccessible site in the rhinovirus canyon. By contrast, three monoclonal antibodies bound to sICAM-1 with a single rate constant of 17,000-48,000 M(-1) s(-1). The dissociation rate constant for RRV3 was 1.7 +/- 0.1 x 10(-3) s(-1), giving calculated dissociation constants of 0.7 +/- 0.1 and 12.5 +/- 1.2 mu M. Agreement was good with saturation binding in solution, which showed two sites of similar abundance with K-D of 0.55 +/- 0.2 and 5.7 +/- 2.0 mu M. A bivalent chimera of ICAM-1 with the IgA1 Fc region bound with K-D = 50 and 410 nar, showing 17-fold enhanced affinity. Lowering pH from 8.0 to 6.0 reduced affinity by approximately 50-fold, primarily by reducing the on rate. Thermodynamic measurements showed that binding of ICAM-1 to HRV3 is endothermic, by contrast to binding to monoclonal antibody. The heat that is absorbed of 3.5 and 6.3 kcal/mol for the two classes of ICAM-1 binding sites may contribute to receptor-mediated disruption of virions, which has an activation energy of about 42 kcal/mol. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT PATHOL,BOSTON,MA 02115. RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 NR 35 TC 81 Z9 82 U1 0 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 2 PY 1995 VL 270 IS 22 BP 13216 EP 13224 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RB439 UT WOS:A1995RB43900043 PM 7768920 ER PT J AU HENSON, JW SCHNITKER, BL LEE, TS MCALLISTER, J AF HENSON, JW SCHNITKER, BL LEE, TS MCALLISTER, J TI CELL-SPECIFIC ACTIVATION OF THE GLIAL-SPECIFIC JC VIRUS EARLY PROMOTER BY LARGE T-ANTIGEN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-BRAIN; TRANSCRIPTIONAL ACTIVATION; TATA; EXPRESSION; ENHANCER; MULTIPLE; ELEMENTS; BINDS AB JC virus causes the human demyelinating disease progressive multifocal leukoencephalopathy by selective infection of glial cells. This cell specificity results from glial-specific expression of viral early genes (large and small T antigens). Analysis of transcriptional regulation by the MH1 JC virus early promoter demonstrates that glial specificity is directed by the basal promoter. Because T antigen regulates the basal region of several viral and cellular promoters, we investigated whether it controls the JC virus basal promoter in a glial-specific manner. A JC virus T antigen expression plasmid generated a 95-kDa protein which exhibited nuclear localization and physical association with p53. T antigen repressed the JC virus and SV40 early promoters 4- to 5-fold in glioma cells. Conversely, T antigen induced 100- to 200-fold activation of the JC virus early promoter in nonglial cells, whereas the SV40 promoter was repressed. Activation required the JC virus TATA box sequence and a pentanucleotide repeat immediately upstream of the TATA box, but was independent of the upstream enhancer region. These data demonstrate that the JC virus basal promoter is responsible for glial-specific gene expression and suggest a mechanism for this regulation. RP HENSON, JW (reprint author), MASSACHUSETTS GEN HOSP EAST,MOLEC NEUROONCOL LAB,149 13TH ST,BOSTON,MA 02129, USA. FU NINDS NIH HHS [NS 01605] NR 24 TC 17 Z9 17 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 2 PY 1995 VL 270 IS 22 BP 13240 EP 13245 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RB439 UT WOS:A1995RB43900046 PM 7768922 ER PT J AU CHIAPPELLI, F GOTTESFELD, Z AF CHIAPPELLI, F GOTTESFELD, Z TI INTRODUCTION TO THE SYMPOSIUM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material ID FETAL ALCOHOL SYNDROME; PROLIFERATIVE RESPONSE; ETHANOL INUTERO; EXPOSURE ALTERS; LYMPHOID ORGANS; LIVER-DISEASE; IMMUNE; CELLS; SUPPRESSION; EXPRESSION C1 W LOS ANGELES VET AFFAIRS MED CTR,HUMAN IMMUNOL & PSYCHONEUROIMMUNOL LAB,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT ANAT & CELL BIOL,LOS ANGELES,CA 90024. UNIV TEXAS,SCH MED,DEPT ANAT & NEUROBIOL,HOUSTON,TX. RP CHIAPPELLI, F (reprint author), UNIV CALIF LOS ANGELES,SCH MED,SCH DENT,DIV DIAGNOST SCI,HUMAN ORAL & MOLEC IMMUNOL LAB,LOS ANGELES,CA 90095, USA. FU NIDA NIH HHS [DA07683] NR 56 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1995 VL 19 IS 3 BP 535 EP 538 DI 10.1111/j.1530-0277.1995.tb01544.x PG 4 WC Substance Abuse SC Substance Abuse GA RE228 UT WOS:A1995RE22800001 PM 7573770 ER PT J AU CHIAPPELLI, F KUNG, M LEE, P PHAM, L MANFRINI, E VILLANUEVA, P AF CHIAPPELLI, F KUNG, M LEE, P PHAM, L MANFRINI, E VILLANUEVA, P TI ALCOHOL MODULATION OF HUMAN NORMAL T-CELL ACTIVATION, MATURATION, AND MIGRATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE LYMPHOCYTES; T-CELL ACTIVATION; T-CELL MIGRATION; CD26; CD62L ID DIPEPTIDYL PEPTIDASE-IV; LYMPHOCYTES-T; EXPRESSION; ETHANOL; CD26 AB We are interested in the characterization of the effects of alcohol on human T-cell activation, maturation, and migration, because this cell population is crucial in the initiation, regulation, and propagation of cellular immunity. We and others have described the effects of both acute and chronic exposure of human immune cells to ethanol (EtOH) in vitro. Herein, we briefly, review these reports and expand this body of literature with the inclusion of new data recently obtained in our laboratory. We confirm the blunting effects of EtOH on the production of interleukin-2 and mitogen proliferative response following T-cell mitogen stimulation, and on the expression of membrane markers of activation. We show that EtOH significantly alters the expression of the CD4 cell-associated marker of activation, CD26. We report the effect of EtOH on the expression of the homing receptor CD62L by CD4(+) cells, and on their ability to adhere by a CD18-mediated process to a defined cellular substratum. Furthermore, we demonstrate the effects of EtOH and EtOH and beta-endorphin pretreatment on the activation of CD4(+) lymphocytes endowed with the homing receptor CD62L. C1 W LOS ANGELES VET AFFAIRS MED CTR, HUMAN IMMUNOL & PSYCHONEUROIMMUNOL LAB, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, DEPT ANAT & CELL BIOL, LOS ANGELES, CA 90024 USA. RP CHIAPPELLI, F (reprint author), UNIV CALIF LOS ANGELES, SCH DENT, DIV DIAGNOST SCI, HUMAN ORAL & MOLEC IMMUNOL LAB, CHS 63-090, LOS ANGELES, CA 90095 USA. FU NIDA NIH HHS [DA07683] NR 31 TC 36 Z9 36 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1995 VL 19 IS 3 BP 539 EP 544 DI 10.1111/j.1530-0277.1995.tb01545.x PG 6 WC Substance Abuse SC Substance Abuse GA RE228 UT WOS:A1995RE22800002 PM 7573771 ER PT J AU TAYLOR, AN TIO, DL CHIAPPELLI, F AF TAYLOR, AN TIO, DL CHIAPPELLI, F TI FETAL ALCOHOL AND THYMOCYTE PHENOTYPES IN OFFSPRING - RESPONSE TO FOOD-DEPRIVATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE FETAL ALCOHOL EXPOSURE; THYMUS; THYMOCYTES; FOOD RESTRICTION; PLASMA CORTICOSTERONE ID DIETARY RESTRICTION; PROLIFERATIVE RESPONSE; ETHANOL EXPOSURE; RATS; EXPRESSION; INUTERO; STRESS; CELLS AB Restriction of food availability is a reliable stimulus that leads to significant hypothalamo-pituitary-adrenal (HPA) activation to which rats do not habituate. Based on our previous data that indicated that the HPA response to some, but not all, stressful stimuli is significantly greater in adult offspring of Sprague-Dawley darns exposed to 35% alcohol during the last 2 weeks of gestation than that of control rats and on the mounting neuroendocrine-immune literature that describes the role of pituitary-adrenal products in modulating cellular immunity, we hypothesized that the outcomes of food restriction would be significantly more marked in fetal alcohol-exposed (FAE) offspring, compared with control rats. Data we report herein show that-whereas food restriction at 30-35 days of age produced significant changes in body weight, thymus weight-to-body weight ratio, adrenal weight-to-body weight ratio, plasma corticosterone revels, and in thymocyte number, as well as in the percentage and absolute number of CD4(+) and CD8(+) thymocytes that express CD45RC-FAE and control rats were equally affected. We conclude that food restriction is another example of a stressful stimulus that fails to distinguish satisfactorily between FAE and control rats of prepubertal age. C1 UNIV CALIF LOS ANGELES,SCH MED,PSYCHONEUROIMMUNOL PROGRAM,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,ALCOHOL RES LAB,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,HUMAN IMMUNOL & PSYCHONEUROIMMUNOL LAB,LOS ANGELES,CA. RP TAYLOR, AN (reprint author), UNIV CALIF LOS ANGELES,SCH MED,BRAIN RES INST,DEPT ANAT & CELL BIOL,LOS ANGELES,CA 90024, USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1995 VL 19 IS 3 BP 545 EP 550 DI 10.1111/j.1530-0277.1995.tb01546.x PG 6 WC Substance Abuse SC Substance Abuse GA RE228 UT WOS:A1995RE22800003 PM 7573772 ER PT J AU BOHN, MJ KRAHN, DD STAEHLER, BA AF BOHN, MJ KRAHN, DD STAEHLER, BA TI DEVELOPMENT AND INITIAL VALIDATION OF A MEASURE OF DRINKING URGES IN ABSTINENT ALCOHOLICS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOLISM; URGES; CRAVING; QUESTIONNAIRE ID COMPULSIVE CHARACTERISTICS; DEPENDENCE; ABUSE; QUESTIONNAIRE; NALTREXONE AB Although drinking urges and cravings are commonly reported by alcoholics, prospective studies have found inconsistent associations between such urges and drinking relapses. Previous studies have measured drinking urges by use of single-item ratings of alcohol craving or other measures of unknown reliability and validity. To permit improved evaluation of hypotheses regarding alcohol craving, a 49-item questionnaire that reflects several urge-related domains was developed and pretested. items assessed subjects' desire for a drink, expectations of positive effects following drinking, relief of withdrawal and negative affect following drinking, and intention to drink. Exploratory and confirmatory factor analyses of the responses of 351 abstinent, treatment-seeking alcoholics indicated that alcohol urges are best described by a single factor. Based on these analyses, an internally consistent, reliable, and psychometrically valid 8-item scale, the Alcohol Urge Questionnaire (AUG), was developed. Data indicated that AUQ scores were strongly related to alcohol dependence severity and to cognitive preoccupation with alcohol, and that they declined with prolonged abstinence. The AUQ may be useful in alcoholism treatment research and in laboratory studies of reactivity to alcohol or other manipulations. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,PSYCHIAT SERV,MADISON,NJ. WILLIAM S MIDDLETON MEM VET ADM MED CTR,OUTPATIENT SUBSTANCE ABUSE TREATMENT PROGRAM,MADISON,NJ. RP BOHN, MJ (reprint author), UNIV WISCONSIN,SCH MED,DEPT PSYCHIAT,MADISON,WI 53792, USA. FU NIAAA NIH HHS [R29-AA09948-0] NR 39 TC 270 Z9 272 U1 0 U2 16 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1995 VL 19 IS 3 BP 600 EP 606 DI 10.1111/j.1530-0277.1995.tb01554.x PG 7 WC Substance Abuse SC Substance Abuse GA RE228 UT WOS:A1995RE22800011 PM 7573780 ER PT J AU FISHER, JP PICARD, MH MIKAN, JS FRAM, DB FISHER, JR KLUGER, J WATERS, DD GILLAM, LD AF FISHER, JP PICARD, MH MIKAN, JS FRAM, DB FISHER, JR KLUGER, J WATERS, DD GILLAM, LD TI QUANTITATION OF MYOCARDIAL DYSFUNCTION IN ISCHEMIC-HEART-DISEASE BY ECHOCARDIOGRAPHIC ENDOCARDIAL SURFACE MAPPING - CORRELATION WITH HEMODYNAMIC STATUS SO AMERICAN HEART JOURNAL LA English DT Article ID VENTRICULAR EJECTION FRACTION; CARDIOGENIC-SHOCK; DIMENSIONAL ECHOCARDIOGRAPHY; MEDICAL THERAPY; WALL MOTION; INFARCTION; FAILURE; SUBSETS; EXTENT; MODEL AB Autopsy studies have suggested that infarction of >35% of the myocardium is associated with cardiogenic shock. However, the relation between the extent of myocardial dysfunction and hemodynamic status has not been defined in patients in vivo. This study investigated, in patients with short-term and chronic left ventricular dysfunction, the relation between hemodynamic status and the extent of regional dyssynergia measured by two-dimensional echocardiography with quantitative endocardial surface mapping. Sixty patients were classified into hemodynamic groups by pulmonary capillary wedge pressure and cardiac index. Two-dimensional echocardiograms were used to calculate left ventricular endocardial surface area index (ESAi), abnormal wall motion index (AWMi), percentage myocardial dysfunction (%MD), and number of wall motion abnormalities. All patients in class 4 (high pulmonary capillary wedge pressure and low cardiac index had greater than or equal to 60% MD. With univariate analysis, hemodynamic class correlated with ESAi, AWMi, %MD, the number of wall motion abnormalities, and two clinical variables (number of infarctions and use of diuretic agents). By stepwise linear regression, only AWMi and the number of infarctions were independently predictive of hemodynamic status. C1 UNIV CONNECTICUT,HARTFORD HOSP,DIV CARDIOL,HARTFORD,CT 06102. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA. OI Picard, Michael/0000-0002-9264-3243 NR 25 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 1995 VL 129 IS 6 BP 1114 EP 1121 DI 10.1016/0002-8703(95)90391-7 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RA821 UT WOS:A1995RA82100009 PM 7754941 ER PT J AU WEISSMANN, DJ FERRY, JA HARRIS, NL LOUIS, DN DELMONICO, F SPIRO, I AF WEISSMANN, DJ FERRY, JA HARRIS, NL LOUIS, DN DELMONICO, F SPIRO, I TI POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDERS IN SOLID-ORGAN RECIPIENTS ARE PREDOMINANTLY AGGRESSIVE TUMORS OF HOST ORIGIN SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDER; LYMPHOMA; HOST ORIGIN; DONOR ORIGIN ID BONE-MARROW TRANSPLANTATION; RENAL-ALLOGRAFT RECIPIENT; B-CELL LYMPHOMA; MALIGNANT-LYMPHOMA; DONOR ORIGIN; REPEAT-POLYMORPHISM; DISEASE; LIVER; DNA AB Patients immunosuppressed after organ transplantation have an increased frequency of lymphoproliferative disorders, known as posttransplantation lymphoproliferative disorders (PTLDs). In recipients of bone marrow allografts, PTLDs are often of donor origin, In only a few cases of lymphoma arising in solid-organ transplant recipients has the origin from host or donor lymphocytes been established. The authors have analyzed 11 cases of PTLD from Massachusetts General Hospital, arising in seven male and four female patients, aged 8 to 63, five with renal, four with cardiac, and two with hepatic allografts, Using the polymerase chain reaction (PCR) to investigate genetic polymorphism at the D4S174 locus on chromosome 4, the Rb1.20 locus on chromosome 13, and the D19S178 locus on chromosome 19, only one tumor (previously reported) was of donor origin, whereas 10 were of host origin, Follow-up revealed that six patients died of PTLD, one was alive with recurrent PTLD, and four were alive and well or had died of other causes, including the patient with donor-origin PTLD, Based on these cases and on a review of previously reported cases, the authors conclude that the majority of PTLDs in solid organ recipients are of host origin, There appears to be a trend toward a greater likelihood of persistent or recurrent PTLD among solid organ recipients with host-origin tumors than among those with donor-origin tumor. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC NEUROONCOL LAB & NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA 57683] NR 32 TC 96 Z9 97 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 1995 VL 103 IS 6 BP 748 EP 755 PG 8 WC Pathology SC Pathology GA RC241 UT WOS:A1995RC24100016 PM 7785662 ER PT J AU ZUKERBERG, LR YANG, WI ARNOLD, A HARRIS, NL AF ZUKERBERG, LR YANG, WI ARNOLD, A HARRIS, NL TI CYCLIN D1 EXPRESSION IN NON-HODGKINS-LYMPHOMAS - DETECTION BY IMMUNOHISTOCHEMISTRY SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE CYCLIN D1; BCL-1; ONCOGENE; IMMUNOHISTOCHEMISTRY; LYMPHOMA; LEUKEMIA ID CHROMOSOME-11 BCL-1 LOCUS; CENTROCYTIC LYMPHOMA; MULTIPLE-MYELOMA; BREAST-CANCER; SQUAMOUS-CELL; LYMPHOCYTIC LYMPHOMA; 11Q13 AMPLIFICATION; CANDIDATE ONCOGENE; REARRANGEMENT; GENE AB Cyclin D1/PRAD1 (bcl-1) is a recently discovered proto-oncogene that is overexpressed in mantle cell lymphomas and several other human tumors. In a previous study, the authors demonstrated expression of cyclin D1 in 15 of 15 cases of mantle cell lymphoma and 1 of 8 cases of B-chronic lymphocytic leukemia (B-CLL) using a polyclonal antibody and microwave enhanced immunohistochemical staining method on paraffin-embedded tissue sections, In this study, 107 additional B- and T-cell neoplasms were studied, including 47 cases of high grade lymphoma (33 diffuse large B-cell type, 9 Burkitt and Burkitt-like, 4 precursor T-lymphoblastic lymphoma, and 1 adult T-cell lymphoma/leukemia), 38 additional cases of low grade B-cell lymphoma (18 CLL, 15 hairy cell leukemia and 5 mantle cell lymphoma), and 22 plasmacytomas for expression of cyclin D1 using the same immunohistochemical staining technique. All cases of mantle cell lymphoma showed diffuse nuclear staining. No additional cases of CLL showed cyclin D1 expression, In contrast, 1 of 15 hairy cell leukemias and 1 of 22 plasmacytomas showed cyclin D1 staining, None of the high grade lymphomas demonstrated expression of cyclin D1 protein by immunostaining, including three cases of large B-cell lymphoma that coexpressed CD5, The authors conclude that cyclin D1 is expressed in all cases of mantle cell lymphoma, and only in very rare cases of B-CLL, hairy cell leukemia and plasmacytoma/myeloma. Cyclin D1 does not appear to play an important role in high grade lymphomas, In addition, most CD5 positive high grade B-cell lymphomas do not express cyclin D1, and are not likely to be derived from mantle cell lymphoma or other lymphomas with t(11;14). C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [5F32CA09260-3, CA55909] NR 46 TC 105 Z9 110 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 1995 VL 103 IS 6 BP 756 EP 760 PG 5 WC Pathology SC Pathology GA RC241 UT WOS:A1995RC24100017 PM 7540362 ER PT J AU FRAZIER, L COLDITZ, G AF FRAZIER, L COLDITZ, G TI REPRODUCIBILITY OF THE RECALL OF DIET DURING HIGH-SCHOOL AMONG A PROSPECTIVE COHORT OF WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1995 VL 141 IS 11 SU S BP S12 EP S12 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RA788 UT WOS:A1995RA78800046 ER PT J AU RUBIN, PAD BILYK, JR DUNYA, IM WEBER, AL AF RUBIN, PAD BILYK, JR DUNYA, IM WEBER, AL TI SPIRAL CT OF AN ORBITAL VENOUS MALFORMATION SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE VEINS, ABNORMALITIES AND ANOMALIES; ORBITS, NEOPLASMS; COMPUTED TOMOGRAPHY, TECHNIQUE ID VARIX AB Spiral CT with a single breath-hold technique was useful in diagnosing an orbital venous malformation by demonstrating an increase in size of the lesion during a Valsalva maneuver. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. RP RUBIN, PAD (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EYE PLAST & ORBIT SERV,243 CHARLES ST,1ST FLOOR,BOSTON,MA 02114, USA. NR 9 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 1995 VL 16 IS 6 BP 1255 EP 1257 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA RC950 UT WOS:A1995RC95000011 PM 7677019 ER PT J AU CERMAK, SA KATZ, N MCGGUIRE, E GREENBAUM, S PERALTA, C MASERFLANAGAN, V AF CERMAK, SA KATZ, N MCGGUIRE, E GREENBAUM, S PERALTA, C MASERFLANAGAN, V TI PERFORMANCE OF AMERICANS AND ISRAELIS WITH CEREBROVASCULAR ACCIDENT ON THE LOEWENSTEIN OCCUPATIONAL-THERAPY COGNITIVE ASSESSMENT (LOTCA) SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE CEREBROVASCULAR DISORDERS; COGNITION; CULTURE (SOCIOLOGY); PERCEPTION ID MARYS CVA EVALUATION; CONTINUED CONSTRUCT-VALIDATION AB Objective. The Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) measures the cognitive performance of persons with cerebrovascular accident (CVA). Although this assessment was developed and standardized in Israel, it is frequently used in the United States. The purpose of this study was to identify whether differences in performance on the LOTCA existed between Americans and Israelis who have had strokes. Additionally, this study was designed to compare the Performance of persons with right CVA with the performance of persons with left CVA because the normative data for the LOTCA does not include separate information for these two groups. Method. The LOTCA was administered to 25 Americans with CVA (19 right CVA and 6 left CVA) and 56 Israelis with CVA (26 right CVA and 30 left CVA). Results. On the majority of LOTCA subtests, there were no significant differences between American and Israeli subjects. Only one subtest, Orientation to Time, revealed significant differences between Americans and Israeli subjects both for subjects with right CVA and subjects with left CVA. Examination of subjects with right CVA versus subjects with left CVA also indicated few differences. Only one subtest, Pegboard Construction, revealed significant differences between subjects with right CVA and subjects with left CVA for both American and Israeli subjects. Conclusion. The LOTCA is an appropriate tool for occupational therapists to use in assessing Americans who have had strokes. In addition, for the most part, the subtests of the LOTCA assess cognitive-perceptual abilities that are not specific to the right or left cerebral hemisphere. C1 HEBREW UNIV JERUSALEM,SCH OCCUPAT THERAPY,JERUSALEM,ISRAEL. LOEWENSTEIN HOSP & REHABIL CTR,DEPT OCCUPAT THERAPY,RANNANA,ISRAEL. MASSACHUSETTS EYE & EAR INFIRM,VIS REHABIL SERV,BOSTON,MA 02114. SPAULDING HOSP & REHABIL CTR,DEPT OCCUPAT THERAPY,BOSTON,MA. RP CERMAK, SA (reprint author), BOSTON UNIV,SARGENT COLL ALLIED HLTH PROFESS,DEPT OCCUPAT THERAPY,635 COMMONWEALTH AVE,BOSTON,MA 02215, USA. NR 31 TC 19 Z9 21 U1 0 U2 0 PU AMER OCCUPATION THERAPY ASSN PI ROCKVILLE PA 1383 PICCARD DRIVE PO BOX ROCKVILLE, MD 20850-4375 SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD JUN PY 1995 VL 49 IS 6 BP 500 EP 506 PG 7 WC Rehabilitation SC Rehabilitation GA QZ563 UT WOS:A1995QZ56300003 PM 7645662 ER PT J AU NETLAND, PA GROSSKREUTZ, CL FEKE, GT HART, LJ AF NETLAND, PA GROSSKREUTZ, CL FEKE, GT HART, LJ TI COLOR DOPPLER ULTRASOUND ANALYSIS OF OCULAR CIRCULATION AFTER TOPICAL CALCIUM-CHANNEL BLOCKER SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; RETINAL BLOOD-FLOW; INTRAOCULAR-PRESSURE; LOW-TENSION; MANAGEMENT AB PURPOSE: To investigate the effect of topical administration of the calcium channel blocker verapamil on intraocular pressure and retrobulbar hemodynamics. METHODS: Tn this randomized, prospective, double-masked study, we examined the effects of single-dose topical administration of verapamil in ten normal human volunteers by using color Doppler ultrasound imaging to measure hemodynamic parameters. Limitations of this study in elude single-dose application of verapamil and relatively small sample size. RESULTS: No systemic effect on heart rate or blood pressure was detected after administration of topical verapamil. The intraocular pressure significantly decreased compared with baseline two hours after topical 0.125% and 0.25% verapamil (P = .015 and .040, respectively). Pourcelot's ratio, an index of vascular resistance, measured in the central retinal artery was significantly reduced after topical application of 0.125% verapamil (P = .008). The change in Pourcelot's ratio primarily resulted from an increased end diastolic velocity in the central retinal artery. No significant difference es compared with baseline values were detected in the color Doppler ultrasound measurements of the posterior ciliary arteries and the central retinal vein two hours after topically administered verapamil. CONCLUSIONS: Topical administration of verapamil decreases intraocular pressure and alters ocular hemodynamics, reducing the vascular resistance index in the central retinal artery. 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 23 TC 56 Z9 57 U1 0 U2 1 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 1995 VL 119 IS 6 BP 694 EP 700 PG 7 WC Ophthalmology SC Ophthalmology GA RC235 UT WOS:A1995RC23500002 PM 7785682 ER PT J AU YAMAMOTO, S PAVANLANGSTON, D TADA, R YAMAMOTO, R KINOSHITA, S NISHIDA, K SHIMOMURA, Y TANO, Y AF YAMAMOTO, S PAVANLANGSTON, D TADA, R YAMAMOTO, R KINOSHITA, S NISHIDA, K SHIMOMURA, Y TANO, Y TI POSSIBLE ROLE OF HERPES-SIMPLEX VIRUS IN THE ORIGIN OF POSNER-SCHLOSSMAN SYNDROME SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Note AB PURPOSE/METHODS: We conducted this study to determine if the herpesviruses are possible etiologic agents in Posner-Schlossman syndrome. We aspirated aqueous humor samples from three patients during acute attacks of the syndrome. Ten normal aqueous humor specimens from patients undergoing cataract surgery were used as controls. DNA was extracted and subjected to polymerase chain reaction amplification and Southern blot hybridization. RESULTS/CONCLUSION: All three specimens were positive for amplified genomic fragments of herpes simplex virus and negative for varicellazoster virus and cytomegalovirus. Ten normal aqueous specimens were negative for all three. Herpes simplex virus may play a role in the origin of Posner-Schlossman syndrome. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. OSAKA UNIV,SCH MED,DEPT OPHTHALMOL,OSAKA,JAPAN. KYOTO PREFECTURAL UNIV MED,DEPT OPHTHALMOL,KYOTO 602,JAPAN. RP YAMAMOTO, S (reprint author), SCHEPENS EYE RES INST,DEPT VIROL,20 STANIFORD ST,BOSTON,MA 02114, USA. NR 6 TC 47 Z9 55 U1 0 U2 3 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 1995 VL 119 IS 6 BP 796 EP 798 PG 3 WC Ophthalmology SC Ophthalmology GA RC235 UT WOS:A1995RC23500018 PM 7785697 ER PT J AU PRAT, AG XIAO, YF AUSIELLO, DA CANTIELLO, HF AF PRAT, AG XIAO, YF AUSIELLO, DA CANTIELLO, HF TI CAMP-INDEPENDENT REGULATION OF CFTR BY THE ACTIN CYTOSKELETON SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Note DE ION CHANNEL REGULATION BY ACTIN FILAMENTS; CHLORIDE AND ADENOSINE 5'-TRIPHOSPHATE CHANNELS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CHLORIDE CHANNEL; CELLS; ACTIVATION; FILAMENTS; SEQUENCE; PROTEINS; CONTAIN; VILLIN; DOMAIN AB Protein kinase A (PKA)-activation of epithelial Na+ channels requires actin filaments. Mouse mammary adenocarcinoma cells expressing the human cystic fibrosis transmembrane conductance regulator (CFTR) or mock transfectants were used to determine whether CFTR is also modulated by the actin cytoskeleton. The actin filament disrupter cytochalasin D (CD; similar to 5 mu g/ml) readily activated whole cell currents in CFTR but not in mock-transfected (MOCK) cells. Addition of actin to the cytosolic side of quiescent excised inside-out patches of CFTR but not MOCK cells also activated CFTR. The actin-activated Cl- channels (symmetrical Cl-) had a linear conductance of 9.3 pS and were inhibited by diphenylamine-2-carboxylate and monoclonal antibodies raised against CFTR. Channel activity was also blocked by addition of the actin-binding proteins deoxyribonuclease I and filamin. Incubation of CFTR cells with CD (similar to 15 mu g/ml) for > 6 h prevented CFTR activation by the addition of either 8-bromoadenosine 3',5'-cyclic monophosphate plus forskolin under whole cell conditions or PKA under excised inside-out conditions. However, CFTR activation was restored by subsequent addition of actin. The data indicate that CFTR is regulated by actin filaments whose effect may, in turn, be associated with the PKA-dependent pathway. C1 MASSACHUSETTS GEN HOSP EAST, RENAL UNIT, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. NR 17 TC 85 Z9 85 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 1995 VL 268 IS 6 BP C1552 EP C1561 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RE363 UT WOS:A1995RE36300032 ER PT J AU DELPRATO, S RICCIO, A DEKREUTZENBERG, SV DORELLA, M TIENGO, A DEFRONZO, RA AF DELPRATO, S RICCIO, A DEKREUTZENBERG, SV DORELLA, M TIENGO, A DEFRONZO, RA TI BASAL PLASMA-INSULIN LEVELS EXERT A QUALITATIVE BUT NOT QUANTITATIVE EFFECT ON GLUCOSE-MEDIATED GLUCOSE-UPTAKE SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE HYPERGLYCEMIA; INSULINOPENIA; GLYCOLYSIS; INTERMEDIARY METABOLISM ID CONSCIOUS DOG; HYPERGLYCEMIA; HUMANS; METABOLISM; OXIDATION; DISPOSAL; RATES; SECRETION; KINETICS; INFUSION AB We assessed the effect of hyperglycemia on glucose uptake in the presence of normal basal insulin levels or somatostatin-induced hypoinsulinemia in seven normal volunteers during a 200-min hyperglycemic clamp (+9 mmol/l) carried out with [3-H-3]glucose and indirect calorimetry. Hyperglycemia increased glucose uptake to 22.4 +/- 2.6 and 21.3 +/- 1.6 mu mol . kg(-1). min(-1) with and without insulin replacement, respectively. Normoinsulinemia increased glucose oxidation (Delta = +4.5 +/- 0.6 mu mol . kg(-1). min(-1)) and nonoxidative glucose metabolism (Delta = +5.2 +/- 1.7 mu mol . kg(-1). min(-1)), whereas with insulinopenia, glucose oxidation did not change (Delta = -0.3 +/- 0.6 mu mol . kg(-1). min(-1)), and nonoxidative glucose metabolism increased (Delta = +8.7 +/- 0.8 mu mol . kg(-1). min(-1)). Nonoxidative glucose metabolism was higher during insulinopenic (13.5 +/- 1.8 mu mol . kg(-1). min(-1)) than normoinsulinemic hyperglycemia (9.8 +/- 2.7 mu mol . kg(-1). min(-1); P < 0.01). Plasma FFA concentration and lipid oxidation were higher with insulinopenia. Blood lactate and alanine concentrations were greater with normoinsulinemia. In conclusion: I)hyperglycemia promotes glucose uptake by stimulating both nonoxidative and oxidative glucose disposal; 2) the ability of hyperglycemia to enhance total body glucose uptake is similar with and without normoinsulinemia; 3) although acute insulinopenia does not impair the ability of hyperglycemia to stimulate glucose uptake, it plays a critical role in determining the intracellular metabolic fate of glucose taken up in response to hyperglycemia. C1 UNIV TEXAS, HLTH SCI CTR, DIV DIABET, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY VET AFFAIRS HOSP, SAN ANTONIO, TX 78284 USA. RP DELPRATO, S (reprint author), UNIV PADUA, CATTEDRA MALATTIE METAB, VIA GIUSTINIANI 2, I-35128 PADUA, ITALY. NR 31 TC 21 Z9 21 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 1995 VL 268 IS 6 BP E1089 EP E1095 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA RE366 UT WOS:A1995RE36600009 ER PT J AU WANG, TC BABYATSKY, MW OATES, PS ZHANG, ZS TILLOTSON, L CHULAK, M BRAND, SJ SCHMIDT, EV AF WANG, TC BABYATSKY, MW OATES, PS ZHANG, ZS TILLOTSON, L CHULAK, M BRAND, SJ SCHMIDT, EV TI A RAT GASTRIN HUMAN GASTRIN CHIMERIC TRANSGENE DIRECTS ANTRAL G-CELL-SPECIFIC EXPRESSION IN TRANSGENIC MICE SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE RAT GASTRIN GENE; HUMAN GASTRIN GENE; STOMACH-SPECIFIC EXPRESSION; PEPTIDE YY ID DNA-BINDING PROTEINS; ENDOCRINE-CELLS; GENE-EXPRESSION; GLUCAGON GENE; PEPTIDE-YY; DEVELOPMENTAL EXPRESSION; FUSION GENES; GUT; GROWTH; INTESTINE AB Gastrin gene expression in the gastrointestinal tract is under both developmental and spatial regulation. In the mature animal, gastrin, an important regulator of parietal acid secretion, is expressed primarily in G cells of the antrum. To determine whether specific promoter elements can direct expression to the gastric antrum in vivo, 450 nucleotides of the proximal rat gastrin promoter were cloned and used to construct a rat gastrin-human gastrin reporter chimeric transgene, which was injected into the mouse germ line. Northern blot analysis, in situ hybridization, and double-label immunocytochemistry studies demonstrated expression of the transgene specifically in antral G cells. Low levels of transgene expression were observed in the ileum and colon, where immunohistochemical studies demonstrated colocalization in enteroendocrine cells expressing peptide YY. The same 450-nucleotide rat gastrin promoter, when joined to the human growth hormone gene, did not result in antral expression. Similarly, a human gastrin-human gastrin reporter transgene also did not achieve antral expression, although it did express in the liver. These results suggest that cis-acting elements present in both the basal 450-nucleotide rat gastrin promoter and the intragenic sequences of the human gastrin gene are necessary to direct expression of a transgene specifically to antral G cells. C1 MASSACHUSETTS GEN HOSP, CTR CANC, BOSTON, MA 02129 USA. RP WANG, TC (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED, GASTROINTESTINAL UNIT, GRJ 724, 32 FRUIT ST, BOSTON, MA 02114 USA. NR 41 TC 14 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 1995 VL 268 IS 6 BP G1025 EP G1036 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA RF527 UT WOS:A1995RF52700019 ER PT J AU YANG, H TACHE, Y AF YANG, H TACHE, Y TI PYY IN BRAIN-STEM NUCLEI INDUCES VAGAL-STIMULATION OF GASTRIC-ACID SECRETION IN RATS SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE THYROTROPIN-RELEASING HORMONE; DORSAL MOTOR NUCLEUS OF THE VAGUS; RAPHE PALLIDUS; RAPHE OBSCURUS; NUCLEUS AMBIGUUS; SEROTONIN; PREPRO-THYROTROPIN-RELEASING HORMONE-(160--169); (+/-)-1-(4-METHYL-1-PIPERAZINYL)-PYRROLO(1,2-A)QUINOXALINE; VAGUS ID THYROTROPIN-RELEASING-HORMONE; MEDULLARY RAPHE NUCLEI; PEPTIDE-YY; RECEPTOR-BINDING; TRH ANALOG; COMPLEX; SEROTONIN; SITES; NEURONS; PROJECTIONS AB The influence of peptide YY (PYY) microinjected into brain stem nuclei on gastric acid secretion (GAS) was investigated in urethan-anesthetized rats with gastric cannula. PYY (30-200 ng) microinjected into the dorsal motor nucleus of the vagus (DMN) induces a dose-related and vagal-dependent stimulation of GAS (net increase from 13 +/- 4 to 59 +/- 12 mu mol/90 min). PYY (200 ng) injected intravenously or intracisternally into sites adjacent to the DMN had no effect. GAS induced by PYY into the DMN was potentiated by coinjection of thyrotropin-releasing hormone (TRH, 30 ng) or the serotonin receptor (5-HT2) agonist (+/-)-1-(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline (357 ng) and by microinjection of kainic acid (1 ng) into the raphe pallidus. Prepro-TRH-(160-169) (200 ng into the DMN) did not influence the stimulatory effect of PYY. PYY (200 ng) microinjected into the raphe pallidus, raphe obscurus, and nucleus ambiguus also increased GAS, although the response was of shorter duration than that in the DMN. These results indicate that PYY acts in brain stem nuclei involved in the vagal regulation of GAS and that PYY action in the DMN is potentiated by TRH or 5-HT2 receptor agonist acting at this site. C1 UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, BRAIN RES INST, LOS ANGELES, CA 90073 USA. RP YANG, H (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, CTR ULCER RES & EDUC, CTR GASTROENTER BIOL, BLDG 115, RM 207, LOS ANGELES, CA 90073 USA. FU NIDDK NIH HHS [DK-30110]; NIMH NIH HHS [MH-00663] NR 40 TC 31 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 1995 VL 268 IS 6 BP G943 EP G948 PG 6 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA RF527 UT WOS:A1995RF52700009 PM 7611415 ER PT J AU KATO, S IVESTER, CT COOPER, G ZILE, MR MCDERMOTT, PJ AF KATO, S IVESTER, CT COOPER, G ZILE, MR MCDERMOTT, PJ TI GROWTH EFFECTS OF ELECTRICALLY STIMULATED CONTRACTION ON ADULT FELINE CARDIOCYTES IN PRIMARY CULTURE SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE PROTEIN SYNTHESIS; CELL CULTURE; HYPERTROPHY ID RAT VENTRICULAR MYOCYTES; MOUSE SENSORY NEURONS; CAT RIGHT VENTRICLE; PROTEIN-SYNTHESIS; CARDIAC MYOCYTES; PRESSURE OVERLOAD; GENE-EXPRESSION; LOAD REGULATION; CELL-CULTURE; MUSCLE-CELLS AB The purpose of this study was to determine effects of long-term electrical stimulation of cardiocyte contraction on protein synthesis rates and total protein content. Adult feline cardiocytes were plated on laminin-coated culture trays and maintained in a serum-free medium consisting of M199 supplemented with ascorbate, bovine serum albumin, creatine, carnitine, taurine, and 10(-7) M recombinant insulin. Cardiocytes were electrically stimulated to contract with use of continuous electrical pulses of alternating polarity at a frequency of 1 Hz and pulse duration of 5 ms. Nonstimulated cardiocytes are normally quiescent and were used as the control group. In control quiescent cardiocytes, protein synthesis rate decreased by 14% between days 1 and 4 in culture and then remained stable through day 7. In electrically stimulated cardiocytes, protein synthesis rates increased by 19% between days 1 and 7. Protein synthesis rates were 18% higher on day 4 and 43% higher on day 7 in electrically stimulated than in quiescent cardiocytes. Protein content per cell was determined by measuring total fluorescence per cell by use of confocal microscopy of fluorescein isothiocyanate-stained cells. Electrical stimulation significantly increased cellular protein content by 52% after 7 days compared with controls. Quiescent and electrically stimulated cardiocytes remained rod shaped, retained their myofibrillar architecture, and were responsive to electrical stimulation over the 7-day period. These data demonstrated that electrically stimulated contraction of adult cardiocytes resulted in cell growth, as assessed by an increase in protein content per cell over 7 days in culture. This increase was due, at least in part, to an acceleration of steady-state protein synthesis rates. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR, CARDIOL SECT, CHARLESTON, SC 29401 USA. GAZES CARDIAC RES INST, DEPT MED, CHARLESTON, SC 29401 USA. GAZES CARDIAC RES INST, DEPT PHYSIOL, CHARLESTON, SC 29401 USA. GAZES CARDIAC RES INST, DEPT CELL BIOL & ANAT, CHARLESTON, SC 29401 USA. NR 43 TC 41 Z9 41 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 1995 VL 268 IS 6 BP H2495 EP H2504 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA RE373 UT WOS:A1995RE37300039 ER PT J AU JENDEN, DJ SCREMIN, OU AF JENDEN, DJ SCREMIN, OU TI EFFECTS OF HYPOXIA AND HYPERCAPNIA ON WHOLE-BODY RELEASE AND CLEARANCE OF CHOLINE SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE CHOLINE TURNOVER; CHOLINE CLEARANCE; CHOLINE RELEASE; METABOLIC ACIDOSIS; COMPARTMENT MODEL ID PLASMA CHOLINE; ESSENTIAL NUTRIENT; BRAIN CHOLINE; RAT-BRAIN; ACETYLCHOLINE; TRANSPORT; KINETICS; TURNOVER; EXCHANGE; INVIVO AB We have recently demonstrated an increase in arterial blood choline (Ch) concentration in normocapnic hypoxia and apnea. This could be due to enhanced release of free Ch from tissues, to decreased Ch clearance, or both. The present investigation was undertaken to determine the individual contributions of these processes to the whole body balance of Ch, using an intravenous infusion of tracer quantities of [H-2(4)]Ch to assess the bidirectional flux between the central pool and peripheral pools. Rats were subjected to normocapnic hypoxia or hypercapnia; release and clearance of Ch were calculated using a simple model. Hypoxia caused an increase in Ch production and a decrease in Ch clearance. At severe levels of hypoxia, Ch clearance was essentially zero. Hypoxia was attended by progressive acidosis that was related to the magnitude of the hypoxic challenge. To determine the possible effects of acidosis per se on the variables measured, respiratory acidosis with normoxia was provoked by controlled administration of CO2. Under these conditions, parallel decreases in Ch production and Ch clearance were observed. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT PHARMACOL, LOS ANGELES, CA 90095 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PHYS, LOS ANGELES, CA 90095 USA. W LOS ANGELES VET AFFAIRS MED CTR, CTR GERIATR RES EDUC & CLIN, LOS ANGELES, CA 90073 USA. NR 27 TC 5 Z9 5 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.-Regulat. Integr. Compar. Physiol. PD JUN PY 1995 VL 268 IS 6 BP R1520 EP R1525 PG 6 WC Physiology SC Physiology GA RE357 UT WOS:A1995RE35700024 ER PT J AU DORMAN, RL WHITMAN, GJ CHEW, FS AF DORMAN, RL WHITMAN, GJ CHEW, FS TI THORACIC SARCOIDOSIS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 5 TC 1 Z9 1 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 1995 VL 164 IS 6 BP 1368 EP 1368 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QZ542 UT WOS:A1995QZ54200008 PM 7754874 ER PT J AU JONES, EC PINS, M DICKERSIN, GR YOUNG, RH AF JONES, EC PINS, M DICKERSIN, GR YOUNG, RH TI METANEPHRIC ADENOMA OF THE KIDNEY - A CLINICOPATHOLOGICAL, IMMUNOHISTOCHEMICAL, FLOW CYTOMETRIC, CYTOGENETIC, AND ELECTRON-MICROSCOPIC STUDY OF 7 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE KIDNEY; ADENOMA; METANEPHROS; WILMS TUMOR ID RENAL-CELL CARCINOMA; WILMS-TUMOR; NEPHROBLASTOMATOSIS; ADENOCARCINOMA; ULTRASTRUCTURE; METASTASES; CHILDHOOD; PATHOLOGY; CANCER; ADULT AB We report seven examples of a distinctive adenomatous tubular cortical neoplasm of the adult kidney. The average age of the patients (six women and one man) was 48.6 years (range, 38-64 years). In six patients the tumor was discovered during investigation of unrelated conditions, and all were treated with total nephrectomy. One tumor was found at autopsy. The tumors were well-circumscribed, nodular, tan-pink masses localized to the kidney, ranging in size from 0.6 to 8 cm. Histological examination demonstrated orderly, closely packed, small round tubules lined by bland, darkly staining oval cells with little cytoplasm, merging with rounded nests of similar cells. Occasional branching, elongated tubules, and papillary infoldings of glomeruloid-like bodies were present but blastema was absent. The tumor cells were immunoreactive for Leu 7 (three of five cases) and vimentin (four of six cases), and a few tumors were immunoreactive for cytokeratin (two of six cases), epithelial membrane antigen (one of six cases), and muscle-specific antigen (one of six cases). Ultrastructural examination of two tumors revealed tubular and solid nests of epithelial cells surrounded by basal lamina, with prominent cell junctions, microvilli, and apical secretory granules. DNA content analysis by flow cytometry yielded diploid histograms (four of four cases). Cytogenetic analysis of one case revealed a normal male karyotype. Clinical followup, available for six patients, revealed no evidence of recurrence (mean follow-up, 60.8 months). We believe this is a benign tumor, best classified as a metanephric adenoma because of its embryonic architectural and cytological appearance, that can be recognized by its very characteristic pathological features. C1 UNIV BRITISH COLUMBIA, VANCOUVER, BC, CANADA. MASSACHUSETTS GEN HOSP, JAMES HOMER WRIGHT PATHOL LABS, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. RP JONES, EC (reprint author), VANCOUVER HOSP & HLTH SCI CTR, DEPT PATHOL, 855 W 12TH AVE, VANCOUVER, BC V5Z 1M9, CANADA. NR 47 TC 108 Z9 115 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUN PY 1995 VL 19 IS 6 BP 615 EP 626 DI 10.1097/00000478-199506000-00001 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA QY755 UT WOS:A1995QY75500001 PM 7755148 ER PT J AU GASTFRIEND, DR FILSTEAD, WJ REIF, S NAJAVITS, LM PARRELLA, DP AF GASTFRIEND, DR FILSTEAD, WJ REIF, S NAJAVITS, LM PARRELLA, DP TI VALIDITY OF ASSESSING TREATMENT READINESS IN PATIENTS WITH SUBSTANCE USE DISORDERS SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID MOTIVATION; ALCOHOLISM; DRINKING; SEVERITY AB The Recovery Attitude and Treatment Evaluator-Clinical Evaluation (RAATE-CE) assesses resistance and impediments to addiction treatment participation. The authors conducted a preliminary test of the RAATE-CE's predictive validity. Addiction counselors conducted RAATE-CE assessments on 220 adults who were newly admitted to a hospital detoxification unit. Relationships between scores and disposition were examined using analysis of variance. All RAATE-CE dimensions show, significant associations with subsequent treatment placements in the expected directions. Preliminary findings of predictive validity warrant further research on the RAATE-CE for clinical research and treatment planning. RP GASTFRIEND, DR (reprint author), MASSACHUSETTS GEN HOSP,ADDICT SERV,15 PARKMAN ST,ACC-812,BOSTON,MA 02114, USA. NR 24 TC 11 Z9 11 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SUM PY 1995 VL 4 IS 3 BP 254 EP 260 DI 10.3109/10550499509038110 PG 7 WC Substance Abuse SC Substance Abuse GA RP438 UT WOS:A1995RP43800007 ER PT J AU BORCZUK, P AF BORCZUK, P TI PREDICTORS OF INTRACRANIAL INJURY IN PATIENTS WITH MILD HEAD TRAUMA SO ANNALS OF EMERGENCY MEDICINE LA English DT Article AB Study objective: To determine the prevalence of abnormal computed tomography (CT) scans and define high-risk clinical variables in patients with mild head injury. Design: Retrospective descriptive study of patients with Glasgow Coma Scale (GCS) scores of 13 or greater who presented to the emergency department with blunt head trauma and who underwent cranial CT. Setting: Level 1 trauma center, university ED. Results: During the 15-month study period, 1,448 patients underwent CT scanning for mild head injury. Abnormalities resulting from the trauma were found in 119(8.2%), and 11 patients(.76%) required neurosurgical intervention. Patients with higher GCS scores had a greater chance of having a solitary CT abnormality (P=004). Bicyclists and pedestrians struck by cars were more likely than others to sustain intracranial injury. High-risk clinical variables included the presence of cranial soft-tissue injury, a focal neurologic deficit, signs of basilar skull fracture and age older than 60 years. A strategy using those variables had a sensitivity of 98.6% and a specificity of 46.2% for detecting a CT abnormality. None of the patients missed by this strategy required medical or neurosurgical management for the CT finding. Conclusion: Abnormalities on CT scans in patients with mild head trauma are fairly common, although the need for neurosurgical intervention is rare. Clinical decision rules can be used to identify those patients with more serious intracranial pathology. Such strategies should be validated prospectively in various ED settings. RP BORCZUK, P (reprint author), MASSACHUSETTS GEN HOSP,DEPT EMERGENCY MED,CLIN 117,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 126 Z9 129 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUN PY 1995 VL 25 IS 6 BP 731 EP 736 DI 10.1016/S0196-0644(95)70199-0 PG 6 WC Emergency Medicine SC Emergency Medicine GA RA349 UT WOS:A1995RA34900001 PM 7755192 ER PT J AU ASCH, DA HERSHEY, JC AF ASCH, DA HERSHEY, JC TI WHY SOME HEALTH POLICIES DONT MAKE SENSE AT THE BEDSIDE SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID DECISION-ANALYSIS; INDIVIDUAL PATIENTS; PORTFOLIO THEORY; UTILITY; RISK AB Cost-effectiveness analysis and other forms of decision analysis are becoming more common in the medical literature and are increasingly influential in the development of health policy. Nevertheless, many clinicians find it difficult to apply policies developed from these analyses to individual encounters with patients. We examine the assumptions behind these analyses and argue that the perspective they embody can make clinical strategies appear to be less risky in theory than they are at the bedside. We believe that this problem underlies the intuitive concern many physicians have about policy analyses and calls into question the value of these analyses in shaping clinical practice. These analyses aggregate the benefits and burdens of alternative interventions across different individual persons. Thus, overall population risk appears blunted, as it would in a diversified portfolio of stocks that react differently to financial forces or in a herd of cattle that react differently to veterinary interventions. The assumptions behind these analyses make sense if aggregate outcome is what matters, but not if one cares about each individual investment or animal. Because such aggregation tends to understate individual risk, when applied to human health policy, it may misrepresent the interests of patients and cannot be assumed to provide useful guidelines for decision making at the bedside. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,WHARTON SCH,PHILADELPHIA,PA 19104. FU NHGRI NIH HHS [R011HG00621, R011HG00616] NR 26 TC 72 Z9 73 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 JUN 1 PY 1995 VL 122 IS 11 BP 846 EP 850 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA RA139 UT WOS:A1995RA13900007 PM 7741370 ER PT J AU POLSEN, C ANOUS, M NETSCHER, D SHENAQ, S SAFI, HJ AF POLSEN, C ANOUS, M NETSCHER, D SHENAQ, S SAFI, HJ TI HYPOTHERMIA AND CARDIOPULMONARY BYPASS DURING RESECTION OF EXTENSIVE ARTERIOVENOUS MALFORMATION FOLLOWED BY MICROVASCULAR RECONSTRUCTION SO ANNALS OF PLASTIC SURGERY LA English DT Note ID INTRA-ARTERIAL EMBOLIZATION; CIRCULATORY ARREST; VASCULAR MALFORMATIONS; SURGICAL-TREATMENT; DEEP HYPOTHERMIA; HEMANGIOMAS; ANEURYSM; SURGERY; INFANCY AB A patient is presented in whom hypothermic hypoperfusion and cardiopulmonary bypass were used to aid in resection of a mandibular arteriovenous malformation, This was followed by immediate microvascular reconstruction using a fibular osteocutaneous microvascular free tissue transfer. Prior attempted resection after highly selective embolization had proved inadequate, We found that the operative field, using hypothermic hypoperfusion was bloodless and enabled safe, rapid excision of the malformation, After patient rewarming, microvascular reconstruction was readily performed, No neurologic sequelae resulted, and no recurrence of the malformation has been noted. C1 BAYLOR COLL MED,DIV PLAST SURG,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT ANESTHESIA,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT SURG,HOUSTON,TX 77030. DEPT VET AFFAIRS MED CTR,SURG SERV,HOUSTON,TX. NR 47 TC 3 Z9 3 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD JUN PY 1995 VL 34 IS 6 BP 642 EP 649 DI 10.1097/00000637-199506000-00014 PG 8 WC Surgery SC Surgery GA RC512 UT WOS:A1995RC51200016 PM 7661544 ER PT J AU MARTIN, KJ VASSALLO, CD TEICHER, BA KADDURAHDAOUK, R AF MARTIN, KJ VASSALLO, CD TEICHER, BA KADDURAHDAOUK, R TI MICROTUBULE STABILIZATION AND POTENTIATION OF TAXOL ACTIVITY BY THE CREATINE ANALOG CYCLOCREATINE SO ANTI-CANCER DRUGS LA English DT Article DE COMBINATION CHEMOTHERAPY; CREATINE KINASE; CYCLOCREATINE; MICROTUBULES; TAXOL ID KINASE ISOENZYMES; ENERGY-METABOLISM; CELL LINE; TUBULIN; MECHANISM; ENZYME; ATP; PHOSPHOCREATINE; MEMBRANE; INVITRO AB Creatine kinase (CK), a key enzyme of cellular energetics, has been implicated in tumorigenesis. Cyclocreatine (CCr), which forms a stable phosphagen with a reduced rate of ATP regeneration through CK, inhibits the growth of many solid tumors. We report that CCr induces the formation of unusually stable microtubules that resist depolymerization by nocodazole. By reducing ATP availability, CCr may modulate the activity of kinases that regulate microtubule dynamics. Further, combinations of CCr and taxol resulted in the synergistic killing of breast tumor cells indicating that CCr may be a useful addition to chemotherapy's that include taxanes. C1 DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. RP MARTIN, KJ (reprint author), REPLIGEN CORP,AMIRA INC,1 KENDALL SQ,CAMBRIDGE,MA 02139, USA. NR 46 TC 14 Z9 14 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JUN PY 1995 VL 6 IS 3 BP 419 EP 426 DI 10.1097/00001813-199506000-00009 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA RB825 UT WOS:A1995RB82500009 PM 7670140 ER PT J AU ALLENDOERFER, R LOEBENBERG, D RINALDI, MG GRAYBILL, JR AF ALLENDOERFER, R LOEBENBERG, D RINALDI, MG GRAYBILL, JR TI EVALUATION OF SCH51048 IN AN EXPERIMENTAL-MODEL OF PULMONARY ASPERGILLOSIS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE ASPERGILLOSIS AB The efficacy of a novel triazole, SCH51048, was assessed with a murine model of pulmonary aspergillosis and was compared with those of SCH39304 and itraconazole. A wide range of doses of SCH51048 (5 to 50 mg/kg of body weight) was evaluated. Mortality was significantly delayed in mice treated with doses of 5 mg of SCH51048 per kg or greater in comparison with mortality in controls (P < 0.05). Both SCH51048 and SCH39304 at higher doses (30 and 50 mg/kg) reduced the number of viable Aspergillus fumigatus organisms in lung tissue (P < 0.05). In the present model, itraconazole neither delayed mortality nor significantly reduced the counts in tissue at the doses used, We conclude that SCH51048 is an effective therapy for murine pulmonary aspergillosis. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX. AUDIE L MURPHY VET AFFAIRS HOSP,SAN ANTONIO,TX. SCHERING PLOUGH CORP,RES INST,KENILWORTH,NJ. NR 14 TC 17 Z9 18 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 1995 VL 39 IS 6 BP 1345 EP 1348 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA RB370 UT WOS:A1995RB37000023 PM 7574528 ER PT J AU WALSH, TJ PETER, J MCGOUGH, DA FOTHERGILL, AW RINALDI, MG PIZZO, PA AF WALSH, TJ PETER, J MCGOUGH, DA FOTHERGILL, AW RINALDI, MG PIZZO, PA TI ACTIVITIES OF AMPHOTERICIN-B AND ANTIFUNGAL AZOLES ALONE AND IN COMBINATION AGAINST PSEUDALLESCHERIA-BOYDII SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID CENTRAL NERVOUS-SYSTEM; PETRIELLIDIUM-BOYDII; BRAIN-ABSCESS; TRANSPLANT RECIPIENT; FUNGAL-INFECTIONS; ENDOCARDITIS; KETOCONAZOLE; KERATITIS AB In order to develop new approaches to treatment of infections due to Pseudallescheria boydii, the in vitro antifungal activity of amphotericin B alone and in combination with miconazole, itraconazole, and fluconazole was studied. Combinations of amphotericin B and antifungal azoles were synergistic, additive, or indifferent in their interaction against P. boydii. Antagonism was not observed. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,FUNGUS TESTING LAB,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. RP WALSH, TJ (reprint author), NCI,INFECT DIS SECT,BLDG 10,RM 13N-240,BETHESDA,MD 20892, USA. NR 28 TC 94 Z9 96 U1 0 U2 2 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 1995 VL 39 IS 6 BP 1361 EP 1364 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA RB370 UT WOS:A1995RB37000026 PM 7574531 ER PT J AU RENSHAW, AA PAULUS, W JOSEPH, JT AF RENSHAW, AA PAULUS, W JOSEPH, JT TI CD34 AND EPITHELIAL MEMBRANE ANTIGEN DISTINGUISH DURAL HEMANGIOPERICYTOMA AND MENINGIOMA SO APPLIED IMMUNOHISTOCHEMISTRY LA English DT Article DE HEMANGIOPERICYTOMA; MENINGIOMA; ANGIOBLASTIC MENINGIOMA; CD34; EMA; IMMUNOHISTOCHEMISTRY ID TERM FOLLOW-UP; MENINGEAL HEMANGIOPERICYTOMA; ANGIOBLASTIC MENINGIOMA; HISTOLOGICAL SUBTYPES; ELECTRON-MICROSCOPY; NERVOUS-SYSTEM; GLOMUS TUMORS; SOFT-TISSUE; IMMUNOHISTOCHEMISTRY; DIFFERENTIATION AB Whether hemangiopericytoma (HPC) of the dura is a variant of meningioma or a distinct entity is a controversial issue. We examined the immunohistochemical reactivity for CD34 and epithelial membrane antigen (EMA) of 20 dural-based HPCs from 17 patients and compared the results with 25 meningiomas from 25 patients (five meningothelial, nine transitional, seven fibrous, two atypical, one psammomatous, and one secretory). Histologically, the HPCs could be divided into round, spindle, and ''pseudopapillary'' cell types; two tumors were mixed. Eighteen of the 20 HPCs stained strongly and diffusely with CD34, whereas only two of 20 were focally positive for EMA. In contrast, only one of 25 meningiomas was focally positive for CD34, whereas 25 of 25 were positive for EMA. We conclude that immunohistochemistry using CD34 and EMA is helpful in distinguishing HPC and meningioma, and CD34 is a sensitive marker for HPC. C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA. RP RENSHAW, AA (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 49 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1062-3345 J9 APPL IMMUNOHISTOCHEM JI Appl. Immunohistochem. PD SUM PY 1995 VL 3 IS 2 BP 108 EP 114 PG 7 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA RB472 UT WOS:A1995RB47200006 ER PT J AU VITKIN, IA WILSON, BC ANDERSON, RR AF VITKIN, IA WILSON, BC ANDERSON, RR TI ANALYSIS OF LAYERED SCATTERING MATERIALS BY PULSED PHOTOTHERMAL RADIOMETRY - APPLICATION TO PHOTON PROPAGATION IN TISSUE SO APPLIED OPTICS LA English DT Article DE LASER; OPTICAL DIFFUSION; IR RADIOMETRY; 2-LAYER MEDIUM ID OPTICAL-PROPERTIES; TURBID MEDIA; DIFFUSION; MODEL AB A model of pulsed photothermal radiometry (PPTR) based on optical diffusion theory is presented for a turbid, two-layer, semi-infinite medium containing a surface layer whose optical absorption and scattering properties differ from that of the underlying layer. Assuming one-dimensional geometry, we develop expressions for the depth-dependent fluence distributions and radiant-energy-density profiles and for the time dependence of the PPTR signal. Experimental tests of the PPTR model in a series of layered phantoms of varying optical properties are described. The results of these tests are consistent with the model predictions. C1 MCMASTER UNIV,HAMILTON,ON L8V 1C3,CANADA. PRINCESS MARGARET HOSP,ONTARIO CANC INST,DEPT CLIN PHYS,TORONTO,ON M4X 1K9,CANADA. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO,ON M4X 1K9,CANADA. MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Vitkin, Alex/I-8166-2012 NR 25 TC 33 Z9 33 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD JUN 1 PY 1995 VL 34 IS 16 BP 2973 EP 2982 PG 10 WC Optics SC Optics GA RB344 UT WOS:A1995RB34400022 PM 21052451 ER PT J AU COMPTON, CC TONG, Y TROOKMAN, N ZHAO, HF ROY, D PRESS, W AF COMPTON, CC TONG, Y TROOKMAN, N ZHAO, HF ROY, D PRESS, W TI TRANSFORMING GROWTH-FACTOR-ALPHA GENE-EXPRESSION IN CULTURED HUMAN KERATINOCYTES IS UNAFFECTED BY CELLULAR AGING SO ARCHIVES OF DERMATOLOGY LA English DT Article ID THICKNESS BURN WOUNDS; EPIDERMAL-CELLS; LEG ULCERS; EPITHELIAL ALLOGRAFTS; SKIN EQUIVALENTS; MESSENGER-RNA; Y-CHROMOSOME; DONOR SITES; GRAFTS; SURVIVAL AB Background: Cultured human keratinocyte grafts have been shown to stimulate endogenous reepithelialization of both chronic nonhealing and acute partial-thickness wounds. This effect is most likely mediated by cytokines that stimulate keratinocyte growth, such as transforming growth factor alpha. The effect of cellular age on cytokine expression by cultured grafts used for this purpose is presently undefined. In this study, transforming growth factor alpha gene expression in cultured foreskin keratinocytes from donors varying in age from 2 to 82 years was analyzed semiquantitatively by two separate methods, ie, Northern hybridization and competitive polymerase chain reaction. Results: No pattern of decline in transforming growth factor alpha messenger RNA expression with increasing cellular age was observed by either analysis. Conclusion: The results indicate that expression of transforming growth factor alpha by cultured grafts may not be significantly affected by increasing cellular. age and suggest that, even in the elderly, cultured autografts may be effective as pharmacologic agents for wound treatment. C1 SHRINERS HOSP CRIPPLED CHILDREN,BOSTON BURNS INST,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT MED,DIABET UNIT,BOSTON,MA. RP COMPTON, CC (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,WARREN 2,15 FRUIT ST,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [R01-GM35242]; PHS HHS [15880] NR 57 TC 11 Z9 11 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 1995 VL 131 IS 6 BP 683 EP 690 DI 10.1001/archderm.131.6.683 PG 8 WC Dermatology SC Dermatology GA RC497 UT WOS:A1995RC49700008 PM 7778920 ER PT J AU ARBISER, JL DZIECZKOWSKI, JS HARMON, JV DUNCAN, LM AF ARBISER, JL DZIECZKOWSKI, JS HARMON, JV DUNCAN, LM TI LEUKOCYTOCLASTIC VASCULITIS FOLLOWING STAPHYLOCOCCAL PROTEIN-A COLUMN IMMUNOADSORPTION THERAPY - 2 CASES AND A REVIEW OF THE LITERATURE SO ARCHIVES OF DERMATOLOGY LA English DT Article ID IMMUNOGLOBULIN-G; SELECTIVE REMOVAL; IMMUNE-COMPLEXES; BINDING; PLASMA AB Background: Protein A immunoadsorption is a novel therapy for the treatment of diseases mediated by pathogenic autoantibodies. This procedure consists of circulating patients' plasma through a column containing staphylococcal protein A, which binds to the Fc portion of IgG, enabling removal of IgG. Presently, protein A immunoadsorption is used in the treatment of idiopathic thrombocytopenic purpura, but may be more widely used as an immunomodulator in human immunodeficiency virus infection and metastatic carcinoma. Observations: We present two histologically documented cases of leukocytoclastic vasculitis in the setting of protein A immunoadsorption. This potentially severe adverse effect is probably more common than the literature reflects and should be recognized by physicians who are treating patients with protein A column pheresis. Conclusions: The pathogenesis of protein A therapy-associated leukocytoclastic vasculitis remains unclear. Further study of vasculitis in the setting of protein A column pheresis may lead to modifications of this therapy, resulting in fewer adverse effects. Protein A-associated leukocytoclastic vasculitis may serve as a useful model of the relation of immune complexes and vasculitis. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,DERMATOPATHOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. WAYNE STATE UNIV,DEPT PATHOL,DETROIT,MI. UNIV MINNESOTA,DEPT SURG,MINNEAPOLIS,MN. NR 16 TC 11 Z9 11 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 1995 VL 131 IS 6 BP 707 EP 709 DI 10.1001/archderm.131.6.707 PG 3 WC Dermatology SC Dermatology GA RC497 UT WOS:A1995RC49700012 PM 7778924 ER PT J AU SPENCER, T WILENS, T BIEDERMAN, J FARAONE, SV ABLON, JS LAPEY, K AF SPENCER, T WILENS, T BIEDERMAN, J FARAONE, SV ABLON, JS LAPEY, K TI A DOUBLE-BLIND, CROSSOVER COMPARISON OF METHYLPHENIDATE AND PLACEBO IN ADULTS WITH CHILDHOOD-ONSET ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MINIMAL BRAIN-DYSFUNCTION; PSYCHIATRIC STATUS; FOLLOW-UP; RESIDUAL TYPE; RISK-FACTORS; CHILDREN; COMORBIDITY; PREVALENCE; METABOLISM; COGNITION AB Background: There are few controlled studies of methylphenidate hydrochloride in adults with attention-deficit hyperactivity disorder (ADHD), and their results have been equivocal. The discrepancies among these studies may be related to low doses, diagnostic uncertainties, and lack of attention to comorbid disorders. Methods: We conducted a randomized, 7-week, placebo-controlled, crossover study of methylphenidate in 23 adult patients with DSM-III-R ADHD using standardized instruments for diagnosis, separate assessments of ADHD and depressive and anxiety symptoms, and a robust daily dose of methylphenidate hydrochloride, 1.0 mg/kg per day. Results: We found a marked therapeutic response for methylphenidate treatment of ADHD symptoms that exceeded the placebo response (78% vs 4%, P<.0001). Response to methylphenidate was independent of gender, psychiatric comorbidity with anxiety or moderate depression, or family history of psychiatric disorders. Conclusion: Robust doses of methylphenidate are effective in the treatment of adult ADHD. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP SPENCER, T (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC725,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 57 TC 303 Z9 306 U1 2 U2 14 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 JUN PY 1995 VL 52 IS 6 BP 434 EP 443 PG 10 WC Psychiatry SC Psychiatry GA RC025 UT WOS:A1995RC02500002 PM 7771913 ER PT J AU BIEDERMAN, J MILBERGER, S FARAONE, SV KIELY, K GUITE, J MICK, E ABLON, S WARBURTON, R REED, E AF BIEDERMAN, J MILBERGER, S FARAONE, SV KIELY, K GUITE, J MICK, E ABLON, S WARBURTON, R REED, E TI FAMILY-ENVIRONMENT RISK-FACTORS FOR ATTENTION-DEFICIT HYPERACTIVITY DISORDER - A TEST OF RUTTERS INDICATORS OF ADVERSITY SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CHILD PSYCHIATRIC-DISORDERS; LEARNING-DISABILITIES; ADHD CHILDREN; FOLLOW-UP; COMORBIDITY; ADOLESCENT; PSYCHOPATHOLOGY; ADJUSTMENT; PATTERNS; PROBANDS AB Background: This study investigated whether family-environment risk factors are associated with attention-deficit hyperactivity disorder (ADHD). Compelling work by Rutter and coworkers revealed that it was the aggregate of adversity factors (severe marital discord, low social class, large family size, paternal criminality, maternal mental disorder, and foster care placement) rather than the presence of any single factor that led to impaired development. Based on the work of Rutter, we hypothesized a positive association between indicators of adversity and the diagnosis of ADHD and ADHD-associated impairments. Methods: We studied 140 ADHD and 120 normal control probands. Subjects were non-Hispanic white boys between the ages of 6 and 17 years. Rutter's indicators of adversity were used to predict ADHD-related psychopathology as well as impaired cognitive and psychosocial functioning. Results: The odds ratio for the diagnosis of ADHD increased as the number of Rutter's adversity indicators increased. Higher scores on Rutter's adversity index predicted ADHD-related psychopathology (depression, anxiety, and conduct disorder), learning disabilities, cognitive impairment, and psychosocial dysfunction. Conclusions: A positive association appears to exist between adversity indicators and the risk for ADHD as well as for its associated psychiatric, cognitive, and psychosocial impairments. These findings support the work of Rutter and stress the importance of adverse family-environment variables as risk factors for children with ADHD. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,FRUIT ST,BOSTON,MA 02114, USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 53 TC 249 Z9 255 U1 4 U2 38 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 JUN PY 1995 VL 52 IS 6 BP 464 EP 470 PG 7 WC Psychiatry SC Psychiatry GA RC025 UT WOS:A1995RC02500005 PM 7771916 ER PT J AU TAKASHITA, N HOMMA, S ROTTELLO, RJ FERNANDEZ, PA YUAN, JY OPPENHEIM, RW YAGINUMA, H AF TAKASHITA, N HOMMA, S ROTTELLO, RJ FERNANDEZ, PA YUAN, JY OPPENHEIM, RW YAGINUMA, H TI EXPRESSION OF APOGENS AND ENGULFENS DURING PROGRAMMED CELL-DEATH IN THE NERVOUS-SYSTEM OF THE CHICK-EMBRYO SO ARCHIVES OF HISTOLOGY AND CYTOLOGY LA English DT Article ID SPINAL-CORD; RETINA; HOMOLOG; GROWTH; GENE AB Two categories of cell death related to antigens, apogens and engulfens, have been reported to be expressed by apoptotic cells and the cells involved in their engulfment in the immune system, and in mesenchymal tissue in the limb of the chick embryo (ROTTELLO et al., 1994). To determine whether these antigens are also expressed during the process of neuronal death, the distribution of immunoreactivity to both anti-apogen and anti-engulfen antibodies was examined in the spinal cord and the dorsal root ganglia of the chick embryo. Anti-apogen antibodies labeled a sub-population of the profiles of dying cells in regions where cell death was occurring. The extent of labeling by anti-apogens varied from 3% to 70% of the total number of dying profiles depending on the specific antibody used and the neuronal region examined. Immunoreactive labeling by the anti-engulfen antibodies mainly involved large cells that contained debris of dead cells. These results indicate that at least some dying neuronal cells express common antigens that are shared by dying mesenchymal cells during programmed cell death, and that phagocytotic cells of the immune system are involved in the engulfment of neuronal cells that have undergone programmed cell death. C1 UNIV TSUKUBA, INST BASIC MED SCI, DEPT ANAT, TSUKUBA, IBARAKI 305, JAPAN. MASSACHUSETTS GEN HOSP, CARDIOVASC RES CTR, BOSTON, MA USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT NEUROBIOL & ANAT, WINSTON SALEM, NC USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, PROGRAM NEUROSCI, WINSTON SALEM, NC USA. FU NINDS NIH HHS [NS 31380, NS 20402] NR 21 TC 1 Z9 1 U1 1 U2 2 PU INT SOC HISTOLOGY & CYTOLOGY PI NIIGATA PA C/O DIV MICROSCOPIC ANAT&BIO-IMAGING, NIIGATA UNIV GRAD SCH MED & DENTAL SCI, 1-757 ASAHIMACHI-DORI, NIIGATA, CHUO-KU 951-8510, JAPAN SN 0914-9465 EI 1349-1717 J9 ARCH HISTOL CYTOL JI Arch. Histol. Cytol. PD JUN PY 1995 VL 58 IS 2 BP 243 EP 248 DI 10.1679/aohc.58.243 PG 6 WC Cell Biology SC Cell Biology GA RH371 UT WOS:A1995RH37100011 PM 7576875 ER PT J AU TALAMO, JH WAGONER, MD LEE, SY AF TALAMO, JH WAGONER, MD LEE, SY TI MANAGEMENT OF ABLATION DECENTRATION FOLLOWING EXCIMER PHOTOREFRACTIVE KERATECTOMY SO ARCHIVES OF OPHTHALMOLOGY LA English DT Note RP TALAMO, JH (reprint author), MASSACHUSETTS EYE & EAR INFIRM,CORNEA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 5 TC 11 Z9 12 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 1995 VL 113 IS 6 BP 706 EP 707 PG 2 WC Ophthalmology SC Ophthalmology GA RC170 UT WOS:A1995RC17000016 PM 7786205 ER PT J AU MILLER, JW WALSH, AW KRAMER, M HASAN, T MICHAUD, N FLOTTE, TJ HAIMOVICI, R GRAGOUDAS, ES AF MILLER, JW WALSH, AW KRAMER, M HASAN, T MICHAUD, N FLOTTE, TJ HAIMOVICI, R GRAGOUDAS, ES TI PHOTODYNAMIC THERAPY OF EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION USING LIPOPROTEIN-DELIVERED BENZOPORPHYRIN SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID MOUSE-TUMOR MODEL; MACULAR DEGENERATION; SULFONATED PHTHALOCYANINE; IRIS NEOVASCULARIZATION; PLASMA-LIPOPROTEINS; NATURAL-HISTORY; CELLULAR-UPTAKE; PHOTOSENSITIZATION; PERMEABILITY; VESSELS AB Objective: To investigate photodynamic therapy of experimental choroidal neovascularization using benzoporphyrin derivative monoacid (Verteporfin). Methods: Photodynamic therapy using benzoporphyrin derivative monoacid was investigated in cynomolgus monkeys. Following intravenous injection of benzoporphyrin derivative monoacid (1 to 2 mg/kg) complexed with low-density lipoprotein, the eyes were irradiated with 692-nm light at a fluence of 50 to 150J/cm(2) and irradiance of 150 to 600 mW/cm(2). Choroidal neovascularization was documented before photodynamic therapy and closure was demonstrated by fundus photography, fluorescein angiography, and right and electron microscopic examination. Results: Following photodynamic therapy, vessels within choroidal neovascularization were occluded, and there was damage to the choroidal neovascularization endothelium and the subjacent choriocapillaris. Damage to the retinal pigment epithelium and photoreceptors was also observed. Conclusion: Photodynamic therapy with lipoprotein delivered benzoporphyrin derivative monoacid was effective in this animal model of choroidal neovascularization and may be a promising, potentially selective, therapy for choroidal neovascularization. C1 MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP MILLER, JW (reprint author), MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,LASER RES LAB,243 CHARLES ST,BOSTON,MA 02114, USA. NR 45 TC 148 Z9 155 U1 1 U2 2 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 1995 VL 113 IS 6 BP 810 EP 818 PG 9 WC Ophthalmology SC Ophthalmology GA RC170 UT WOS:A1995RC17000037 PM 7540388 ER PT J AU RYAN, EA LEE, S CHERN, S AF RYAN, EA LEE, S CHERN, S TI USE OF INTRAVITREAL AUTOLOGOUS BLOOD TO IDENTIFY POSTERIOR CORTICAL VITREOUS IN MACULAR HOLE SURGERY SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article AB Surgical management of macular holes involves removal of tractional prefovial vitreous cortex. Accurately identifying this adherent tissue can potentially decrease intraoperative complications. A new, effective technique using autologous whole blood can be used to identify and facilitate separation of the posterior cortical vitreous. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 5 TC 16 Z9 16 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 1995 VL 113 IS 6 BP 822 EP 823 PG 2 WC Ophthalmology SC Ophthalmology GA RC170 UT WOS:A1995RC17000039 PM 7786226 ER PT J AU CHENEY, ML GLIKLICH, RE AF CHENEY, ML GLIKLICH, RE TI THE USE OF CALVARIAL BONE IN NASAL RECONSTRUCTION SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID ENDOCHONDRAL BONE; OUTER-TABLE; GRAFTS; AUGMENTATION; REVASCULARIZATION; CARTILAGE; FIXATION; SITE AB Objective: To demonstrate the utility of calvariaI bone as a primary graft choice in nasal reconstruction. Design: Case series. Setting: Academic tertiary care center. Pattern: Thirty-five consecutive patients who underwent split calvarial bone grafting to the nasal dorsum between June 1988 and September 1993 and who had postoperative follow-up. Outcome Measures: Serial clinical examination to assess volume loss, movement of the graft, and complications. Standardized photographs to assess nasal contour. Results: Fixation of the graft was accomplished using a technique that promotes bone-to-bone healing without fixation screws or wires. The most common complication was seroma or hematoma of the scalp (8%). There were no dural tears or intracranial complications. Longterm donor site morbidity consisted of one case of local alopecia (2.8%). A good nasal contour was achieved in 97% of patients. Conclusion: Based on the experimental evidence reviewed and our clinical experience, split calvarial bone is recommended as a material of choice for nasal dorsal reconstruction. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP CHENEY, ML (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,DIV FACIAL PLAST & RECONSTRUCT SURG,BOSTON,MA 02114, USA. NR 40 TC 15 Z9 16 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 1995 VL 121 IS 6 BP 643 EP 648 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA RC174 UT WOS:A1995RC17400008 PM 7772316 ER PT J AU KRAG, DN MEIJER, SJ WEAVER, DL LOGGIE, BW HARLOW, SP TANABE, KK LAUGHLIN, EH ALEX, JC AF KRAG, DN MEIJER, SJ WEAVER, DL LOGGIE, BW HARLOW, SP TANABE, KK LAUGHLIN, EH ALEX, JC TI MINIMAL-ACCESS SURGERY FOR STAGING OF MALIGNANT-MELANOMA SO ARCHIVES OF SURGERY LA English DT Article ID CUTANEOUS LYMPHOSCINTIGRAPHY; SURGICAL-MANAGEMENT; PROGNOSTIC FACTORS; STAGE-1 MELANOMA; LYMPH-NODES; METASTASES; EXCISION; THICKNESS; MARGINS AB Objective: To develop a simple, minimally invasive technique of determining whether regional node metastasis has occurred in patients with melanoma. Setting: Teaching hospital tertiary care and private practice settings. Patients: Between February 1993 and October 1994, 121 patients with invasive malignant melanoma and clinically negative lymph nodes were enrolled in this clinical trial. Design: Consecutive sample clinical trial. Within 24 hours prior to lymph node resection, a radioactive tracer was injected into the dermis around the site of the primary melanoma. Forty-four patients also had blue dye injected immediately prior to surgical resection. Measurement of radioactivity in the lymph nodes and surgical localization were made using a handheld gamma detector. Radiolabeled nodes were selectively removed with the least dissection possible. In patients with pathologically positive radiolabeled nodes, regional lymphadenectomy was performed. Outcome Measures: Successful identification of radiolabeled sentinel lymph nodes, correlation of radiolabeling with injection of blue dye, and regional node recurrence rate. Results: Surgeons successfully resected the radiolabeled sentinel lymph nodes in 118 (98%) of 121 patients. One hundred percent of blue-stained lymph nodes were successfully radiolabeled. Fifteen patients had pathologically positive sentinel lymph nodes. In 10 patients, the sentinel node was the only node with metastasis. Two systemic and one regional node recurrences occurred during a mean follow-up of 220 days. Conclusions: Selective gamma probe-guided resection of the radiolabeled sentinel lymph node is possible in over 95% of patients with melanoma. This technique offers a simple and reliable method of staging of regional lymph nodes in these patients without performing a regional lymphadenectomy. C1 UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. FREE UNIV AMSTERDAM,DEPT SURG,AMSTERDAM,NETHERLANDS. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT SURG,WINSTON SALEM,NC 27103. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. RP KRAG, DN (reprint author), UNIV VERMONT,DEPT SURG,GIVEN BLDG,E309C,BURLINGTON,VT 05405, USA. NR 38 TC 349 Z9 352 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUN PY 1995 VL 130 IS 6 BP 654 EP 658 PG 5 WC Surgery SC Surgery GA RB457 UT WOS:A1995RB45700017 PM 7539252 ER PT J AU POLISSON, RP SCHOENBERG, OI FISCHMAN, A RUBIN, R SIMON, LS ROSENTHAL, D PALMER, WE AF POLISSON, RP SCHOENBERG, OI FISCHMAN, A RUBIN, R SIMON, LS ROSENTHAL, D PALMER, WE TI USE OF MAGNETIC-RESONANCE-IMAGING AND POSITRON EMISSION TOMOGRAPHY IN THE ASSESSMENT OF SYNOVIAL VOLUME AND GLUCOSE-METABOLISM IN PATIENTS WITH RHEUMATOID-ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Article ID DRUG-THERAPY AB Objective. To measure the anatomic and physiologic changes in the synovium of patients with active rheumatoid arthritis (RA) before and after the initiation of treatment with low-dose systemic glucocorticoids and methotrexate (MTX), Methods, Two patients with RA with active synovitis-involving the carpus we're evaluated by imaging parameters at baseline and again after 14 weeks (of treatment with low-dose prednisone and MTX), Standard clinical parameters, laboratory measurements, and contrast-enhanced magnetic resonance imaging (MRI) (synovial volume estimate) and positron emission tomography (PET) with F-18-fluoro-2-deoxyglucose (18-FDG) (synovial metabolism estimate) were performed, Results, Compared with baseline, standard clinical parameters (i,e,, joint count, joint index, morning stiffness, global assessments of arthritis activity, and erythrocyte sedimentation rate) improved dramatically in both patients after treatment with low-dose prednisone and MTX, In concert with this trend, the synovial volume of the affected wrist was reduced by 60%, and 76% and the metabolism of 18-FDG was reduced by 66% and 69% in the 2 patients, Conclusion, These preliminary observations indicate that a volumetric estimate of inflamed synovium (using contrast-enhanced MRI) and quantification of synovial deoxyglucose metabolism (using PET) are technically feasible and, in the 2 reported casts, correlate well with standard outcome measures; These imaging modalities may provide new objective parameters to determine RA disease activity and effectiveness of antirheumatic medications; however, the potential clinical utility of these measures remains to be defined. C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,BOSTON,MA. RP POLISSON, RP (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ARTHRIT UNIT,BULFINCH 165,BOSTON,MA 02114, USA. FU NCRR NIH HHS [RR-01066] NR 12 TC 88 Z9 88 U1 1 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1995 VL 38 IS 6 BP 819 EP 825 DI 10.1002/art.1780380616 PG 7 WC Rheumatology SC Rheumatology GA RC253 UT WOS:A1995RC25300014 PM 7779126 ER PT J AU BRANIGAN, PJ GERARD, HC SAAIBI, D HUDSON, AP SCHUMACHER, HR AF BRANIGAN, PJ GERARD, HC SAAIBI, D HUDSON, AP SCHUMACHER, HR TI SCREENING OF SYNOVIAL TISSUE VS FLUID FROM PATIENTS WITH REITERS-SYNDROME (RS), OTHER SPONDYLOARTHROPATHIES, OR REACTIVE ARTHRITIS (REA) FOR CHLAMYDIA VIA POLYMERASE CHAIN-REACTION (PCR) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,VET AFFAIRS MED CTR,SCH MED,PHILADELPHIA,PA 19104. MED COLL PENN,PHILADELPHIA,PA 19104. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1995 VL 38 IS 6 SU S BP R20 EP R20 PG 1 WC Rheumatology SC Rheumatology GA RD908 UT WOS:A1995RD90800062 ER PT J AU GERARD, HC BRANIGAN, PJ SCHUMACHER, HR HUDSON, AP AF GERARD, HC BRANIGAN, PJ SCHUMACHER, HR HUDSON, AP TI INAPPARENTLY INFECTING CHLAMYDIA-TRACHOMATIS IN THE SYNOVIA OF REITERS-SYNDROME (RS) REACTIVE ARTHRITIS (REA) PATIENTS ARE VIABLE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MED COLL PENN,VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1995 VL 38 IS 6 SU S BP R24 EP R24 PG 1 WC Rheumatology SC Rheumatology GA RD908 UT WOS:A1995RD90800077 ER PT J AU PARK, J GOWIN, K SCHUMACHER, HR AF PARK, J GOWIN, K SCHUMACHER, HR TI STEROID-SPARING EFFECT OF METHOTREXATE IN RELAPSING POLYCHONDRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA VA MED CTR,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1995 VL 38 IS 6 SU S BP R30 EP R30 PG 1 WC Rheumatology SC Rheumatology GA RD908 UT WOS:A1995RD90800112 ER PT J AU FOA, EB RIGGS, DS MASSIE, ED YARCZOWER, M AF FOA, EB RIGGS, DS MASSIE, ED YARCZOWER, M TI THE IMPACT OF FEAR ACTIVATION AND ANGER ON THE EFFICACY OF EXPOSURE TREATMENT FOR POSTTRAUMATIC-STRESS-DISORDER SO BEHAVIOR THERAPY LA English DT Article ID THERAPY; INFORMATION; BEHAVIOR; IMAGERY; VICTIMS AB This paper explores the hypothesis that fear activation during exposure treatment promotes improvement. Twelve female assault victims diagnosed with posttraumatic stress disorder (PTSD) received treatment that included prolonged repeated reliving of the assault in imagination. Two measures of fear activation were used: facial fear expression coded from videotapes of the first reliving session and the client's highest reported distress score during the same session. The results indicated that clients who evidenced more severe PTSD prior to treatment displayed more intense facial fear expressions during the first reliving of the assault and benefitted more from treatment than did clients who had less severe PTSD and displayed less fear. In contrast, clients who reported more anger prior to treatment tended to display less fear expression during reliving of the trauma and benefitted less from treatment than less angry clients. The relationship of pretreatment PTSD and anger severity to improvement seems to be mediated by fear facial expression and were not simply a product of regression toward the mean of extreme pretreatment scores. The results are discussed within an emotional processing theory of fear. C1 BRYN MAWR COLL,BRYN MAWR,PA 19010. BOSTON VA MED CTR,NATL CTR PTSD,BOSTON,MA. RP FOA, EB (reprint author), MED COLL PENN,EASTERN PENN PSYCHIAT INST,DEPT PSYCHIAT,3200 HENRY AVE,PHILADELPHIA,PA 19129, USA. NR 39 TC 220 Z9 222 U1 2 U2 18 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 1995 VL 26 IS 3 BP 487 EP 499 DI 10.1016/S0005-7894(05)80096-6 PG 13 WC Psychology, Clinical SC Psychology GA RV045 UT WOS:A1995RV04500007 ER PT J AU GOULD, RA CLUM, GA AF GOULD, RA CLUM, GA TI SELF-HELP PLUS MINIMAL THERAPIST CONTACT IN THE TREATMENT OF PANIC DISORDER - A REPLICATION AND EXTENSION SO BEHAVIOR THERAPY LA English DT Article ID AGORAPHOBIA AB A self-help (SH) treatment for panic disorder was compared to a wait-list (WL) control. The SH treatment consisted of reading the book Coping With Panic, watching a 15-minute videotape providing information regarding panic attacks and instruction in diaphragmatic breathing, and being provided with a relaxation tape that taught progressive muscle relaxation. Evidence strongly supported the effectiveness of SH relative to WL both at posttreatment and at 2-month follow-up. The results provide support for the possible treatment of panic disorder with SH methods. C1 VIRGINIA POLYTECH INST & STATE UNIV,BLACKSBURG,VA 24061. RP GOULD, RA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BEHAV THERAPY UNIT,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 21 TC 60 Z9 60 U1 3 U2 6 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 1995 VL 26 IS 3 BP 533 EP 546 DI 10.1016/S0005-7894(05)80099-1 PG 14 WC Psychology, Clinical SC Psychology GA RV045 UT WOS:A1995RV04500010 ER PT J AU LIPSITZ, SR FITZMAURICE, GM SLEEPER, L ZHAO, LP AF LIPSITZ, SR FITZMAURICE, GM SLEEPER, L ZHAO, LP TI ESTIMATION METHODS FOR THE JOINT DISTRIBUTION OF REPEATED BINARY OBSERVATIONS SO BIOMETRICS LA English DT Article DE BAHADUR REPRESENTATION; CORRELATED BINARY DATA; MARGINAL MODEL ID REGRESSION; MODEL AB The joint distribution of repeated binary observations is multinomial, and can be specified using a representation first suggested by Bahadur (1961, in Studies in Item Analysis and Prediction, 158-168. Stanford, California: Stanford University Press), and later by Cox (1972, Applied Statistics 21, 113-120). Using the Bahadur representation, the marginal probabilities of success can be related to a set of covariates using the logistic link function, or any other suitable link function. Besides the parameters of the marginal regression model, we may also have interest in the probability of success on any of the repeated measures. For example, in the Six Cities study, a longitudinal study of the health effects of air pollution, we have interest in both the marginal probability of a child wheezing at age t (t = 10, 11, 12), and the ''union'' probability of wheezing at any of the three ages. This ''union'' probability can be specified in terms of the joint probabilities between the repeated measures, which can be expressed as functions of the marginal probabilities and the second and higher-order correlations. We discuss several methods of estimating the parameters of the Bahadur model. C1 DANA FARBER CANC INST,DEPT BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. UNIV HAWAII,CANC RES CTR HAWAII,PROGRAM EPIDEMIOL,HONOLULU,HI 96813. RP LIPSITZ, SR (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIEHS NIH HHS [ES07142]; NIGMS NIH HHS [GM29745]; NIMH NIH HHS [MH17119] NR 12 TC 9 Z9 9 U1 0 U2 0 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 1995 VL 51 IS 2 BP 562 EP 570 DI 10.2307/2532944 PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA RJ816 UT WOS:A1995RJ81600017 PM 7662845 ER PT J AU BISCHOF, JC PADANILAM, J HOLMES, WH EZZELL, RM LEE, RC TOMPKINS, RG YARMUSH, ML TONER, M AF BISCHOF, JC PADANILAM, J HOLMES, WH EZZELL, RM LEE, RC TOMPKINS, RG YARMUSH, ML TONER, M TI DYNAMICS OF CELL-MEMBRANE PERMEABILITY CHANGES AT SUPRAPHYSIOLOGICAL TEMPERATURES SO BIOPHYSICAL JOURNAL LA English DT Article ID PROTEIN DENATURATION; HYPERTHERMIA; TRANSITIONS; PERMEATION; HEMOLYSIS; BILAYERS; HEAT AB A quantitative fluorescent microscopy system was developed to characterize, in real time, the effects of supraphysiological temperatures between 37 degrees and 70 degrees C on the plasma membrane of mouse 3T3 fibroblasts and isolated rat skeletal muscle cells. Membrane permeability was assessed by monitoring the leakage as a function of time of the fluorescent membrane integrity probe calcein. The kinetics of dye leakage increased with increasing temperature in both the 3T3 fibroblasts and the skeletal muscle cells. Analytical solutions derived from a two-compartment transport model showed that, for both cell types, a time-dependent permeability assumption provided a statistically better fit of the model predictions to the data than a constant permeability assumption. This finding suggests that the plasma membrane integrity is continuously being compromised while cells are subjected to supraphysiological temperatures. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,SHRINERS BURN INST,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. MIT,DEPT MECH ENGN,CAMBRIDGE,MA 02139. UNIV CHICAGO,DEPT SURG,CHICAGO,IL 60637. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ. NR 33 TC 65 Z9 65 U1 2 U2 29 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 1995 VL 68 IS 6 BP 2608 EP 2614 PG 7 WC Biophysics SC Biophysics GA RH660 UT WOS:A1995RH66000042 PM 7647264 ER PT J AU BALL, TC HIRAYAMA, F OGAWA, M AF BALL, TC HIRAYAMA, F OGAWA, M TI LYMPHOHEMATOPOIETIC PROGENITORS OF NORMAL MICE SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; DIFFERENTIATION; COLONIES; PROLIFERATION; ORIGIN AB We have identified and characterized the lymphohematopoietic progenitors in the bone marrow of normal mice using a single-step methylcellulose culture assay, Lineage-negative Ly-6A/E (Sca-1)(+) progenitors isolated from normal mice were plated in methylcellulose culture containing steel factor (SF), interleukin-7 (IL-7), erythropoietin (Ep), and IL-11, After 16 to 17 days of culture, pre-B-cell-containing multilineage myeloid colonies can be microscopically identified; however, flow-cytometric analysis of individual colonies for B220-positive cells proved superior to in situ microscopic identification of lymphomyeloid colonies, Approximately 10% (6/66) of the mixed colonies without a conspicuous B-cell component had B22O-positive cells, The single cell origin of the lymphomyeloid colonies was confirmed by micromanipulation, Although the combination of SF, IL-7, and Ep was sufficient to support formation of lymphomyeloid colonies, addition of IL-11, granulocyte colony-stimulating factor or IL-12 to the combination of SF, IL-7, and Ep increased the number of lymphomyeloid colonies, IL-1 alpha and IL-3 independently inhibited the expression of the B-lymphoid lineage when added to the combination of SF, IL-7, Ep, and IL-ll. Approximately four times more lymphohematopoietic progenitors are present in normal mice than in mice treated with 5-fluorouracil. (C) 1995 by The American Society of Hematology. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29401. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. FU NIDDK NIH HHS [DK32294] NR 12 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 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1995 VL 85 IS 11 BP 3086 EP 3092 PG 7 WC Hematology SC Hematology GA RA136 UT WOS:A1995RA13600010 PM 7756642 ER PT J AU ISHIMARU, F SHIPP, MA AF ISHIMARU, F SHIPP, MA TI ANALYSIS OF THE HUMAN CD10/NEUTRAL ENDOPEPTIDASE-24.11 PROMOTER REGION - 2 SEPARATE REGULATORY ELEMENTS SO BLOOD LA English DT Article ID BOMBESIN-LIKE PEPTIDES; THYMIDINE KINASE GENE; FACTOR RECEPTOR GENE; NEUTRAL ENDOPEPTIDASE; LEUKEMIA ANTIGEN; EPITHELIAL-CELLS; RETINOBLASTOMA GENE; MOLECULAR-CLONING; ETS ONCOGENE; FETAL LUNG AB The cell surface zinc metalloproteinase CD10/neutral endopeptidase 24.11 (NEP) is expressed on normal and malignant lymphoid progenitors, granulocytes, and a variety of epithelial cells. To further define the tissue-specific and developmentally related expression of CD10/NEP, we have characterized two separate regulatory regions that control the transcription of 5' alternatively spliced CD10/NEP transcripts. These type 1 and 2 CD10/NEP regulatory regions are both characterized by the presence of multiple transcription initiation sites and the absence of classic TATA boxes and consensus initiator elements. The purine-rich type 1 regulatory region, which includes 5' UTR exon 1 sequence, is characterized by multiple putative PU.1 binding sites and consensus ets-binding motifs. In marked contrast, the GC-rich type 2 regulatory region contains multiple putative Sp1 binding sites, a potential consensus retinoblastoma control element (RCE), and an inverted CCAAT box. In the majority of tissues examined to date, type 2 CD10/NEP transcripts were more abundant; the abundance of type 1 transcripts was more variable, with the highest type 1 levels in fetal thymus and certain lymphoblastic leukemia cell lines. (C) 1995 by The American Society of Hematology. C1 DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA55095] NR 57 TC 38 Z9 39 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 1995 VL 85 IS 11 BP 3199 EP 3207 PG 9 WC Hematology SC Hematology GA RA136 UT WOS:A1995RA13600024 PM 7756651 ER PT J AU HILDEBRANDT, N CAPLAN, D AF HILDEBRANDT, N CAPLAN, D TI THE WORD-SUPERIORITY IN ACQUIRED DYSLEXIA SO BRAIN AND COGNITION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD JUN PY 1995 VL 28 IS 1 BP 115 EP 115 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA RF548 UT WOS:A1995RF54800098 ER PT J AU TRAVERS, RL SOBER, AJ BERWICK, M MIHM, MC BARNHILL, RL DUNCAN, LM AF TRAVERS, RL SOBER, AJ BERWICK, M MIHM, MC BARNHILL, RL DUNCAN, LM TI INCREASED THICKNESS OF PREGNANCY-ASSOCIATED MELANOMA SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; PROGESTERONE RECEPTORS; DEPENDENT TUMOR; SURVIVAL; ESTROGEN; TAMOXIFEN; SEX; HORMONES AB The effects of pregnancy on the pathophysiology of melanoma remain unclear, Although a gender-specific advantage for women vs. men is seen for characteristics such as stage at presentation, site of primary tumour, and survival time, an adverse effect of pregnancy on melanoma development and progression has been reported. In a retrospective study, we investigated the tumour characteristics of women who developed pregnancy-associated melanoma, and compared them with melanomas arising in non-pregnant women of child-bearing age. The patient records of the Massachusetts General Hospital Pigmented Lesion Clinic were reviewed, and 465 women of reproductive age (16-45 years) who developed melanoma were identified. Of these, in 45 women (age 21-42 years) there was a close temporal relationship between diagnosis of the tumour and pregnancy. Clinical and histological characteristics of the primary tumours were recorded. Differences in tumour thickness, site and histological type were analysed. The mean thickness of pregnancy-associated melanomas was significantly greater than that of non-pregnancy-associated tumours (2.28 vs, 1.22 mm, respectively; P < 0.007). No differences in histological type (P = 0.64) or site (P = 0.74) of the primary tumours were found between the two patient groups. Not surprisingly, multivariate analysis revealed that tumour thickness was a statistically significant variable in determining prognosis (P = 0.001). An unexpected finding, on multivariate analysis, was a possible pregnancy-associated prognostic advantage (P = 0.08). Melanomas arising during pregnancy are thicker, but are not necessarily associated with a less favourable prognosis than tumours arising in non-pregnant women of child-bearing age. The mechanisms by which pregnancy may lead to increased thickness of melanoma have yet to be elucidated, and merit further study. C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. RP TRAVERS, RL (reprint author), MASSACHUSETTS GEN HOSP,DERMATOPATHOL UNIT,WARREN 827,BOSTON,MA 02114, USA. RI Berwick, Marianne/E-9608-2010; Duncan, Lyn/E-9878-2013; OI Berwick, Marianne/0000-0001-5062-2180 NR 45 TC 59 Z9 60 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JUN PY 1995 VL 132 IS 6 BP 876 EP 883 PG 8 WC Dermatology SC Dermatology GA RC522 UT WOS:A1995RC52200004 PM 7662565 ER PT J AU GRELLIER, P YEE, D GONZALEZ, M ABBOUD, SL AF GRELLIER, P YEE, D GONZALEZ, M ABBOUD, SL TI CHARACTERIZATION OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS (IGFBP) AND REGULATION OF IGFBP-4 IN BONE-MARROW STROMAL CELLS SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE INSULIN-LIKE GROWTH FACTOR; BINDING PROTEIN; BONE MARROW; STROMAL CELLS; HEMATOPOIESIS ID MESSENGER-RIBONUCLEIC-ACID; OSTEOBLAST-LIKE CELLS; BREAST-CANCER CELLS; FACTOR-I; HUMAN FIBROBLASTS; RAT; EXPRESSION; LINE; GENE; POTENTIATION AB Bone marrow stromal cells synthesize and secrete insulin-like growth factor (IGF)-I and IGF-binding proteins (IGFBP). IGFBPs may modulate the action of IGF-I or IGF-II on haemopoiesis. However, the specific IGFBPs produced by various stromal cell types have not been identified. We examined six different stromal phenotypes for IGFBP protein and IGFBP-1 to -6 mRNA expression. [I-125]IGF-I ligand blot analysis of conditioned medium demonstrate different patterns of IGFBP secretion by each cell type. The most prominent IGFBPs were 24 and 29 kD species, consistent with IGFBP4 and IGFBP5, respectively, RNase protection assays demonstrate that, overall, stromal cells express IGFBP-2 to -6 mRNAs, with IGFBP4, IGFBP5 and IGFBP6 mRNAs predominating, Since agents that modulate cAMP levels may influence haemopoiesis via the release of stromal-derived cytokines, we determined the effect of forskolin, a cAMP agonist, on IGFBP4 expression in TC-1 cells, Forskolin (10(-5) M) up-regulated IGFBP4 mRNA and protein secretion in a time-dependent manner, These findings suggest that IGFBP-4, -5 and -6 released by stromal cells may be key modulators of the haemopoietic response to IGFs. Release of IGFBP4 by agents that increase cAMP may be an important mechanism involved in regulating IGF bioavailability in the marrow microenvironment. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT ONCOL,SAN ANTONIO,TX. 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 [P30-CA54174, CA52952]; NIAMS NIH HHS [AR42306] NR 36 TC 22 Z9 23 U1 0 U2 1 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 1995 VL 90 IS 2 BP 249 EP 257 DI 10.1111/j.1365-2141.1995.tb05144.x PG 9 WC Hematology SC Hematology GA RB868 UT WOS:A1995RB86800003 PM 7540852 ER PT J AU REMULLA, JFC GAUDIO, AR MILLER, S SANDBERG, MA AF REMULLA, JFC GAUDIO, AR MILLER, S SANDBERG, MA TI FOVEAL ELECTRORETINOGRAMS AND CHOROIDAL PERFUSION CHARACTERISTICS IN FELLOW EYES OF PATIENTS WITH UNILATERAL NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID BRUCH MEMBRANE CHANGE; ABNORMALITY; EVOLUTION; ERG AB Aims/Background-A prolonged choroidal filling phase on fluorescein angiography has been reported to be a common finding and associated with visual function abnormalities in patients with age-related macular degeneration (AMD). This investigation was carried out to determine whether this perfusion defect was related to the slowing of foveal cone electroretinogram (ERG) implicit time seen in patients with AMD. Methods-Fluorescein angiograms and foveal cone ERGs were evaluated in the fellow eyes of 67 patients with unilateral neovascular AMD. Results-Twenty eight (42%) of the eyes had a choroidal perfusion defect. ERG implicit times averaged 1 ms slower (p=0.0167) and were more likely to be delayed (p=0.0078) in eyes with abnormal choroidal perfusion than in eyes with normal choroidal filling; significant relations were found also after controlling for age. ERG implicit time was also inversely related to ETDRS visual acuity and positively related to the extent of macular drusen; and the latter showed a borderline significant tendency to be more prevalent in eyes with prolonged choroidal perfusion. However, an association of a delayed ERG implicit time with prolonged choroidal filling remained after controlling for age, acuity, and the extent of drusen. Conclusion-These findings further establish prolonged choroidal perfusion as a common finding in AMD and link it to retinal malfunction. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. FU NEI NIH HHS [EY08398] NR 15 TC 53 Z9 56 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUN PY 1995 VL 79 IS 6 BP 558 EP 561 DI 10.1136/bjo.79.6.558 PG 4 WC Ophthalmology SC Ophthalmology GA RB148 UT WOS:A1995RB14800012 PM 7542915 ER PT J AU Holden, SA Teicher, BA Robinson, MF Northey, D Rosowsky, A AF Holden, SA Teicher, BA Robinson, MF Northey, D Rosowsky, A TI Antifolates can potentiate topoisomerase II inhibitors in vitro and in vivo SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE antifolates; topoisomerase II inhibitors; etoposide; PT523; combination therapy; cytotoxicity ID DNA STRAND BREAKS; CHINESE HAMSTER-CELLS; LEUKEMIA-CELLS; FRACTIONATED-IRRADIATION; NOVOBIOCIN INHIBITION; METHOTREXATE ANALOGS; ANTICANCER DRUGS; CROSS-LINKING; REPLICATION; APOPTOSIS AB Antifolates have been shown to increase the DNA strand breaks produced by the topoisomerase inhibitor etoposide. PT523 is a potent new antifolate that cannot be polyglutamated. Human SCC-25 squamous carcinoma cells were exposed to methotrexate, trimetrexate or PT523 at a concentration of 5 mu M for 24 h along with various concentrations of etoposide or novobiocin during the final 2 h. Isobologram analysis of the treatment combinations indicated that exposure of the cells to PT523/etoposide, methotrexate/etoposide, PT523/novobiocin, methotrexate/novobiocin and trimetrexate/novobiocin resulted in greater than additive cytotoxicity. DNA alkaline elution studies with the same drug combinations indicated that there were three- to four-fold increases in the radiation equivalent (rad equivalent) strand breaks in the cellular DNA with etoposide or novobiocin along with the antifolate compared with the topoisomerase II inhibitors alone. Tumor growth delay studies were carried out in the murine SCC VII squamous carcinoma. PT523 (0.5 mg/kg) and methotrexate (2 mg/kg) were administered by 7-day continuous infusion while trimetrexate (3.75 mg/kg) was administered intraperitoneally daily on days 7-9. Etoposide (10 mg/kg) and novobiocin (100 mg/kg) were administered intraperitoneally on alternate days (7, 9, 11). The combinations of PT523 with etoposide or novobiocin were significantly more effective than methotrexate and etoposide or novobiocin, producing tumor growth delays of 8.4 days and 6.9 days, respectively. Overall, the antifolate/topoisomerase II inhibitor treatment combinations produced tumor growth delays that were apparently additive to greater than additive. C1 DANA FARBER CANC INST, BOSTON, MA 02115 USA. FU NCI NIH HHS [R01CA25394, P01-CA19589] NR 70 TC 17 Z9 18 U1 0 U2 0 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 1995 VL 36 IS 2 BP 165 EP 171 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA QY585 UT WOS:A1995QY58500013 PM 7767954 ER PT J AU NAGAI, H SPIELMAN, AI DASSO, M HUQUE, T BRAND, JG AF NAGAI, H SPIELMAN, AI DASSO, M HUQUE, T BRAND, JG TI RAPID KINETICS OF 2ND MESSENGER PRODUCTION IN BITTER TASTE SO CHEMICAL SENSES LA English DT Meeting Abstract C1 SUNTORY LTD,SUNTORY RES CTR,INST FUNDAMENTAL RES,SHIMAMOTO,OSAKA 618,JAPAN. MONELL CHEM SENSES CTR,PHILADELPHIA,PA 19104. NYU,COLL DENT,NEW YORK,NY. UNIV PENN,VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD JUN PY 1995 VL 20 IS 3 BP 358 EP 358 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA RE979 UT WOS:A1995RE97900032 ER PT J AU ROSENZWEIG, AC NORDLUND, P TAKAHARA, PM FREDERICK, CA LIPPARD, SJ AF ROSENZWEIG, AC NORDLUND, P TAKAHARA, PM FREDERICK, CA LIPPARD, SJ TI GEOMETRY OF THE SOLUBLE METHANE MONOOXYGENASE CATALYTIC DIIRON CENTER IN 2 OXIDATION-STATES SO CHEMISTRY & BIOLOGY LA English DT Article DE CARBOXYLATE SHIFT; DINUCLEAR IRON CENTER; METHANE OXIDATION; METHYLOCOCCUS CAPSULATUS (BATH); X-RAY CRYSTALLOGRAPHY ID RIBONUCLEOTIDE REDUCTASE; HYDROXYLASE COMPONENT; CRYSTAL-STRUCTURE; PROTEIN; IDENTIFICATION; SUBSTRATE; COMPLEX; CYCLE; SITES AB Background: The hydroxylase component of soluble methane monooxygenase (sMMO) contains a dinuclear iron center responsible for the oxidation of methane to methanol. As isolated, the center is in the oxidized, diiron(III) state. The 2.2 Angstrom resolution X-ray structure of the oxidized hydroxylase, H-OX, from Methylococcus capsulatus (Bath) was previously determined at 4 degrees C. In this structure the two iron atoms are bridged by a glutamate, a hydroxide ion, and an acetate ion, and additionally coordinated to two His residues, three Glu residues, and a water molecule. Results: The 1.7 Angstrom resolution crystal structures of the sMMO hydroxylase from Methylococcus capsulatus (Bath) in both its oxidized diiron(III), H-OX, and dithionite-treated, reduced diiron(II), H-red, oxidation states were determined at -160 degrees C. The structure of the diiron center in H-OX differs from that previously reported at 2.2 Angstrom resolution and 4 degrees C. Although the hydroxide bridge is retained, the bidentate, bridging ligand assigned as acetate is replaced by a weakly coordinating monoatomic water bridge. In the resulting four-membered Fe(OH)Fe(OH2) ring, the Fe ... Fe distance is shortened from 3.4 Angstrom to 3.1 Angstrom. In protomer A of H-red, the hydroxide bridge is displaced by an oxygen atom of Glu243, which undergoes a carboxylate shift from its terminal monodentate binding mode in H-OX to a mode in which the carboxylate is both monoatomic bridging and bidentate chelating. We therefore conclude that the center has been reduced to the diiron(II) oxidation state. Both iron atoms are coordinated to five ligands and weakly to a sixth water molecule in the resulting structure. The diiron center in protomer B of H-red has the same composition as those in H-OX. In both the oxidized and reduced structures, the diiron core is connected through hydrogen bonds involving exogenous species to Thr213 in the active site cavity. Conclusions: The diiron center in H-OX can change its exogenous ligand coordination and geometry, a property that could be important in the catalytic cycle of sMMO. In H-red, a carboxylate shift occurs, extruding hydroxide ion and opening coordination sites for reaction with O-2 to form the diiron(III) peroxo intermediate, H-peroxo. Residue Thr213 may function in catalysis. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. UNIV STOCKHOLM,DEPT BIOL MOLEC,S-10691 STOCKHOLM,SWEDEN. RP ROSENZWEIG, AC (reprint author), MIT,DEPT CHEM,CAMBRIDGE,MA 02139, USA. NR 38 TC 346 Z9 347 U1 1 U2 22 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JUN PY 1995 VL 2 IS 6 BP 409 EP 418 DI 10.1016/1074-5521(95)90222-8 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RH722 UT WOS:A1995RH72200009 PM 9383443 ER PT J AU MAREL, M STASTNY, B MELINOVA, L SVANDOVA, E LIGHT, RW AF MAREL, M STASTNY, B MELINOVA, L SVANDOVA, E LIGHT, RW TI DIAGNOSIS OF PLEURAL EFFUSIONS - EXPERIENCE WITH CLINICAL-STUDIES, 1986 TO 1990 SO CHEST LA English DT Article DE CEA; PLEURAL EFFUSION; PLEURAL FLUID; PLEURAL MALIGNANCY ID THORACOSCOPY AB Objectives: To identify in patients with pleural effusion which procedures are most useful in separating malignant from nonmalignant pleural effusions and to identify which procedures most commonly lead to a definitive diagnosis. Design: Prospective consecutive case series. Setting: Pulmonary referral hospital in Prague, Czech Republic. Patients: One hundred seventy-one adults between ages 18 and 70 years with a pleural effusion and a Karnofsky score of 70 or above. Interventions: All patients underwent history, physical, pleural fluid cytologic study, laboratory evaluation of serum and pleural fluid, pleural biopsy, bronchoscopy, and lung scan and/or pulmonary arteriogram. Results: In this series in which 45% of the patients had malignant effusions, 19% had paramalignant effusions, and 36% had benign diseases, the pleural fluid cytologic study was the best for establishing a diagnosis. The pleural fluid carcinoembryonic antigen (CEA) levels above 10 had a high specificity (90%) for malignancy but had low sensitivity (37%). The pleural fluid CEA level was increased only in 19% of patients with paramalignant effusions. Although there were statistically significant differences in the mean results on several biochemical tests of pleural fluid, none were very accurate in separating malignant from benign disease. Conclusion: From this study, we conclude that patients with an undiagnosed pleural effusion should be evaluated in an individualized stepwise manner. If malignancy is strongly considered, the initial three steps should be relatively noninvasive and include clinical evaluation and cytologic study. C1 CHARLES UNIV,PNEUMOL CLIN,PRAGUE,CZECH REPUBLIC. US DEPT VET AFFAIRS,PULM SECT,LONG BEACH,CA. NR 14 TC 75 Z9 79 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1995 VL 107 IS 6 BP 1598 EP 1603 DI 10.1378/chest.107.6.1598 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RD451 UT WOS:A1995RD45100024 PM 7781353 ER PT J AU DEMETRI, GD AF DEMETRI, GD TI HEMATOPOIETIC GROWTH-FACTORS - DEFINING THE APPROPRIATE CLINICAL ROLE IN MULTIMODALITY CANCER-THERAPY SO CHEST LA English DT Article; Proceedings Paper CT Harvard-Medical-School Symposium on Multimodality Therapy of Chest Malignancies-Update 94 CY APR 07-09, 1994 CL BOSTON, MA SP Harvard Med Sch, Dana Farber Canc Inst, Dept Oncol, Brigham & Womens Hosp, Div Thorac Surg ID COLONY-STIMULATING FACTOR; DRUG-THERAPY; GRANULOCYTE; CHEMOTHERAPY; NEUTROPENIA AB Laboratory investigations have begun to elucidate the regulatory molecules that control the processes of blood cell growth and differentiation. Recombinant human colony-stimulating factors are examples of biotechnology-produced molecules that have epitomized the translation of such basic scientific investigation into therapeutic advances. Small cell lung cancer, a malignancy that is overall highly sensitive to aggressive myelosuppressive chemotherapy at initial presentation, has been used as a clinical model in which the activity of human colony-stimulating factors has been tested. In this article, the clinical applications of hematopoietic growth factors are reviewed in brief. The appropriate clinical use of these agents may allow novel therapeutic strategies to be developed in a research setting. Similarly, these agents have the potential to improve supportive care and improve certain clinical outcomes in the non-research clinical care of patients. Issues of cost of treatment are raised by these agents, but the true clinical value of hematopoietic growth factors needs to be studied more rigorously, with emphasis on quality of life and redistribution of care costs outside of hospitals before definitive statements can be made. C1 DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP DEMETRI, GD (reprint author), DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115, USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1995 VL 107 IS 6 SU S BP S255 EP S260 DI 10.1378/chest.107.6_Supplement.255S PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RE291 UT WOS:A1995RE29100009 PM 7540124 ER PT J AU ELIAS, AD AF ELIAS, AD TI DOSE-INTENSIVE THERAPY FOR SMALL-CELL LUNG-CANCER SO CHEST LA English DT Article; Proceedings Paper CT Harvard-Medical-School Symposium on Multimodality Therapy of Chest Malignancies-Update 94 CY APR 07-09, 1994 CL BOSTON, MA SP Harvard Med Sch, Dana Farber Canc Inst, Dept Oncol, Brigham & Womens Hosp, Div Thorac Surg ID BONE-MARROW TRANSPLANTATION; PHASE-III TRIAL; BRONCHOGENIC-CARCINOMA; CHEMOTHERAPY; CYCLOPHOSPHAMIDE; DOXORUBICIN; VINCRISTINE AB Enhancement of dose and dose intensity increases tumor response and may enhance long-term progression-free survival in patients with small cell lung cancer. Several strategies are identified to intensify therapy safely: a traditional induction/intensification mode, in which high-dose therapy with hematopoietic stem cell support is used to treat patients responding to conventional-dose therapy; and multicycle dose-intensive approaches, in which higher-dose therapy is administered over multiple cycles at initiation of therapy. This paper reviews some of the recently completed and activated trials (particularly those developed at the Dana-Farber Cancer Institute) exploring these concepts. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP ELIAS, AD (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 25 TC 9 Z9 9 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1995 VL 107 IS 6 SU S BP S261 EP S266 DI 10.1378/chest.107.6_Supplement.261S PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RE291 UT WOS:A1995RE29100010 PM 7781403 ER PT J AU MENTZER, SJ DECAMP, MM HARPOLE, DH SUGARBAKER, DJ AF MENTZER, SJ DECAMP, MM HARPOLE, DH SUGARBAKER, DJ TI THORACOSCOPY AND VIDEO-ASSISTED THORACIC-SURGERY IN THE TREATMENT OF LUNG-CANCER SO CHEST LA English DT Article; Proceedings Paper CT Harvard-Medical-School Symposium on Multimodality Therapy of Chest Malignancies-Update 94 CY APR 07-09, 1994 CL BOSTON, MA SP Harvard Med Sch, Dana Farber Canc Inst, Dept Oncol, Brigham & Womens Hosp, Div Thorac Surg ID MEDIASTINOSCOPY AB The contemporary surgical repertoire for the evaluation and treatment of patients with lung cancer includes the bronchoscope, mediastinoscope, thoracoscope, and standard surgical instrumentation. The recent advances in video optics and the development of endoscopic instruments have significantly expanded the surgical options for patients with lung cancer. Thoracoscopy, or the more inclusive term of video-assisted thoracic surgery (VATS), has been characterized as ''minimally invasive'' surgery. Thoracoscopy and VATS have decreased operative trauma and facilitated surgical staging prior to neoadjuvant therapy. Bn ancillary benefit to diminished surgical morbidity. is shorter hospital stays with a concomitant reduction in costs to the patient and health-care system. These advantages make VATS ideal for elderly patients or patients with significant comorbidity. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP MENTZER, SJ (reprint author), BRIGHAM & WOMENS HOSP,DIV THORAC SURG,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL47078] NR 12 TC 9 Z9 9 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1995 VL 107 IS 6 SU S BP S298 EP S301 DI 10.1378/chest.107.6_Supplement.298S PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RE291 UT WOS:A1995RE29100017 PM 7781410 ER PT J AU STRAUSS, GM GLEASON, RE SUGARBAKER, DJ AF STRAUSS, GM GLEASON, RE SUGARBAKER, DJ TI CHEST-X-RAY SCREENING IMPROVES OUTCOME IN LUNG-CANCER - A REAPPRAISAL OF RANDOMIZED TRIALS ON LUNG-CANCER SCREENING SO CHEST LA English DT Article; Proceedings Paper CT Harvard-Medical-School Symposium on Multimodality Therapy of Chest Malignancies-Update 94 CY APR 07-09, 1994 CL BOSTON, MA SP Harvard Med Sch, Dana Farber Canc Inst, Dept Oncol, Brigham & Womens Hosp, Div Thorac Surg ID FOLLOW-UP; STATISTICS; RISK; MORTALITY; SMOKING; PROGRAM; EPIDEMIOLOGY; SURVIVAL; PROSTATE; RATES AB It is believed that population-based screening for cancer should be advocated only when screening reduces disease-specific mortality. Four randomized controlled studies on lung cancer screening have been conducted in male cigarette smokers, and none has demonstrated reduced mortality. Accordingly, no organization that formulates screening policy advocates any specific early detection strategies for lung cancer. Yet, despite this public policy against screening, there is considerable evidence that chest x-ray screening is associated with earlier detection and improved survival. Two randomized trials, the Memorial Sloan-Kettering and Johns Hopkins Lung Projects, were specifically designed to evaluate the effectiveness of sputum cytologic study. Both evaluated the efficacy of the addition of sputum cytologic studies to annual chest radiographs, and both demonstrated that cytologic study did not favorably influence outcome. All individuals in experimental and control groups in both studies had annual chest radiographs. Because survival rates observed in both studies were about three times higher than predicted, based either on the National Cancer Institute's Surveillance Epidemiology and End Results database or based on the American Cancer Society's annual Cancer Statistics, raises the possibility that the periodic chest radiographs performed in all patients in both studies contributed to an improved outcome. In the Mayo Lung Project and in the Czechoslovak study on lung cancer screening, the experimental groups underwent a program of relatively intensive and regular rescreening with chest radiographs and sputum cytologic study, while the control groups underwent either less-frequent rescreening or no rescreening. In both studies, the screened groups achieved meaningful improvements in stage distribution, resectability, and survival. However, increases in cumulative incidence of lung cancer in the experimental group in both studies (which in the Mayo Lung Project reached statistical significance) prevented significant improvements in survival from translating into corresponding reductions in mortality. The possibility that screening may be associated with lung cancer ''overdiagnosis'' has been widely postulated to account for higher survival and incidence rates and equivalent mortality rates. However, analysis of autopsy information and of disease outcome in individuals with screen-detected early stage lung cancer who do not undergo surgical resection strongly supports the conclusion that screening does not lead to overdiagnosis of lung cancer. Similarly, lead-time and length bias do not adequately account for the differences in cumulative incidence observed in the Mayo and Czech studies. Because chest radiographs lead to meaningful improvements in stage distribution, resectability, and survival in lung cancer, and because neither overdiagnosis bias nor lead-time bias accounts for these improvements in outcome, a reconsideration of the role of chest radiographs in the early detection of lung cancer would be appropriate. A consensus conference would be a suitable forum to reexamine fully the existing data on lung cancer screening and to formulate specific guidelines for early detection strategies in individuals at high risk for lung cancer. C1 BRIGHAM & WOMENS HOSP,CLIN RES CTR,DEPT MED,DIV HEMATOL ONCOL,ENDOCRINOL & HYPERTENS UNIT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV THORAC SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP STRAUSS, GM (reprint author), DANA FARBER CANC INST,DIV MED ONCOL,D1550A,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCRR NIH HHS [5M01RR02635] NR 58 TC 49 Z9 50 U1 1 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1995 VL 107 IS 6 SU S BP S270 EP S279 DI 10.1378/chest.107.6_Supplement.270S PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RE291 UT WOS:A1995RE29100012 PM 7781405 ER PT J AU Wong, JR Ho, C Mauch, P Coleman, N Berman, S Chen, LB AF Wong, JR Ho, C Mauch, P Coleman, N Berman, S Chen, LB TI Removal of carcinoma cells from contaminated bone marrow using the lipophilic cation rhodamine 123 SO CLINICAL CANCER RESEARCH LA English DT Article ID HEMATOPOIETIC STEM-CELLS; HIGH-DOSE CHEMOTHERAPY; LUNG-CANCER CELLS; NON-HODGKINS LYMPHOMA; COLONY-FORMING CELLS; PHASE-I TRIAL; MONOCLONAL-ANTIBODY; BREAST-CANCER; CONSOLIDATION THERAPY; PROGENITOR CELLS AB Autologous bone marrow transplants for solid tumor treatment are severely limited by the potential presence of residual cancer cells in the reinfused bone marrow and can lead to future tumor recurrence. This article presents a novel method of removing carcinoma cells from bone marrow with contaminating cancer cells, This method is based on our previous studies demonstrating that carcinoma cells have a higher uptake of lipophilic cations such as rhodamine 123 than their normal epithelial counterparts, When the relative differences in rhodamine 123 uptake are quantified, carcinoma cell lines demonstrated a 7.4-21 times greater uptake of rhodamine 123 than normal mouse bone marrow cells, More important, when normal bone marrow cells and carcinoma cell lines are mixed to simulate carcinoma-contaminated bone marrow, individual cell populations continue to exhibit characteristic and identifiable relative differences (10-20 times) in rhodamine 123 uptake, Differential sorting of bone marrow/carcinoma cell mixtures with respect to rhodamine 123 fluorescence intensity resulted in the removal of 95-99% of the ''contaminating carcinoma cells.'' The recovered bone marrow cells were fully viable as ascertained by their ability to form splenic colonies. In our preliminary experiments, sorted bone marrow cells transplanted into lethally irradiated C57BL6 mice allowed the mice to survive for more than 8 months, Tn light of these promising results, we propose that lipophilic cations may play a role in the purification of autologous bone marrow used in transplants for patients with advanced solid tumors. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. CORNELL UNIV,COLL MED,NEW YORK HOSP,DEPT RADIOL,STICH RADIAT CTR,NEW YORK,NY 10021. FU NIGMS NIH HHS [GM38318] NR 58 TC 3 Z9 3 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1995 VL 1 IS 6 BP 621 EP 630 PG 10 WC Oncology SC Oncology GA TL081 UT WOS:A1995TL08100007 PM 9816024 ER PT J AU GUDRAIS, P HANBURY, CM AF GUDRAIS, P HANBURY, CM TI EVALUATION OF CA-125 ON THE FULLY-AUTOMATED TOSOH AIA-1200 SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. 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 1995 VL 41 IS 6 SU S BP S72 EP S72 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400173 ER PT J AU KHOURY, RH SMITH, PC TOTH, T TAYLOR, AE AF KHOURY, RH SMITH, PC TOTH, T TAYLOR, AE TI FUNCTIONAL ASSAY IS BETTER THAN IMMUNOASSAY OF DAY-3 SERUM FSH AS AN INDICATOR OF IVF PREGNANCY OUTCOME SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 1995 VL 41 IS 6 SU S BP S40 EP S40 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400030 ER PT J AU KHOURY, RH WANG, QF TOTH, T LEYKIN, L SCHNEYER, AL SLUSS, PM AF KHOURY, RH WANG, QF TOTH, T LEYKIN, L SCHNEYER, AL SLUSS, PM TI PROGESTERONE AND FOLLISTATIN LEVELS IN FOLLICULAR-FLUID CORRELATE WITH FERTILIZATION AND PREGNANCY OUTCOMES IN IVF PATIENTS SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 1995 VL 41 IS 6 SU S BP S39 EP S39 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RD904 UT WOS:A1995RD90400029 ER PT J AU TOH, CL JUPITER, JB AF TOH, CL JUPITER, JB TI THE INFECTED NONUNION OF THE TIBIA SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID LOWER-EXTREMITY; CHRONIC OSTEOMYELITIS; FREE-TISSUE; BONE; MANAGEMENT; TRANSFERS; DEFECTS; WOUNDS; GRAFT AB Ununited fracture of the tibia complicated by infection is not only a complex surgical problem but also a chronic and at times debilitating condition. The principle methods used to diagnose and stage posttraumatic tibial osteomyelitis are described. Infected nonunions of the tibia are characterized by the extent of bony loss and the presence of a functional ipsilateral fibula. Using this tibial staging criteria, a series of 37 infected nonunions of the tibia are reviewed. Twenty patients were male and 16 were female, with an average age of 33 years. The distal third of the tibia was involved in 19 patients, the middle third in 11, and proximal third in 7. Twenty three of the tibia were infected with >1 organism. Thirty were Type 3 (tibial defect of 6 cm or less with a long and usable fibula), 4 Type 4 (tibial defect >6 cm with usable fibula), and 3 Type 5 (tibial defect >6 cm without usable fibula). The patients were evaluated at an average of 61 months after treatment. Union and eradication of infection were achieved in 35 of 37 patients. The results of the Health Impact Analysis suggest that the infected nonunion of the tibia represented a chronic and debilitating disorder with a lasting impact. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED TRAUMA SERV,BOSTON,MA 02114. NR 39 TC 31 Z9 32 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUN PY 1995 IS 315 BP 176 EP 191 PG 16 WC Orthopedics; Surgery SC Orthopedics; Surgery GA RC035 UT WOS:A1995RC03500019 PM 7634666 ER PT J AU COSIMI, AB AF COSIMI, AB TI CURRENT AND FUTURE APPLICATION OF MONOCLONAL-ANTIBODIES IN CLINICAL IMMUNOSUPPRESSIVE PROTOCOLS SO CLINICAL TRANSPLANTATION LA English DT Article DE MONOCLONAL ANTIBODIES; IMMUNE SUPPRESSION RP COSIMI, AB (reprint author), MASSACHUSETTS GEN HOSP,GEN SURG SERV,TRANSPLANTAT UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-18646] NR 0 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 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD JUN PY 1995 VL 9 IS 3 BP 219 EP 226 PN 2 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA RD860 UT WOS:A1995RD86000003 PM 7670167 ER PT J AU TOLKOFFRUBIN, NE RUBIN, H AF TOLKOFFRUBIN, NE RUBIN, H TI NEW STRATEGIES FOR THE CONTROL OF VIRAL-INFECTION IN ORGAN-TRANSPLANTATION SO CLINICAL TRANSPLANTATION LA English DT Article DE ORGAN; TRANSPLANT; INFECTION AB Control of viral infection in organ transplant recipients requires attention to the following interventions: prevention, whenever possible of viral acquisition; the proper deployment of active and passive immunization, with hyperimmune globulin preparations directed against cytomegalovirus, hepatitis B, varicella, and, perhaps, respiratory syncytial virus, offering significant benefit when used appropriately; and the prescription of antiviral agents at critical points in the post-transplant course. Two important principles should be kept in mind when approaching this problem: prevention is the goal, as treatment of established infection is fraught with difficulty; and effective preventative strategies must be linked to the intensity of the immunosuppressive program being employed. To achieve these goals, the addition of pre-emptive therapy (therapy geared to a laboratory marker of impending disease or to escalation in the immunosuppressive program) to standard prophylactic regimens represents a significant advance. C1 MASSACHUSETTS GEN HOSP,DIALYSIS UNIT,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD JUN PY 1995 VL 9 IS 3 BP 255 EP 259 PN 2 PG 5 WC Surgery; Transplantation SC Surgery; Transplantation GA RD860 UT WOS:A1995RD86000008 PM 7670172 ER PT J AU SOLENSKI, NJ HALEY, EC KASSELL, NF KONGABLE, G GERMANSON, T TRUSKOWSKI, L TORNER, JC AF SOLENSKI, NJ HALEY, EC KASSELL, NF KONGABLE, G GERMANSON, T TRUSKOWSKI, L TORNER, JC TI MEDICAL COMPLICATIONS OF ANEURYSMAL SUBARACHNOID HEMORRHAGE - A REPORT OF THE MULTICENTER, COOPERATIVE ANEURYSM STUDY SO CRITICAL CARE MEDICINE LA English DT Article DE SUBARACHNOID HEMORRHAGE; CEREBRAL ANEURYSM; CEREBRAL ISCHEMIA; TRANSIENT; ARRHYTHMIA; PULMONARY EDEMA; LIVER DISEASE; KIDNEY DISEASE; THROMBOCYTOPENIA; CRITICAL CARE ID RUPTURED INTRACRANIAL ANEURYSMS; CARDIAC-ARRHYTHMIAS; SURGERY; HYPONATREMIA AB Objectives: This report examines the frequency, type, and prognostic factors of medical (nonneurologic) complications after subarachnoid hemorrhage in a large, prospective study. The influences of contemporary neurosurgical, neurological, and critical care practice on mortality and morbidity rates after aneurysmal subarachnoid hemorrhage are evaluated. Design: A study of medical complications observed in the placebo limb of a large, randomized, controlled trial of the calcium antagonist, nicardipine, after subarachnoid hemorrhage. Setting: Patients were recruited from 50 hospitals in 41 neurosurgical centers in the United States and Canada. Patients: A total of 451 patients with subarachnoid hemorrhage, greater than or equal to 18 yrs of age, were randomly assigned to the placebo group. All patients arrived at the participating center within 7 days (mean 1.0 +/- 1.8 [SD] days) of rupture of an angiographically documented saccular aneurysm. Measurements and Main Results: The frequency rates of symptomatic vasospasm, rebleeding, and total mortality rate after subarachnoid hemorrhage at 3-month follow-up were 46%, 7%, and 19%, respectively. The frequency of having at least one severe (life-threatening) medical complication was 40%. The proportion of deaths from medical complications was 23%. This value was comparable with the proportion of deaths attributed to the direct effects of the initial hemorrhage (19%), rebleeding (22%), and vasospasm (23%) after aneurysmal rupture. The frequency of life-threatening cardiac arrhythmias was 5%; less ominous rhythm disturbances occurred in 30% of the patients. There was an increased frequency of cardiac arrhythmias on the day of, or day after, aneurysm surgery. Pulmonary edema occurred in 23% of the patients, with a 6% occurrence rate incidence of severe pulmonary edema. There was a wide variation from center to center, with the greatest frequency on days 3 through 7. There was a nonsignificant association of pulmonary edema with the use of hypertensive hypervolemic therapy (p = .10), and a significant association with the timing of surgery (p < .05). Some degree of hepatic dysfunction was noted in 24% of patients, the majority with only mild abnormalities of hepatic enzymes with no clinical accompaniment (4% frequency of severe hepatic dysfunction). Thrombocytopenia occurred in 4% of patients, usually in the setting of sepsis. Renal dysfunction was reported in 7% of the patients, with 15% of that figure deemed to be of life-threatening severity. There was an association (p = .001) with antibiotic therapy. Conclusions: Potentially preventable medical complications after ruptured cerebral aneurysm add to the total mortality rate of patients, and may increase length of hospital stay in the critical care setting. The proportion of deaths after subarachnoid hemorrhage from medical complications equals those deaths from either direct effects, rebleeding, or vasospasm individually. Pulmonary complications are the most common nonneurologic cause of death. Cardiac arrhythmia, although frequent, was not associated with significant mortality. The frequency of cardiac arrhythmia and pulmonary edema increased on the day of, or day after, aneurysm surgery. Renal and hepatic dysfunction, and blood dyscrasias, were also observed, underscoring the need for meticulous monitoring for metabolic and hematologic derangements. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT NEUROL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,DEPT NEUROL SURG,CHARLOTTESVILLE,VA 22908. UNIV ARIZONA,BARROW NEUROL INST,PHOENIX,AZ. UNIV ARIZONA,BARROW NEUROL INST,TUCSON,AZ. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. CLEVELAND CLIN,CLEVELAND,OH 44106. COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY 10032. DUKE UNIV,DURHAM,NC. INDIANA UNIV,INDIANAPOLIS,IN 46204. INDIANAPOLIS NEUROSURG GRP,INDIANAPOLIS,IN. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,RICHMOND,VA. NOTRE DAME HOSP,MONTREAL,PQ,CANADA. ST VINCENTS HOSP,NEW YORK,NY. UNIV ALABAMA,BIRMINGHAM,AL. UNIV ALBERTA,EDMONTON,AB,CANADA. UNIV BRITISH COLUMBIA,VANCOUVER,BC,CANADA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV CINCINNATI,CINCINNATI,OH. UNIV FLORIDA,GAINESVILLE,FL. UNIV IOWA,IOWA CITY,IA. UNIV KENTUCKY,LEXINGTON,KY. UNIV LOUISVILLE,LOUISVILLE,KY 40292. UNIV MANITOBA,WINNIPEG,MB,CANADA. UNIV MARYLAND,BALTIMORE,MD 21201. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV MISSISSIPPI,JACKSON,MS 39216. UNIV MISSOURI,COLUMBIA,MO. UNIV N CAROLINA,CHAPEL HILL,NC. UNIV OTTAWA,OTTAWA,ON,CANADA. UNIV PENN,PHILADELPHIA,PA 19104. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV SO CALIF,LOS ANGELES,CA. UNIV TEXAS,HOUSTON,TX. UNIV TEXAS,DALLAS,TX 75230. UNIV UTAH,SALT LAKE CITY,UT. UNIV VIRGINIA,CHARLOTTESVILLE,VA. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV WISCONSIN,MADISON,WI. WASHINGTON UNIV,ST LOUIS,MO. FU NINDS NIH HHS [NS24806] NR 27 TC 320 Z9 330 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 1995 VL 23 IS 6 BP 1007 EP 1017 DI 10.1097/00003246-199506000-00004 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA RC117 UT WOS:A1995RC11700004 PM 7774210 ER PT J AU BERGELSON, JM HEMLER, ME AF BERGELSON, JM HEMLER, ME TI INTEGRIN-LIGAND BINDING - DO INTEGRINS USE A MIDAS TOUCH TO GRASP AN ASP SO CURRENT BIOLOGY LA English DT Note ID CD11B/CD18; ADHESION; DOMAIN; SITE; RGD AB Integrins use divalent cations, held within a novel 'MIDAS' motif, for ligand binding. It is proposed that a missing coordination site for the cation is provided by a critical acidic residue in the ligand. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 15 TC 45 Z9 45 U1 0 U2 3 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 1995 VL 5 IS 6 BP 615 EP 617 DI 10.1016/S0960-9822(95)00124-2 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RD452 UT WOS:A1995RD45200014 PM 7552170 ER PT J AU MERAYOLLOVES, J CALONGE, M FOSTER, CS AF MERAYOLLOVES, J CALONGE, M FOSTER, CS TI EXPERIMENTAL-MODEL OF ALLERGIC CONJUNCTIVITIS TO RAGWEED IN GUINEA-PIG SO CURRENT EYE RESEARCH LA English DT Article DE ALLERGY; ATOPY; HAY FEVER CONJUNCTIVITIS; IL-4; RAGWEED; GUINEA PIG ID IGE PRODUCTION; DISEASE; MICE AB An experimental model of ocular allergy was developed in the guinea pig by exposing these animals to ragweed through topical contact on nasal and conjunctival mucosae, followed by subsequent challenge with ragweed contact on the conjunctiva. Animals developed clinical and histological signs of allergy with and without the use of interleukin 4 as adjuvant. This model mimics human hay fever conjunctivitis more naturally than do animal models previously reported, and it may be subsequently more valuable in the study of the response of allergic conjunctivitis to different therapeutic approaches. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,IMMUNOL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,HILLES IMMUNOL LAB,BOSTON,MA 02114. UNIV VALLADOLID,INST OFTALMOBIOL APLICADA,VALLADOLID,SPAIN. RI Calonge, Margarita/K-2839-2014 OI Calonge, Margarita/0000-0001-8178-4836 NR 28 TC 21 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUN PY 1995 VL 14 IS 6 BP 487 EP 494 DI 10.3109/02713689509003760 PG 8 WC Ophthalmology SC Ophthalmology GA RD950 UT WOS:A1995RD95000009 PM 7671631 ER PT J AU FISHEL, R KOLODNER, RD AF FISHEL, R KOLODNER, RD TI IDENTIFICATION OF MISMATCH REPAIR GENES AND THEIR ROLE IN THE DEVELOPMENT OF CANCER SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID NONPOLYPOSIS COLORECTAL-CANCER; BASE-PAIR MISMATCHES; HETERODUPLEX PLASMID DNA; MUTS-ENCODED PROTEIN; EMBRYONIC STEM-CELLS; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; MICROSATELLITE INSTABILITY; NUCLEAR EXTRACTS; DIFFERENT EFFICIENCIES AB Mismatched base pairs are generated by damage to DNA, by damage to nucleotide precursors, by errors that occur during DNA replication, and during the formation of intermediates in genetic recombination. Enzyme systems that faithfully repair these DNA aberrations have been identified in a wide variety of organisms. At least some of the components of these repair systems have been conserved, both structurally and functionally, throughout evolutionary time. In humans, defective mismatch repair genes have been linked to hereditary nonpolyposis colon cancer as well as to sporadic cancers that exhibit length polymorphisms in simple repeat (microsatellite) DNA sequences. The involvement of mismatch repair defects in microsatellite instability and tumorigenesis suggests that a generalized mutator phenotype is responsible for the large number of genetic alterations observed in tumors. C1 HARVARD UNIV,SCH MED,DIV HUMAN CANC GENET,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA. RP FISHEL, R (reprint author), UNIV VERMONT,SCH MED,MARKEY CTR MOLEC GENET,DEPT MICROBIOL & MOLEC GENET,BURLINGTON,VT 05405, USA. NR 158 TC 255 Z9 257 U1 2 U2 6 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 1995 VL 5 IS 3 BP 382 EP 395 DI 10.1016/0959-437X(95)80055-7 PG 14 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA RC119 UT WOS:A1995RC11900015 PM 7549435 ER PT J AU JAIN, J LOH, C RAO, A AF JAIN, J LOH, C RAO, A TI TRANSCRIPTIONAL REGULATION OF THE IL-2 GENE SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID LYMPHOKINE MESSENGER-RNA; T-CELL ACTIVATION; NF-KAPPA-B; LYMPHOCYTES-T; INTERLEUKIN-2 GENE; CYCLOSPORINE-A; SIGNAL-TRANSDUCTION; NUCLEAR FACTOR; FOS PROTEINS; C-JUN AB The past two years have seen significant advances in our understanding of IL-2 gene transcription. Many of the relevant transcription factors have been identified, the intracellular mechanisms regulating their functions are being elucidated, and the multiple roles oi calcineurin are beginning to be appreciated. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP JAIN, J (reprint author), DANA FARBER CANC INST,DEPT CELLULAR & MOLEC BIOL,B446,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI35297]; NIGMS NIH HHS [GM42667] NR 112 TC 466 Z9 477 U1 2 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1995 VL 7 IS 3 BP 333 EP 342 DI 10.1016/0952-7915(95)80107-3 PG 10 WC Immunology SC Immunology GA RK656 UT WOS:A1995RK65600006 PM 7546397 ER PT J AU PUGLIESE, A GIANANI, R MOROMISATO, R AWDEH, ZL ALPER, CA ERLICH, HA JACKSON, RA EISENBARTH, GS AF PUGLIESE, A GIANANI, R MOROMISATO, R AWDEH, ZL ALPER, CA ERLICH, HA JACKSON, RA EISENBARTH, GS TI HLA-DQB1-ASTERISK-0602 IS ASSOCIATED WITH DOMINANT PROTECTION FROM DIABETES EVEN AMONG ISLET-CELL ANTIBODY-POSITIVE FIRST-DEGREE RELATIVES OF PATIENTS WITH IDDM SO DIABETES LA English DT Article ID STIFF-MAN SYNDROME; GLUTAMIC-ACID DECARBOXYLASE; GENETIC SUSCEPTIBILITY; HIGH-RISK; MELLITUS; HETEROGENEITY; POLYMORPHISM; IDENTIFICATION; AUTOIMMUNITY; RESISTANCE AB HLA-DQB1 alleles confer susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM), me investigated whether the susceptibility alleles DQB1*0302 and DQB1*0201 affect progression to diabetes among islet cell antibody-positive (ICA(+)) first-degree relatives of IDDM patients and whether the protective allele DQB1*0602 can be found and is still protective among such relatives, We human leukocyte antigen-typed and periodically tested beta-cell function (first-phase insulin release [FPIR] during the intravenous glucose tolerance test) in 72 ICA(+) relatives, of whom 30 became diabetic on follow-up (longest follow-up 12 years); 54 (75%) relatives carried DQB1*0302 and/or DQB1*0201, The frequency of DQB1*0302 and DQB1*0201 and of the highrisk genotype DQB1*0302/DQB1*0201 did not differ significantly between diabetic relatives and those remaining nondiabetic. On follow-up, progression to IDDM was not statistically different for relatives with or without the DQB1*0302/DQB1*0201 genotype, However, those relatives with the DQB1*0302/DQB1*0201 genotype had a tendency to develop diabetes at an earlier age (log-rank P = 0.02), We found DQB1*0602 in 8 of 72 (11.1%) ICA relatives, Relatives with DQB1*0602 did not develop diabetes or show any decline of FPIR versus 28 of 64 DQB1*0602(-) relatives who developed IDDM (log-rank P = 0.006; Wilcoxon's P = 0.02). The protective allele DQB1*0602 is found in ICA(+) relatives who have minimal risk of progression to IDDM. Therefore, DQB1*0602 is associated with protection from IDDM both in population studies and among relatives with evidence of autoimmunity who should not enter prevention trials. C1 UNIV COLORADO,HLTH SCI CTR,BARBARA DAVIS CTR CHILDHOOD DIABET,DENVER,CO 80262. UNIV MIAMI,DIABET RES INST,MIAMI,FL 33152. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. ROCHE MOLEC SYST,DEPT HUMAN GENET,ALAMEDA,CA. FU NIDDK NIH HHS [R01-DK-43279, R37-DK-32083] NR 40 TC 150 Z9 151 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1995 VL 44 IS 6 BP 608 EP 613 DI 10.2337/diabetes.44.6.608 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RB888 UT WOS:A1995RB88800002 PM 7789622 ER PT J AU POLONSKY, WH ANDERSON, BJ LOHRER, PA WELCH, G JACOBSON, AM APONTE, JE SCHWARTZ, CE AF POLONSKY, WH ANDERSON, BJ LOHRER, PA WELCH, G JACOBSON, AM APONTE, JE SCHWARTZ, CE TI ASSESSMENT OF DIABETES-RELATED DISTRESS SO DIABETES CARE LA English DT Article ID METABOLIC CONTROL; GLYCEMIC CONTROL; GLUCOSE CONTROL; SOCIAL SUPPORT; COPING STYLES; MELLITUS; RELIABILITY; HYPOGLYCEMIA; ADOLESCENTS; ADJUSTMENT AB OBJECTIVE - To describe a new measure of psychosocial adjustment specific to diabetes, thr Problem Areas in Diabetes Survey (PAID), and to present initial information on its reliability and validity. RESEARCH DESIGN AND METHODS - Before their routine clinic appointments, 451 female patients with type I and type II diabetes, all of whom required insulin, completed a self-report sun ey. Included in the survey was the PAID, a 20-item questionnaire in which each item represents a unique area of diabetes-related psychosocial distress, Each item is rated on a six-point Likert scale, reflecting the degree to which the item is perceived as currently problematic. A total scale score, hypothesized to reflect the overall level of diabetes-related emotional distress, is computed by summing the total item responses. To examine the concurrent validity of the PAID, the survey also included a series of standardized questionnaires assessing psychosocial functioning (general emotional distress, fear of hypoglycemia, and disordered eating), attitudes toward diabetes, and self-care behaviors. All subjects were assessed for HbA(1) within 30 days of survey completion and again similar to 1-2 years later. Finally, long-term diabetic complications were determined through chart review. RESULTS - Internal reliability of the PAID was high, with good item-to-total correlations. Approximately 60% of the subject sample reported at least one serious diabetes-related concern, As expected, the PAID was positively associated with relevant psychosocial measures of distress, including general emotional distress, disordered eating, and fear of hypoglycemia, short- and long-term diabetic complications, and HbA(1), and negatively associated with reported self-care behaviors. The PAID accounted for similar to 9% of the variance in HbA(1). Diabetes-related emotional distress, as measured by the PAID, was found to be a unique contributor to adherence to self-cart behaviors after adjustment for age, diabetes duration, and general emotional distress, In addition, the PAID was associated with HbA(1) even after adjustment for age, diabetes duration, general emotional distress, and adherence to self-cart behaviors. CONCLUSIONS - These findings suggest that the PAID, a brief, easy-to-administer instrument, may be valuable in assessing psychosocial adjustment to diabetes. In addition to high internal reliability, the consistent pattern of correlational findings indicates that the PAID is tapping into relevant aspects of emotional distress and that its particular feature, the measurement of diabetes-related emotional distress, is uniquely associated with diabetes-relevant outcomes, These data are also consistent with the hypothesis that diabetes-related emotional distress, separate from general emotional distress, is an independent and major contributor to poor adherence. Given that the study was limited to female patients using insulin, further examination of the clinical usefulness of the PAID will need to focus on more heterogeneous samples. C1 JOSLIN DIABET CTR,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,CTR NEUROL DIS,BOSTON,MA 02115. NR 29 TC 441 Z9 460 U1 8 U2 46 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 1995 VL 18 IS 6 BP 754 EP 760 DI 10.2337/diacare.18.6.754 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RB510 UT WOS:A1995RB51000002 PM 7555499 ER PT J AU BONORA, E GULLI, G BONADONNA, R DELPRATO, S SOLINI, A DEFRONZO, RA AF BONORA, E GULLI, G BONADONNA, R DELPRATO, S SOLINI, A DEFRONZO, RA TI INSULIN SENSITIVITY IS NOT IMPAIRED IN MEXICAN-AMERICAN WOMEN WITHOUT A FAMILY HISTORY OF DIABETES SO DIABETES CARE LA English DT Article ID ABDOMINAL FAT; GLUCOSE-METABOLISM; BODY-COMPOSITION; PIMA-INDIANS; MELLITUS; OBESITY; MUSCLE; POPULATION; RESISTANCE; NONOBESE AB OBJECTIVE - The purpose of this research was to compare insulin sensitivity in Mexican-Americans and non-Hispanic whites without a family history of diabetes to establish whether insulin resistance is a defect intrinsically related to subjects of Mexican origin. RESEARCH DESIGN AND METHODS - In study A, we compared insulin sensitivity in 12 Mexican-American and 12 non-Hispanic white women with normal glucose tolerance and no family history of diabetes. In study B, we compared insulin sensitivity in two groups of normal glucose-tolerant Mexican-Americans, nine with a positive (FHD+) and nine with a negative (FHD-) family history of diabetes. In both studies, the groups were closely matched for age, total body fat content, and fat topography. Insulin sensitivity was assessed with the euglycemic insulin clamp (20 mU . min(-1) . m(2) surface area) which was performed in combination with tritiated glucose infusion and indirect calorimetry. Total fat mass and fat-free mass (FFM) were assessed by a tritiated water dilution technique, and regional fat distribution was evaluated by anthropometry and magnetic resonance imaging. RESULTS - During a 4-h euglycemic insulin clamp (study A), rates (mg . min(-1) . kg FFM(-1)) of total (6.32 +/- 0.64 vs. 6.62 +/- 0.81), oxidative (3.54 +/- 0.24 vs. 3.51 +/- 0.19), and nonoxidative (2.78 +/- 0.48 vs. 3.11 +/- 0.75) glucose utilization were similar in Mexican-Americans and non-Hispanic whites; hepatic glucose production (0.33 +/- 0.13 vs. 0.35 +/- 0.13) was suppressed similarly in both groups. During a 2-h euglycemic insulin clamp (study B), Mexican-Americans with FHD+ had lower rates of insulin-mediated total (3.55 +/- 0.39 vs. 5.93 +/- 0.59, P < 0.001), oxidative (3.31 +/- 0.25 vs. 4.32 +/- 0.17, P < 0.01), and nonoxidative (0.24 +/- 0.28 vs. 1.61 +/- 0.49, P < 0.01) glucose disposal than subjects with FHD-; suppression of hepatic glucose production (0.24 +/- 0.14 vs. 0.18 +/- 0.12) was similar in both groups. CONCLUSIONS - These results indicate that in the absence of a family history of noninsulin-dependent diabetes mellitus, Mexican-American women are not less sensitive to insulin than non-Hispanic white women. C1 UNIV TEXAS,HLTH SCI CTR,DEPT INTERNAL MED,DIV DIABET,SAN ANTONIO,TX. AUDIE L MURPHY VET AFFAIRS HOSP,SAN ANTONIO,TX. RI Del Prato, Stefano/K-3405-2016; Solini, Anna/K-4666-2016; OI Del Prato, Stefano/0000-0002-5388-0270; Solini, Anna/0000-0002-7855-8253; BONORA, Enzo/0000-0003-1074-5164 FU NCRR NIH HHS [M01-RR-01346]; NIADDK NIH HHS [AM-24092] NR 38 TC 6 Z9 6 U1 0 U2 0 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 1995 VL 18 IS 6 BP 825 EP 833 DI 10.2337/diacare.18.6.825 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RB510 UT WOS:A1995RB51000012 PM 7555509 ER PT J AU CUSI, K CUNNINGHAM, GR COMSTOCK, JP AF CUSI, K CUNNINGHAM, GR COMSTOCK, JP TI SAFETY AND EFFICACY OF NORMALIZING FASTING GLUCOSE WITH BEDTIME NPH INSULIN ALONE IN NIDDM SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; SECONDARY FAILURE; DAYTIME SULFONYLUREA; THERAPY; SECRETION; OBESE; TRIAL; RESISTANCE; 1ST-PHASE; DISEASE AB OBJECTIVE - To examine the safety and overall clinical effects of normalizing the fasting plasma glucose (FPG) level with bedtime NPH insulin alone in patients with non-insulin-dependent diabetes mellitus (NIDDM) that is poorly controlled with maximal doses of sulfonylureas. RESEARCH DESIGN AND METHODS - Twelve obese male NIDDM subjects were treated for 16 weeks with bedtime insulin after a 4-week sulfonylurea washout. The insulin dosage was increased until the FPG level was normalized. The 24-h plasma glucose profiles and lipid and HbA(1c) levels were measured at the beginning and end of the study, and the incidence and severity of hypoglycemic episodes were closely monitored. In addition, hyperglycemic clamp studies were performed to assess insulin secretion and provide an indirect measurement of insulin sensitivity. RESULTS - FPG (14.6 +/- 0.9 mmol/l at week 0) was normalized (<6.4 mmol/l) within 6 weeks (5.9 +/- 0.6 mmol/l) and remained at target levels until the end of the study (4.0 +/- 0.03 mmol/l at week 16, P < 0.001). The insulin dose was 80 +/- 9 U/day (0.86 +/- 0.10 U/kg). Improved glycemic control was confirmed by a reduction in HbA(1c)(10.9 +/- 0.05 vs. 7.2 +/- 0.2%, P < 0.001) and mean 24-h glucose (17.2 +/- 0.2 vs. 7.4 +/- 0.2 mmol/l, P < 0.001). The incidence of mild or moderate hypoglycemic episodes was 3.4 +/- l/patient for the entire 16-week study, and no patient experienced severe hypoglycemia. Bedtime insulin significantly improved total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglyceride levels (P < 0.01). Weight gain was 2.4 +/- 0.7 kg, and blood pressure was unchanged. During the hyperglycemic clamp, there was an improvement in the first phase (P < 0.001) and in the second phase (P < 0.01) of insulin secretion. There also was an increase in the rate of exogenous glucose infused (M) (P < 0.01) and in the M/C-peptide ratio (P < 0.02), suggesting enhanced insulin sensitivity. CONCLUSIONS - NPH insulin given at bedtime in amounts sufficient to achieve a normal FPG level does not cause excessive or severe hypoglycemia and does lead to good glycemic and lipid control in NIDDM. Bedtime insulin therapy also is accompanied by improved insulin secretion and insulin sensitivity. We conclude that a single dose of insulin alone at bedtime merits consideration as a therapeutic strategy in patients with poorly controlled NIDDM. C1 METHODIST HOSP,GEN CLIN RES CTR,HOUSTON,TX. DEPT VET AFFAIRS MED CTR,ENDOCRINOL SECT,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. FU NCRR NIH HHS [MO1-RR-00350-25] NR 49 TC 57 Z9 57 U1 0 U2 0 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 1995 VL 18 IS 6 BP 843 EP 851 DI 10.2337/diacare.18.6.843 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RB510 UT WOS:A1995RB51000014 PM 7555511 ER PT J AU GOLDSTEIN, DE LITTLE, RR LORENZ, RA MALONE, JI NATHAN, D PETERSON, CM AF GOLDSTEIN, DE LITTLE, RR LORENZ, RA MALONE, JI NATHAN, D PETERSON, CM TI TESTS OF GLYCEMIA IN DIABETES SO DIABETES CARE LA English DT Review ID SERUM FRUCTOSAMINE CONCENTRATION; GLYCOSYLATED HEMOGLOBIN LEVELS; BLOOD-GLUCOSE; GLYCATED HEMOGLOBIN; CLINICAL USEFULNESS; PROTEIN-CONCENTRATION; PLASMA-PROTEIN; URINE GLUCOSE; UNITED-STATES; ASSAY C1 UNIV HOSP & CLIN, SCH MED, DEPT CHILD HLTH, COLUMBIA, MO USA. UNIV HOSP & CLIN, SCH MED, DIV DIABET & ENDOCRINOL, COLUMBIA, MO USA. VANDERBILT UNIV, SCH MED, CTR DIABET RES & TRAINING, NASHVILLE, TN 37212 USA. UNIV S FLORIDA, COLL MED, TAMPA, FL USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DIABET UNIT, BOSTON, MA USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DIABET RES CTR, BOSTON, MA USA. SANSUM MED RES FDN, SANTA BARBARA, CA USA. OI Little, Randie/0000-0001-6450-8012 NR 144 TC 139 Z9 146 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1995 VL 18 IS 6 BP 896 EP 909 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RB510 UT WOS:A1995RB51000031 PM 7555528 ER PT J AU GIORDANO, M CASTELLINO, P CARROLL, CA DEFRONZO, RA AF GIORDANO, M CASTELLINO, P CARROLL, CA DEFRONZO, RA TI COMPARISON OF THE EFFECTS OF HUMAN RECOMBINANT INSULIN-LIKE GROWTH-FACTOR-I AND INSULIN ON PLASMA AMINO-ACID-CONCENTRATIONS AND LEUCINE KINETICS IN HUMANS SO DIABETOLOGIA LA English DT Article DE LEUCINE; KETOISOCAPROATE; INSULIN; IGF-I; PROTEIN METABOLISM ID IGF-I; RENAL-FUNCTION; GLUCOSE; METABOLISM; SECRETION; RECEPTORS; INFUSION; BINDING AB We examined the effects of recombinant human insulin-like growth factor I (IGF-I) and insulin on the plasma amino acid (AA) profile and leucine kinetics in eight normal subjects. IGF-I was infused at 52 pmol . kg(-1). min(-1) in combination with prime-continuous [1-C-14] leucine infusion, to obtain steady-state plasma concentrations of total (54 +/- 3 nmol/l) and free (7.3 +/- 1 nmol/l) IGF-I (study 1). In response to IGF-I, plasma AA levels declined by 37 +/- 3% (1975 +/- 198 to 1368 +/- 120 mu mol/l) and total branched chain amino acids (BCAA) declined by 34 +/- 3% (390 +/- 21 to 256 +/- 13 mu mol/l). This hypoaminoacidaemic effect was associated with a decline in endogenous leucine flux of 17 +/- 2% (1.88 +/- 0.05 to 1.57 +/- 0.04 mu mol . kg(-1). min(-1)) and leucine oxidation of 17 +/- 1% (0.31 +/- 0.02 vs 0.26 +/- 0.02 mu mol . kg(-1). min(-1)) (both p < 0.01 vs basal), The same subjects underwent a second study (study 2) in which insulin was infused at 6.22 pmol . kg(-1). min(-1) to obtain a steady-state plasma insulin concentration of 530 +/- 25 pmol/l while maintaining euglycaemia. The infusion rate was designed to match the declines in plasma BCAA levels and leucine turnover observed during IGF-I infusion. The rates of glucose infusion necessary to maintain euglycaemia during IGF-I and insulin infusion were 4.9 +/- 1.0 and 7.8 +/- 0.6 mg . kg(-1). min(-1), respectively. During insulin infusion total BCAA declined by 39% from 369 +/- 23 to 226 +/- 20 mu mol/l, leucine flux declined by 16 +/- 2% from 1.90 +/- 0.05 to 1.61 +/- 0.03 mu mol . kg(-1). min(-1), and leucine oxidation declined by 19 +/- 2% from 0.32 +/- 0.02 to 0.26 +/- 0.02 mu mol . kg(-1). min(-1). On a molar basis IGF-I was 7.3% as potent as insulin in inhibiting proteolysis. These results demonstrate that in humans: (i) the hypoaminoacidaemic response to IGF-I can be entirely ascribed to the inhibition of proteolysis; (ii) qualitatively, the effects of IGF-I and insulin on plasma AA profile and protein metabolism are similar; (iii) quantitatively, IGF-I is 14-fold less potent than insulin in suppressing protein degradation. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV DIABET,SAN ANTONIO,TX 78284. UNIV NAPLES 2,INST INTERNAL MED & NEPHROL,NAPLES,ITALY. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. OI CASTELLINO, Pietro/0000-0002-9014-2007 FU NCRR NIH HHS [M01-RR-01346] NR 26 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 1995 VL 38 IS 6 BP 732 EP 738 DI 10.1007/BF00401848 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QZ605 UT WOS:A1995QZ60500017 PM 7672498 ER PT J AU MONTOYA, ID LEVIN, FR FUDALA, PJ GORELICK, DA AF MONTOYA, ID LEVIN, FR FUDALA, PJ GORELICK, DA TI DOUBLE-BLIND COMPARISON OF CARBAMAZEPINE AND PLACEBO FOR TREATMENT OF COCAINE DEPENDENCE SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE COCAINE; DEPENDENCE; CARBAMAZEPINE ID USERS; LIDOCAINE; SEIZURES; DESIGN; DRUGS; RATS AB This study was conducted to determine the effectiveness of carbamazepine (CBZ) for treatment of cocaine dependence. Sixty-two (CBZ = 28, placebo = 34) cocaine-dependent (DSM-III-R criteria) volunteers consented to be treated for eight weeks with standardized outpatient individual counseling twice a week plus double-blind CBZ or inactive placebo. During the 8-week trial, both groups showed increased number of urine samples negative for cocaine, significantly (P < 0.01) decreased self-reported cocaine use (money spent and grams used), and decreased Beck Depression Inventory and Symptom Check List-90-Revised (SCL-90-R) total scores. However, there were no significant differences between CBZ and placebo. This study does not support the effectiveness of CBZ for outpatient treatment of cocaine dependence. C1 NIDA,INTRAMURAL RES PROGRAM,TREATMENT BRANCH,BALTIMORE,MD 21224. COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY. UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. UNIV MARYLAND,DEPT PSYCHIAT,BALTIMORE,MD. FU Intramural NIH HHS [Z99 DA999999] NR 37 TC 44 Z9 44 U1 1 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN PY 1995 VL 38 IS 3 BP 213 EP 219 DI 10.1016/0376-8716(95)01101-4 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA RF947 UT WOS:A1995RF94700003 PM 7555621 ER PT J AU CORNISH, JW MAANY, I FUDALA, PJ NEAL, S POOLE, SA VOLPICELLI, P OBRIEN, CP AF CORNISH, JW MAANY, I FUDALA, PJ NEAL, S POOLE, SA VOLPICELLI, P OBRIEN, CP TI CARBAMAZEPINE TREATMENT FOR COCAINE DEPENDENCE SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE CARBAMAZEPINE; COCAINE DEPENDENCE; PHARMACOTHERAPY; URINARY BENZOYLECGONINE; CRAVING ID METHADONE-MAINTAINED PATIENTS; DESIPRAMINE; AMANTADINE; DETOXIFICATION; BROMOCRIPTINE; DOPAMINE AB We report on a double-blind, placebo-controlled study of carbamazepine (CBZ) treatment for cocaine dependence. A previously reported uncontrolled study found CBZ to be a beneficial pharmacotherapy for cocaine dependence. Statistical analyses were performed on data from 82 subjects who were randomized to 10 weeks' treatment with either CBZ, titrated to 4-12 mu g/ml, (n = 37) or placebo (n = 45). The two treatment groups did not differ for primary outcome measures of retention time in treatment, urine samples positive for cocaine metabolite, subject reported desire for cocaine or for subject reported side-effects. CBZ was not an effective treatment in this study. C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. RUTGERS STATE UNIV,DEPT PSYCHOL,NEW BRUNSWICK,NJ 08903. RP CORNISH, JW (reprint author), UNIV PENN,PHILADELPHIA VA MED CTR,DEPT PSYCHIAT,3900 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. FU NIDA NIH HHS [DA 00144, DA 05186] NR 26 TC 40 Z9 40 U1 3 U2 3 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN PY 1995 VL 38 IS 3 BP 221 EP 227 DI 10.1016/0376-8716(95)01102-5 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA RF947 UT WOS:A1995RF94700004 PM 7555622 ER PT J AU RAHIMI, P WANG, CY STASHENKO, P LEE, SK LORENZO, JA GRAVES, DT AF RAHIMI, P WANG, CY STASHENKO, P LEE, SK LORENZO, JA GRAVES, DT TI MONOCYTE CHEMOATTRACTANT PROTEIN-1 EXPRESSION AND MONOCYTE RECRUITMENT IN OSSEOUS INFLAMMATION IN THE MOUSE SO ENDOCRINOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; BONE-RESORPTION; ENDOTHELIAL-CELLS; INTERLEUKIN-1; MACROPHAGES; CYTOKINES; IDENTIFICATION; TISSUES; FAMILY; SYSTEM AB In bone, early events in inflammation involve the production and release of primary proinflammatory cytokines, such as interleukin-1 beta. By activation of target cells, these cytokines are thought to induce a second wave of cytokines, including monocyte chemoattractant protein-1 (MCP-1). MCP-1 is a cytokine that stimulates chemotaxis of monocytes. Experiments were undertaken to examine the expression of MCP-1 in bone-associated cells in vivo. To observe in vivo expression of MCP-1, an inflammatory lesion was created in the murine mandible. Immunohistochemistry experiments using specific antibodies to MCP-1 were conducted to identify MCP-1-expressing cells in inflamed and noninflamed bone. We found that osteoblasts were the principal cells expressing MCP-1 in inflamed bone. There was little or no MCP-1 expression in noninflamed bone. Immunohistochemistry experiments were carried out to assess monocyte recruitment during osseous inflammation. The number of MCP-1-positive cells was significantly correlated to the number of monocytes/macrophages present (n = 15; r = 0.69; P < = 0.01). These in vivo results strongly suggest that MCP-1 is an important mediator involved in the recruitment of monocytes/macrophages in inflamed bone. C1 BOSTON UNIV,SCH GRAD DENT,DEPT ORAL BIOL,BOSTON,MA 02118. FORSYTH RES CTR,DEPT IMMUNOL,BOSTON,MA 02115. DEPT VET AFFAIRS MED CTR,DEPT MED,DIV ENDOCRINOL & METAB,NEWINGTON,CT 06111. UNIV CONNECTICUT,FARMINGTON,CT 06030. FU NIAMS NIH HHS [AR-42362]; NIDCR NIH HHS [DE-07559, DE-09581] NR 45 TC 68 Z9 68 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1995 VL 136 IS 6 BP 2752 EP 2759 DI 10.1210/en.136.6.2752 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RA394 UT WOS:A1995RA39400051 PM 7750500 ER PT J AU WICH, BK CARNES, M AF WICH, BK CARNES, M TI MENOPAUSE AND THE AGING FEMALE REPRODUCTIVE-SYSTEM SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID ESTROGEN REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; PROGESTERONE RECEPTORS; MENSTRUAL-CYCLE; HORMONE-THERAPY; ELDERLY WOMEN; PREVALENCE; MANAGEMENT; ESTRADIOL; SYMPTOMS AB Menopause is a fact of life for women, who live the last third of their lives in a postmenopausal state. Although estrogen replacement therapy offers primary prevention and treatment of vasomotor, urogenital, and osteoporotic symptoms of estrogen deprivation and seems to have beneficial effects on cardiovascular mortality, only 20% of women in the United States currently are taking hormone supplements. This article discusses the menopause-influencing changes in the hypothalamic-pituitary-ovarian axis with associated neuroendocrine and sex hormone changes, their physiologic consequences on the reproductive system, and current recommendations for hormone replacement therapy. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON GERIATR RES EDUC & CLIN CTR,MADISON,WI 53705. UNIV WISCONSIN,DEPT MED,MADISON,WI. NR 101 TC 25 Z9 25 U1 0 U2 5 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 1995 VL 24 IS 2 BP 273 EP 295 PG 23 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RD631 UT WOS:A1995RD63100005 PM 7656892 ER PT J AU LIN, GS FINGER, E GUTIERREZRAMOS, JC AF LIN, GS FINGER, E GUTIERREZRAMOS, JC TI EXPRESSION OF CD34 IN ENDOTHELIAL-CELLS, HEMATOPOIETIC PROGENITORS AND NERVOUS CELLS IN FETAL AND ADULT-MOUSE TISSUES SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD34; ENDOTHELIAL CELLS; HEMATOPOIETIC; NERVOUS CELLS ID STEM-CELLS; MARROW-CELLS; MOLECULE; ANTIGEN; LINES; GENE; INTERLEUKIN-3; SIALOMUCIN AB The human cell surface molecule CD34 is selectively expressed on uncommitted and committed hematopoietic progenitor cells and on vascular endothelial cells. It has been suggested that CD34 regulates early events in blood cell migration and differentiation, possibly as a cell adhesion molecule. To characterize the patterns of expression of CD34 in the mouse embryo and in the adult, as well as to dissect the function of different portions of the extracellular domain of this molecule, we have generated the first monoclonal antibodies (mAb) specific for mouse CD34. The epitope(s) recognized by these mAb are not carbohydrate moieties, and are comprised either within the immunoglobulin-like domain or within a portion of the mucin domain, containing approximately half of the predicted O- and N-linked carbohydrate attachment sites. The specificity of the antibodies was established by ELISA and Western blotting. Western analysis revealed that these mAb recognize a protein of approximately 110 kDa in PA6 stromal cell lysates, which can be specifically blocked by the recombinant CD34 protein. To establish the reactivity of these mAb on different cell lineages, a panel of cell lines was stained. This analysis showed strong reactivities with 3T3 fibroblasts, stromal cell lines from fetal liver and with the endothelial cell line D10. Bone marrow hematopoietic progenitors were also stained by these mAb. Immunostaining of frozen sections from embryonic and adult tissues revealed a strong reactivity against vascular endothelial cells at different stages of development, including sinusoidal cells in the fetal liver, yolk sac, and in the fetal bone marrow, endothelial cells from adult lung and kidney, and neural cells, including those of the neural tube of midgestation embryos and neuronal bodies in adult brain. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. FU NHLBI NIH HHS [1POIHL 48675-02] NR 34 TC 95 Z9 96 U1 2 U2 3 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 1995 VL 25 IS 6 BP 1508 EP 1516 DI 10.1002/eji.1830250606 PG 9 WC Immunology SC Immunology GA RG465 UT WOS:A1995RG46500005 PM 7542195 ER PT J AU DURE, LS WIESS, S STANDAERT, DG RUDOLF, G TESTA, CM YOUNG, AB AF DURE, LS WIESS, S STANDAERT, DG RUDOLF, G TESTA, CM YOUNG, AB TI DNA FRAGMENTATION AND IMMEDIATE-EARLY GENE-EXPRESSION IN RAT STRIATUM FOLLOWING QUINOLINIC ACID ADMINISTRATION SO EXPERIMENTAL NEUROLOGY LA English DT Article ID DELAYED NEURONAL DEATH; PROGRAMMED CELL-DEATH; NERVOUS-SYSTEM; C-FOS; GLUTAMATE; APOPTOSIS; PROTEIN; JUN; EXCITOTOXINS; IMPAIRMENT AB Excitotoxic cell death is hypothesized to contribute to numerous neuropathologic conditions, including hypoxic/ischemic encephalopathy, hypoglycemia, Parkinson's disease, and Huntington's disease. Neuronal death from excitotoxic lesions has been shown to be an active process, with activation of immediate early gene transcription, resulting in secondary changes in gene expression. Another feature of neurotoxic cell death that has been examined is the presence of DNA fragmentation, which presumably indicates impending nuclear disintegration. A technique has been described for labeling fragmented DNA in situ, allowing precise determination of the anatomic and temporal distribution of neurons after an excitotoxic lesion. To investigate this phenomenon, we performed in situ nick translation on brain tissue from rats that have undergone stereotaxically placed intrastriatal quinolinic acid injections. Furthermore, in these same animals we analyzed the expression of c-fos mRNA to compare the time course and regional distribution of DNA fragmentation with immediate early gene activation after an excitotoxic lesion. Our analysis indicates that c-fos expression increases soon after quinolinic acid injection, is widespread in rat brain, but is effectively absent by 24 h postinjection. DNA fragmentation, however, is limited to striatum and is maximal at 24 h after injection. These results demonstrate the sensitivity of in situ nick translation for the detection of regional neuropathology and illustrate the temporal and spatial relationship of c-fos expression to excitotoxic neuronal death. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL NEUROL RES,BOSTON,MA 02114. RP DURE, LS (reprint author), UNIV ALABAMA,DEPT PEDIAT,DIV NEUROL,BIRMINGHAM,AL 35294, USA. RI Dure, Leon/B-3243-2008; OI Standaert, David/0000-0003-2921-8348 FU NICHD NIH HHS [HD00983] NR 48 TC 17 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 1995 VL 133 IS 2 BP 207 EP 214 DI 10.1006/exnr.1995.1023 PG 8 WC Neurosciences SC Neurosciences & Neurology GA RP124 UT WOS:A1995RP12400011 PM 7649226 ER PT J AU TOMERA, JF LILFORD, K HARAKAL, C AF TOMERA, JF LILFORD, K HARAKAL, C TI MULTIPLE LINEAR-REGRESSION ANALYSIS OF HYPERTROPHY, CALCIUM AND CADMIUM IN HYPERTENSIVE AND NONHYPERTENSIVE STATES SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION MECHANISMS; SURFACE AREA BURN; POLYINOSITOL PHOSPHATES; MULTIVARIATE INFLUENCE; INOSITOL PHOSPHATES; SKELETAL-MUSCLE; CROSS-TALK; TRAUMA; DIAPHRAGM AB Heart disease remains a major public health issue. In this study we aimed to achieve a greater mathematical and mechanistic understanding of the relationship between exposure to heavy metals and heart disease. Measurements of calcium and cadmium levels were made by flame atomic absorption spectrophotometry in tissue from hypertensive and non-hypertensive rabbits. Relationships between hypertrophy, calcium and cadmium were tested using multiple regression analysis. Multiple linear relationships occurred that showed the dependence of hypertrophy on calcium and cadmium levels, and of calcium accumulation on cadmium and hypertrophy. These data provide an insight into the mechanisms of heavy metal accumulation and the development of cardiovascular hypertrophy. C1 HARVARD UNIV,SCH MED,DEPT ANAESTHESIOL,BOSTON,MA 02114. SHRINERS BURNS INST,ANESTHESIA SERV,CLIN PHARMACOL LAB,CINCINNATI,OH 45219. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. TEMPLE UNIV,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19140. FU NHLBI NIH HHS [HL 14217] NR 30 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUN PY 1995 VL 33 IS 6 BP 529 EP 535 DI 10.1016/0278-6915(95)00014-S PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA RF835 UT WOS:A1995RF83500010 PM 7797180 ER PT J AU GINN, GO AF GINN, GO TI BUSINESS STRATEGY AND FINANCIAL STRUCTURE - AN EMPIRICAL-ANALYSIS OF ACUTE-CARE HOSPITALS SO HOSPITAL & HEALTH SERVICES ADMINISTRATION LA English DT Article ID CAPITAL STRUCTURE; MILES; PERFORMANCE AB This study investigated the relationship between business strategy and financial structure in the U.S. hospital industry. We studied two dimensions of financial structure-liquidity and leverage. Liquidity was assessed by the acid ratio, and leverage was assessed using the equity funding ratio. Drawing from managerial, finance, and resource dependence perspectives, we developed and tested hypotheses about the relationship between Miles and Snow strategy types and financial structure. Relevant contextual financial and organizational variables were controlled for statistically through the Multivariate Analysis of Covariance technique. The relationship between business strategy and financial structure was found to be significant. Among the Miles and Snow strategy types, defenders were found to have relatively high liquidity and low leverage. Prospectors typically had low liquidity and high leverage. Implications for financial planning, competitive assessment, and reimbursement policy are discussed. C1 US DEPT VET AFFAIRS,BOSTON,MA. BOSTON UNIV,SCH PUBL HLTH,BOSTON,MA 02215. UNIV NEVADA,DEPT MANAGERIAL SCI,RENO,NV 89557. RP GINN, GO (reprint author), CLARKSON COLL,101 S 42ND ST,OMAHA,NE 68131, USA. NR 33 TC 4 Z9 4 U1 1 U2 8 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 SN 8750-3735 J9 HOSP HEALTH SERV ADM JI Hosp. Health Serv. Adm. PD SUM PY 1995 VL 40 IS 2 BP 191 EP 209 PG 19 WC Health Policy & Services SC Health Care Sciences & Services GA QZ638 UT WOS:A1995QZ63800002 PM 10143031 ER PT J AU TROLLIET, MR KRIEGER, JE KOIKE, G SIMON, J KRIEGER, EM STEC, D ROMAN, R LANDER, ES DZAU, VJ JACOB, HJ AF TROLLIET, MR KRIEGER, JE KOIKE, G SIMON, J KRIEGER, EM STEC, D ROMAN, R LANDER, ES DZAU, VJ JACOB, HJ TI SEX-SPECIFIC AND SEX-LINKED INFLUENCES ON BLOOD-PRESSURE IN THE SHR SO HYPERTENSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA. UNIV SAO PAULO,INST HEART,BR-05508 SAO PAULO,BRAZIL. STANFORD UNIV,CARDIOVASC RES CTR,STANFORD,CA 94305. MED COLL WISCONSIN,MILWAUKEE,WI. MIT,WHITEHEAD GENOME CTR,CAMBRIDGE,MA 02139. RI Krieger, Jose/C-3117-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 1995 VL 25 IS 6 BP 1375 EP 1375 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RB882 UT WOS:A1995RB88200125 ER PT J AU MCCORMICK, BA MILLER, SI CARNES, D MADARA, JL AF MCCORMICK, BA MILLER, SI CARNES, D MADARA, JL TI TRANSEPITHELIAL SIGNALING TO NEUTROPHILS BY SALMONELLAE - A NOVEL VIRULENCE MECHANISM FOR GASTROENTERITIS SO INFECTION AND IMMUNITY LA English DT Article ID CULTURED EPITHELIAL MONOLAYER; TYPHIMURIUM INVASION; MAMMALIAN-CELLS; EXPRESSION; COLITIS; INTERLEUKIN-8; MIGRATION; MUTANTS; LINES; MODEL AB Salmonella serotypes which elicit human enteritis cannot he distinguished from those that do not on the basis of their in vitro Interactions with eukaryotic cells. We have recently reported that an enteritis-producing strain of Salmonella typhimurium signals intact intestinal epithelium to recruit subepithelial neutrophils to migrate across the epithelia (B. A. McCormick, S. P. Colgan, C. D. Archer, S. I. Miller, and J. L. Madara, J. Cell Biol. 123:895-907, 1993). We now utilize a cell culture model of human intestinal epithelium (with T84 cells) to examine whether such transepithelial signaling to neutrophils by salmonellae is predictive of potential to elicit gastroenteritis. Various Salmonella serotypes, including S. typhimurium, S. enteritidis, S. pullorum S. arizonae, S. typhi, and S. paratyphi, as well as invasion-defective mutants of S. typhimurium, were studied. Strains or serotypes which elicit diffuse enteritis in humans (defined histologically as transepithelial migration of neutrophils) exhibited transepithelial signaling to neutrophils across epithelial cell monolayers, while those which do not elicit diffuse enteritis in humans did not display transepithelial signaling. In contrast, the ability to enter the apical surface of T84 cells did not differentiate strains or serotypes which induce diffuse enteritis from those which do not. These results strongly suggest that the ability of salmonellae to elicit transepithelial signaling to neutrophils is a key virulence mechanism underlying Salmonella-elicited enteritis. C1 MASSACHUSETTS GEN HOSP,DEPT MED,DIV INFECT DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,CTR DIGEST DIS,BOSTON,MA 02115. RP MCCORMICK, BA (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV GASTROENTEROL PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK08837, DK47662, DK35932] NR 36 TC 137 Z9 137 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 1995 VL 63 IS 6 BP 2302 EP 2309 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RA191 UT WOS:A1995RA19100031 PM 7768613 ER PT J AU KACMAREK, RM AF KACMAREK, RM TI PROPHYLACTIC BRONCHIAL HYGIENE FOLLOWING CARDIAC-SURGERY - WHAT IS NECESSARY SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID POSTOPERATIVE PULMONARY COMPLICATIONS; CARDIOPULMONARY BYPASS; PHYSIOTHERAPY REGIMENS; INCENTIVE SPIROMETRY; CONSERVATIVE THERAPY; GENERAL-ANESTHESIA; ATELECTASIS; PREVENTION; LUNG RP KACMAREK, RM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RESP CARE,BOSTON,MA 02114, USA. NR 17 TC 0 Z9 0 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 JUN PY 1995 VL 21 IS 6 BP 467 EP 468 DI 10.1007/BF01706198 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA RF406 UT WOS:A1995RF40600001 PM 7560488 ER PT J AU UEDA, Y LEVINE, BL HUANG, ML FREEMAN, GJ NADLER, LM JUNE, CH WARD, SG AF UEDA, Y LEVINE, BL HUANG, ML FREEMAN, GJ NADLER, LM JUNE, CH WARD, SG TI BOTH CD28 LIGANDS CD80 (B7-1) AND CD86 (B7-2) ACTIVATE PHOSPHATIDYLINOSITOL 3-KINASE, AND WORTMANNIN REVEALS HETEROGENEITY IN THE REGULATION OF T-CELL IL-2 SECRETION SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE B7-1; 87-2; CD28; CD80; CD86 ID PROTEIN-KINASE-C; LYMPHOCYTES-T; D-3 PHOSPHOINOSITIDES; MATURE THYMOCYTES; PHOSPHOLIPASE-C; RECEPTOR; ANTIGEN; INTERLEUKIN-2; RESPONSES; LIGATION AB In this report, the co-stimulatory signals provided by CD80 (B7-1) or CD86 (B7-2) were compared to CD28 ligation by mAb. We demonstrate that while both anti-CD3 and anti-CD28 antibodies induced activation of phosphoinositide (PI) 3-kinase, the kinetics of activation differed. Anti-CD28 produced a sustained activation of PI 3-kinase while anti-CD3 induced activation was transient. Both B7-1 and B7-2 could induce prolonged activation of PI 3-kinase. The co-stimulatory effects of B7-1 and B7-2 were dependent on CD28 cross-linking, based on complete inhibition of PI 3-kinase activation by CD28 antibody Fab fragments. While Jurkat T cells co-stimulated with anti-CD3 and B7-1 or B7-2 secreted high levels of IL-2, there were distinct effects of anti-CD28 mAb and B7-1 or B7-2 on IL-2 secretion in conjunction with protein kinase C activation. To assess functional effects of CD28 ligation, pharmacologic inhibitors of PI 3-kinase were evaluated. In Jurkat cells, efficient inhibition of PI 3-kinase activation after B7-2 stimulation was achieved using wortmannin; however, we observed a surprising increase in IL-2 secretion after B7 or anti-CD28 stimulation. The effect of wortmannin was concentration dependent. Moreover, the effect was specific for receptor-mediated activation as wortmannin did not enhance phorbol ester plus ionomycin-induced IL-2 secretion. Another inhibitor of PI 3-kinase, LY294002, also resulted in augmentation of anti-CD28-induced IL-2 secretion by Jurkat cells. The effects of wortmannin on IL-2 secretion were also examined in primary T cells. In marked contrast, wortmannin resulted in a potent inhibition of anti-CD3 plus B7-1 or anti-CD28-induced IL-2 secretion while phorbol ester plus ionomycin-induced IL-2 secretion was wortmannin resistant. Together these observations demonstrate that signal transduction by both B7-1 and B7-2 involves PI 3-kinase, and that PI 3-kinase or other wortmannin-sensitive targets are important for IL-2 secretion. Finally, treatment of Jurkat cells with PI 3-kinase inhibitors alone was sufficient to induce low levels of IL-2 secretion. This is consistent with the notion that a wortmannin-sensitive target such as PI 3-kinase may down-regulate IL-2 secretion in Jurkat cells. C1 USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20889. GEOCENTERS INC,FT WASHINGTON,MD 20744. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCY,BOSTON,MA 02115. UNIV BATH,SCH PHARM & PHARMACOL,DEPT PHARMACOL,BATH BA2 7AY,AVON,ENGLAND. RI Levine, Bruce/D-1688-2009 NR 58 TC 77 Z9 80 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 1995 VL 7 IS 6 BP 957 EP 966 DI 10.1093/intimm/7.6.957 PG 10 WC Immunology SC Immunology GA RF403 UT WOS:A1995RF40300008 PM 7577804 ER PT J AU LJUNGGREN, HG VANKAER, L SABATINE, MS AUCHINCLOSS, H TONEGAWA, S PLOEGH, HL AF LJUNGGREN, HG VANKAER, L SABATINE, MS AUCHINCLOSS, H TONEGAWA, S PLOEGH, HL TI MHC CLASS-I EXPRESSION AND CD8(+) T-CELL DEVELOPMENT IN TAP1/BETA(2)-MICROGLOBULIN DOUBLE MUTANT MICE SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CLASS I; CYTOTOXICITY; MHC CLASS I; SELECTION; T LYMPHOCYTE ID HEAVY-CHAINS; HISTOCOMPATIBILITY ANTIGEN; DEFICIENT MICE; LYMPHOCYTES-T; RMA-S; BETA-2-MICROGLOBULIN; MOLECULES; PEPTIDES; SURFACE; CD8+ AB We have bred to homozygosity gene disruptions for the transporter associated with antigen processing 1 (TAP1) and beta(2)-microglobulin (beta 2m), each of which plays a distinct role in providing class I MHC subunits, Surface expression of H-2K(b) or D-b on cells derived from TAP1/beta 2m -/- mice was undetectable by immunofluorescence or immunoprecipitation, unlike the situation observed for TAP1 -/- and beta 2m -/- single mutant mice, Yet, TAP1/beta 2m -/- cells were able to elicit a CD8(+) cytotoxic T cell (CTL) response in mice of different H-2 haplotypes and could be killed by anti-H-2(b) specific CTL. Furthermore, TAP1/beta 2m -/- skin grafts were rejected by bm1 mutant mice, This suggests that very low levels of conformed class I heavy chains can reach the cell surface even in the complete absence of TAP1 and beta 2m gene products, and that these molecules may select a functional CD8(+) T cell repertoire, Indeed, CD4(-)CD8(+) T cells were detected in TAP1/beta 2m -/- mice, but in numbers lower than in either of the single mutant mice. Nonetheless, it was possible to elicit a CD8(+) altospecific and H-2(b) reactive CTL response in TAP1/beta 2m -/- mice, In line with this, TAP1/beta 2m -/- mice rapidly rejected TAP1/beta 2m +/- skin grafts, Our results suggest that some MHC class I heavy chains in TAP1/beta 2m -/- cells can reach the cell surface in a form that allows recognition by allospecific CTL and positive selection of CD8(+) T cells. C1 MIT,HOWARD HUGHES MED INST,CTR CANC RES,CAMBRIDGE,MA 02139. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,TRANSPLANTAT UNIT,BOSTON,MA 02114. RI Van Kaer, Luc/H-1033-2015 OI Van Kaer, Luc/0000-0001-5275-2309 NR 45 TC 54 Z9 54 U1 1 U2 1 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 1995 VL 7 IS 6 BP 975 EP 984 DI 10.1093/intimm/7.6.975 PG 10 WC Immunology SC Immunology GA RF403 UT WOS:A1995RF40300010 PM 7577806 ER PT J AU CARLSON, HE GRABER, ML GELATO, MC HERSHMAN, JM AF CARLSON, HE GRABER, ML GELATO, MC HERSHMAN, JM TI ENDOCRINE EFFECTS OF ERYTHROPOIETIN SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS LA English DT Article DE ERYTHROPOIETIN; HORMONES; HEMODIALYSIS ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; IMPROVED SEXUAL FUNCTION; HEMODIALYSIS-PATIENTS; THERAPY; TESTOSTERONE; PROLACTIN; RHUEPO AB Uremic men may manifest a variety of hormonal abnormalities, including decreased serum concentrations of testosterone and thyroid hormones and increased serum levels of growth hormone and prolactin. Some previous investigations have reported that erythropoietin therapy may reverse these hormonal changes. To investigate this possibility further, we measured serum prolactin, testosterone, LH, FSH, TSH, free thyroxine, triiodothyronine, growth hormone and IGF-I in 21 generally elderly male hemodialysis patients before and during erythropoietin therapy; many of the patients also received an anabolic steroid or metoclopramide treatment. Despite a significant erythropoietic response in a majority of the subjects, no significant changes were seen in any of the hormonal parameters other than a small decrease in serum growth hormone concentrations. Advanced age and chronic illness in our patients may have played a role in limiting the hormonal response reported by others. C1 NORTHPORT VET ADM MED CTR,RES SERV,NORTHPORT,NY 11768. SUNY STONY BROOK,DEPT MED,STONY BROOK,NY 11794. W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. RP CARLSON, HE (reprint author), NORTHPORT VET ADM MED CTR,MED SERV 111,NORTHPORT,NY 11768, USA. NR 18 TC 3 Z9 6 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0391-3988 J9 INT J ARTIF ORGANS JI Int. J. Artif. Organs PD JUN PY 1995 VL 18 IS 6 BP 309 EP 314 PG 6 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA RY122 UT WOS:A1995RY12200003 PM 8593965 ER PT J AU BANDETTINI, PA WONG, EC AF BANDETTINI, PA WONG, EC TI EFFECTS OF BIOPHYSICAL AND PHYSIOLOGICAL-PARAMETERS ON BRAIN ACTIVATION-INDUCED R(2)ASTERISK AND R(2) CHANGES - SIMULATIONS USING A DETERMINISTIC DIFFUSION-MODEL SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; NITRIC-OXIDE; MAGNETIC-SUSCEPTIBILITY; MOTOR CORTEX; MR CONTRAST; MICROCIRCULATION; OXYGENATION; ARCHITECTURE; STIMULATION AB A central issue in magnetic resonance imaging of human brain function using blood oxygenation level-dependent (BOLD) contrast is the accurate interpretation of the signal changes that are observed. Using a method that incorporates repeated phase rotation and convolution with a smoothing function to simulate spin diffusion in the presence of magnetic field perturbers, the dependencies of the absolute and relative changes in transverse relaxation rates (Delta R(2)* and Delta R(2)) on biophysical and physiologic parameters were explored. First we introduce the modeling methodology. Then we simulate Delta R(2)* and Delta R(2) as physiologic and biophysical parameters are modulated within the ranges that they vary across subjects and voxels in the brain. The simulations demonstrate that the Delta R(2)* and Delta R(2) values that occur with activation-induced changes in blood oxygenation depend most strongly on the resting state blood volume and field strength. The Delta R(2)*/Delta R(2) ratios depend most strongly on the vessel radius and spin diffusion coefficient. (C) 1995 John Wiley & Sons, Inc. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV CALIF SAN DIEGO,DEPT RADIOL,SAN DIEGO,CA 92103. UNIV CALIF SAN DIEGO,DEPT PSYCHIAT,SAN DIEGO,CA 92103. RP BANDETTINI, PA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR NMR,BOSTON,MA 02129, USA. NR 78 TC 52 Z9 52 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-9457 J9 INT J IMAG SYST TECH JI Int. J. Imaging Syst. Technol. PD SUM-FAL PY 1995 VL 6 IS 2-3 BP 133 EP 152 DI 10.1002/ima.1850060203 PG 20 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA TG991 UT WOS:A1995TG99100002 ER PT J AU CHESLER, DA KWONG, KK AF CHESLER, DA KWONG, KK TI AN INTUITIVE GUIDE TO THE T-1 BASED PERFUSION MODEL SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY LA English DT Article AB We explored a number of theoretical and practical approaches used to understand and optimize contrast to noise of the versatile T-1 based perfusion model. The interplay between tissue T-1 and blood T-1 was investigated. We also provided a succinct evaluation of the several popular T-1 based methods currently applied to measure flow and flow change. (C) 1995 John Wiley & Sons, Inc. RP CHESLER, DA (reprint author), MASSACHUSETTS GEN HOSP,CTR NMR 2301,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-9457 J9 INT J IMAG SYST TECH JI Int. J. Imaging Syst. Technol. PD SUM-FAL PY 1995 VL 6 IS 2-3 BP 171 EP 174 DI 10.1002/ima.1850060206 PG 4 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA TG991 UT WOS:A1995TG99100005 ER PT J AU DRYJA, TP BERSON, EL AF DRYJA, TP BERSON, EL TI RETINITIS-PIGMENTOSA AND ALLIED DISEASES - IMPLICATIONS OF GENETIC-HETEROGENEITY SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RHODOPSIN GENE; MUTATION C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,TAYLOR SMITH LAB,BOSTON,MA 02114. RP DRYJA, TP (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. NR 16 TC 72 Z9 73 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1995 VL 36 IS 7 BP 1197 EP 1200 PG 4 WC Ophthalmology SC Ophthalmology GA RD430 UT WOS:A1995RD43000001 PM 7775097 ER PT J AU URENA, P FERREIRA, A KUNG, VT MORIEUX, C SIMON, P ANG, KS SOUBERBIELLE, JC SEGRE, GV DRUEKE, TB DEVERNEJOUL, MC AF URENA, P FERREIRA, A KUNG, VT MORIEUX, C SIMON, P ANG, KS SOUBERBIELLE, JC SEGRE, GV DRUEKE, TB DEVERNEJOUL, MC TI SERUM PYRIDINOLINE AS A SPECIFIC MARKER OF COLLAGEN BREAKDOWN AND BONE METABOLISM IN HEMODIALYSIS-PATIENTS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID CHRONIC-RENAL-FAILURE; TERMINAL EXTENSION PEPTIDE; URINARY-EXCRETION; CROSS-LINKS; IMMUNORADIOMETRIC ASSAY; PYRIDINIUM CROSSLINKS; PAGETS-DISEASE; OSTEODYSTROPHY; IMMUNOASSAY; RESORPTION AB Type I collagen represents more than 90% of bone matrix Quantitative analysis of collagen cross-link molecules such as pyridinoline (PYD) provides valuable information on bone resorption rate. We have studied 37 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Eighteen of them had tetracycline double labeling, allowing to determine dynamic, in addition to static bone parameters. Measurement of serum-free PYD was performed using a new competitive enzyme immunoassay. Serum PYD values were compared with those of three other serum markers of bone metabolism, namely intact PTH (iPTH), bone-specific alkaline phosphatase (bAP), and osteocalcin, for the correlations with bone histomorphometric parameters. Serum PYD levels (mean +/- SD) were significantly higher in dialysis patients than in normal individuals, 90.6 +/- 99.6 nM versus 1.9 +/- 0.4 nM, respectively. Patients with high turnover bone disease had significantly higher serum PYD levels than patients with normal or low bone turnover, 108.8 +/- 108.0 nM versus 34.1 +/- 12.8 nM, respectively. Serum PYD levels were positively correlated with bone resorption parameters including osteoclast surface (r = 0.59, p < 0.0001) and osteoclast number/mm(2) (r = 0.61, p < 0.0001), and also with bone formation parameters, osteoblast surface (p = 0.43, p < 0.008), double-labeled surface (r = 0.81, p < 0.001), and BFR (r = 0.91, p < 0.0001). The BFR was better correlated with serum PYD levels than with either serum iPTH or osteocalcin concentrations. However, correlation with serun bAP was comparable. Serum cross-linked type I carboxy-terminal telopeptide (ICTP) and type I carboxy-terminal extension peptide (PICP) levels were also significantly increased in both groups of dialysis patients but they did not correlate with any of the bone turnover parameters. In conclusion, PYD, which is a specific serum marker of collagen breakdown, provides valuable information on bone turnover in hemodialysis patients. C1 HOP LARIBOISIERE,INSERM,U349,F-75475 PARIS,FRANCE. METRA BIOSYST INC,PALO ALTO,CA. CTR HOSP ST BRIEUC,SERV NEPHROL,ST BRIEUC,FRANCE. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. RP URENA, P (reprint author), HOP NECKER ENFANTS MALAD,DEPT NEPHROL,INSERM,U90,161 RUE SEVRES,F-75743 PARIS 15,FRANCE. OI Ferreira, Anibal/0000-0002-3300-6033 NR 32 TC 72 Z9 72 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 1995 VL 10 IS 6 BP 932 EP 939 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RM876 UT WOS:A1995RM87600013 PM 7572317 ER PT J AU LENNON, PF RISK, SC AF LENNON, PF RISK, SC TI SUCCESSFUL TREATMENT OF LOW CARDIAC-OUTPUT SYNDROME WITH BETA-ADRENERGIC-BLOCKADE BECAUSE OF IMPROVED EFFECTIVENESS OF AN INTRAAORTIC BALLOON PUMP SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Note DE ADRENERGIC RECEPTOR; ATRIAL FIBRILLATION; AMRINONE; CARDIAC FAILURE; COUNTERPULSATION ID HEMODYNAMIC-CHANGES; PROTAMINE; SURGERY; ESMOLOL C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HOLY CROSS HOSP,SILVER SPRING,MD. RP LENNON, PF (reprint author), BRIGHAM & WOMENS HOSP,DEPT ANESTHESIA,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 20 TC 1 Z9 1 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD JUN PY 1995 VL 9 IS 3 BP 297 EP 300 DI 10.1016/S1053-0770(05)80324-6 PG 4 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA RE608 UT WOS:A1995RE60800012 PM 7669963 ER PT J AU CRAIG, WA AF CRAIG, WA TI ONCE-DAILY VERSUS MULTIPLE-DAILY DOSING OF AMINOGLYCOSIDES SO JOURNAL OF CHEMOTHERAPY LA English DT Article; Proceedings Paper CT Meeting on Isepamicin Once a Day - Enhancing Traditional Aminoglycoside Therapy CY SEP 24-25, 1994 CL ROTHERWICK, ENGLAND DE ISEPAMICIN; AMINOGLYCOSIDES; ONCE-DAILY ADMINISTRATION AB The pharmacodynamic characteristics of isepamicin and other aminoglycosides, both in terms of efficacy and toxicity, explain why once-daily administration of these agents should be the optimal dosing regimen. Isepamicin, as with other aminoglycosides, exhibits concentration-dependent bactericidal activity and produces prolonged post-antibiotic effects against susceptible organisms. High concentrations of these drugs would be expected to produce more rapid and extensive bacterial killing than lower levels. Furthermore, the post-antibiotic effect would protect against bacterial regrowth when serum and tissue concentrations fall below inhibitory levels. In animal models, the magnitude of the peak serum concentration or the area under the concentration-time curve, are the important determinants of efficacy for isepamicin and the other aminoglycosides. Isepamicin also exhibits the ''first-exposure effect'', i.e. initial exposure of bacteria to isepamicin down-regulates subsequent uptake of the drug. During this period of down-regulation, bacteria exhibit decreased killing and shorter post-antibiotic effects. Since the first-exposure effect lasts for several hours, once-daily administration of the aminoglycosides allows for this effect to dissipate completely between doses. High peak concentrations, greater than 8-10 times the minimum inhibitory concentration (MIG), will also decrease the emergence of resistant strains. With regard to toxicity, one of the first steps in the uptake of aminoglycosides into sites of toxicity is their binding to the brush borders of renal cells and to the cochlea and vestibular membranes. Binding to these membranes demonstrates saturable kinetics. As a result, uptake of the aminoglycosides is more efficient with low sustained concentrations than with high intermittent levels. Once-daily dosing of aminoglycosides has consistently been less toxic than more frequent dosing in animals. In clinical studies, once-daily dosing of aminoglycosides compared to two- or three-times daily administration has generally exhibited similar efficacy and toxicity. However, a few studies have shown greater efficacy or lower toxicity with once-daily dosing of aminoglycosides. Once-daily dosing of the aminoglycosides has the potential to enhance efficacy, reduce toxicity, and lower administration costs for this drug class. RP CRAIG, WA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705, USA. NR 0 TC 43 Z9 44 U1 0 U2 2 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD JUN PY 1995 VL 7 SU 2 BP 47 EP 52 PG 6 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA TG379 UT WOS:A1995TG37900006 PM 8622110 ER PT J AU CULLEN, DJ AF CULLEN, DJ TI ANNUAL-REPORT OF THE JOURNAL-OF-CLINICAL-ANESTHESIA - 1994 SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material RP CULLEN, DJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 1995 VL 7 IS 4 BP 271 EP 272 DI 10.1016/0952-8180(95)00031-C PG 2 WC Anesthesiology SC Anesthesiology GA RF556 UT WOS:A1995RF55600001 ER PT J AU MAGRE, J GOLDFINE, AB WARRAM, JH KROLEWSKI, AS KAHN, CR AF MAGRE, J GOLDFINE, AB WARRAM, JH KROLEWSKI, AS KAHN, CR TI ANALYSIS OF THE INSULIN-RECEPTOR GENE IN NONINSULIN-DEPENDENT DIABETES-MELLITUS BY DENATURING GRADIENT GEL BLOTS - A CLINICAL RESEARCH-CENTER STUDY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DNA-SEQUENCE POLYMORPHISMS; TYROSINE KINASE DOMAIN; SINGLE-BASE CHANGES; PIMA-INDIANS; GENOMIC DNA; RESISTANCE; MUTATIONS; NIDDM; ELECTROPHORESIS; PATHOGENESIS AB We have used a new technique of denaturing gradient gel blotting to determine the prevalence of alterations in the intracellular domain of the insulin receptor in normal individuals and subjects with noninsulin-dependent diabetes mellitus (NIDDM). This method detects DNA sequence differences as restriction fragment melting polymorphisms (RFMP) and is sensitive to changes in sequence at both restriction sites and within the fragments themselves. Using restriction digests with AluI, HaeIII, HinfI, RsaI, Sau3A, and Sau96, 12 RFMPs were found to localize to the region of the beta-subunit of the insulin receptor gene. Using exon-specific probes, these RFMPs could be localized to specific regions surrounding individual exons, including exons 14, 15, 17, 19, 20, and 22. In general, linkage disequilibrium between polymorphisms was inversely related to their distance in the gene structure, although there was a ''hot spot'' for recombination between exons 19 and 20. No difference in melting temperatures or allele frequency was observed between NIDDM patients and controls. These data indicate that the region of the insulin receptor gene coding, for the intracellular portion of the beta-subunit is highly polymorphic and that polymorphisms surrounding specific exons can be identified by denaturing gradient gel blotting, but there is no evidence that variation at this locus contributes to NIDDM susceptibility in most individuals. C1 JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. RI MAGRE, Jocelyne/D-4788-2015 FU NIDDK NIH HHS [DK 31036, DK-36836] NR 36 TC 3 Z9 3 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 JUN PY 1995 VL 80 IS 6 BP 1882 EP 1887 DI 10.1210/jc.80.6.1882 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RC751 UT WOS:A1995RC75100022 PM 7775636 ER PT J AU EMANUEL, EJ AF EMANUEL, EJ TI EMPIRICAL-STUDIES ON EUTHANASIA AND ASSISTED SUICIDE SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID DECISION-MAKING; PHYSICIANS; DEATH C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP EMANUEL, EJ (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 18 TC 12 Z9 12 U1 0 U2 0 PU UNIV PUBL GROUP, INC PI FREDERICK PA 12 SOUTH MARKET ST, STE 301, FREDERICK, MD 21701 SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SUM PY 1995 VL 6 IS 2 BP 158 EP 160 PG 3 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA RQ996 UT WOS:A1995RQ99600007 PM 7496021 ER PT J AU GORN, AH RUDOLPH, SM FLANNERY, MR MORTON, CC WEREMOWICZ, S WANG, JT KRANE, SM GOLDRING, SR AF GORN, AH RUDOLPH, SM FLANNERY, MR MORTON, CC WEREMOWICZ, S WANG, JT KRANE, SM GOLDRING, SR TI EXPRESSION OF 2 HUMAN SKELETAL CALCITONIN RECEPTOR ISOFORMS CLONED FROM A GIANT-CELL TUMOR OF BONE - THE FIRST INTRACELLULAR DOMAIN MODULATES LIGAND-BINDING AND SIGNAL-TRANSDUCTION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE OSTEOCLAST; CYCLIC AMP; G PROTEIN; G PROTEIN-COUPLED RECEPTOR; CHROMOSOMAL MAPPING ID BETA-ADRENERGIC-RECEPTOR; HORMONE-RELATED PEPTIDE; MOLECULAR-CLONING; BETA-2-ADRENERGIC RECEPTOR; PARATHYROID-HORMONE; CYTOPLASMIC DOMAINS; SYNTHETIC PEPTIDES; PROTEIN; IDENTIFICATION; RAT AB Two distinct calcitonin (CT) receptor (CTR)-encoding cDNAs (designated GC-2 and GC-10) were cloned and characterized from giant cell tumor of bone (GCT). Both GC-2 and GC-10 differ structurally from the human ovarian cell CTR (o-hCTR) that we cloned previously, but differ from each other only by the presence (GC-10) or absence (GC-2) of a predicted 16-amino acid insert in the putative first intracellular domain, Expression of all three CTR isoforms in COS cells demonstrated that GC-2 has a lower binding affinity for salmon (s) CT (K-d similar to 15 nM) than GC-10 or o-hCTR (K-d similar to 1.5 nM). Maximal stimulatory concentrations of CT resulted in a mean accumulation of cAMP in GC-2 transfected cells that was greater than eight times higher than in cells transfected with GC-10 after normalizing for the number of receptor-expressing cells, The marked difference in maximal cAMP response was also apparent after normalizing for receptor number, GC-2 also demonstrated a more potent ligand-mediated cAMP response compared with GC-1O for both human (h) and sCT (the ECS, values for GC-2 were similar to 0.2 nM for sCT and similar to 2 nM for hCT; EC(50) values for GC-10 were similar to 6 nM for sCT and similar to 25 nM for hCT), Reverse transcriptase PCR of GCT RNA indicated that GC-2 transcripts are more abundant than those encoding for GC-10. In situ hybridization on GCT tissue sections demonstrated CTR mRNA expression in osteoclast-like cells. We localized the human CTR gene to chromosome 7 in band q22. The distinct functional characteristics of GC-2 and GC-10, which differ in structure only in the first intracellular domain, indicate that the first intracellular domain of the CTR plays a previously unidentified role in modulating ligand binding and signal transduction via the G protein/adenylate cyclase system. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MED SERV,ARTHRITIS UNIT,BOSTON,MA 02114. NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAMS NIH HHS [AR-03564, AR-07258]; NIDDK NIH HHS [DK-46773] NR 66 TC 84 Z9 85 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 PY 1995 VL 95 IS 6 BP 2680 EP 2691 DI 10.1172/JCI117970 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RB212 UT WOS:A1995RB21200033 PM 7769107 ER PT J AU DELAMATA, J UY, HL GUISE, TA STORY, B BOYCE, BF MUNDY, GR ROODMAN, GD AF DELAMATA, J UY, HL GUISE, TA STORY, B BOYCE, BF MUNDY, GR ROODMAN, GD TI INTERLEUKIN-6 ENHANCES HYPERCALCEMIA AND BONE-RESORPTION MEDIATED BY PARATHYROID HORMONE-RELATED PROTEIN IN-VIVO SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE OSTEOCLAST; MALIGNANCY; CYTOKINE; PARATHYROID HORMONE-RELATED PROTEIN; INTERLEUKIN-6 ID CELL-LINES; NUDE-MICE; IL-6; CARCINOMA; CACHEXIA; MURINE; SERUM AB Tumors frequently induce the multifunctional cytokine IL-6, which has been linked to several paraneoplastic syndromes, most notably cachexia. IL-6 stimulates osteoclast formation, causes mild hypercalcemia, and is produced by bone cells in vitro upon exposure to systemic hormones. Since IL-6 is produced together with parathyroid hormone-related protein (PTH-rP) in some patients with cancer, we tested the hypothesis that production of IL-6 potentiates the effects of PTH-rP on Ca2+ homeostasis and osteoclastic bone resorption and examined potential mechanisms for these interactions in vivo. Chinese hamster ovarian (CHO) cells stably transfected with cDNAs for IL-6 (CHO/IL-6) and PTH-rP sense (CIIO/PTH-rP) or antisense (CHO/PTH-rP AS) were inoculated intramuscularly into nude mice. Experimental groups included CHO/IL-6 plus CHO/PTH-rP; CHO/IL-6 plus CHO/PTH-rP AS; CHO/IL-6 alone; and CHO/PTH-rP alone. Blood ionized Ca2+ was measured on days 0, 7, 10, 12, and 13. Three different developmental stages in the osteoclast lineage were examined at day 13: the early multipotential precursor, granulocyte macrophage colony-forming units (CFU-GM); more mature mononuclear osteoclast precursors, assessed by their capacity to form tartrate-resistant acid phosphatase-positive multinucleated cells in marrow cultures; and mature osteoclasts, assessed by histomorphometry, IL-6 increased CFU-GM but not bone resorption or Ca2+. In contrast, PTH-rP induced hypercalcemia and bone resorption and increased multinucleated osteoclasts and more mature precursors cells; but not CFU-GM. However, mice treated with both IL-6 and PTH-rP had very marked hypercalcemia and osteoclastosis as well as an increase in the number of both CFU-GM: and mature osteoclast precursors. These data demonstrate that IL-6 enhances PTH-rP-mediated hypercalcemia and bone resorption, most likely by increasing the pool of early osteoclast precursors that in turn can differentiate to mature osteoclasts. We conclude that IL-6 stimulatory effects on osteoclast precursors may enhance the effects of other bone resorption factors that act at later stages in the osteoclast lineage. C1 AUDIE L MURPHY MEM VET ADM MED CTR,RES SERV 151,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. FU NIAMS NIH HHS [K08-AR01899, P01-AR39529]; NIDCR NIH HHS [DE08569] NR 21 TC 170 Z9 173 U1 1 U2 3 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 PY 1995 VL 95 IS 6 BP 2846 EP 2852 DI 10.1172/JCI117990 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RB212 UT WOS:A1995RB21200053 PM 7769125 ER PT J AU ALLES, AJ WALDRON, MA SIERRA, LS MATTIA, AR AF ALLES, AJ WALDRON, MA SIERRA, LS MATTIA, AR TI PROSPECTIVE COMPARISON OF DIRECT IMMUNOFLUORESCENCE AND CONVENTIONAL STAINING METHODS FOR DETECTION OF GIARDIA AND CRYPTOSPORIDIUM SPP IN HUMAN FECAL SPECIMENS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID OOCYSTS; CYSTS AB In a prospective comparative study, 2,696 consecutive fresh stool specimens over the course of 1 year were examined for Giardia lamblia and Cryptosporidium parvum by using a direct immunofluorescent-monoclonal antibody stain (for unspun specimens) and conventional staining methods (chlorazol black E for Giardia cysts and modified Kinyoun acid-fast for Cryptosporidium oocysts). The direct immunofluorescent-monoclonal antibody method resulted in a significantly increased detection rate for both giardia (118 versus 79 specimens, 49.4%; P = 0.006) and cryptosporidia (39 versus 23 specimens, 69.6%; P = 0.055). C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CLIN MICROBIOL LAB,BOSTON,MA 02114. NR 15 TC 43 Z9 52 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1995 VL 33 IS 6 BP 1632 EP 1634 PG 3 WC Microbiology SC Microbiology GA QZ723 UT WOS:A1995QZ72300040 PM 7544365 ER PT J AU CALIENDO, AM JORDAN, CD RUOFF, KL AF CALIENDO, AM JORDAN, CD RUOFF, KL TI HELCOCOCCUS, A NEW GENUS OF CATALASE-NEGATIVE, GRAM-POSITIVE COCCI ISOLATED FROM CLINICAL SPECIMENS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID BACTEREMIA AB Clinical data from 10 patients whose cultures yielded Helcococcus kunzii are reviewed in order to investigate a possible clinical role for this recently described catalase-negative, facultatively anaerobic, gram-positive coccus. C1 MASSACHUSETTS GEN HOSP,MICROBIOL LABS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 8 TC 22 Z9 24 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1995 VL 33 IS 6 BP 1638 EP 1639 PG 2 WC Microbiology SC Microbiology GA QZ723 UT WOS:A1995QZ72300042 PM 7650202 ER PT J AU ANDERSON, KC AF ANDERSON, KC TI WHO BENEFITS FROM HIGH-DOSE THERAPY FOR MULTIPLE-MYELOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; PLASMA-CELL MYELOMA; COMBINATION CHEMOTHERAPY; INTENSIVE THERAPY; MELPHALAN; BLOOD; CHEMORADIOTHERAPY; CYCLOPHOSPHAMIDE; BUSULFAN; INDUCTION RP ANDERSON, KC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 69 TC 29 Z9 29 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 1995 VL 13 IS 6 BP 1291 EP 1296 PG 6 WC Oncology SC Oncology GA RB208 UT WOS:A1995RB20800002 PM 7751873 ER PT J AU WILLETT, CG WARLAND, G HAGAN, MP DALY, WJ COEN, J SHELLITO, PC COMPTON, CC AF WILLETT, CG WARLAND, G HAGAN, MP DALY, WJ COEN, J SHELLITO, PC COMPTON, CC TI TUMOR PROLIFERATION IN RECTAL-CANCER FOLLOWING PREOPERATIVE IRRADIATION SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL NUCLEAR ANTIGEN; DNA POLYMERASE-DELTA; GROWTH FRACTION; PARAFFIN SECTIONS; RADIATION-THERAPY; MONOCLONAL-ANTIBODIES; AUXILIARY PROTEIN; EMBEDDED TISSUES; FLOW-CYTOMETRY; CYCLIN PCNA AB Purpose: This study examines the effect of preoperative irradiation on tumor proliferation in rectal cancer. Patients and Methods: One hundred twenty-two patients with locally advanced rectal cancer received 45 to 50 Gy of preoperative irradiation followed by surgery, Pretreatment tumor biopsies and postirradiation surgical specimens were scored for proliferative activity by assaying the extent of Ki-67 and proliferating-cell nuclear antigen (PCNA) immunostaining and the number of mitoses per 10 high-power fields (hpf), Preirradiation and postirradiation proliferative activity was determined and correlated to clinical outcome. Results: There was an overall reduction in the tumor proliferative activity of rectal cancer after irradiation compared with its preirradiation state. Decreases in the activity of all three markers of tumor proliferation (Ki-67 and PCNA immunostaining, and mitotic counts) were observed in irradiated tumors compared with pretreatment biopsies, postirradiation tumor proliferative activity was associated with pathologic tumor stage. A high level of proliferative activity was observed in tumors downstaged to the rectal wall (T1-2) compared with tumors that retained transmural penetration (T3-4), Multivariate analysis indicated that postirradiation proliferative activity and stage were independently associated with survival following surgery. patients with tumors that exhibited elevated proliferative activity postirradiation had improved survival compared with patients with tumors that showed less proliferative activity. Conclusion: Moderate- to high-dose preoperative irradiation decreases both the tumor size and proliferative activity of rectal cancers, Elevated postirradiation tumor proliferative activity correlates strongly with improved survival. This may aid in identifying high-risk patients following preoperative irradiation and surgery. (C) 1995 by American Society of Clinical Oncology. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT GEN SURG,BOSTON,MA 02114. RP WILLETT, CG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,COX BLDG,100 BLOSSOM ST,BOSTON,MA 02114, USA. NR 42 TC 90 Z9 93 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 1995 VL 13 IS 6 BP 1417 EP 1424 PG 8 WC Oncology SC Oncology GA RB208 UT WOS:A1995RB20800019 PM 7751887 ER PT J AU ETTINGER, DS FINKELSTEIN, DM SARMA, RP JOHNSON, DH AF ETTINGER, DS FINKELSTEIN, DM SARMA, RP JOHNSON, DH TI PHASE-II STUDY OF PACLITAXEL IN PATIENTS WITH EXTENSIVE-DISEASE SMALL-CELL LUNG-CANCER - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP STUDY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TAXOL; INVITRO; TRIAL AB Purpose: To evaluate the efficacy and safety of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ), a novel diterpene plant product in the treatment of previously untreated patients with extensive-disease small-cell lung cancer (SCLC). Patients and Methods: Patients with extensive-disease SCLC received paclitaxel 250 mg/m(2) intravenously over 24 hours every 3 weeks. Nonresponders or partial responders, who received the maximum number of cycles (n=4) of paclitaxel recieved salvage chemotherapy that consisted of etoposide (VP-16) 120 mg/m(2) intravenously over 45 minutes on days 1,2, and 3, and cisplatin 60 mg/m(2) intravenously as a short infusion on day 1. Cycles were repeated every 3 weeks. Results: Of 36 patients entered onto the study, 34 and 32 patients were assessable for toxicity and response, respectively. No complete responses (CRs) were observed. Eleven patients (34%) had a partial response (PR) and six (19%) had stable disease (SD). In three of six patients categorized as having SD, there was greater than 50% tumor shrinkage. However, no 4-week follow-up measurements were made, so these could not be considered PRs, in part because patients received salvage chemotherapy by study design. In this trial, induction and salvage chemotherapy resulted in a response (two Crs and 15 PRs)(53%) in 17 patients. The estimated median survival duration was 43 weeks. Dose-limiting toxicity was leukopenia, with 19 patients who experienced other grade 4 toxicities were as follows: pulmonary, three (9%); liver, two (6%); cardiac, one (3%); stomatitis, one (3%); and allergic reaction, one (3%). Four additional patients had grade 3 leukopenia and one patient (3%) died of sepsis (grade 5 toxicity). Conclusion: Paclitaxel is an active new agent in the treatment of SCLC. Further investigation of this agent in combination with other agents is appropriate. (C) 1995 by American Society Clinical Oncology. C1 DANA FARBER CANC INST,BOSTON,MA 02115. EMORY UNIV,ATLANTA,GA 30322. VANDERBILT UNIV,NASHVILLE,TN. RP ETTINGER, DS (reprint author), JOHNS HOPKINS UNIV,CTR ONCOL,DEPT ONCOL,600 N WOLFE ST,BALTIMORE,MD 21287, USA. RI Johnson, David/A-7437-2009 FU NCI NIH HHS [CA16116, CA49957, CA66636] NR 15 TC 163 Z9 164 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 1995 VL 13 IS 6 BP 1430 EP 1435 PG 6 WC Oncology SC Oncology GA RB208 UT WOS:A1995RB20800021 PM 7751889 ER PT J AU AISNER, J CIRRINCIONE, C PERLOFF, M PERRY, M BUDMAN, D ABRAMS, J PANASCI, L MUSS, H CITRON, M HOLLAND, J WOOD, W HENDERSON, IC AF AISNER, J CIRRINCIONE, C PERLOFF, M PERRY, M BUDMAN, D ABRAMS, J PANASCI, L MUSS, H CITRON, M HOLLAND, J WOOD, W HENDERSON, IC TI COMBINATION CHEMOTHERAPY FOR METASTATIC OR RECURRENT CARCINOMA OF THE BREAST - A RANDOMIZED PHASE-III TRIAL COMPARING CAF VERSUS VATH VERSUS VATH ALTERNATING WITH CMFVP - CANCER AND LEUKEMIA GROUP-B STUDY-8281 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHEMO-IMMUNOTHERAPY; 5-FLUOROURACIL CAF; PROGNOSTIC FACTORS; PREDNISONE CMFVP; ADRIAMYCIN; METHOTREXATE; THERAPY; VINCRISTINE; CYCLOPHOSPHAMIDE; VINBLASTINE AB Purpose: We sought to compare three doxorubicin based therapies for metastatic breast cancer for response frequency, time to treatment failure (TTF), and survival. Materials and Methods: Women with metastatic breast cancer who had measurable disease, required laboratory tests, had received no prior chemotherapy for metastases, had a Cancer and Leukemia Group B (CALGB) performance status less than or equal to 2, and provided informed consent were eligible. Treatment included the following: arm I-cyclophosphamide, doxorubicin, and fluorouracil (CAF); arm II-vinblastine, doxorubicin, thiotepa, and halotestin (VATH); and arm III-VATH alternating with cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) on cycles 3, 5, 7, 9, etc. Doses were modified for toxicities. Standard CALGB response and toxicity criteria were used. Results: Between August 1982 and February 1987, 497 women were entered and 491 were treated on study. Pretreatment characteristics were well balanced and the median follow-up duration was 79 months. There were no significant differences in response (complete [CR] plus partial [PR]) at 50% on arm I, 57% on arm II, and 51% on arm III. The median TTFs were 8, 8, and 9 months, respectively, in favor of arm ill when compared with arm I (P = .028). The median survival times for treatment arms I, II, and III were 15, 17, and 17 months, respectively. After multivariate regression analyses, only estrogen receptors (ER), performance status, and number of metastatic sites influenced TTF and survival. Leukopenia was the most common grade 3 or 4 toxicity, occurring in 90%, 80%, and 92% of patients per arm, respectively, Lethal toxicities were seen in four, five, and six women, respectively. Overall, there were more grade greater than or equal to 3 toxicities on arm II than I, and most occurred on arm III (P = .02). Conclusion: The VATH regimen appears similarly effective to the CAF regimen as initial therapy. Alternating CMFVP with VATH did not improve response rate or survival. After accounting for other variables, treatment arm was not related to outcome. New therapeutic regimens are still needed. (C) 1995 by American Society of Clinical Oncology. C1 UNIV MARYLAND, CTR CANC, BALTIMORE, MD 21201 USA. CTR STAT, CANC & LEUKEMIA GRP B, DURHAM, NC USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, WINSTON SALEM, NC USA. MT SINAI MED CTR, COLUMBIA PRESBYTERIAN MED CTR, NEW YORK, NY 10029 USA. LONG ISL JEWISH MED CTR, LONG ISL, NY USA. UNIV MISSOURI, ELLIS FISCHEL CANC CTR, COLUMBIA, MO USA. MCGILL UNIV, JEWISH GEN HOSP, MONTREAL, PQ H3T 1E2, CANADA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. FU NCI NIH HHS [CA31983, CA33601, CA12011] NR 45 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1995 VL 13 IS 6 BP 1443 EP 1452 PG 10 WC Oncology SC Oncology GA RB208 UT WOS:A1995RB20800023 PM 7751891 ER PT J AU FALKSON, G HOLCROFT, C GELMAN, RS TORMEY, DC WOLTER, JM CUMMINGS, FJ AF FALKSON, G HOLCROFT, C GELMAN, RS TORMEY, DC WOLTER, JM CUMMINGS, FJ TI 10-YEAR FOLLOW-UP-STUDY OF PREMENOPAUSAL WOMEN WITH METASTATIC BREAST-CANCER - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP STUDY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LEUKEMIA-GROUP-B; LONG-TERM SURVIVAL; COMBINATION CHEMOTHERAPY; 5-FLUOROURACIL CAF; PROGNOSTIC FACTORS; RANDOMIZED TRIAL; CYCLOPHOSPHAMIDE; METHOTREXATE; ADRIAMYCIN; THERAPY AB Purpose: To investigate the long-term survival of premenopausal women with previously untreated first recurrence or metastases of breast cancer entered on Eastern Cooperative Oncology Group (ECOG) study 2177 (EST 2177), which completed accrual in June 1983, Materials and Methods: One hundred forty-seven premenopausal women with metastatic breast cancer were entered onto the study, Eighty-nine patients with estrogen receptor (ER)-positive and ER-unknown disease were randomized to receive cyclophosphamide (CTX), doxorubicin (ADR), and fluorouracil (FU) (CAF) or surgical oophorectomy plus CAF (O + CAF). Fifty eight patients with known ER-negative disease were treated with CAF. Survival time was measured from the time of study entry, Randomization was stratified by performance status (PS), dominant metastatic site, and ER status, Results: One hundred thirty patients were eligible. The median survival time of randomized patients was 35 months (90% confidence interval, 28.9 to 54.3), with 28% alive at 5 years. The overall median survival duration, including ER-negative patients, wets 30 months, There was no significant difference in survival time between the randomized treatments (median, 42 months for O + CAF and 30 months for CAF). In models of survival time, age greater than or equal to 45 years and last menstruation within 1 month were associated with significantly longer survival (P < .004 for each). There were also three significant interactions with treatment (even after correction for multiple comparisons): age (P = .00009; O + CAF associated with longer survival in patients < 45 years, CAF associated with longer survival in patients > 45 years), PS (P = .002; O + CAF associated with consistently better survival in PS O patients), and disease-free interval (DFI), Conclusion: Long-term follow-vp data of premenopausal women with metastatic breast cancer show ct longer than expected median survival time at 2.5 years overall and close to 5 years for patients treated with O + CAF who were ER-positive or had a good PS. (C) 1995 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,BOSTON,MA 02115. AMC,CTR CANC RES,DENVER,CO. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. ROGER WILLIAMS GEN HOSP,PROVIDENCE,RI 02908. RP FALKSON, G (reprint author), UNIV PRETORIA,DEPT MED ONCOL,POB 667,PRETORIA 0001,SOUTH AFRICA. FU NCI NIH HHS [CA23318, CA21115, CA21692] NR 27 TC 52 Z9 53 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 1995 VL 13 IS 6 BP 1453 EP 1458 PG 6 WC Oncology SC Oncology GA RB208 UT WOS:A1995RB20800024 PM 7751892 ER PT J AU MIGUEL, EC COFFEY, BJ BAER, L SAVAGE, CR RAUCH, SL JENIKE, MA AF MIGUEL, EC COFFEY, BJ BAER, L SAVAGE, CR RAUCH, SL JENIKE, MA TI PHENOMENOLOGY OF INTENTIONAL REPETITIVE BEHAVIORS IN OBSESSIVE-COMPULSIVE DISORDER AND TOURETTES DISORDER SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Academy-of-Child-and-Adolescent-Psychiatry CY OCT 26-31, 1993 CL SAN ANTONIO, TX SP Amer Acad Child & Adolescent Psychiat ID SCALE; INVENTORY AB Background: Recent evidence suggests that obsessive-compulsive disorder (OCD) and Tourette's disorder are related and have overlapping clinical features. The purpose of this study was to test the following hypotheses regarding intentional repetitive behaviors in these two disorders: (1) In OCD without comorbid Tourette's, they are preceded by cognitive phenomena and autonomic anxiety, but not sensory phenomena, and (2) in Tourette's without comorbid OCD, they are preceded by sensory phenomena, but not cognitive phenomena nor autonomic anxiety. Method: Fifteen adult OCD outpatients without tics and 17 adult Tourette's outpatients without OCD were evaluated with a structured interview. Questions assessed cognitive, sensory, and affective experiences related to intentional repetitive behaviors. Results: Five of 17 Tourette's subjects were excluded because they had only unintentional or occasionally intentional tics. All OCD patients reported some cognitions preceding their intentional repetitive behaviors, whereas only 2 of 12 Tourette's patients reported cognitions. In comparison, all Tourette's patients reported sensory phenomena preceding repetitive behaviors, and none of the OCD patients reported such sensations. In addition, 13 OCD patients reported at least mild autonomic anxiety associated with their repetitive behaviors, whereas no Tourette's patients reported such symptoms. Conclusion: Intentional repetitive behaviors in OCD differ from those in Tourette's and are associated with cognitive and autonomic phenomena. Sensory phenomena preceded intentional repetitive behaviors in Tourette's but not in OCD patients. The dimensions examined in this study (cognition, sensory phenomena, and autonomic anxiety) may represent valid clinical factors for characterization of repetitive behaviors in OCD and Tourette's. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MCLEAN HOSP,DEPT PSYCHIAT,TOURETTE CLIN,BELMONT,MA 02178. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV SAO PAULO,SCH MED,DEPT PSYCHIAT,SAO PAULO,BRAZIL. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,OCD CLIN & RES UNIT,BOSTON,MA 02114. RI Miguel, Euripedes/B-2871-2008 NR 21 TC 91 Z9 94 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 1995 VL 56 IS 6 BP 246 EP 255 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA RD447 UT WOS:A1995RD44700005 PM 7775367 ER PT J AU SUBRAMANIAM, M SAFFARIPOUR, S WATSON, SR MAYADAS, TN HYNES, RO WAGNER, DD AF SUBRAMANIAM, M SAFFARIPOUR, S WATSON, SR MAYADAS, TN HYNES, RO WAGNER, DD TI REDUCED RECRUITMENT OF INFLAMMATORY CELLS IN A CONTACT HYPERSENSITIVITY RESPONSE IN P-SELECTIN-DEFICIENT MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID MAST-CELLS; T-CELLS; ANTIBODY; ALPHA; EXPRESSION; MOLECULE AB The inflammatory response at sites of contact hypersensitivity induced by oxazolone was examined in the ears of P-selectin-deficient and wild-type mice. Accumulation of CD4(+) T lymphocytes, monocytes, and neutrophils was reduced significantly in the mutant mice, as well as mast cell degranulation. In contrast, there was no significant difference in vascular permeability or edema between the two genotypes. The results demonstrate a role for P-selectin in recruitment of CD4(+) T lymphocytes and show that P-selectin plays a role in long-term inflammation as well as in acute responses. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02215. MIT,DEPT BIOL,CTR CANC RES,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. GENENTECH INC,DEPT IMMUNOL,S SAN FRANCISCO,CA 94080. FU NHLBI NIH HHS [P01 HL-42443, P01 HL-41484]; PHS HHS [R01 H153756] NR 35 TC 131 Z9 132 U1 1 U2 2 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 1995 VL 181 IS 6 BP 2277 EP 2282 DI 10.1084/jem.181.6.2277 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RA605 UT WOS:A1995RA60500038 PM 7539046 ER PT J AU GERACI, JM ASHTON, CM KUYKENDALL, DH JOHNSON, ML WU, L AF GERACI, JM ASHTON, CM KUYKENDALL, DH JOHNSON, ML WU, L TI IN-HOSPITAL COMPLICATIONS AMONG SURVIVORS OF ADMISSION FOR CONGESTIVE-HEART-FAILURE, CHRONIC OBSTRUCTIVE PULMONARY-DISEASE, OR DIABETES-MELLITUS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE COMPLICATIONS; CONGESTIVE HEART FAILURE; DIABETES MELLITUS; CHRONIC OBSTRUCTIVE PULMONARY DISEASE; IATROGENIC DISEASE AB OBJECTIVE: To determine the frequency of hospital complications among survivors of inpatient treatment for congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), or diabetes mellitus (DM). DESIGN: Retrospective cohort study, SETTING: Nine Veterans Affairs hospitals in the southern United States. PATIENTS: 1,837 men veterans discharged alive following hospitalization for CHF, COPD, or DM between January 1987 and December 1989. This patient population represents a subset of cases gathered to study the process of care in the hospital and subsequent early readmission; thus, veterans who died in the hospital were not included. MEASUREMENTS: Medical record review to record the occurrence of any of 30 in-hospital complications such as cardiac arrest, nosocomial infections, or delirium (overall agreement between two reviewers = 84%,kappa = 0.37), RESULTS: Complications occurred in 15.7% of the CHF cases, 13.1% of the COPD cases, and 14.8% of the DM cases, Hypoglycemic reactions were the most frequent individual adverse events in the CHF and DM cases (3.6% and 11.4% of the cases, respectively), and theophylline toxicity was most frequent among the COPD cases (4.9%). Patient age, the presence of comorbid diseases, and the Acute Physiology Score (APS) of APACHE II were associated with complication occurrence, For each disease, the patients who had a complication had significantly longer mean hospital stays than did the patients who did not have complications (14.6 to 14.9 days vs 7.2 to 8.2 days, p < 0.01), CONCLUSIONS: Complications are frequent among patients discharged alive with CHF, COPD, or DM, The patients who experienced complications were more ill on admission and had longer hospital stays. RP GERACI, JM (reprint author), BAYLOR COLL MED,HOUSTON VAMC,HOUSTON CTR QUAL CARE & UTILIZAT STUDIES,MED SERV IIIC,HOUSTON,TX 77030, USA. NR 0 TC 17 Z9 17 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 1995 VL 10 IS 6 BP 307 EP 314 DI 10.1007/BF02599949 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA RD788 UT WOS:A1995RD78800002 PM 7562121 ER PT J AU BOZIC, CR KOLAKOWSKI, LF GERARD, NP GARCIARODRIGUEZ, C VONUEXKULLGULDENBAND, C CONKLYN, MJ BRESLOW, R SHOWELL, HJ GERARD, C AF BOZIC, CR KOLAKOWSKI, LF GERARD, NP GARCIARODRIGUEZ, C VONUEXKULLGULDENBAND, C CONKLYN, MJ BRESLOW, R SHOWELL, HJ GERARD, C TI EXPRESSION AND BIOLOGIC CHARACTERIZATION OF THE MURINE CHEMOKINE KC SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-2; INTERCRINE CYTOKINE FAMILY; EPITHELIOID CELL-LINE; HUMAN EOSINOPHILS; GROWTH-FACTOR; INTERLEUKIN-8; RECEPTOR; CLONING; RANTES; ACTIVATION AB KC, the product of an immediate early gene induced in mouse fibroblasts by platelet-derived growth factor, was expressed in Escherichia coli by using a maltose binding protein vector and biochemically characterized as a ligand for both murine and human polymorphonuclear neutrophils (PMN). On murine PMN, KC is both a potent chemoattractant and up-regulator of Mac-1 cell surface expression. On human PMN, in contrast, KC exhibits dissociation of its chemoattractant and Mac-1 up-regulatory activities. Although KC strongly increases Mac-1 expression on human PMN, it does not induce chemotaxis in vitro. I-125-KC-Tyr binds to both mouse and human PMN with two classes of binding sites, including high affinity sites of 0.8 and 2 nM, with similar to 9,000 and 10,000 sites per cell, respectively. On mouse PMN, human macrophage inflammatory protein (MIP)-2 alpha and MIP-2 beta compete for I-125-KC-Tyr binding with high affinity, whereas the murine beta-chemokine TCA-3 does not compete. KC binds to human PMN by the IL-8 type B receptor and to murine PMN by a murine IL-8 type B receptor homologue. I-125-KC-Tyr also binds to human RBC with a single class of high affinity sites. KC mRNA is constitutively expressed in multiple murine tissues. With human IL-8 and KC cDNA as probes, a mouse neutrophil exudate library was screened: KC and MIP-2 were the dominant chemokine species found. Thus, KC appears to be intimately involved in murine inflammation and its constitutive expression may have a role in the basal trafficking of neutrophils. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,INA SUE PERLMUTTER LAB,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,THORNDIKE LAB,BOSTON,MA 02115. PFIZER INC,CENT RES,DIV INFECT DIS & IMMUNOL,GROTON,CT 06340. FU NHLBI NIH HHS [HL71910, HL36162] NR 42 TC 247 Z9 249 U1 0 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 1995 VL 154 IS 11 BP 6048 EP 6057 PG 10 WC Immunology SC Immunology GA RB197 UT WOS:A1995RB19700048 PM 7751647 ER PT J AU HAMMOND, SA JOHNSON, RP KALAMS, SA WALKER, BD TAKIGUCHI, M SAFRIT, JT KOUP, RA SILICIANO, RF AF HAMMOND, SA JOHNSON, RP KALAMS, SA WALKER, BD TAKIGUCHI, M SAFRIT, JT KOUP, RA SILICIANO, RF TI AN EPITOPE-SELECTIVE, TRANSPORTER ASSOCIATED WITH ANTIGEN PRESENTATION (TAP)-1/2-INDEPENDENT PATHWAY AND A MORE GENERAL TAP-1/2-DEPENDENT ANTIGEN-PROCESSING PATHWAY ALLOW RECOGNITION OF THE HIV-1 ENVELOPE GLYCOPROTEIN BY CD8(+) CTL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; HUMAN-IMMUNODEFICIENCY-VIRUS; TOXIC LYMPHOCYTES-T; CLASS-I MOLECULES; MUTANT-CELL LINE; HLA-B ANTIGENS; ENDOPLASMIC-RETICULUM; SIGNAL-SEQUENCE; INFLUENZA-VIRUS; DEFECTIVE PRESENTATION AB The lysis of virally infected cells by CTLs requires the recognition of processed fragments of viral proteins presented in association with class I MHC molecules on the surfaces of infected cells. Processing begins in the cytosol with the degradation of viral proteins into peptides that are then transported into the endoplasmic reticulum (ER) for association with newly synthesized class I molecules. Transport is mediated by a heterodimer of the MHC-encoded proteins, transporter associated with Ag presentation (TAP)-1 and TAP-2. Uncertainty exists over the site of processing of viral envelope (env) proteins. The extracellular domains of env proteins are not present in the cytosol, the site in which the class I-restricted Ag-processing pathway begins. Rather, the ecto-domains of env proteins are cotranslationally translocated into the ER during biosynthesis. We have analyzed the processing of the HIV-1 env protein by using a large series of env-specific human CD8(+) CTL clones. These studies have led to the delineation of two distinct processing pathways. The first pathway permits a subset of class I-restricted epitopes in the ectodomain of the env protein to be generated efficiently by a TAP-1/2-independent mechanism localized to the ER or a premedial Golgi compartment. A second, more general pathway that is capable of generating all env epitopes uses as a substrate env protein mislocalized to the cytosol and produces peptides that are transported from the cytoplasm to the ER in a TAP-1/2-dependent fashion. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV TOKYO,INST MED SCI,TOKYO,JAPAN. NYU,SCH MED,NEW YORK,NY 10016. AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. RI Takiguchi, Masafumi/E-7468-2013 FU NIAID NIH HHS [AI28108, AI30358, AI32871] NR 85 TC 70 Z9 71 U1 0 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 1995 VL 154 IS 11 BP 6140 EP 6156 PG 17 WC Immunology SC Immunology GA RB197 UT WOS:A1995RB19700058 PM 7538543 ER PT J AU DEZUBE, BJ LEDERMAN, MM SPRITZLER, JG CHAPMAN, B KORVICK, JA FLEXNER, C DANDO, S MATTIACCI, MR AHLERS, CM ZHANG, L NOVICK, WJ KASDAN, P FAHEY, JL PARDEE, AB CRUMPACKER, CS AF DEZUBE, BJ LEDERMAN, MM SPRITZLER, JG CHAPMAN, B KORVICK, JA FLEXNER, C DANDO, S MATTIACCI, MR AHLERS, CM ZHANG, L NOVICK, WJ KASDAN, P FAHEY, JL PARDEE, AB CRUMPACKER, CS TI HIGH-DOSE PENTOXIFYLLINE IN PATIENTS WITH AIDS - INHIBITION OF TUMOR-NECROSIS-FACTOR PRODUCTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID BLOOD MONONUCLEAR-CELLS; REPLICATION; EXPRESSION; DECREASES AB Tumor necrosis factor-alpha (TNF) may activate human immunodeficiency virus (HIV), antagonize zidovudine activity, and contribute to AIDS wasting syndrome. Pentoxifylline decreases TNF production. In cell culture, pentoxifylline decreases HIV replication and gene expression, Since an AIDS Clinical Trial Group study suggested that pentoxifylline (400 mg thrice daily) is safe in AIDS patients and decreases TNF mRNA levels in peripheral blood mononuclear cells (PBMC), a second cohort received 800 mg thrice daily for 8 weeks, During treatment, the median decrease in TNF production by PBMC cultured with 0.1 mu g/mL lipopolysaccharide (LPS) was 40%. The median change in TNF mRNA was a 34% decrease, Pentoxifylline did not affect HIV levels as detected by quantitative microculture or serum p24 antigen measurements, nor did it alter zidovudine pharmacokinetics. The most common toxicity was gastrointestinal. Pentoxifylline at dosages of less than thrice-daily 800 mg is well tolerated and may decrease TNF mRNA levels and LPS-induced TNF production. C1 BETH ISRAEL HOSP,DEPT MED,DIV INFECT DIS,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA. CASE WESTERN RESERVE UNIV,SCH MED,DIV INFECT DIS,CLEVELAND,OH. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIAID,DIV AIDS,BETHESDA,MD. AIDS CLIN TRIALS GRP,OPERAT OFF,ROCKVILLE,MD. HOECHST ROUSSEL PHARMACEUT PROPRIETARY LTD,SOMERVILLE,NJ. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. RP DEZUBE, BJ (reprint author), BETH ISRAEL HOSP,DEPT MED,DIV HEMATOL ONCOL,330 BROOKLINE AVE,DANA 601,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI-95030, AI-27668, AI-62534] NR 14 TC 49 Z9 49 U1 0 U2 1 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 1995 VL 171 IS 6 BP 1628 EP 1632 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RB298 UT WOS:A1995RB29800037 PM 7769305 ER PT J AU RAJADHYAKSHA, M GROSSMAN, M ESTEROWITZ, D WEBB, RH AF RAJADHYAKSHA, M GROSSMAN, M ESTEROWITZ, D WEBB, RH TI IN-VIVO CONFOCAL SCANNING LASER MICROSCOPY OF HUMAN SKIN - MELANIN PROVIDES STRONG CONTRAST SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID HUMAN EPIDERMIS; OPHTHALMOSCOPE; LIGHT AB Confocal scanning laser microscopy of live human skin was performed to investigate the correlation of in vivo cellular and morphologic features to histology, the effect of wavelength on imaging, and the role of melanin as a contrast agent. We built a video-rate confocal scanning laser microscope for in vivo imaging of human skin. Using a 100 x microscope objective, we imaged high-contrast optical ''sections'' of normal skin, vitiliginous skin, and a compound nevus. In vivo ''confocal histology'' correlated well with conventional histology. The maximum imaging depth increased with wavelength: the epidermis was imaged with visible 400-700-nm wavelengths; the superficial papillary dermis and blood cells (erythrocytes and leukocytes) in the deeper capillaries were imaged with the near infrared 800-900-nm wavelengths. For confocal reflectance imaging, melanin provided strong contrast by increased backscattering of light such that the cytoplasm in heavily pigmented cells imaged brightly. In vivo confocal microscopy potentially offers dermatologists a diagnostic tool that is instant and entirely non-invasive compared to conventional histopathology. RP RAJADHYAKSHA, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 22 TC 625 Z9 646 U1 5 U2 62 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1995 VL 104 IS 6 BP 946 EP 952 DI 10.1111/1523-1747.ep12606215 PG 7 WC Dermatology SC Dermatology GA RC142 UT WOS:A1995RC14200014 PM 7769264 ER PT J AU WAZNAWESLY, JM MERANDA, DL CAREY, P SHENKER, Y AF WAZNAWESLY, JM MERANDA, DL CAREY, P SHENKER, Y TI EFFECT OF ATRIAL NATRIURETIC HORMONE ON VASOPRESSIN AND THIRST RESPONSE TO OSMOTIC STIMULATION IN HUMAN-SUBJECTS SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID FACTOR INHIBITS DEHYDRATION; RAT POSTERIOR PITUITARY; WATER-INTAKE; HEALTHY-VOLUNTEERS; PEPTIDE; RELEASE; POLYPEPTIDE; SECRETION; OSMOLALITY; INFUSION AB To evaluate the effect of systemically administered atrial natriuretic hormone (ANH) on osmotically induced secretion of arginine vasopressin (AVP) and thirst sensation, 11 healthy men, aged 18 to 28 years, were studied on four occasions. The intravenous infusions of placebo (P) or one of three doses of ser-tyr(28) human ANH (0.6 [LD], 1.8 [MD], and 5.4 [HD] pmol/kg/min) were given in random order over 2 hours. During the second hour, subjects also received a 5% saline (HS) infusion (0.1 ml/kg/min). The baseline parameters were similar on each of the study days. Plasma ANH levels increased approximately twofold, eightfold, and 25-fold during LD, MD, and HD infusions, respectively. HS infusion caused increases in serum sodium level (5 to 7 mEq/L) and osmolality (14 to 15 mOsm/L) (p < 0.001). During HS infusion on P day, ANH levels almost doubled (p < 0.001). AVP levels remained stable during the first hour of ANH infusions. An addition of HS caused a significant increase in AVP levels (p < 0.001). The magnitude of this increase was similar on each of the study days. Similarly, thirst perception increased significantly (p < 0.01) and to the same extent during HS infusion on all study days. Both AVP levels and thirst showed a very good correlation with serum osmolality on each of the study days, and there were no significant differences between any of the slopes or intercepts. We conclude that short-term elevation of plasma ANH levels up to 25-fold affects neither the osmotically stimulated secretion of AVP nor thirst perception. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MED SERV,ENDOCRINE SECT,MADISON,WI 53705. UNIV WISCONSIN,MADISON,WI. FU NCRR NIH HHS [RR-03186]; NIDDK NIH HHS [1-R29-DK-38444] NR 50 TC 6 Z9 6 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD JUN PY 1995 VL 125 IS 6 BP 734 EP 742 PG 9 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA RB445 UT WOS:A1995RB44500012 PM 7769367 ER PT J AU AFTRING, RP FREEMAN, MW AF AFTRING, RP FREEMAN, MW TI STRUCTURE OF THE MURINE MACROPHAGE SCAVENGER RECEPTOR GENE AND EVALUATION OF SEQUENCES THAT REGULATE EXPRESSION IN THE MACROPHAGE CELL-LINE, P388D(1) SO JOURNAL OF LIPID RESEARCH LA English DT Article DE GENE TRANSCRIPTION REGULATION ID LOW-DENSITY-LIPOPROTEIN; TRANSFERRIN RECEPTOR; LIGAND-BINDING; SITE; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS; DEGRADATION; ENDOCYTOSIS; PROTEIN; CLONING AB The structure of the entire murine scavenger receptor gene was determined; it consists of eleven exons spanning more than 60 kilobases. Primer extension showed that transcription initiates at a cluster of sites unassociated with a TATAA element. DNA sequences adjacent to these transcription start sites are highly conserved in murine, human, and bovine genes. When transcriptional activity was tested using a luciferase reporter gene, a promoter fragment (-124 to +20) stimulated luciferase production in P388D(1) macrophage-like cells but not in non-macrophage COS-7 or 3T3 cells. A longer promoter fragment (approximately 5 kb) stimulated luciferase activity a further 10-fold in P388D(1) cells. However, using a series of fragments from -67 to -1500 bp, a 127 bp fragment (-67 to +50) was as active as a 1500 bp fragment in these assays. Mutation of a putative AP-1 element in the -67 to +50 promoter fragment reduced luciferase activity by 40%; mutation of a putative GATA factor element to TATA increased luciferase activity nearly 2-fold while mutation to AATA had no effect and deletion of the GATA sequence inhibited activity by about 50%. The results suggest that a scavenger receptor promoter fragment can confer cell-specific transcription and that the activity may be mediated in part by factors that recognize the AP-1 and GATA elements. C1 MASSACHUSETTS GEN HOSP,DEPT MED,LIPID METAB UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-45098]; NIDDK NIH HHS [DK07028-17] NR 39 TC 15 Z9 16 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 JUN PY 1995 VL 36 IS 6 BP 1305 EP 1314 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RG151 UT WOS:A1995RG15100015 PM 7666008 ER PT J AU SHEKELLE, PG HURWITZ, EL COULTER, I ADAMS, AH GENOVESE, B BROOK, RH AF SHEKELLE, PG HURWITZ, EL COULTER, I ADAMS, AH GENOVESE, B BROOK, RH TI THE APPROPRIATENESS OF CHIROPRACTIC SPINAL MANIPULATION FOR LOW-BACK-PAIN - A PILOT-STUDY SO JOURNAL OF MANIPULATIVE AND PHYSIOLOGICAL THERAPEUTICS LA English DT Article DE CHIROPRACTIC MANIPULATION; BACK PAIN; QUALITY OF CARE AB Objective: Spinal manipulation is an efficacious therapy for some patients with low back pain (LBP). In this pilot study, we tested the feasibility of assessing the appropriateness of chiropractic spinal manipulation for patients with LBP. Methods: Criteria for the appropriate and inappropriate use of spinal manipulation for low back pain were developed using the RAND/UCLA appropriateness method. Two separate expert panels, one multidisciplinary and one all chiropractic, each rated a comprehensive array of clinical scenarios for appropriateness. A random sample of practicing chiropractors was selected, and data were collected from ten randomly selected office records from each participating clinician. Assessment of the appropriateness for the use of spinal manipulation was made by comparing the care delivered with the appropriateness criteria determined by each expert panel. Results: Eight of thirteen (62%) eligible chiropractors agreed to participate. For the remainder, by the multidisciplinary panel's criteria, 38% of care was appropriate and 26% of care was inappropriate. By the all-chiropractic panel's criteria, the same cases were judged 74% appropriate and 7% inappropriate. The two panel's appropriateness ratings were in agreement on 48% of all cases. Conclusions: In this geographic area, the rate of appropriate care is between 38% and 74% and the rate of inappropriate care is between 7% and 19%, depending on the criteria used to assess appropriateness. Data from other geographic areas of the U.S. will be needed before inferences to a larger population may be drawn, and we have demonstrated that such a study is feasible. C1 LOS ANGELES COLL CHIROPRACT,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP SHEKELLE, PG (reprint author), RAND CORP,HLTH SCI PROGRAM,1700 MAIN ST,POB 2138,SANTA MONICA,CA 90407, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0161-4754 J9 J MANIP PHYSIOL THER JI J. Manip. Physiol. Ther. PD JUN PY 1995 VL 18 IS 5 BP 265 EP 270 PG 6 WC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation SC Health Care Sciences & Services; Integrative & Complementary Medicine; Rehabilitation GA RD335 UT WOS:A1995RD33500001 PM 7673792 ER PT J AU LEGUERN, C SHIMADA, H EMERY, DW GERMANA, S SHAFER, GE SACHS, DH AF LEGUERN, C SHIMADA, H EMERY, DW GERMANA, S SHAFER, GE SACHS, DH TI RETROVIRUS-MEDIATED TRANSFER OF MHC CLASS-II CDNA INTO SWINE BONE-MARROW CELLS SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE MHC; RETROVIRUS; GENE TRANSFER; BONE MARROW; TRANSPLANTATION; TOLERANCE ID HEMATOPOIETIC STEM-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; HUMAN ADENOSINE-DEAMINASE; HUMAN GENE-THERAPY; MINIATURE SWINE; RENAL-ALLOGRAFTS; MONOCLONAL-ANTIBODIES; HIGH-FREQUENCY; FOREIGN GENE; EXPRESSION RP LEGUERN, C (reprint author), MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,13TH ST,BOSTON,MA 02129, USA. FU NHLBI NIH HHS [5 RO1 HL46532]; NIAID NIH HHS [3 RO1 AI31046, 5 RO1 AI33053] NR 86 TC 19 Z9 19 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0946-2716 J9 J MOL MED-JMM JI J. Molec. Med.-JMM PD JUN PY 1995 VL 73 IS 6 BP 269 EP 278 PG 10 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA RF826 UT WOS:A1995RF82600001 PM 7583449 ER PT J AU PAROLIN, C SODROSKI, J AF PAROLIN, C SODROSKI, J TI A DEFECTIVE HIV-1 VECTOR FOR GENE-TRANSFER TO HUMAN-LYMPHOCYTES SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE HIV-1; RETROVIRAL VECTOR; GENE TRANSFER ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 VPU PROTEIN; VIRION-ASSOCIATED PROTEIN; DEFICIENCY SYNDROME AIDS; TERM MARROW CULTURE; VIRAL MESSENGER-RNA; OPEN READING FRAME; CELL-SURFACE CD4; RETROVIRAL VECTORS; HTLV-III/LAV C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. RP PAROLIN, C (reprint author), HARVARD UNIV,SCH MED,DEPT PATHOL,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691] NR 175 TC 7 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0946-2716 J9 J MOL MED-JMM JI J. Molec. Med.-JMM PD JUN PY 1995 VL 73 IS 6 BP 279 EP 288 PG 10 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA RF826 UT WOS:A1995RF82600002 PM 7583450 ER PT J AU CONNOLLY, S MANJI, H MCALLISTER, RH GRIFFIN, GB LOVEDAY, C KIRKIS, C SWEENEY, B SARTAWI, O DURRANCE, P FELL, M BOLAND, M FOWLER, CJ NEWMAN, SP WELLER, IVD HARRISON, MJG AF CONNOLLY, S MANJI, H MCALLISTER, RH GRIFFIN, GB LOVEDAY, C KIRKIS, C SWEENEY, B SARTAWI, O DURRANCE, P FELL, M BOLAND, M FOWLER, CJ NEWMAN, SP WELLER, IVD HARRISON, MJG TI NEUROPHYSIOLOGICAL ASSESSMENT OF PERIPHERAL-NERVE AND SPINAL-CORD FUNCTION IN ASYMPTOMATIC HIV-1 INFECTION - RESULTS FROM THE UCMSM MEDICAL-RESEARCH-COUNCIL NEUROLOGY COHORT SO JOURNAL OF NEUROLOGY LA English DT Article DE HIV INFECTION; SPINAL CORD; PERIPHERAL NERVE; NEUROPHYSIOLOGY ID HUMAN-IMMUNODEFICIENCY-VIRUS; MULTICENTER AIDS COHORT; NEUROPSYCHOLOGICAL PERFORMANCE; SEROPOSITIVE MEN; HOMOSEXUAL MEN; ABNORMALITIES; COMPLICATIONS; INVOLVEMENT; NEUROPATHY; MANIFESTATIONS AB As part of the Medical Research Council prospective study of the neurological complications of HIV infection, neurophysiological tests of spinal cord and peripheral nerve function were recorded in a cohort of homosexual or bisexual men. The studies included motor and sensory nerve conduction studies, vibration perception thresholds, somatosensory evoked potentials and motor evoked potentials elicited by magnetic stimulation. The results were compared with markers of immune function. The findings from 114 volunteers were analysed in a cross-sectional study. Fifty-nine were HIV-seropositive but asymptomatic, 26 had progressed to the symptomatic stages of HIV disease and 29 were persistently HIV-seronegative. There was some evidence of a mild sensory axonopathy in the symptomatic HIV-seropositive group, No differences were detected between the asymptomatic HIV-seropositive group and the HIV-seronegative comparison group. There were no consistently significant correlations between the neurophysiological measurements and CD4 counts and beta(2) microglobulin levels. On repeated testing, there was no evidence of a trend towards deterioration over a mean period of approximately 3 years in 36 HIV-seropositive subjects who remained asymptomatic compared with 22 HIV-seronegatives. These findings have failed to demonstrate neurophysiological evidence of spinal cord or peripheral nerve dysfunction in the asymptomatic stages of HIV infection. C1 UCL, MIDDLESEX HOSP, SCH MED, DEPT PSYCHIAT, LONDON, ENGLAND. UCL, MIDDLESEX HOSP, SCH MED, ACAD DEPT GENITOURINARY MED, LONDON, ENGLAND. UCL, MIDDLESEX HOSP, SCH MED, DIV VIROL, LONDON, ENGLAND. RP CONNOLLY, S (reprint author), MASSACHUSETTS GEN HOSP, DEPT CLIN NEUROPHYSIOL, BIGELOW 12, BOSTON, MA 02114 USA. RI Fowler, Clare /B-2812-2009; Boylan, Geraldine/F-3019-2012; Sweeney, Brian/D-2569-2013 FU Wellcome Trust NR 34 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUN PY 1995 VL 242 IS 6 BP 406 EP 414 DI 10.1007/BF00868398 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA RE747 UT WOS:A1995RE74700010 PM 7561971 ER PT J AU GUHA, A GLOWACKA, D CARROLL, R DASHNER, K BLACK, PM STILES, CD AF GUHA, A GLOWACKA, D CARROLL, R DASHNER, K BLACK, PM STILES, CD TI EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR AND PLATELET-DERIVED GROWTH-FACTOR RECEPTOR MESSENGER-RNA IN A GLIOBLASTOMA FROM A PATIENT WITH LI-FRAUMENI SYNDROME SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE ASTROCYTOMA; PLATELET DERIVED GROWTH FACTOR; LI-FRAUMENI SYNDROME ID P53 MUTATIONS; BRAIN-TUMOR; AMPLIFICATION; SARCOMAS; CELLS AB Expression of platelet derived growth factor (PDGF) and PDGF-receptor mRNA was examined from a glioblastoma taken from a patient with Li-Fraumeni syndrome. Northern blot analysis and in situ hybridisation showed very high concentrations of both PDGF-A and PDGF alpha-receptor mRNA in the tumour. The overall pattern of PDGF expression was similar to those found in sporadic glioblastomas. Mutations in p53 has been implicated as an early pathogenic event leading to sporadic low grade astrocytomas, and is the third most common tumour type in patients with Li-Fraumeni syndrome, where they are predisposed due to a germline mutation in the p53 tumour suppressor gene. This study suggests that progression towards a glioblastoma in both the general population and in patients with Li-Fraumeni syndrome may involve potential autocrine and paracrine stimulation by growth factors such as PDGF. C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV TORONTO,DIV NEUROSURG & SURG ONCOL,TORONTO,ON,CANADA. BRIGHAM & WOMENS HOSP,DIV NEUROSURG,BOSTON,MA 02115. NR 13 TC 19 Z9 19 U1 0 U2 0 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 1995 VL 58 IS 6 BP 711 EP 714 DI 10.1136/jnnp.58.6.711 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA RC686 UT WOS:A1995RC68600015 PM 7608673 ER PT J AU MORTEL, KF MEYER, JS AF MORTEL, KF MEYER, JS TI LACK OF POSTMENOPAUSAL ESTROGEN REPLACEMENT THERAPY AND THE RISK OF DEMENTIA SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID ISCHEMIC VASCULAR DEMENTIA; ADRDA WORK GROUP; ALZHEIMERS-DISEASE; CARDIOVASCULAR-DISEASE; CLINICAL-DIAGNOSIS; BASAL FOREBRAIN; GROWTH-FACTOR; FOLLOW-UP; WOMEN; STROKE AB Estrogen replacement therapy (EXT) and associated risks for ischemic vascular dementia (IVD) and dementia of the Alzheimer's type (DAT) among postmenopausal women were investigated by determining whether EXT was differently distributed among control subjects than among subjects with dementia. Subjects included 93 with probable DAT, 65 with probable IVD, and 148 normal control subjects. The proportion of control subjects on EXT was almost 2:1, and this ratio holds for both dementia groups. Logistic regression suggests lack of EXT is associated with increased risk for dement ia among elderly women. EXT may eventually prove to be a useful prophylactic agent for reducing risk of DAT and IVD among postmenopausal women. C1 DEPT VET AFFAIRS MED CTR,CEREBRAL BLOOD FLOW LAB,HOUSTON,TX. BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX 77030. NR 33 TC 99 Z9 101 U1 1 U2 3 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 1995 VL 7 IS 3 BP 334 EP 337 PG 4 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RL779 UT WOS:A1995RL77900010 PM 7580193 ER PT J AU ABRAHAM, SA MIRECKI, FN LEVINE, D NUNN, AD STRAUSS, HW GEWIRTZ, H AF ABRAHAM, SA MIRECKI, FN LEVINE, D NUNN, AD STRAUSS, HW GEWIRTZ, H TI MYOCARDIAL TECHNETIUM-99M-TEBOROXIME ACTIVITY IN ACUTE CORONARY-ARTERY OCCLUSION AND REPERFUSION - RELATION TO MYOCARDIAL BLOOD-FLOW AND VIABILITY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE TECHNETIUM-99M-TEBOROXIME; CORONARY REPERFUSION; MYOCARDIAL INFARCTION; MYOCARDIAL VIABILITY, MYOCYTES ID CLEARANCE KINETICS; STENOSIS; EXTRACTION; TEBOROXIME; THALLIUM; STRESS; TL-201; DISTAL; CELLS AB The purpose of this study was to test the hypothesis that Tc-99m-teboroxime retention within the heart depends at least in part on the presence of viable myocytes. Methods: We used a porcine model of acute myocardial infarction with reperfusion and compared the myocardial uptake of labeled microspheres at 1 hr of reperfusion with that of Tc-99m-teboroxime. Eleven domestic swine had measurements of hemodynamics and regional myocardial blood flow (microspheres) at baseline, at 10 and 50 min of left anterior descending (LAD) coronary artery occlusion and at 10 and 60 min of LAD reperfusion. Technetium-99m-teboroxime was injected intravenously at 60 min of reperfusion and the animal was killed 5-7 min later. The heart was then perfused with triphenyl tetrazolium chloride to identify infarcted and jeopardized myocardium in the occlusion zone and with Evans blue dye to mark normally perfused myocardium. After imaging, tissue sections were digested and colored microspheres were extracted and counted to determine myocardial blood flow, Results: After coronary occlusion, infarct zone (MIZ) to normal zone (NZ) blood flow ratios declined from 0.95 +/- 0.27 (preocclusion) to 0.18 +/- 0.15 at 10 min and 0.25 +/- 0.35 at 50 min of occlusion (both p < 0.05). The MIZ:NZ count ratio at 60 min of reperfusion was less than the MIZ:NZ blood flow ratio in every animal and over the entire range of flow ratios (0.55-3.64). Conclusion: Technetium-99m-teboroxime requires viable myocytes for retention within the heart and is not exclusively a tracer of myocardial blood flow when imaged 5-7 min after injection. Additional in vivo imaging studies are required to determine the extent to which reduced retention of the tracer by reperfused but nonviable myocardium influences the appearance of clinical scans. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. RHODE ISL HOSP,DEPT MED,DEPT MED,PROVIDENCE,RI 02903. BROWN UNIV,SCH MED,PROVIDENCE,RI 02912. NR 19 TC 7 Z9 7 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 JUN PY 1995 VL 36 IS 6 BP 1062 EP 1068 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RB816 UT WOS:A1995RB81600037 PM 7769429 ER PT J AU WANG, CC KELLY, J AUGUST, M DONOFF, B AF WANG, CC KELLY, J AUGUST, M DONOFF, B TI EARLY CARCINOMA OF THE ORAL CAVITY - A CONSERVATIVE APPROACH WITH RADIATION-THERAPY SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID TONGUE; CANCER C1 MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,ORAL MAXILLOFACIAL SERV,BOSTON,MA 02117. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 1995 VL 53 IS 6 BP 687 EP 690 DI 10.1016/0278-2391(95)90172-8 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RB307 UT WOS:A1995RB30700016 PM 7776052 ER PT J AU SKATRUD, JB MORGAN, B AF SKATRUD, JB MORGAN, B TI HYPERTENSION AND SLEEP-APNEA SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE ASPHYXIA; AUTONOMIC NERVOUS SYSTEM; CAROTID CHEMOREFLEX; HYPERTENSION; HYPOXIA; SLEEP APNEA; SYMPATHETIC NERVOUS SYSTEM ID APNEA; PRESSURE; HYPOXIA AB Epidemiological data indicate a link between sleep-disordered breathing and elevation of arterial pressure. Previous studies suggest increased activity of the sympathetic nervous system in patients with sleep apnoea. The response of muscle sympathetic nerve activity was further investigated in normal, awake subjects following exposure to 20 minutes of asphyxia. Sympathetic nerve traffic increased during exposure and remained elevated even after the return to room air breathing. These findings raise the possibility that this sustained elevation of sympathetic nerve traffic could play a role in the development of daytime hypertension in patients with sleep-disordered breathing. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. UNIV WISCONSIN,DEPT KINESIOL,MADISON,WI. RP SKATRUD, JB (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD JUN PY 1995 VL 4 SU 1 BP 34 EP 36 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RK094 UT WOS:A1995RK09400007 ER PT J AU SOUBA, WW AF SOUBA, WW TI SAND, SANDSTORMS, AND SANDCASTLES SO JOURNAL OF SURGICAL RESEARCH LA English DT Editorial Material RP SOUBA, WW (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,COX 626,100 BLOSSOM ST,BOSTON,MA 02114, USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN PY 1995 VL 58 IS 6 BP 545 EP 551 DI 10.1006/jsre.1995.1086 PG 7 WC Surgery SC Surgery GA RE631 UT WOS:A1995RE63100001 PM 7791326 ER PT J AU PAN, M WASA, M SOUBA, WW AF PAN, M WASA, M SOUBA, WW TI PROTEIN-KINASE-C ACTIVATION INHIBITS GLUTAMATE TRANSPORT BY ENDOTHELIAL-CELLS SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 16-19, 1994 CL ALBUQUERQUE, NM SP Assoc Acad Surg ID DIACYLGLYCEROL PRODUCTION; INTERFERON-ALPHA; RELAXING FACTOR; PHORBOL ESTERS; NITRIC-OXIDE; L-ARGININE; ISOENZYMES; ISOFORM; RELEASE; FAMILY AB The role of protein kinase C (PKC) in regulating endothelial cell glutamate transport was investigated. Glutamate transport studies were performed in confluent human umbilical vein endothelial cells which were treated with the phorbol ester la-myristate 13-acetate (TPA, 0-1000 nM), a compound which directly activates PKC. TPA inhibited Na+-independent System X(AG)(-) glutamate transport by 70% but only slightly reduced Na+-dependent activity. The TPA-mediated reduction in transport activity was dose-dependent, beginning at 5 min and lasting for at least 24 hr. TPA inhibition of glutamate transport had two distinctive phases: an acute phase (<1 hr, not affected by either cycloheximide or actinomycin D) in which TPA decreased System X(AG)(-) glutamate transporter affinity (TPA K-m = 522 +/- 25 mu M vs control K-m = 329 +/- 85 mu M, P < 0.01) but did not alter transporter capacity (TPA V-max = 4426 +/- 230 pmole/mg/min vs control V-max = 4535 +/- 750 pmole/ mg/min, P = NS) and a chronic phase (4-24 hr) in which TPA inhibition of glutamate transport was due to a reduced transporter capacity (V-max = 2895 +/- 570 pmole/mg/min) without altering transporter affinity (K-m = 370 +/- 60 mu M glutamate) and was abrogated by cycloheximide or actinomycin D. The protein kinase C inhibitor chelerythrine chloride abrogated TPA's inhibition effect in both the acute and chronic phases. These data indicate that protein kinase C activation decreases glutamate transport in human umbilical vein endothelial cells via protein synthesis dependent and independent mechanisms. (C) 1995 Academic Press, Inc. RP PAN, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV SURG ONCOL,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [R01 HL44986] NR 27 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN PY 1995 VL 58 IS 6 BP 630 EP 635 DI 10.1006/jsre.1995.1099 PG 6 WC Surgery SC Surgery GA RE631 UT WOS:A1995RE63100014 PM 7791339 ER PT J AU PAN, M WASA, M SOUBA, WW AF PAN, M WASA, M SOUBA, WW TI TUMOR-NECROSIS-FACTOR STIMULATES SYSTEM X(AG)(-) TRANSPORT ACTIVITY IN HUMAN ENDOTHELIUM SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 16-19, 1994 CL ALBUQUERQUE, NM SP Assoc Acad Surg ID FACTOR-ALPHA; GLUTAMINE; CELLS; INTERLEUKIN-1; EXPRESSION; ENDOTOXIN; INJURY; ACID AB System X(AG)(-) is responsible for the carrier-mediated Na+-independent transport of anionic amino acids such as glutamate and aspartate across the plasma membrane of cells. In order to examine a possible role for cytokines in regulating System X(AG)(-) activity, the effect of TNF on [H-3]glutamate transport in cultured human umbilical vein endothelial cells (HUVECs) was studied. Carrier-mediated glutamate uptake was accomplished by two high-affinity carriers, predominantly by a Na+-independent carrier (System x(AG)(-), 75% of total glutamate uptake) and, to a lesser extent by a Na+-dependent carrier (System X(AG)(-), 24% of total uptake). TNF treatment (10 ng/ml far 10 hr) resulted in an 80% increase in Na+-independent glutamate transport activity with no change in System X(AG)(-) activity. The TNF stimulatory effect was blocked by actinomycin D and cycloheximide. TNF treatment increased System X(AG)(-) glutamate transporter V-max by 51% (control V-max = 2359 +/- 345 pmole/mg protein/min vs TNF V-max = 3569 +/- 436 pmole/mg protein/min, P < 0.01) without altering transporter affinity (control K-m, 229 +/- 40 mu M glutamate vs TNF K-m = 224 +/- 60 mu M glutamate, P = NS). The protein kinase C (PKC) inhibitor chelerythrine chloride had no effect on the TNF-stimulated glutamate transport, indicating that the augmented glutamate transport was not mediated by PKC activation. These data indicate that the TNF-stimulated glutamate transport in HUVECs requires do novo protein synthesis, possibly of the System x(AG)(-) transporter protein itself. Accelerated glutamate transport provides a precursor for the biosynthesis of macromolecules and glutamine. (C) 1995 Academic Press, Inc. RP PAN, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV SURG ONCOL,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [R01 HL44986] NR 24 TC 3 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN PY 1995 VL 58 IS 6 BP 659 EP 664 DI 10.1006/jsre.1995.1104 PG 6 WC Surgery SC Surgery GA RE631 UT WOS:A1995RE63100019 PM 7791344 ER PT J AU INOUE, Y BODE, BP ABCOUWER, S SOUBA, WW AF INOUE, Y BODE, BP ABCOUWER, S SOUBA, WW TI ATTENUATION OF THE ENDOTOXIN-STIMULATED INCREASE IN HEPATIC AMINO-ACID-TRANSPORT WITH A GLUCOCORTICOID RECEPTOR ANTAGONIST SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 16-19, 1994 CL ALBUQUERQUE, NM SP Assoc Acad Surg ID PLASMA-MEMBRANE VESICLES; RAT HEPATOCYTES; HORMONAL-REGULATION; METABOLISM; GLUTAMINE; MUSCLE; LIVER AB The role of the glucocorticoid hormones in mediating the accelerated hepatic amino acid transport that is characteristic of endotoxemia was investigated. To determine the role of these steroid hormones, rats that received endotoxin (LPS) were pretreated with the glucocorticoid receptor antagonist RU38486. The activities of the Na+-dependent amino acid transport systems A, ASC, and N and the Na+-independent systems L, y(+), n, b(0,+), and asc in hepatic plasma membrane vesicles were measured 4 hr after exposure to LPS. Endotoxin treatment resulted in time- and dose-dependent Ei-fold (System A), 2.5-fold (System N), 2.6-fold (System ASC), and 2-fold (System y(+) and b(0,+)) increases in transport activity attributable to an increase in carrier V-max. The activities of L, asc, and n were unchanged by LPS administration. Pretreatment of endotoxemic animals with RU38486 attenuated the LPS-induced enhancement in transport activity by 20-60% by diminishing carrier V-max, with no effect on transport K-m. We conclude that the marked increase in hepatic amino acid transport activity that occurs during endotoxemia requires participation of the glucocorticoid hormones. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV FLORIDA,COLL MED,DEPT SURG,GAINESVILLE,FL. RP INOUE, Y (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NCI NIH HHS [R01 CA56790] NR 21 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN PY 1995 VL 58 IS 6 BP 693 EP 701 DI 10.1006/jsre.1995.1109 PG 9 WC Surgery SC Surgery GA RE631 UT WOS:A1995RE63100024 PM 7791348 ER PT J AU WILENS, TE BIEDERMAN, J KIELY, K BREDIN, E SPENCER, TJ AF WILENS, TE BIEDERMAN, J KIELY, K BREDIN, E SPENCER, TJ TI PILOT-STUDY OF BEHAVIORAL AND EMOTIONAL DISTURBANCES IN THE HIGH-RISK CHILDREN OF PARENTS WITH OPIOID DEPENDENCE SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE SUBSTANCE ABUSE; PSYCHOPATHOLOGY; RISK FACTORS ID ATTENTION-DEFICIT DISORDER; DRUG-USE; PSYCHIATRIC DIAGNOSES; ALCOHOLIC PARENTS; HYPERACTIVE BOYS; YOUNG ADULTHOOD; SUBSTANCE USE; PSYCHOPATHOLOGY; CONVERGENCE; COMORBIDITY AB Objective: Despite the prevalence of nonalcohol substance abuse disorders, few data are available on the high-risk children of parents with these disorders. To this end as a preliminary study, children of opioid-dependent parents were assessed on measures of emotional and behavioral problems. Method: Child Behavior Checklist data from 15 girls and 29 boys (mean age 10.4 years) from 27 families of parents receiving treatment in a methadone maintenance clinic were compared with matched data from referred children with attention-deficit hyperactivity disorder: plus comorbid psychiatric disorders (''comorbid ADHD children'') and medically referred children without ADHD (''controls''). Results: The children of opioid-dependent parents had significantly poorer competency scores, and higher scores on both Internalizing and Externalizing subscales of the Child Behavior Checklist, compared with controls (p values < .01), but not compared with comorbid ADHD children. Twenty-four children (55%) of opioid-dependent parents had elevated subscale scores indicative of significant psychopathology. Conclusions: These pilot data seem to indicate that the 4- to 18-year-old children of parents with opioid dependence have high rates of psychopathology and significant dysfunction and suggest the need for further controlled studies in this population. C1 HARVARD UNIV,SCH MED,BOSTON,MA. BAY COVE SUBST ABUSE CLIN,BOSTON,MA. RP WILENS, TE (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,ACC 725,BOSTON,MA 02114, USA. NR 48 TC 55 Z9 55 U1 3 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 1995 VL 34 IS 6 BP 779 EP 785 DI 10.1097/00004583-199506000-00019 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA QZ536 UT WOS:A1995QZ53600019 PM 7608052 ER PT J AU PAVRI, BB ONUNAIN, SS NEWELL, JB RUSKIN, JN DEC, GW AF PAVRI, BB ONUNAIN, SS NEWELL, JB RUSKIN, JN DEC, GW TI PREVALENCE AND PROGNOSTIC-SIGNIFICANCE OF ATRIAL ARRHYTHMIAS AFTER ORTHOTOPIC CARDIAC TRANSPLANTATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-TRANSPLANTATION; FLUTTER; SUPERSENSITIVITY; ISOPROTERENOL; FIBRILLATION; SENSITIVITY; INDUCTION; ADENOSINE AB Objectives. We studied the duration and prognostic significance of atrial arrhythmias in the denervated transplanted heart, specifically the occurrence of atrial fibrillation in the absence of vagal modulation. Background. Substantial animal data indicate that vagally induced dispersion of atrial refractoriness plays a central role in the induction and maintenance of atrial fibrillation. Methods. We studied the occurrence of atrial arrhythmias in the denervated hearts of 88 consecutive orthotopic transplantations in 85 patients by means of continuous telemetry and all available electrocardiographic tracings. Results. Fifty percent of recipients (43 of 88) developed at least one atrial arrhythmia. Atrial fibrillation occurred 23 times (21 recipients), atrial flutter 39 times (26 recipients), ectopic atrial tachycardia 3 times (3 recipients) and supraventricular tachycardia 18 times (11 recipients). The number of atrial fibrillation and atrial putter episodes did not differ (23 vs. 39, p = 0.072), but the mean duration of atrial flutter was longer than that of atrial fibrillation (37.0 +/- 10 vs, 6.6 +/- 3.6 h, p = 0.014). Atrial fibrillation was associated with an increased risk of subsequent death (10 of 21 recipients with vs. 15 of 67 without atrial fibrillation, risk ratio 3.15 +/- 0.18, p = 0.005 by Cox proportional hazards model). All 5 recipients who developed ''late'' atrial fibrillation (>2 weeks after transplantation) died versus 5 of 16 who developed atrial fibrillation within the first 2 weeks (p = 0.007). Causes of death included rejection (three recipients), allograft failure (two recipients), infection (three recipients) and multiorgan failure (two recipients). Atrial fibrillation was not associated with age, gender, ischemic time, reason for transplantation, echocardiographic variables, invasive hemodynamic variables or biopsy grade. Mean time from atrial arrhythmia to echocardiology was 2.7 +/- 3.3 days; that to biopsy was 4.8 +/- 6.3 days. Atrial flutter was not associated with subsequent death. Only 7 (15.9%) of 44 recipients demonstrated moderate or severe allograft rejection at the time of the arrhythmia. Conclusions. Atrial arrhythmias occur frequently in the denervated transplanted heart, often in the absence of significant rejection. Late atrial fibrillation may be associated with an increased all cause mortality. C1 MASSACHUSETTS GEN HOSP,MED SERV,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 36 TC 58 Z9 60 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO 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 JUN PY 1995 VL 25 IS 7 BP 1673 EP 1680 DI 10.1016/0735-1097(95)00047-8 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RA480 UT WOS:A1995RA48000031 PM 7759722 ER PT J AU BRIONES, ER IBER, FL AF BRIONES, ER IBER, FL TI LIVER AND BILIARY-TRACT CHANGES AND INJURY ASSOCIATED WITH TOTAL PARENTERAL-NUTRITION - PATHOGENESIS AND PREVENTION SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE TOTAL PARENTERAL NUTRITION; HEPATIC COMPLICATIONS; CHOLESTASIS; STEATOSIS; NUTRIENT DEFICIENCY; GALLSTONES ID INFLAMMATORY BOWEL-DISEASE; ESCHERICHIA-COLI ENDOTOXIN; CRITICALLY ILL PATIENTS; SERUM HEPATIC ENZYME; PERFUSED RAT-LIVER; BACTERIAL TRANSLOCATION; CARNITINE DEFICIENCY; LIPID EMULSIONS; FUNCTION TESTS; INTESTINAL TRANSPLANTATION AB Total parenteral nutrition (TPN), now widely used, is successful in preventing and reversing malnutrition in individuals with various diseases and conditions. However, hepatic and biliary complications of TPN are encountered in both adult and pediatric patients. Certain complications, such as sepsis and TPN-associated cholestasis, occur more frequently in very young infants. Continuing problems commonly seen in adults are steatosis and steatonecrosis. Reasons for the development of these complications are multifactorial. Etiologies of hepatic complications, especially the role of deficiency/excess of nutrients in the pathogenesis of hepatobiliary disorders, are summarized. Complications caused by the duration of TPN are discussed with emphasis on prevention and management. Evidence now suggests that prompt enteral feeding, even in minimal amounts, may prevent many of the metabolic complications associated with TPN. TPN should be used only in amounts meeting needs and for a duration essential to survival. C1 US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,GASTROENTEROL SERV,HINES,IL 60141. UNIV ILLINOIS,CHICAGO,IL. NR 116 TC 34 Z9 37 U1 2 U2 2 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD JUN PY 1995 VL 14 IS 3 BP 219 EP 228 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RB237 UT WOS:A1995RB23700005 PM 8586769 ER PT J AU GERETY, MB AF GERETY, MB TI HEALTH-CARE REFORM - BENEFITS OR HAZARDS FOR THE FRAIL AND THEIR DOCTORS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. RP GERETY, MB (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,GRECC 116C,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 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 1995 VL 43 IS 6 BP 718 EP 719 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RB444 UT WOS:A1995RB44400024 PM 7775738 ER PT J AU BROMLEY, B BENACERRAF, B AF BROMLEY, B BENACERRAF, B TI USING THE NUMBER OF YOLK SACS TO DETERMINE AMNIONICITY IN EARLY 1ST-TRIMESTER MONOCHORIONIC TWINS SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID MEMBRANE THICKNESS; CHORIONICITY; PREGNANCIES; PREDICTION; GESTATIONS; ULTRASOUND AB The purpose of this study was to evaluate the relationship between the number of yolk sacs and amnionicity in monochorionic twin pregnancies scanned early in the first trimester. We retrospectively reviewed images of all monochorionic twins scanned between 6 and 9.5 weeks' gestation and with pathologic or sonographic confirmation of chorionicity-amnionicity. Each film was reviewed for the number of yolk sacs present, as well as for the gestational age at which the amniotic membrane was first visualized. Twenty monochorionic-diamniotic pregnancies and two monochorionic-monoamniotic pregnancies met the criteria for inclusion in the study. In diamniotic pregnancies scanned at less than 8 weeks' gestation, only the yolk sacs were identified; none of the dividing amniotic membranes were detected. Two yolk sacs were identified in all but one case. In this case, although one yolk sac was seen at 6 weeks, follow-up scanning at 8 weeks revealed two yolk sacs. In each of the monochorionic-monoamniotic twin pregnancies, one yolk sac was seen at 9 weeks and a single amnion encircled both embryos. We conclude that the sonographic identification of two yolk sacs in monochorionic twins enables us to make the diagnosis of diamniotic twins early in the first trimester, before the amniotic membrane can be imaged. The presence of one yolk sac should prompt a follow-up ultrasonogram to assign amnionicity definitively. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 13 TC 40 Z9 40 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 JUN PY 1995 VL 14 IS 6 BP 415 EP 419 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA QZ897 UT WOS:A1995QZ89700002 PM 7658507 ER PT J AU BISSADA, NK KACZMAREK, AT AF BISSADA, NK KACZMAREK, AT TI COMPLETE REMISSION OF HORMONE-REFRACTORY ADENOCARCINOMA OF THE PROSTATE IN RESPONSE TO WITHDRAWAL OF DIETHYLSTILBESTROL SO JOURNAL OF UROLOGY LA English DT Note DE DIETHYLSTILBESTROL; PROSTATE; ADENOCARCINOMA; ANDROGEN ANTAGONISTS ID FLUTAMIDE WITHDRAWAL; COMBINATION THERAPY; CANCER AB The phenomenon of regression of adenocarcinoma of the prostate after the withdrawal of antiandrogens is well documented. However, to our knowledge we report the first case of durable complete remission of hormone refractory prostate cancer after cessation of diethylstilbestrol. The drug was discontinued because the patient had disease progression while on diethylstilbestrol and withdrawal resulted in durable remission. In more than 3 years of followup since discontinuing diethylstilbestrol there has been no evidence of clinical or biochemical recurrence. C1 RALPH H JOHNSON VET ADM HOSP,CHARLESTON,SC. RP BISSADA, NK (reprint author), MED UNIV S CAROLINA,DEPT UROL,CHARLESTON,SC 29425, USA. NR 13 TC 47 Z9 47 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 1995 VL 153 IS 6 BP 1944 EP 1945 DI 10.1016/S0022-5347(01)67364-6 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA QX369 UT WOS:A1995QX36900064 PM 7752364 ER PT J AU MANDELL, J BROMLEY, B PETERS, CA BENACERRAF, BR AF MANDELL, J BROMLEY, B PETERS, CA BENACERRAF, BR TI PRENATAL SONOGRAPHIC DETECTION OF GENITAL MALFORMATIONS SO JOURNAL OF UROLOGY LA English DT Article DE ULTRASONOGRAPHY, PRENATAL; GENITALIA, FEMALE; GENITALIA, MALE; FETUS; ABNORMALITIES ID DIAGNOSIS AB Postnatal clinical and pathological correlation of sonographically identified genital malformations in 17 fetuses was undertaken to determine the outcome of these findings. Diagnoses confirmed at autopsy or by postnatal examination and surgery included male (XY) pseudohermaphroditism in 2 cases, hypospadias with chordee in 3, microphallus in 2, cloacal anomaly in 2, congenital adrenal hyperplasia in 3, penoscrotal transposition in 2, intra-abdominal testes in 1, megalourethra in 1 and cloacal exstrophy variant in 1. Additional abnormalities included congenital heart defects, cleft palate, and renal, anorectal, cranial and cerebral malformations. Four fetuses with a sonographically abnormal appearing phallus were found to have an endocrine disorder (3 congenital adrenal hyperplasia and 1 panhypopituitarism). Outcomes included 2 abortions and 1 neonatal death with the remaining neonates undergoing medical and reconstructive treatment. Prenatal detection of genital abnormalities can be helpful in evaluating those fetuses with severe multi-system anomalies as well as lesions more amenable to correction in the neonatal period. Detection is particularly important in neonates with endocrine disorders, and complex genitourinary and anorectal malformations. C1 CHILDRENS HOSP,DIV UROL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. OI Peters, Craig/0000-0001-7598-0865 NR 7 TC 25 Z9 25 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 JUN PY 1995 VL 153 IS 6 BP 1994 EP 1996 DI 10.1016/S0022-5347(01)67389-0 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA QX369 UT WOS:A1995QX36900089 PM 7752382 ER PT J AU LAMURAGLIA, GM KLYACHKIN, ML ADILI, F ABBOTT, WM AF LAMURAGLIA, GM KLYACHKIN, ML ADILI, F ABBOTT, WM TI PHOTODYNAMIC THERAPY OF VEIN GRAFTS - SUPPRESSION OF INTIMAL HYPERPLASIA OF THE VEIN GRAFT BUT NOT THE ANASTOMOSIS SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 29-30, 1994 CL NEWPORT, RI SP NEW ENGLAND SOC VASC SURG ID SAPHENOUS-VEIN; SULFONATED PHTHALOCYANINE; INHIBITION; HEPARIN; RECONSTRUCTIONS; PROLIFERATION; ARTERIES AB Purpose: There is no clinically useful therapy for the suppression of vein bypass graft intimal hyperplasia (IH). Photodynamic therapy (PDT), a technique that uses light to activate otherwise biologically inert photosensitizers to produce cytotoxic effects, has been demonstrated to successfully inhibit experimental IH in balloon-injured arteries. The purpose of this study was to investigate the efficacy of PDT as a method to reduce vein graft IH. Methods: Reversed external jugular vein bypass grafts of the common carotid artery were performed in 28 male Sprague-Dawley rats. The animals received either chloroaluminum sulfonated phthalocyanine (2.5 mg/kg intravenously) 24 hours before the ex vivo irradiation of the vein grafts (VG) with 100 joule/cm(2) at 675 nm (PDT VG) or saline solution as control (CON VG). Preharvest bromodeoxyuridine was administered to label proliferating cells. All vein grafts were perfusion fixed within 96 hours for a pilot study or at 2 and 4 weeks for the main study. Histology, immunohistochemistry, and morphometric analysis were performed. Results: There was no acute thrombus formation in the hypocellular PDT VG with occasional platelets but no leukocytes adherent to the luminal surface. Intimal areas of the PDT VG were 18% at 2 weeks and 53% at 4 weeks of the CON VGs (p < 0.05). Medial areas and percent of stenoses were also significantly less in PDT than in CON VG. However, intimal hyperplasia noted in the longitudinal sections within 2 mm of the anastomoses did not demonstrate a difference between PDT and CON VG. Intimal hyperplasia of both PDT and CON VG consisted of smooth muscle cells, verified by immunohistochemistry. Bromodeoxyuridine-labeled cells were more abundant in 2-week than in 4-week specimens, were found most frequently in the intimal areas of the CON VG body, and were equivalent in the anastomoses of PDT VG and CON VG. Conclusions: These data suggest that PDT of vein grafts suppresses the development of IH in the body of the vein graft but does not affect IH adjacent to the anastomoses. The artery may be the source of proliferating smooth muscle cells that contribute to the anastomotic vein graft IH. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,VASC RES LAB,BOSTON,MA 02114. RP LAMURAGLIA, GM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,DIV VASC SURG,ACC 464,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL02583] NR 31 TC 14 Z9 16 U1 0 U2 0 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 JUN PY 1995 VL 21 IS 6 BP 882 EP 890 DI 10.1016/S0741-5214(95)70215-6 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA RC470 UT WOS:A1995RC47000002 PM 7776467 ER PT J AU PETERSEN, MJ CAMBRIA, RP KAUFMAN, JA LAMURAGLIA, GM GERTLER, JP BREWSTER, DC GELLER, SC WALTMAN, AC LITALIEN, GJ ABBOTT, WM AF PETERSEN, MJ CAMBRIA, RP KAUFMAN, JA LAMURAGLIA, GM GERTLER, JP BREWSTER, DC GELLER, SC WALTMAN, AC LITALIEN, GJ ABBOTT, WM TI MAGNETIC-RESONANCE ANGIOGRAPHY IN THE PREOPERATIVE EVALUATION OF ABDOMINAL AORTIC-ANEURYSMS SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 29-30, 1994 CL NEWPORT, RI SP NEW ENGLAND SOC VASC SURG ID MR-ANGIOGRAPHY; AORTOGRAPHY; ARTERIOGRAPHY AB Purpose: Contrast arteriography (CA) is a useful but invasive technique for the preoperative evaluation of patients with abdominal aortic aneurysms (AAA). To evaluate the use of magnetic resonance arteriography (MRA) as a preoperative study we prospectively studied 38 patients undergoing AAA repair. Methods: Ah patients underwent biplane CA and MRA with use of a gadolinium-enhanced technique. Radiographic studies were then independently evaluated by blinded radiologists for anatomic findings with CA used as the standard. Studies were then independently evaluated by blinded vascular surgeons, and a surgical plan was made. Results: With CA and intraoperative findings as the standards, MRA proved highly accurate in the determination of multiple key anatomic elements. The proximal extent of aneurysmal disease was correctly predicted in 87% (33/38) patients. Significant iliofemoral occlusive disease was identified with a sensitivity of 83% (5/6). Iliac or femoral aneurysms were detected with a sensitivity of 79% (22/28) and specificity of 86% (41/48). Significant renal artery stenosis was detected with a sensitivity of 71% (12/17) and a specificity of 99% (72/73). Accessory renal arteries were correctly identified in 71% (12/17). Surgeon evaluators correctly predicted the proximal cross-clamp site in 87% (33/38) of patients with use of MRA as compared with the actual operative conduct. Proximal anastomotic sites were correctly predicted in 95% (36/38) with MRA and 97% (37/38) with CA. Renal revascularization was predicted by MRA with a sensitivity of 91% (10/11) and specificity of 100% (65/65). The use of bifurcated aortic prostheses was correctly predicted by MRA in 75% (12/16), which was similar to that predicted by CA (81%, 13/16). Conclusions: MRA can provide preoperative anatomic information that is equivalent to CA for surgical planning. Because of favorable cost and patient safety considerations MRA will assume increasing importance in the preoperative evaluation of AAA. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV VASC SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 23 TC 41 Z9 42 U1 0 U2 0 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 JUN PY 1995 VL 21 IS 6 BP 891 EP 899 DI 10.1016/S0741-5214(95)70216-4 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA RC470 UT WOS:A1995RC47000003 PM 7776468 ER PT J AU CAMBRIA, RP BREWSTER, DC LITALIEN, G KOUSTAS, G ATAMIAN, S LAMURAGLIA, GM GERTLER, JP ABBOTT, WM AF CAMBRIA, RP BREWSTER, DC LITALIEN, G KOUSTAS, G ATAMIAN, S LAMURAGLIA, GM GERTLER, JP ABBOTT, WM TI SIMULTANEOUS AORTIC AND RENAL-ARTERY RECONSTRUCTION - EVOLUTION OF AN 18-YEAR EXPERIENCE SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 29-30, 1994 CL NEWPORT, RI SP NEW ENGLAND SOC VASC SURG ID RENOVASCULAR DISEASE; NATURAL-HISTORY; REVASCULARIZATION; MANAGEMENT; SURGERY; ATHEROSCLEROSIS; OPERATIONS; STENOSIS; RISKS AB Purpose: We reviewed an 18-year experience with combined abdominal aortic and renal artery reconstruction (AOR) with a particular focus on patients' clinical risk profile and surgical results in contemporary practice as compared with earlier experience. Methods: One hundred seventy patients underwent AOR during the interval January 1, 1976 to June 30, 1994. To examine parameters representative of current practice, the cohort was divided into group I patients (n = 110) treated before 1990 and group II (n = 60) treated between 1990 and 1994. Median follow-up duration for the entire cohort was 8.4 +/- 0.6 years. Renal artery reconstruction patency and patient survival rates were calculated by Life-table methods. Logistic and Cox regression analysis were used to determine predictors of perioperative and long-term morbidity/mortality rates. Results: Although demographic features changed Little over the review period, the detection (56% vs 73%, p = 0.03) and treatment with percutaneous transluminal coronary angioplasty/coronary artery bypass grafting (11% vs 40%, p = 0.0001) of associated coronary artery disease were more frequent in group II versus group I patients. Alternatively, renal insufficiency was more frequent in group I patients. The operative mortality rate for the entire cohort was 6.5% (group I = 9% vs group II = 2%, p = 0.06). Changing trends of surgical techniques over the review period included (group I vs II, respectively) increased use of bilateral simultaneous renal artery repair (12% vs 25%, p < 0.005) and transaortic endarterectomy as the renal artery reconstruction technique (3% vs 25%, p < 0.0001). Favorable response in blood pressure control was noted in 68% of group II patients. The cumulative 5-year survival rate for all patients was 75% with an initial serum creatinine of 2.0 mg/dl or greater being the only negative predictor of late survival after regression analysis. Conclusion: The current operative mortality rate for AOR is in the range anticipated for aortic surgery alone, and this appears to be related to improved detection and treatment of associated coronary artery disease and intervention before major deterioration in renal function. These findings coupled with currently available natural history data relative to renovascular disease justify an aggressive approach with AOR when significant renal artery stenosis is detected during evaluation of aortic disease. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. RP CAMBRIA, RP (reprint author), MASSACHUSETTS GEN HOSP,DIV VASC SURG,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 33 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 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 1995 VL 21 IS 6 BP 916 EP 925 DI 10.1016/S0741-5214(95)70219-9 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA RC470 UT WOS:A1995RC47000006 PM 7776471 ER PT J AU LITALIEN, GJ CAMBRIA, RP CUTLER, BS LEPPO, JA PAUL, SD BREWSTER, DC HENDEL, RC ABBOTT, WM EAGLE, KA AF LITALIEN, GJ CAMBRIA, RP CUTLER, BS LEPPO, JA PAUL, SD BREWSTER, DC HENDEL, RC ABBOTT, WM EAGLE, KA TI COMPARATIVE EARLY AND LATE CARDIAC MORBIDITY AMONG PATIENTS REQUIRING DIFFERENT VASCULAR-SURGERY PROCEDURES SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 29-30, 1994 CL NEWPORT, RI SP NEW ENGLAND SOC VASC SURG ID ABDOMINAL AORTIC-ANEURYSMS; CORONARY-ARTERY DISEASE; INTERMITTENT CLAUDICATION; MYOCARDIAL-INFARCTION; FOLLOW-UP; MANAGEMENT; MORTALITY; RISK; IMPACT AB Purpose: The evaluation of coronary artery disease (CAD) in patients undergoing vascular surgery can provide information with respect to perioperative and long-term risk for CAD-related events. However, the extent to which the required surgical procedure itself imparts additional risk beyond that dictated by the presence of CAD determinants remains in question. The purpose of this study was to quantify the relative contributions of specific vascular procedures and CAD markers on perioperative and long-term cardiac risk. Methods: The study cohort comprised 547 patients undergoing vascular surgery from two medical centers who underwent clinical evaluation, dipyridamole thallium testing, and either aortic (n = 321), infrainguinal (n = 177), or carotid (n = 49) vascular surgery between 1984 and 1991. Perioperative and late cardiac risk of fatal or nonfatal myocardial infarction (MI) was compared for the three procedures before and after adjustment for the influence of comorbid factors. These adjusted estimates may be regarded as the component of risk because of type of surgery. Results: Perioperative MI occurred in 6% of patients undergoing aortic and carotid artery surgery, and in 13% of patients undergoing infrainguinal procedures (p = 0.019). Significant (p < 0.05) predictors of MI were history of angina, fixed and reversible dipyridamole thallium defects, and ischemic ST depression during testing. Although patients undergoing infrainguinal procedures exhibited more than twice the risk for perioperative MI compared with patients undergoing aortic surgery (relative risk: 2.4[1.2 to 4.5, p = 0.008]), this value was reduced to insignificant levels (1.6[0.8 to 3.2, p = 0.189]) after adjustment for comorbid factors. There was little change in comparative risk between carotid artery and aortic procedures before (1.0[0.3 to 3.6, p = 0.95]) or after (0.6[0.2 to 2.3, p = 0.4]) covariate adjustment. The 4-year cumulative event-free survival rate was 90% +/- 2% for aortic, 74% +/- 5% for infrainguinal, and 78% +/- 7% for carotid artery procedures (p = 0.0001). Predictors of late MI included history of angina, congestive heart failure, diabetes, fixed dipyridamole thallium defects, and perioperative MI. Patients undergoing infrainguinal procedures exhibited a threefold greater risk for late events compared with patients undergoing aortic procedures (relative risk: 3.0[1.8 to 5.1, p = 0.005]), but this value was reduced to 1.3(0.8 to 2.3, p = 0.32) after adjustment. Long-term risk among patients undergoing carotid artery surgery was less dramatically altered by risk factor adjustment. Conclusion: In current practice, among patients referred for dipyridamole testing before operation; observed differences in cardiac risk of vascular surgery procedures may be primarily attributable to readily identifiable CAD risk factors rather than to the specific type of vascular surgery. Thus the cardiac and diabetic status of patients should be given careful consideration whenever possible, regardless of surgical procedure to be performed. C1 MASSACHUSETTS GEN HOSP, DEPT MED, CARDIAC UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, CAMBRIDGE, MA USA. UNIV MASSACHUSETTS, MED CTR, DEPT VASC SURG, WORCESTER, MA USA. UNIV MASSACHUSETTS, MED CTR, DEPT NUCL MED, WORCESTER, MA USA. RP MASSACHUSETTS GEN HOSP, DEPT SURG,DIV VASC SURG,15 PARKMAN ST,ACC 4, SUITE 458, BOSTON, MA 02114 USA. NR 21 TC 99 Z9 100 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 1995 VL 21 IS 6 BP 935 EP 944 DI 10.1016/S0741-5214(95)70221-0 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA RC470 UT WOS:A1995RC47000008 PM 7776473 ER PT J AU CASAZ, P RICE, PW COLE, CN HANSEN, U AF CASAZ, P RICE, PW COLE, CN HANSEN, U TI A TEF-1-INDEPENDENT MECHANISM FOR ACTIVATION OF THE SIMIAN-VIRUS-40 (SV40) LATE PROMOTER BY MUTANT SV40 LARGE T-ANTIGENS SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTIONAL TRANSACTIVATION FUNCTION; TRANSIENT GENE-EXPRESSION; VIRAL-DNA REPLICATION; RNA POLYMERASE-II; TUMOR-ANTIGEN; BINDING PROTEIN; SV40-TRANSFORMED CELLS; TRANSFORMING FUNCTION; NEGATIVE REGULATION; PRODUCT AB Simian virus 40 (SV40) large tumor antigen (T antigen) stimulates the activity of the SV40 late promoter and a number of cellular and other viral promoters. We have characterized the ability of T antigens with mutations in the DNA-binding domain and within the N-terminal 85 residues to activate the SV40 late promoter. T antigens lacking both nonspecific and sequence-specific DNA-binding activities were able to induce the late promoter. Mutations within the N-terminal 85 residues of T antigen diminished activation by less than twofold. Activation by wild-type and most of the mutant T antigens required intact binding sites for the cellular transcription factor TEF-1 in the late promoter. Curiously, two mutants altered in the N-terminal region and an additional mutant altered in the DNA-binding domain activated a late promoter derivative lacking TEF-1 binding sites, indicating the existence of a TEF-1-independent pathway for activation of the late promoter. A consensus binding site for the TATA binding protein, TBP, was created in variants of late promoters either containing or lacking TEF-1 binding sites. Basal expression was increased by the consensus TBP binding site only when TEF-1 binding sites were present, leading to a reduction in the degree of activation by T antigen. However, activation by a mutant T antigen of the promoter lacking TEF-1 sites was unchanged or slightly enhanced by the consensus TBP binding site. These results suggest that some mutant T antigens can stabilize an interaction between TBP and additional factors bound to the late promoter. C1 DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,COMM VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. DARTMOUTH COLL,SCH MED,DEPT BIOCHEM,HANOVER,NH 03755. NR 61 TC 12 Z9 12 U1 0 U2 1 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 1995 VL 69 IS 6 BP 3501 EP 3509 PG 9 WC Virology SC Virology GA QX931 UT WOS:A1995QX93100029 PM 7745697 ER PT J AU CAMPBELL, KS AUGER, KR HEMMINGS, BA ROBERTS, TM PALLAS, DC AF CAMPBELL, KS AUGER, KR HEMMINGS, BA ROBERTS, TM PALLAS, DC TI IDENTIFICATION OF REGIONS IN POLYOMAVIRUS MIDDLE-T AND SMALL-T ANTIGENS IMPORTANT FOR ASSOCIATION WITH PROTEIN PHOSPHATASE-2A SO JOURNAL OF VIROLOGY LA English DT Article ID MEDIUM TUMOR-ANTIGEN; CELLULAR PROTEINS; OKADAIC ACID; PHOSPHATIDYLINOSITOL 3-KINASE; RECOMBINANT RETROVIRUSES; MUTATIONAL ANALYSIS; REGULATORY SUBUNIT; SIMIAN VIRUS-40; RAT-CELLS; TRANSFORMATION AB Two subunits of protein phosphatase 2A (PP2A) have been shown previously to bind to the small t and middle T antigens (ST and MT, respectively) of polyomavirus. To determine sequences important for binding of PP2A to ST and MT, we first constructed a series of ST mutants in regions known to be important for biological activity of ST and MT. Several mutations in two small regions just amino terminal to the Cys-X-Cys-X-X-Cys motifs of ST and MT abolished PP2A binding to ST in vitro. Parallel mutations were constructed in MT to investigate the role of PP2A binding in the function of polyomavirus MT. Wild-type and mutant MT proteins were stably expressed in NIH 3T3 cells and analyzed (i) for their ability to induce transformation and (ii) for associated cellular proteins and corresponding enzymatic activities previously described as associating with wild-type MT. A number of the mutant MTs were found to be defective in binding of PP2A as assayed by coimmunoprecipitation. In contrast,a deletion of the highly conserved stretch of amino acids 42 to 47 (His-Pro-Asp-Lys-Gly-Gly) in the ST-MT-large T antigen common region did not affect PP2A binding to MT, MT mutants defective for PP2A binding were also defective in transformation, providing further evidence that association with PP2A is important for the ability of MT to transform cells. All mutants which were impaired for PP2A binding were similarly or more dramatically impaired for associated protein and lipid kinase activities, supporting the possibility that PP2A binding is necessary for the formation and/or stability of an MT-pp60(c-src) complex. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FRIEDRICH MIESCHER INST,CH-8057 BASEL,SWITZERLAND. FU NCI NIH HHS [R01 CA057327, CA50661-06, CA57327] NR 58 TC 64 Z9 66 U1 0 U2 2 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 1995 VL 69 IS 6 BP 3721 EP 3728 PG 8 WC Virology SC Virology GA QX931 UT WOS:A1995QX93100054 PM 7538174 ER PT J AU MAMMANO, F KONDO, E SODROSKI, J BUKOVSKY, A GOTTLINGER, HG AF MAMMANO, F KONDO, E SODROSKI, J BUKOVSKY, A GOTTLINGER, HG TI RESCUE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MATRIX PROTEIN MUTANTS BY ENVELOPE GLYCOPROTEINS WITH SHORT CYTOPLASMIC DOMAINS SO JOURNAL OF VIROLOGY LA English DT Article ID HOST-RANGE; INTRACELLULAR-TRANSPORT; LEUKEMIA-VIRUS; MATURE VIRIONS; GAG-PROTEINS; GENE; INFECTIVITY; CELLS; REPLICATION; HIV-1 AB The matrix (MA) protein of human immunodeficiency virus type 1 (HIV-1) forms the outer protein shell directly underneath the lipid envelope of the virion. The MA protein has a key role in different aspects of virus assembly, including the incorporation of the HIV-1 Env protein complex, which contains a transmembrane glycoprotein with an unusually long cytoplasmic tail. In this study, we compared the abilities of HIV-1 MA mutants to incorporate Env protein complexes with long and short cytoplasmic tails. While the mutant particles failed to incorporate the authentic HIV-1 Env protein complex, they retained the ability to efficiently and functionally incorporate the amphotropic murine leukemia virus Env protein complex, which has a shore cytoplasmic tail, Moreover, incorporation of the autologous Env protein complex could be restored by a second-site mutation that resulted in the truncation of the cytoplasmic tail of the HIV-1 transmembrane glycoprotein. Remarkably, the second-site mutation also restored the ability of MA mutants to replicate in MT-4 cells. These results imply that the long cytoplasmic tail of the transmembrane glycoprotein is responsible for the exclusion of the HIV-1 Env protein complex from MA mutant particles. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. OI Mammano, Fabrizio/0000-0002-9193-7696 FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691, AI29873] NR 52 TC 121 Z9 121 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUN PY 1995 VL 69 IS 6 BP 3824 EP 3830 PG 7 WC Virology SC Virology GA QX931 UT WOS:A1995QX93100066 PM 7745730 ER PT J AU TATERKA, J CEBRA, JJ RUBIN, DH AF TATERKA, J CEBRA, JJ RUBIN, DH TI CHARACTERIZATION OF CYTOTOXIC-CELLS FROM REOVIRUS-INFECTED SCID MICE - ACTIVATED CELLS EXPRESS NATURAL KILLER-LIKE AND LYMPHOKINE-ACTIVATED KILLER-LIKE ACTIVITY BUT FAIL TO CLEAR INFECTION SO JOURNAL OF VIROLOGY LA English DT Note ID SEVERE COMBINED IMMUNODEFICIENCY; T-CELL; NK CELLS; LIVER; MOUSE; MYOCARDITIS; LYMPHOCYTES; SURFACE; DISEASE AB Severe combined immune deficient (SCID) mice infected orally with reovirus type 1/L die of hepatitis. Leukocytes bearing the cell surface antigens Thy-1.2 and asialoGM-1 (AsGM1) accumulate in the livers of infected animals. These cells display lytic activity toward natural killer-sensitive (YAC-1) and -resistant (P815) cell lines and murine hepatoma line Hepa 1/A1. Although these cells have the capacity to lyse infected hepatoma targets, they cannot clear the virus. C1 VET AFFAIRS MED CTR,DEPT MED,DIV GASTROENTEROL,PHILADELPHIA,PA. VET AFFAIRS MED CTR,DEPT BIOL,PHILADELPHIA,PA. UNIV PENN,DEPT MICROBIOL,PHILADELPHIA,PA 19104. FU NIAID NIH HHS [AI-23970]; NIDDK NIH HHS [T32-DK-07066] NR 27 TC 7 Z9 7 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 1995 VL 69 IS 6 BP 3910 EP 3914 PG 5 WC Virology SC Virology GA QX931 UT WOS:A1995QX93100082 PM 7745745 ER PT J AU DAOUK, GH PALSSON, R ARNAOUT, MA AF DAOUK, GH PALSSON, R ARNAOUT, MA TI INHIBITION OF PROTEINASE-3 BY ANCA AND ITS CORRELATION WITH DISEASE-ACTIVITY IN WEGENERS GRANULOMATOSIS SO KIDNEY INTERNATIONAL LA English DT Article ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; NEUTROPHIL SERINE PROTEINASE; PRIMARY BILIARY-CIRRHOSIS; SYSTEMIC VASCULITIS; AUTOANTIBODIES; AUTOANTIGEN; ENZYME; GLOMERULONEPHRITIS; MYELOPEROXIDASE; AUTOIMMUNITY AB Detection of circulating antineutrophil cytoplasmic antibodies (ANCA) to the neutrophil serine proteinase, proteinase 3 (PR3), has proven valuable for the diagnosis of Wegener's granulomatosis (WG). However, the importance of these autoantibodies in the pathogenesis of WG remains unknown. It was recently reported that anti-PR3 autoantibodies (PR3-ANCA) from some patients with WG inhibit the proteolytic activity of PR3 and interfere with the inactivation of PR3 by the physiologic inhibitor, alpha(1)-proteinase inhibitor (alpha(1)-PI). We have studied the effect of PR3-ANCA on the enzymatic activity of PR3 and its correlation with disease activity in patients with WG. We purified IgG from 21 PR3-ANCA positive sera obtained from 17 patients with WG, and determined its effect on the esterolytic and proteolytic activity of purified human PR3 using Boc-Ala-O-Nitrophenyl ester and fluoresceinated-elastin as enzyme substrates. Controls included seven sera containing anti-MPO autoantibodies (MPO-ANCA) from patients with systemic vasculitis and seven ANCA-negative sera obtained from healthy individuals. We found that PR3-ANCA from 9 of the 17 patients significantly inhibited the activity of PR3. There was no correlation between the titers of PR3-ANCA and their inhibitory activity. For one extensively characterized autoantibody, the inhibition reached 70 to 95% at 20-fold molar excess of IgG to enzyme, with an apparent K(i)app of 56.5 mu M. This inhibition was non-competitive in nature, and was additive to that produced by (alpha(1)-PI. A review of the clinical histories of the patients revealed a strong association between active WG and inhibitory autoantibodies. PR3-ANCA from eight of 10 patients with active disease showed significant inhibition of PR3 activity, whereas only one of seven patients in remission had inhibitory PR3-ANCA. These results suggest that the inhibitory profile of PR3-ANCA may be more reflective of disease activity in patients with WG than the absolute titer, and suggest possible alternative mechanisms for the role of these autoantibodies in the pathogenesis of WG. C1 MASSACHUSETTS GEN HOSP,DEPT MED,PEDIAT NEPHROL & CHILDRENS SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP DAOUK, GH (reprint author), MASSACHUSETTS GEN HOSP,RENAL UNIT,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,WACC 709,15 PARKMAN ST,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK-07540, DK-42722] NR 53 TC 57 Z9 57 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1995 VL 47 IS 6 BP 1528 EP 1536 DI 10.1038/ki.1995.216 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA QZ868 UT WOS:A1995QZ86800006 PM 7643521 ER PT J AU KLEINMAN, JG BESHENSKY, A WORCESTER, EM BROWN, D AF KLEINMAN, JG BESHENSKY, A WORCESTER, EM BROWN, D TI EXPRESSION OF OSTEOPONTIN, A URINARY INHIBITOR OF STONE MINERAL CRYSTAL-GROWTH, IN RAT-KIDNEY SO KIDNEY INTERNATIONAL LA English DT Article ID ENHANCED EXPRESSION; MOUSE KIDNEY; PROTEIN; CDNA; RNA; CLONING; CELLS; IDENTIFICATION; HETEROGENEITY; PURIFICATION AB Cultured mouse kidney cortical cells secrete osteopontin, a bone matrix protein that is also found in urine. Osteopontin is associated with cell proliferation/tumerogenesis and also inhibits kidney stone mineral crystal growth [1]. Using antibodies raised against osteopontin isolated from the culture medium, we localized osteopontin in normal rat kidney. Fluorescence, confocal and electron microscopy revealed osteopontin primarily in cells of the descending thin limb of the loop of Henle (DTL) and in papillary surface epithelium (PSE) in the area of the calyceal fornix. In situ hybridization with labeled RNA made from a cDNA that contains the entire coding sequence for mouse osteopontin revealed message at the same sites at which protein was demonstrated by immunocytochemistry. Immunogold labeling was localized to a population of dense vesicles distinct from lysosomes and endosomes. To examine the turnover of osteopontin, rats were injected with the protein synthesis inhibitor cyclohexamide, 14 mg/kg, six hours prior to kidney fixation. These kidneys no longer demonstrated osteopontin in DTL and the immunofluorescence in the papillary surface was attenuated. Thus, osteopontin is secreted at two sites in the kidney where urine is highly concentrated in stone mineral constituents. It has a relatively rapid turnover, suggesting that it could be subject to physiological regulation. Osteopontin may be important in the normal endogenous defense against kidney stone formation. C1 VET AFFAIRS MED CTR,DEPT MED,DIV NEPHROL,MILWAUKEE,WI. MED COLL WISCONSIN,MILWAUKEE,WI 53226. MASSACHUSETTS GEN HOSP,DEPT PATHOL,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [R01NIDDK42956, DK41725] NR 30 TC 70 Z9 73 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1995 VL 47 IS 6 BP 1585 EP 1596 DI 10.1038/ki.1995.222 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA QZ868 UT WOS:A1995QZ86800012 PM 7643527 ER PT J AU URENA, P MANNSTADT, M HRUBY, M FERREIRA, A SCHMITT, F SILVE, C ARDAILLOU, R LACOUR, B ABOUSAMRA, AB SEGRE, GV DRUEKE, T AF URENA, P MANNSTADT, M HRUBY, M FERREIRA, A SCHMITT, F SILVE, C ARDAILLOU, R LACOUR, B ABOUSAMRA, AB SEGRE, GV DRUEKE, T TI PARATHYROIDECTOMY DOES NOT PREVENT THE RENAL PTH/PTHRP RECEPTOR DOWN-REGULATION IN UREMIC RATS SO KIDNEY INTERNATIONAL LA English DT Article ID HORMONE-RELATED PROTEIN; TUMOR-NECROSIS-FACTOR; OSTEOBLAST-LIKE CELLS; SMOOTH-MUSCLE CELLS; ADENYLATE-CYCLASE; MESSENGER-RNA; AGED RATS; VITAMIN-D; CALCIUM; EXPRESSION AB In a recent study we demonstrated that the PTH/PTHrP receptor (PTH-R) mRNA was markedly down-regulated in the remnant kidney of uremic rats with severe secondary hyperparathyroidism. Among the factors potentially implicated in this downregulation, to date only PTH has been demonstrated to modulate PTH-R expression. Here, we examined the effect of thyroparathyroidectomy (TPTX) on the renal expression of PTH-R in rats with normal renal function or with chronic renal failure (CRF) induced by 5/6 nephrectomy. Four groups of rats were studied: control, TPTX, CRF, and CRF+TPTX. Moderate-degree renal failure was documented by mean(+/- SD) creatinine clearances (mu l/min/100 g body wt) of 259 +/- 40 and 212 +/- 45 in CRF and CRF+TPTX rats, compared with 646 +/- 123 and 511 +/- 156 in control and TPTX rats, respectively. Plasma phosphorus, calcitriol, and ionized calcium were significantly lower in CRF and CRF+TPTX than in control animals. Plasma ionized calcium and calcitriol were also lower in TPTX than in control rats. Plasma PTH levels (pg/ml) were increased in CRF rats (41.8 +/- 29.4), and markedly decreased in TPTX (10.1 +/- 7.8) and CRFfTPTX (8.0 +/- 3.8) rats compared with control rats (21.7 +/- 7.5). Northern blot analysis showed that the level of the steady-state PTH-R mRNA in the kidney of CRF and CRFS-TPTX rats was markedly decreased compared with that of control rats, the ratios of PTH-R mRNA/beta-actin mRNA being 0.28 +/- 0.04 and 0.27 +/- 0.03 versus 0.54 +/- 0.05, respectively. The PTH-R mRNA expression was also found decreased in bone tissue from two uremic animals compared with control rats: 0.59 versus 0.78, respectively. No change was observed in the renal PTH-R mRNA level in TPTX animals. There was also no change in the PTH-R mRNA expression in the liver of uremic rats. The expression of the PTHrP mRNA was comparable in the kidney of control and CRF animals. CRF and CRF+TPTX rats showed a similarly reduced PTH-sensitive adenylyl cyclase activity in crude renal membrane preparations, compared with control rats. Despite the reduction of PTH-R mRNA and PTH-sensitive adenylyl cyclase in the kidney, CRF rats with intact parathyroid glands had lower urinary calcium excretion and higher phosphate excretion than CRF-TPTX rats, suggesting that PTH was still capable of controlling mineral ion metabolism through the remaining PTH-R in the residual nephrons. In conclusion, our data demonstrate that neither an increase in plasma PTH and phosphate nor a decrease in plasma calcium are important in renal PTH-R down-regulation during chronic renal failure. It is also unlikely that an increase in the locally-produced renal PTHrP could down-regulate its own receptor. C1 HOP NECKER ENFANTS MALAD,DEPT NEPHROL,F-75743 PARIS 15,FRANCE. HOP BICHAT,INSERM,U251,PARIS,FRANCE. HOP TENON,INSERM,U63,PARIS,FRANCE. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA. RP URENA, P (reprint author), HOP NECKER ENFANTS MALAD,INSERM,U90,161 RUE SEVRES,F-75743 PARIS 15,FRANCE. OI Ferreira, Anibal/0000-0002-3300-6033; Abou-Samra, Abdul/0000-0001-8735-1142 NR 50 TC 51 Z9 52 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1995 VL 47 IS 6 BP 1797 EP 1805 DI 10.1038/ki.1995.248 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA QZ868 UT WOS:A1995QZ86800038 PM 7643551 ER PT J AU ZUKERBERG, LR YANG, WI GADD, M THOR, AD KOERNER, FC SCHMIDT, EV ARNOLD, A AF ZUKERBERG, LR YANG, WI GADD, M THOR, AD KOERNER, FC SCHMIDT, EV ARNOLD, A TI CYCLIN D1 (PRAD1) PROTEIN EXPRESSION IN BREAST-CANCER - APPROXIMATELY 1/3 OF INFILTRATING MAMMARY CARCINOMAS SHOW OVEREXPRESSION OF THE CYCLIN-D1 ONCOGENE SO MODERN PATHOLOGY LA English DT Article DE ONCOGENE; CYCLIN D1; CARCINOMA; BREAST TUMOR; IMMUNOHISTOCHEMISTRY ID CHROMOSOME 11Q13; CELL-CYCLE; CENTROCYTIC LYMPHOMA; CANDIDATE ONCOGENE; PUTATIVE ONCOGENE; PRAD1/CYCLIN D1; AMPLIFICATION; GENE; TUMORS; BCL-1 AB Amplification of chromosome 11q13 has been observed in 10-20% of breast carcinomas and numerous other tumors, including squamous cell carcinomas of the head, neck, and esophagus; transitional cell carcinomas of the urinary bladder; and epithelial ovarian tumors. Cyclin D1/PRAD1 is a likely ''driver'' gene for this amplicon because of its role in cell cycle control and because it has been specifically implicated as an oncogene in parathyroid adenomas and B-cell lymphomas with 11q13 translocation breakpoints. We examined cyclin D1 protein expression in 48 consecutive cases of infiltrating mammary carcinoma using an affinity-purified polyclonal antisera to cyclin D1 and a microwave/citrate buffer antigen retrieval system. Staining data were correlated with clinicopathological features, protein detection by immunoblots, and 11q13 DNA amplification. Definite nuclear staining was seen in 17/48 (35%) tumors (16 infiltrating ductal carcinomas, predominantly grade 2/3, and one infiltrating lobular carcinoma). There was no nuclear staining of normal breast epithelium, fat cells, or admired lymphocytes. Tumors with overexpression of cyclin D1 were estrogen receptor-positive (P <.005) and usually progesterone receptor-positive (P <.005) but otherwise were similar to other negative cases in the study group. Correlation between Western blot and immunostaining data was excellent (P <.01). Five of the 22 cases studied showed 11q13 DNA amplification as well as increased levels of cyclin D1 protein by Western blot and immunostaining. Four cases with increased cyclin D1 protein by both Western blots and immunohistochemistry did not have detectable 11q13 amplification. Nuclear cyclin D1 protein can be detected in approximately one-third of infiltrating breast carcinomas using an immunohistochemical technique on formalin-fixed, paraffin-embedded tissue. Thus, more breast cancers exhibit cyclin D1 protein overexpression than can be accounted for by 11q13 amplification. These observations suggest that cyclin D1, activated by various mechanisms, is more prevalent and possibly more important in the pathogenesis of breast carcinoma than previously thought. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP ZUKERBERG, LR (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,ENDOCRINE ONCOL UNIT,WARREN 2,FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [5F32CA09260-2, CA44768, CA55909] NR 39 TC 101 Z9 101 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUN PY 1995 VL 8 IS 5 BP 560 EP 567 PG 8 WC Pathology SC Pathology GA RD360 UT WOS:A1995RD36000020 PM 7675778 ER PT J AU BLOBEL, GA SIEFF, CA ORKIN, SH AF BLOBEL, GA SIEFF, CA ORKIN, SH TI LIGAND-DEPENDENT REPRESSION OF THE ERYTHROID TRANSCRIPTION FACTOR GATA-1 BY THE ESTROGEN-RECEPTOR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID COMPOSITE RESPONSE ELEMENT; GLUCOCORTICOID RECEPTOR; DNA-BINDING; STEM-CELLS; C-JUN; EXPRESSION; ACTIVATION; PROTEIN; DIFFERENTIATION; INHIBITION AB High-dose estrogen administration induces anemia in mammals, In chickens, estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation, This delay is associated with down-regulation of many erythroid cell-specific genes, including alpha- and beta-globin, band 3, band 4.1, and the erythroid cell-specific histone H5, We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures, To address potential mechanisms by which estrogens suppress erythropoiesis, we have examined their effects on GATA-1, an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes. We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor (ER) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen, ER-mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site, as well as in the context of an intact promoter which is normally regulated by GATA-1, GATA-1 and ER bind to each other in vitro in the absence of DNA, In coimmunoprecipitation experiments using transfected COS cells, GATA-1 and ER associate in a ligand-dependent manner, Mapping experiments indicate that GATA-1 and the ER form at least two contacts, which involve the finger region and the N-terminal activation domain of GATA-1, We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER. Interference with GATA-binding proteins may be one mechanism by which steroid hormones modulate cellular differentiation. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 46 TC 106 Z9 106 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 JUN PY 1995 VL 15 IS 6 BP 3147 EP 3153 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QZ325 UT WOS:A1995QZ32500026 PM 7760810 ER PT J AU GREEN, M SCHUETZ, TJ SULLIVAN, EK KINGSTON, RE AF GREEN, M SCHUETZ, TJ SULLIVAN, EK KINGSTON, RE TI A HEAT SHOCK-RESPONSIVE DOMAIN OF HUMAN HSF1 THAT REGULATES TRANSCRIPTION ACTIVATION DOMAIN FUNCTION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN HSP70 PROMOTER; DNA-BINDING; ERYTHROLEUKEMIA-CELLS; FACTOR CONTAINS; FACTOR-II; PROTEIN; GENES; OLIGOMERIZATION; LOCALIZATION; ELEMENTS AB Human heat shock factor 1 (HSF1) stimulates transcription from heat shock protein genes following stress. We have used chimeric proteins containing the GAL4 DNA binding domain to identify the transcriptional activation domains of HSF1 and a separate domain that is capable of regulating activation domain function. This regulatory domain conferred heat shock inducibility to chimeric proteins containing the activation domains. The regulatory domain is located between the transcriptional activation domains and the DNA binding domain of HSF1 and is conserved between mammalian and chicken HSF1 but is not found in HSF2 or HSF3. The regulatory domain was found to be functionally homologous between chicken and human HSF1. This domain does not affect DNA binding by the chimeric proteins and does not contain any of the sequences previously postulated to regulate DNA binding of HSF1. Thus, we suggest that activation of HSF1 by stress in humans is controlled by two regulatory mechanisms that separately confer heat shock-induced DNA binding and transcriptional stimulation. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. FU NIGMS NIH HHS [GM43901] NR 40 TC 123 Z9 129 U1 1 U2 4 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 1995 VL 15 IS 6 BP 3354 EP 3362 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QZ325 UT WOS:A1995QZ32500049 PM 7760831 ER PT J AU KASSNER, PD ALON, R SPRINGER, TA HEMLER, ME AF KASSNER, PD ALON, R SPRINGER, TA HEMLER, ME TI SPECIALIZED FUNCTIONAL-PROPERTIES OF THE INTEGRIN ALPHA(4) CYTOPLASMIC DOMAIN SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CELL-ADHESION MOLECULE-1; TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; LYMPHOCYTE MIGRATION; FIBRONECTIN RECEPTOR; MONOCLONAL-ANTIBODY; PLASMA FIBRONECTIN; SYNTHETIC PEPTIDE; FOCAL ADHESIONS; VLA-4 INTEGRIN AB For functional studies of the integrin alpha(4) cytoplasmic domain, we have expressed the following in K562 and Chinese hamster ovary (CHO) cells: 1) wild-type alpha(4) (called X4C4), 2) two chimeric forms of alpha(4) (called X4C2 and X4C5) that contain the cytoplasmic domains of alpha(2) and alpha(5), respectively, and 3) alpha(4) with no cytoplasmic domain (X4CO). Cytoplasmic domain exchange had no effect on VLA-4-dependent static cell adhesion or tethering to VCAM-1 in conditions of shear flow. However, the presence of the alpha(2) alpha(5) tails markedly or a enhanced VLA-4-dependent K562 cells spreading (X4C2 > X4C5 > X4C4 > X4CO), increased localization of VLA-4 into focal adhesion-like complexes in CHO cells (X4C2 > X4C5 > X4C4), and strengthened CHO and K562 cell resistance to detachment from VCAM-1 in conditions of shear flow (X4C2 > X4C5 > X4C4 > X4CO). Conversely, the alpha(4) tail supported greater VLA-4-dependent haptotactic and chemotactic cell migration. In the absence of any alpha tail (i.e., X4CO), robust focal adhesions were observed, even though cell spreading and adhesion strengthening were minimal. Thus, such focal adhesions may have relatively little functional importance, and should not be compared with focal adhesions formed when alpha tails are present. Together, these results indicate that all three alpha-chain tails exert defined positive effects (compared with no tail at all), but suggest that the alpha(4) cytoplasmic domain may be specialized to engage in weaker cytoskeletal interactions, leading to diminished focal adhesion formation, cell spreading, and adhesion strengthening, while augmenting cell migration and facilitating rolling under shear flow. These properties of the alpha(4) tail are consistent with the role of alpha 4 lymphocytes, monocytes and eosinophils. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. FU NCI NIH HHS [CA-31798]; NHLBI NIH HHS [HL-48675]; NIGMS NIH HHS [GM-46526] NR 69 TC 86 Z9 86 U1 0 U2 2 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUN PY 1995 VL 6 IS 6 BP 661 EP 674 PG 14 WC Cell Biology SC Cell Biology GA RD167 UT WOS:A1995RD16700004 PM 7579686 ER PT J AU BORK, P OUZOUNIS, C CASARI, G SCHNEIDER, R SANDER, C DOLAN, M GILBERT, W GILLEVET, PM AF BORK, P OUZOUNIS, C CASARI, G SCHNEIDER, R SANDER, C DOLAN, M GILBERT, W GILLEVET, PM TI EXPLORING THE MYCOPLASMA-CAPRICOLUM GENOME - A MINIMAL CELL REVEALS ITS PHYSIOLOGY SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI GENOME; DNA-SEQUENCE; BACILLUS-SUBTILIS; FIELD ELECTROPHORESIS; REGION; ALIGNMENT; PROTEINS; CLASSIFICATION; PNEUMONIAE; DATABASE AB We report on the analysis of 214 kb of the parasitic eubacterium Mycoplasma capricolum sequenced by genomic walking techniques. The 287 putative proteins detected to date represent about half of the estimated total number of 500 predicted for this organism. A large fraction of these (75%) can be assigned a likely function as a result of similarity searches. Several important features of the functional organization of this small genome are already apparent. Among these are (i) the expected relatively large number of enzymes involved in metabolic transport and activation, for efficient use of host cell nutrients; (ii) the presence of anabolic enzymes; (iii) the unexpected diversity of enzymes involved in DNA replication and repair; and (iv) a sizeable number of orthologues (82 so far) in Escherichia coli. This survey is beginning to provide a detailed view of how M. capricolum manages to maintain essential cellular processes with a genome much smaller than that of its bacterial relatives. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HARVARD UNIV, BOSTON, MA 02138 USA. GEORGE MASON UNIV, FAIRFAX, VA 22030 USA. RP BORK, P (reprint author), EUROPEAN MOLEC BIOL LAB, MEYERHOFSTR 1, D-69012 HEIDELBERG, GERMANY. RI Schneider, Reinhard/C-5441-2009; sander, chris/H-1452-2011; Bork, Peer/F-1813-2013; Ouzounis, Christos/G-2302-2010 OI Bork, Peer/0000-0002-2627-833X; NR 56 TC 62 Z9 80 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD JUN PY 1995 VL 16 IS 5 BP 955 EP 967 DI 10.1111/j.1365-2958.1995.tb02321.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA RK264 UT WOS:A1995RK26400013 PM 7476192 ER PT J AU MORENS, DM GRANDINETTI, A REED, D WHITE, LR ROSS, GW AF MORENS, DM GRANDINETTI, A REED, D WHITE, LR ROSS, GW TI CIGARETTE-SMOKING AND PROTECTION FROM PARKINSONS-DISEASE - FALSE ASSOCIATION OR ETIOLOGIC CLUE SO NEUROLOGY LA English DT Review ID ENVIRONMENTAL RISK-FACTORS; DIAGNOSED ALZHEIMERS-DISEASE; MONOAMINE OXIDASE-B; ALCOHOL-CONSUMPTION; OLFACTORY FUNCTION; YOUNG-ONSET; NICOTINE; DOPAMINE; DEMENTIA; HYPOTHESIS AB We reviewed 46 published reports associating cigarette smoking and Parkinson's disease. Although the majority indicated an approximate halving of smoking frequency in persons with Parkinson's disease, many observers have suggested that the effect could be a spurious result. That the association may be real is suggested by at least six observations: (1) the consistency of findings between independent studies of different design, conducted by different investigators, in different nations, over 35 years; (2) the association's predominance and strength in prospective studies; (3) the apparent detection of a dose-response relation; (4) the inability to explain the association by confounding variables; (5) the flaws in certain arguments against the association's validity; and (6) the identification of a similar association, of similar magnitude, between smoking and reduced occurrence of Alzheimer's disease. A protective association of cigarette smoking for Parkinson's disease may constitute an important etiologic clue. C1 UNIV HAWAII,SCH MED,DEPT TROP MED,HONOLULU,HI 96822. EAST WEST CTR,HONOLULU,HI 96848. BUCK CTR RES AGING,NOVATA,CA. NIA,BETHESDA,MD 20892. NIA,HONOLULU ASIA AGING STUDY,HONOLULU,HI. US DEPT VET AFFAIRS,HONOLULU,HI. RP MORENS, DM (reprint author), UNIV HAWAII,SCH PUBL HLTH,DEPT PUBL HLTH SCI,BIOMED D103,1960 E W RD,HONOLULU,HI 96822, USA. FU NINDS NIH HHS [R01 NS 30371] NR 107 TC 279 Z9 287 U1 0 U2 7 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1995 VL 45 IS 6 BP 1041 EP 1051 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA RC993 UT WOS:A1995RC99300002 PM 7783862 ER PT J AU RAKIC, P CAVINESS, VS AF RAKIC, P CAVINESS, VS TI CORTICAL DEVELOPMENT - VIEW FROM NEUROLOGICAL MUTANTS 2 DECADES LATER SO NEURON LA English DT Review ID REELER MUTANT; NEURONAL MIGRATION; HUMAN BRAIN; MOUSE; NEOCORTEX; CORTEX; MICE; GENE; SPECIFICATION; PROTEIN C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02145. RP RAKIC, P (reprint author), YALE UNIV,SCH MED,NEUROBIOL SECT,333 CEDAR ST,NEW HAVEN,CT 06520, USA. NR 38 TC 227 Z9 231 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD JUN PY 1995 VL 14 IS 6 BP 1101 EP 1104 DI 10.1016/0896-6273(95)90258-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA RF987 UT WOS:A1995RF98700002 PM 7605626 ER PT J AU HUNTER, JV BATCHELDER, KF LO, EH WOLF, GL AF HUNTER, JV BATCHELDER, KF LO, EH WOLF, GL TI IMAGING TECHNIQUES FOR IN-VIVO QUANTITATION OF EXTRACRANIAL LYMPHATIC DRAINAGE OF THE BRAIN SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE LYMPHATICS; BRAIN; RABBIT; CT; CONTRAST; NANOPARTICULATE; CSF; INTERSTITIAL FLUID C1 MASSACHUSETTS GEN HOSP EAST,CIPR,BOSTON,MA. RP HUNTER, JV (reprint author), CHILDRENS HOSP PHILADELPHIA,DEPT NEURORADIOL,34TH & CIVIC CTR,PHILADELPHIA,PA 19104, USA. NR 8 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD JUN PY 1995 VL 21 IS 3 BP 185 EP 188 DI 10.1111/j.1365-2990.1995.tb01049.x PG 4 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA RJ302 UT WOS:A1995RJ30200004 PM 7477726 ER PT J AU TANZI, RE AF TANZI, RE TI CLINICAL IMPLICATIONS OF BASIC RESEARCH - A PROMISING ANIMAL-MODEL OF ALZHEIMERS-DISEASE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP TANZI, RE (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02129, USA. NR 3 TC 10 Z9 10 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 1 PY 1995 VL 332 IS 22 BP 1512 EP 1513 DI 10.1056/NEJM199506013322212 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA RA140 UT WOS:A1995RA14000012 PM 7739692 ER PT J AU NETLAND, PA YE, HQ STREETEN, BW HERNANDEZ, MR AF NETLAND, PA YE, HQ STREETEN, BW HERNANDEZ, MR TI ELASTOSIS OF THE LAMINA-CRIBROSA IN PSEUDOEXFOLIATION SYNDROME WITH GLAUCOMA SO OPHTHALMOLOGY LA English DT Article ID OPTIC-NERVE HEAD; OPEN-ANGLE GLAUCOMA; TERM FOLLOW-UP; ELASTIC FIBERS; EXTRACELLULAR-MATRIX; EXFOLIATION SYNDROME; FIBRILLOPATHY; PROTEIN; IMMUNOLOCALIZATION; HYPERTENSION AB Background: Pseudoexfoliation syndrome is characterized by the presence of glycoprotein fibers in ocular and extraocular tissues, and often is associated with glaucoma. Pseudoexfoliation material may be associated closely with elastic microfibrillar-associated glycoprotein as well as elastin. Methods: Four optic nerve heads of two patients with pseudoexfoliation syndrome and glaucoma were examined using electron microscopy and immunogold detection of elastin. Optic nerve heads from healthy age-matched individuals and patients with primary open-angle glaucoma were used for comparisons. Results: In all eyes with pseudoexfoliation and glaucoma, there was marked and widespread elastosis in the connective tissue of the lamina cribrosa. Elastotic fibers appeared as large and irregular aggregates of electron-dense material labeled with antielastin antibody. Abundant microfibrils were interspersed in the elastotic aggregates, whereas no typical pseudoexfoliation fibers were observed. In contrast, there were less elastotic fibers in the lamina cribrosa from patients with primary open-angle glaucoma compared with pseudoexfoliation glaucoma. Other changes of extracellular matrix were similar to those observed in primary open-angle glaucoma: decreases in collagen fiber density, presence of basement membranes not associated with cell surfaces, and abundant bundles of microfibrils not labeled with elastin antibody. The elastic fibers appeared normal in other locations within the optic nerves of patients with pseudoexfoliation glaucoma, including in the pial septa and blood vessels of the retrolaminar myelinated optic nerve. Conclusion The authors' findings demonstrate marked and site-specific elastosis in the lamina cribrosa of patients with pseudoexfoliation syndrome with glaucoma, suggesting an abnormal regulation of elastin synthesis and/or degradation in the optic nerve of patients with this disease. Ophthalmology 1995;102:878-886 C1 HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. SUNY SYRACUSE,HLTH SCI CTR,DEPT OPHTHALMOL,SYRACUSE,NY. SUNY SYRACUSE,HLTH SCI CTR,DEPT PATHOL,SYRACUSE,NY. RP NETLAND, PA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EYO1602, EYO6416] NR 40 TC 73 Z9 75 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 1995 VL 102 IS 6 BP 878 EP 886 PG 9 WC Ophthalmology SC Ophthalmology GA RC166 UT WOS:A1995RC16600012 PM 7777294 ER PT J AU RIZZO, JF AF RIZZO, JF TI VISUAL-LOSS AFTER NEUROSURGICAL REPAIR OF PARACLINOID ANEURYSMS SO OPHTHALMOLOGY LA English DT Article ID CAROTID-OPHTHALMIC ANEURYSMS; ARTERY ANEURYSMS AB Objective: To describe three cases of unexplained visual loss after technically successful clipping of paraclinoid aneurysms. Design: Three case reports are presented. Results Profound blindness occurred in all three patients. Only one patient had marked visual recovery. Two clinical patterns were observed. A fulminant orbital syndrome presumably from compromise of large draining veins of the orbit was observed in one patient. A retrobulbar optic neuropathy that might have resulted from either direct injury or damage to small dural vessels of the posterior optic nerve was observed in the other two patients. Conclusions: There is a risk of postoperative blindness after clipping of paraclinoid aneurysms. The frequency of this complication may increase because attempts to repair these aneurysms are becoming more common. Patients with paraclinoid aneurysms should receive preoperative and postoperative neuro-ophthalmologic examinations. C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. RP RIZZO, JF (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. NR 26 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 1995 VL 102 IS 6 BP 905 EP 910 PG 6 WC Ophthalmology SC Ophthalmology GA RC166 UT WOS:A1995RC16600016 PM 7777297 ER PT J AU PINEDA, R URBAN, RC BELLOWS, AR JAKOBIEC, FA AF PINEDA, R URBAN, RC BELLOWS, AR JAKOBIEC, FA TI CILIARY BODY NEURILEMOMA - UNUSUAL CLINICAL FINDINGS INTIMATING THE DIAGNOSIS SO OPHTHALMOLOGY LA English DT Article ID MESECTODERMAL LEIOMYOMA; NERVE; TUMOR AB Background: Neurilemomas (schwannomas) rarely occur intraocularly. When present, they pose a diagnostic dilemma for the physician and often are mistaken as a malignant lesion, resulting in enucleation. Methods: The authors report the clinical findings of a 46-year-old man with a slowly progressive growing mass of the anterior chamber, associated with glaucoma and the development of cataract. To further delineate the tumor's features, ancillary techniques, including ultrasonography, computed tomography, and magnetic resonance imaging, were conducted. A definitive anterior chamber biopsy of the tumor was performed with histologic examination and electron microscopy. Results: Ultrasonography, high-resolution computed tomography and magnetic resonance imaging showed a well-delineated mass of the inferior ciliary body involving nearly 5 clock hours of the angle. Two clinical features that suggested a longstanding tumor were brilliant transillumination of the mass (leading to the impression of a ''cystic mass,'' not corroborated by ultrasonography) and retrodisplacement of the involved iris root. The histology, and particularly the electron microscopic features, confirmed the diagnosis of a neurilemoma, a benign tumor of the anterior segment. Conclusion: Intraocular neurilemomas are extremely rare tumors. Few are well documented with modern ancillary techniques. Clinical findings in conjunction with radiographic and ultrasonic features may support the diagnosis of a benign tumor. For this patient, confirmation via biopsy permitted combined cataract and glaucoma surgery to rehabilitate the eye, which retains 20/20 visual acuity 3 years after the procedure. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 25 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 1995 VL 102 IS 6 BP 918 EP 923 PG 6 WC Ophthalmology SC Ophthalmology GA RC166 UT WOS:A1995RC16600018 PM 7777299 ER PT J AU HAFFAJEE, AD SOCRANSKY, SS TAUBMAN, MA SIOSON, J SMITH, DJ AF HAFFAJEE, AD SOCRANSKY, SS TAUBMAN, MA SIOSON, J SMITH, DJ TI PATTERNS OF ANTIBODY-RESPONSE IN SUBJECTS WITH PERIODONTITIS SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE ANTIBODY; PERIODONTITIS; CLUSTER ANALYSIS; DISEASE ACTIVITY; PERIODONTAL PATHOGEN ID ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; IMMUNOLOGICAL FEATURES; JUVENILE PERIODONTITIS; SERUM ANTIBODIES; DISEASES AB Periodontal diseases comprise a heterogeneous group of infections that are difficult to distinguish on a clinical basis alone. The purpose of the present investigation was to group periodontitis subjects according to their elevated serum antibody levels to specific subgingival species. A total of 119 subjects (19-70 years) with evidence of prior periodontal destruction were monitored at 2-month intervals (maximum 8 visits), prior to therapy, using clinical parameters measured at 6 sites per tooth. The probing attachment level was measured twice at each visit, and an increase of >2.5 mm at a site was used to define subjects with progressing disease. Serum samples were obtained from each subject at each visit and the level of antibody determined by enzyme-linked immunosorbent assay to 12 subgingival species. Subgingival plaque samples were taken from the mesial aspect of all teeth in each subject at each visit, and the levels of 14 different subgingival species were determined using a colony-lift method and DNA probes. Subjects were grouped by cluster analysis of their elevated antibody levels using a simple matching coefficient. Ninety-two subjects fell into 9 clusters with 100% similarity; 29 subjects in one cluster group exhibited elevated antibody to none of the test species. Seven subjects in a second cluster group showed elevated antibody to Bacteroides forsythus. Subjects in the other 7 clusters showed elevated antibody to Actinobacillus actinomycetemcomitans serotype a only or in combination with B. forsythus, A. actinomycetemcomitans serotype b, Prevotella intermedia or Porphyromonas gingivalis. Subjects in different cluster groups differed with respect to age, number of active sites, levels of gingivitis, prior periodontal destruction and levels of 11 of 14 microbial species tested. Subjects with multiple elevated antibody levels had significantly more active sites than subjects with 0 or 1 elevated response. The 23 early-onset periodontal disease subjects were confined primarily to 2 clusters or were unclustered and 78% had multiple elevated antibody levels. There appeared to be a finite number of frequently detected antibody patterns that may be useful in categorizing periodontitis. C1 FORSYTH DENT CTR,DEPT IMMUNOL,BOSTON,MA 02115. RP HAFFAJEE, AD (reprint author), FORSYTH DENT CTR,DEPT PERIODONTOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04881] NR 30 TC 30 Z9 30 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD JUN PY 1995 VL 10 IS 3 BP 129 EP 137 DI 10.1111/j.1399-302X.1995.tb00133.x PG 9 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA QZ775 UT WOS:A1995QZ77500001 PM 7567061 ER PT J AU WEBER, AL BROWN, EW HUG, EB LIEBSCH, NJ AF WEBER, AL BROWN, EW HUG, EB LIEBSCH, NJ TI CARTILAGINOUS TUMORS AND CHORDOMAS OF THE CRANIAL BASE SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID INTRACRANIAL CHONDROSARCOMA; CHONDROID CHORDOMAS; CLIVAL CHORDOMAS; SKULL BASE; MR; APPEARANCE; FEATURES; HEAD; NECK; CT AB Chordomas and chondrosarcomas are uncommon skull base tumors that are locally aggressive. Chordomas arise from the clivus with the epicenter in the midline of the skull base. Chondrosarcomas, in contrast, usually arise along the petro-occipital fissure. Occasionally, a chondrosarcoma may be revealed in a midline location and then cannot be differentiated from chordoma. Chordomas rarely calcify whereas calcification is not an uncommon finding in chondrosarcomas. The prognoses of chordomas and chondrosarcomas vary. Long-term survival is usually seen with chondrosarcomas but is still considerably compromised with chordomas. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL ONCOL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. NR 35 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 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD JUN PY 1995 VL 28 IS 3 BP 453 EP 471 PG 19 WC Otorhinolaryngology SC Otorhinolaryngology GA RE782 UT WOS:A1995RE78200004 PM 7675464 ER PT J AU SOM, PM CURTIN, HD AF SOM, PM CURTIN, HD TI LESIONS OF THE PARAPHARYNGEAL SPACE - ROLE OF MR-IMAGING SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID COMPUTED-TOMOGRAPHY; PLEOMORPHIC ADENOMAS; SALIVARY-GLANDS; PAROTID MASSES; TUMORS; NECK; CT; SIALOGRAPHY; INFECTIONS; DIAGNOSIS AB Because the parapharyngeal space is one of the deep spaces of the upper neck, it is a difficult region to examine clinically. On each side of the head, this space is located lateral to the pharynx and medial to the ramus of the mandible, the pterygoid muscles, and the parotid gland. It is only with bimanual palpation that any small fullness within this space may be clinically appreciated. When a parapharyngeal mass is sufficiently large, it displaces the lateral pharyngeal wall and pharyngeal tonsil toward the midline and may cause lateral displacement of the parotid gland. Only when a lesion is very large does it manifest as a fullness near the angle of the mandible. Thus, clinical evaluation of the space is quite limited. C1 CUNY MT SINAI SCH MED,DEPT RADIOL & OTOLARYNGOL,NEW YORK,NY. MASSACHUSETTS GEN HOSP,DEPT RADIOL ONCOL,BOSTON,MA. UNIV PITTSBURGH,SCH MED,DEPT RADIOL,PITTSBURGH,PA. UNIV PITTSBURGH,SCH MED,DEPT OTOLARYNGOL,PITTSBURGH,PA. NR 75 TC 19 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD JUN PY 1995 VL 28 IS 3 BP 515 EP 542 PG 28 WC Otorhinolaryngology SC Otorhinolaryngology GA RE782 UT WOS:A1995RE78200007 PM 7675467 ER PT J AU KRADIN, RL AF KRADIN, RL TI THE IMMUNE SELF - A SELECTIONIST THEORY OF RECOGNITION, LEARNING, AND REMEMBERING WITHIN THE IMMUNE-SYSTEM SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Article ID CELL C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP KRADIN, RL (reprint author), MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02114, USA. NR 47 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0031-5982 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD SUM PY 1995 VL 38 IS 4 BP 605 EP 623 PG 19 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA RM915 UT WOS:A1995RM91500008 PM 7659491 ER PT J AU FERAILLE, E BARLETBAS, C CHEVAL, L ROUSSELOT, M CARRANZA, ML DREHER, D ARYSTARKHOVA, E DOUCET, A FAVRE, H AF FERAILLE, E BARLETBAS, C CHEVAL, L ROUSSELOT, M CARRANZA, ML DREHER, D ARYSTARKHOVA, E DOUCET, A FAVRE, H TI PRESENCE OF 2 ISOFORMS OF NA, K-ATPASE WITH DIFFERENT PHARMACOLOGICAL AND IMMUNOLOGICAL PROPERTIES IN THE RAT-KIDNEY SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE NEPHRON; OUABAIN; ALPHA SUBUNIT ID ALPHA-SUBUNIT; RABBIT NEPHRON; NA+/K+-ATPASE; NA+,K+-ATPASE; AFFINITY; (NA+,K+)-ATPASE; IDENTIFICATION; STIMULATION; MODULATION; EXPRESSION AB Previous studies have demonstrated the presence of two populations of Na,K-ATPase with distinct kinetic, pharmacological and immunological characteristics along the rabbit nephron, indicating that the proximal segments of the nephron express exclusively the alpha(1) isoform of the catalytic subunit, whereas the collecting duct expresses an alpha(3)-like isoform. Because pharmacological studies have shown the existence of two populations of Na,K-ATPase with different sensitivities to ouabain in the rat cortical collecting duct, which may result from the presence in the same nephron segment of the two isoforms demonstrated in the different segments of the rabbit nephron, the present study was undertaken to characterize the properties of Na,K-ATPase along the rat nephron. Results indicate that each segment of the rat nephron contains two subpopulations of Na,K-ATPase: a component highly sensitive to ouabain (IC50 approximate to 5.10(-6) M) which is recognized by an anti-alpha(3) antibody and another moiety of lower affinity for ouabain (IC50 approximate to 5.10(-4) M) which is recognized by an anti-alpha(1) antibody. Whether these two subpopulations correspond to different isoforms of the alpha subunit of Na,K-ATPase (alpha(1) and alpha(3)-like) remains to be determined. C1 CTR ETUD SACLAY,SERV BIOL CELLULAIRE,CNRS,URA 1859,F-91191 GIF SUR YVETTE,FRANCE. HOP CANTONAL UNIV GENEVA,DIV NEPHROL,CH-1211 GENEVA 4,SWITZERLAND. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HOP CANTONAL UNIV GENEVA,DIV PNEUMOL,CH-1211 GENEVA 4,SWITZERLAND. COLL FRANCE,PHYIOL CELLUALAIRE LAB,F-75231 PARIS 05,FRANCE. NR 27 TC 18 Z9 18 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD JUN PY 1995 VL 430 IS 2 BP 205 EP 212 DI 10.1007/BF00374651 PG 8 WC Physiology SC Physiology GA RE851 UT WOS:A1995RE85100007 PM 7675630 ER PT J AU BRANNAN, SK MILLER, A JONES, DJ KRAMER, GL PETTY, F AF BRANNAN, SK MILLER, A JONES, DJ KRAMER, GL PETTY, F TI BETA-ADRENERGIC-RECEPTOR CHANGES IN LEARNED HELPLESSNESS MAY DEPEND ON STRESS AND TEST PARAMETERS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Note DE BETA-ADRENERGIC RECEPTOR; LEARNED HELPLESSNESS; DEPRESSION; NOREPINEPHRINE; ANIMAL MODELS ID INESCAPABLE SHOCK; OLFACTORY BULBECTOMY; MONOAMINE RECEPTORS; ANIMAL-MODELS; RAT-BRAIN; IMIPRAMINE; DEPRESSION; DEFICITS; AMYGDALA; ESCAPE AB Behavioral deficits following inescapable stress (learned helplessness) may serve as an animal model of depression. Previous studies using foot-shock stress to induce learned helplessness and a bar-press test for the stress-induced behavioral deficit have found increased beta-adrenergic receptor density in the hippocampus of learned helpless rats. We replicated these experiments using a tail-shock stress and the shuttle-box test. In our experiments, rats that developed learned helplessness after inescapable stress did not demonstrate any significant differences in beta-adrenergic receptor density or affinity in the frontal cortex, cerebellum, or hippocampus compared to the nonhelpless rats, nor to the tested control rats. These results suggest that beta-adrenergic receptor changes in learned helplessness may depend on the specific stress and test procedures used. C1 VET AFFAIRS MED CTR,PSYCHIAT SERV 116A,DALLAS,TX 75216. UNIV TEXAS,SW MED CTR,DEPT PSYCHIAT,DALLAS,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT ANESTHESIOL,SAN ANTONIO,TX 78284. NR 32 TC 13 Z9 13 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUN-JUL PY 1995 VL 51 IS 2-3 BP 553 EP 556 DI 10.1016/0091-3057(95)00054-Z PG 4 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA RB491 UT WOS:A1995RB49100063 PM 7667386 ER PT J AU DONELAN, MB AF DONELAN, MB TI RECONSTRUCTION OF ELECTRICAL BURNS OF THE ORAL COMMISSURE WITH A VENTRAL TONGUE FLAP SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CHILDREN; MOUTH; MANAGEMENT AB Reconstruction of the oral commissure following electrical burn injury is a challenging problem. The commissure is a thin, delicate structure that is highly mobile and essential to normal facial appearance and expression. When there is full-thickness destruction of vermilion, mucosa, skin, and orbicularis muscle, the resulting contracture alters adjacent structures, displaces the commissure, and distorts facial animation. Utilizing a composite ventral tongue flap of mucosa and muscle in the reconstruction of the commissure permits effective release of scar contracture and replaces destroyed mucosa and muscle bulk. Remaining structures can be returned to their normal location, and the three-dimensional contours of the oral commissure can be better restored. The use of this flap in 21 patients has resulted in improved mobility, more normal facial expression, and more consistent results in the reconstruction of a wide range of commissure deformities. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURN INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP DONELAN, MB (reprint author), MASSACHUSETTS GEN HOSP,DIV PLAST SURG,BOSTON,MA 02114, USA. NR 20 TC 12 Z9 12 U1 2 U2 2 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 JUN PY 1995 VL 95 IS 7 BP 1155 EP 1164 DI 10.1097/00006534-199506000-00003 PG 10 WC Surgery SC Surgery GA RB385 UT WOS:A1995RB38500003 PM 7761501 ER PT J AU BASILE, AP FIALA, TGS YAREMCHUK, MJ MAY, JW AF BASILE, AP FIALA, TGS YAREMCHUK, MJ MAY, JW TI THE ANTITHROMBOTIC EFFECTS OF TICLOPIDINE AND ASPIRIN IN A MICROVASCULAR THROMBOGENIC MODEL SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID REPLANTATION; THROMBOSIS; SURGERY; PHARMACOLOGY; PATENCY; HEPARIN; GRAFTS AB In the effort to reduce a persistently significant failure rate in free tissue transfers and digital replantations, the efficacy of two oral platelet inhibitors, aspirin and ticlopidine, was examined using the arterial inversion graft, a known microvascular thrombogenic model. Forty male New Zealand White rabbits were used to create eighty 5-mm inversion grafts. Four groups were blindly given perioperative oral drug therapy: ticlopidine, aspirin, both, or neither (control). Vessel patency was evaluated at 1 hour and 1 week after surgery. The patency rate for the control group was 20 percent at 1 hour and 5 percent at 1 week. The drug-treated patency rates at 1 hour and 1 week, respectively, were 45 percent (p = 0.046) and 15 percent for ticlopidine, 35 percent and 10 percent for aspirin, and 45 percent (p = 0.046) and 20 percent for the combination therapy. This study shows that ticlopidine alone or in combination with aspirin significantly increases the I-hour patency rates in a reliable thrombosis model, but it fails to show a significant increase in the final patency rates by either drug administered alone or in combination. The benefit in clinical microvascular surgery of either aspirin or ticlopidine is not determined by this study. C1 MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE,DIV PLAST SURG,MICROSURG LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 27 TC 18 Z9 18 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 JUN PY 1995 VL 95 IS 7 BP 1258 EP 1264 DI 10.1097/00006534-199506000-00018 PG 7 WC Surgery SC Surgery GA RB385 UT WOS:A1995RB38500018 PM 7761514 ER PT J AU SMITH, F JACOBY, D BREAKEFIELD, XO AF SMITH, F JACOBY, D BREAKEFIELD, XO TI VIRUS VECTORS FOR GENE DELIVERY TO THE NERVOUS-SYSTEM SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article; Proceedings Paper CT Symposium on Novel Therapeutics in the Nervous System - Gene Transfers and Trophic Factors CY FEB 27-MAR 01, 1995 CL PARIS, FRANCE SP Assoc NeuroPsychoPharm, Inst Rech Int Servier DE VIRUS VECTORS; GENE DELIVERY ID HERPES-SIMPLEX VIRUS; ADENO-ASSOCIATED VIRUS; EPSTEIN-BARR-VIRUS; ADENOASSOCIATED VIRUS; MAMMALIAN-CELLS; BETA-GALACTOSIDASE; RETROVIRAL VECTORS; SENSORY NEURONS; FOREIGN GENE; POL-PROTEINS AB A number of virus vectors have been developed for gene delivery to the nervous system. Virus vectors still provide the most efficient means of gene delivery, and this is critical as only a small Volume of inoculum can be used without damaging neurons. Each of the four types of vectors currently in use have their advantages and disadvantages. Highest liters can be achieved with herpes virus and adenovirus vectors, with retrovirus and adeno-associated virus (AAV) vectors currently yielding lower liters. The transgene capacity of each from highest to lowest is: herpes virus (30 kb), adenovirus (8-10 kb), retrovirus (7-8 kb) and AAV (4.5 kb), All can infect a broad range of cell types in the nervous system, including neurons, glia and endothelial cells. Herpes, adenovirus and AAV vectors can deliver genes to postmitotic, as well as mitotic cells, while retrovirus vectors depend on cell mitosis for gene delivery. Herpes virus can assume a stable extrachromosomal configuration in the nuclei of some neurons (termed latency), while both retrovirus and AAV can integrate into the cell genome. Both integrate at random sites, but AAV can also integrate at a specific chromosomal location. Adenovirus neither assumes a stable state nor integrates, still its genome can persist and be expressed in the host cell for some time (up to a month or so), Stability of gene expression is a problem for all the vectors, due in part to the use of viral promoters which tend to be down-regulated by the host cell over a month or so. Both herpes virus vectors and adenovirus vectors have some toxicity in their current configurations, while retrovirus and AAV tend to be associated with less neuropathogenicity. Many developments in vectors should be occurring over the next few years that should increase the potential of these vectors for therapeutic gene delivery. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,WALTHAM,MA 02154. NR 117 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PD JUN PY 1995 VL 8 IS 1-2 BP 21 EP 34 PG 14 WC Neurosciences SC Neurosciences & Neurology GA RK151 UT WOS:A1995RK15100007 PM 21551801 ER PT J AU ISACSON, O FRIM, DM GALPERN, WR TATTER, SB BREAKEFIELD, XO SCHUMACHER, JM AF ISACSON, O FRIM, DM GALPERN, WR TATTER, SB BREAKEFIELD, XO SCHUMACHER, JM TI CELL-MEDIATED DELIVERY OF NEUROTROPHIC FACTORS AND NEUROPROTECTION IN THE NEOSTRIATUM AND SUBSTANTIA-NIGRA SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article; Proceedings Paper CT Symposium on Novel Therapeutics in the Nervous System - Gene Transfers and Trophic Factors CY FEB 27-MAR 01, 1995 CL PARIS, FRANCE SP Assoc NeuroPsychoPharm, Inst Rech Int Servier ID FIBROBLAST GROWTH-FACTOR; DOPAMINERGIC-NEURONS; EXCITOTOXIC LESIONS; STRIATUM; INVIVO; DEATH; BRAIN; BDNF; NGF C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. LAHEY HITCHCOCK CLIN,DEPT NEUROSURG,BURLINGTON,MA 01805. RP ISACSON, O (reprint author), HARVARD UNIV,MCLEAN HOSP,SCH MED,NEUROREGENERAT LAB,BELMONT,MA 02178, USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PD JUN PY 1995 VL 8 IS 1-2 BP 59 EP 61 PG 3 WC Neurosciences SC Neurosciences & Neurology GA RK151 UT WOS:A1995RK15100013 PM 21551807 ER PT J AU STONE, ME AF STONE, ME TI HISTORICAL STATISTICS OF BLACK-AMERICA - SMITH,JC, HORTON,CP SO RQ LA English DT Book Review RP STONE, ME (reprint author), MASSACHUSETTS GEN HOSP,TREADWELL LAB,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 1995 VL 34 IS 4 BP 522 EP 523 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA RF866 UT WOS:A1995RF86600040 ER PT J AU GAZELLE, GS LEE, MJ MUELLER, PR AF GAZELLE, GS LEE, MJ MUELLER, PR TI CHOLANGIOGRAPHIC SEGMENTAL ANATOMY OF THE LIVER - IMPLICATIONS FOR INTERVENTIONAL RADIOLOGY SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article RP GAZELLE, GS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD JUN PY 1995 VL 12 IS 2 BP 119 EP 125 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RD597 UT WOS:A1995RD59700004 ER PT J AU PAPANICOLAOU, N AF PAPANICOLAOU, N TI RENAL ANATOMY RELEVANT TO PERCUTANEOUS INTERVENTIONS SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article AB The retroperitoneal location of the kidneys allows for safe percutaneous access through a posterior translumbar entry site. Favorable comparison of the results and complications from percutaneous techniques with those from surgery or endoscopy and the evolution of and growing familiarity with angiographic techniques have led to the current widespread use of various percutaneous applications in the diagnosis and management of pathology of the urinary tract. The spectrum of examinations performed today through a percutaneous nephrostomy track includes radiologically and endoscopically guided procedures in the kidney and ureter, such as removal of calculi, biopsy, and fulguration of pyelocalyceal lesions; endopyelotomy for ureteropelvic junction obstruction; stent placement for benign or malignant obstruction; and removal of foreign bodies from the collecting system. To that extent, in-depth knowledge of the renal anatomy and anatomic relations between the kidney and adjacent organs is essential to the radiologist performing percutaneous renal procedures. RP PAPANICOLAOU, N (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD JUN PY 1995 VL 12 IS 2 BP 163 EP 172 DI 10.1055/s-2008-1061323 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RD597 UT WOS:A1995RD59700008 ER PT J AU MCDOWELL, RK MUELLER, PR AF MCDOWELL, RK MUELLER, PR TI PELVIC FLUID COLLECTIONS - ANATOMY FOR INTERVENTIONAL PROCEDURES SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article AB The use of imaging-guided percutaneous interventional procedures has become routine over the last 10 years. During the early experience with imaging-guided intervention, biopsies and drainages of many pelvic lesions were considered inappropriate for percutaneous procedures. This was often due to a lack of a safe access route.(1) Anteriorly, bowel and bladder limit access to deep pelvic lesions. Posteriorly and laterally, the bony elements of the pelvis prevent easy access to pelvic lesions.(2) With advances both in imaging and interventional techniques, many of these previously ''unreachable'' lesions can now be safely accessed. Knowledge of the imaging characteristics of pelvic lesions and of pelvic anatomy is essential for proper planning of an interventional procedure.(3) This chapter will discuss pelvic anatomy relevant to performing percutaneous procedures, specifically biopsies and abscess drainages, along with specific anatomic considerations for various approaches to lesions in the pelvis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 0 TC 3 Z9 4 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD JUN PY 1995 VL 12 IS 2 BP 177 EP 190 DI 10.1055/s-2008-1061325 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RD597 UT WOS:A1995RD59700010 ER PT J AU MUELLER, PR AF MUELLER, PR TI UNTITLED SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Editorial Material RP MUELLER, PR (reprint author), MASSACHUSETTS GEN HOSP,DIV HEAD ABDOMINAL IMAGING & INTERVENT RADIOL,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD JUN PY 1995 VL 12 IS 2 BP U1 EP U1 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RD597 UT WOS:A1995RD59700001 ER PT J AU SWARTZ, BE AF SWARTZ, BE TI UNUSUAL SEIZURE TYPES SO SEMINARS IN NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; ORIGIN; CLASSIFICATION; STIMULATION; PARIETAL; SURGERY C1 UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. RP SWARTZ, BE (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CTR EPILEPSY W127B,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 61 TC 3 Z9 4 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD JUN PY 1995 VL 15 IS 2 BP 151 EP 157 DI 10.1055/s-2008-1041018 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA RM956 UT WOS:A1995RM95600006 PM 7481134 ER PT J AU SANDSON, TA PRICE, BH AF SANDSON, TA PRICE, BH TI TRANSIENT GLOBAL AMNESIA SO SEMINARS IN NEUROLOGY LA English DT Article ID DOMINANT HEMISPHERE; PROGNOSIS; ATTACK; MEMORY; SPECT; DYSFUNCTION; INFARCTION; ISCHEMIA C1 HARVARD UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MCLEAN HOSP,BELMONT,MA 02178. RP SANDSON, TA (reprint author), BETH ISRAEL HOSP,DEPT NEUROL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 51 TC 6 Z9 6 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD JUN PY 1995 VL 15 IS 2 BP 183 EP 187 DI 10.1055/s-2008-1041022 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA RM956 UT WOS:A1995RM95600010 PM 7481138 ER PT J AU SLEDGE, GW ROBERT, N SPARANO, JA COGLEIGH, M GOLDSTEIN, LJ NEUBERG, D ROWINSKY, E BAUGHMAN, C MCCASKILLSTEVENS, W AF SLEDGE, GW ROBERT, N SPARANO, JA COGLEIGH, M GOLDSTEIN, LJ NEUBERG, D ROWINSKY, E BAUGHMAN, C MCCASKILLSTEVENS, W TI EASTERN-COOPERATIVE-ONCOLOGY-GROUP STUDIES OF PACLITAXEL AND DOXORUBICIN IN ADVANCED BREAST-CANCER SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT Fox-Chase-Cancer-Center Paclitaxel Investigators Workshop on the Emerging Role of Paclitaxel in Cancer Chemotherapy CY FEB 23-27, 1994 CL BOCA RATON, FL SP Fox Chase Canc Ctr, Bristol Myers Squibb Co ID COLONY-STIMULATING FACTOR; TAXOL; CHEMOTHERAPY C1 INDIANA UNIV,DEPT MED,INDIANAPOLIS,IN. FAIRFAX HOSP,ANNANDALE,VA. MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,DEPT MED,BRONX,NY 10467. RUSH PRESBYTERIAN ST LUKES MED CTR,RIVERSIDE,IL. FOX CHASE CANC CTR,DEPT MED,PHILADELPHIA,PA 19111. DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. JOHNS HOPKINS ONCOL CTR,DEPT PHARMACOL,BALTIMORE,MD. NR 9 TC 43 Z9 43 U1 0 U2 2 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 1995 VL 22 IS 3 SU 6 BP 105 EP 108 PG 4 WC Oncology SC Oncology GA RG875 UT WOS:A1995RG87500021 PM 7597425 ER PT J AU CUNDARI, L STUTZ, K AF CUNDARI, L STUTZ, K TI ENHANCING LIBRARY-SERVICES - AN EXPLORATION IN MEETING CUSTOMER NEEDS THROUGH TOTAL QUALITY MANAGEMENT SO SPECIAL LIBRARIES LA English DT Article AB Total Quality Management (TQM) is a process which focuses on understanding customer needs and improving customer service and satisfaction, A TQM committee was created at the Deverevx Foundation's Professional library to assess user satisfaction and make recommendations for improving library services to better meet consumer needs. The committee distributed a satisfaction survey to 156 of the most likely library users rind 84 (54%) were returned. Overall survey results indicate that most consumers tire satisfied with tbe materials and services provided by the Professional library. Recommendations for improving library services and strategies for implementing these recommendations are discussed. C1 MASSACHUSETTS GEN HOSP,DEPT GERONTOL,BOSTON,MA 02114. RP CUNDARI, L (reprint author), DEVEREUX INST CLIN TRAINING & RES,INTERAGCY COLLABORAT RES PROJECT,DEVON,PA 19333, USA. NR 2 TC 3 Z9 3 U1 0 U2 1 PU SPECIAL LIBRARIES ASSN PI WASHINGTON PA 1700 EIGHTEENTH ST NW, WASHINGTON, DC 20009-2508 SN 0038-6723 J9 SPEC LIBR JI Spec. Libr. PD SUM PY 1995 VL 86 IS 3 BP 188 EP 194 PG 7 WC Information Science & Library Science SC Information Science & Library Science GA RQ912 UT WOS:A1995RQ91200004 PM 10144945 ER PT J AU FINKLESTEIN, S AF FINKLESTEIN, S TI CEREBRAL HYPOXIA-ISCHEMIA STIMULATES CYTOKINE GENE-EXPRESSION IN PERINATAL RATS - COMMENT SO STROKE LA English DT Editorial Material ID INTERLEUKIN-1 RP FINKLESTEIN, S (reprint author), MASSACHUSETTS GEN HOSP EAST,CNS,GROWTH FACTOR RES LAB,BOSTON,MA, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 1995 VL 26 IS 6 BP 1100 EP 1100 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA RB358 UT WOS:A1995RB35800042 ER PT J AU RAZDAN, K KROLL, MH AF RAZDAN, K KROLL, MH TI IDENTIFICATION OF A NOVEL PROTEIN-KINASE-C SUBSTRATE FROM PLATELETS AND CELLS OF MEGAKARYOCYTE LINEAGE SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 BAYLOR COLL MED,VA MED CTR,HOUSTON,TX 77030. RICE UNIV,HOUSTON,TX 77251. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1995 VL 73 IS 6 BP 988 EP 988 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RP385 UT WOS:A1995RP38500339 ER PT J AU OHLIN, AK MARLAR, RA AF OHLIN, AK MARLAR, RA TI MUTATIONS IN THE THROMBOMODULIN GENE ASSOCIATED WITH THROMBOEMBOLIC DISEASE SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 UNIV LUND HOSP,DEPT CLIN CHEM,S-22185 LUND,SWEDEN. UNIV COLORADO,SCH MED,DEPT PATHOL,BOULDER,CO 80309. DENVER VET AFFAIRS MED CTR,DENVER,CO 80220. NR 0 TC 7 Z9 7 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1995 VL 73 IS 6 BP 1096 EP 1096 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RP385 UT WOS:A1995RP38500748 ER PT J AU HOUNG, A QUEN, S JEAN, LF REED, GI AF HOUNG, A QUEN, S JEAN, LF REED, GI TI CONSTRUCTION OF A RECOMBINANT STREPTOKINASE THAT RESISTS CLEAVAGE AND INACTIVATION BY PLASMIN SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 6 Z9 7 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1995 VL 73 IS 6 BP 1130 EP 1130 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RP385 UT WOS:A1995RP38500880 ER PT J AU FRENETTE, PS RAYBUN, H MAYADAS, TN HYNES, RO WAGNER, DD AF FRENETTE, PS RAYBUN, H MAYADAS, TN HYNES, RO WAGNER, DD TI GENERATION OF P-SELECTIN AND E-SELECTIN DOUBLE-DEFICIENT MICE BY TW ROUNDS OF HOMOLOGOUS RECOMBINATION SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 MIT,CTR CANC RES,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. RI Frenette, Paul/J-8272-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1995 VL 73 IS 6 BP 1152 EP 1152 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RP385 UT WOS:A1995RP38500965 ER PT J AU STODDART, JH WEIDEL, SE LYNCH, DC AF STODDART, JH WEIDEL, SE LYNCH, DC TI CLEARANCE OF HUMAN VON-WILLEBRAND-FACTOR (VWF) IN THE RAT SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1995 VL 73 IS 6 BP 1163 EP 1163 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RP385 UT WOS:A1995RP38501004 ER PT J AU MUSZBEK, L RACZ, E HARAMURA, G LAPOSATA, M LEGRAND, C AF MUSZBEK, L RACZ, E HARAMURA, G LAPOSATA, M LEGRAND, C TI PLATELET MEMBRANE GLYCOPROTEIN-IV (CD 36) IS COVALENTLY MODIFIED WITH FATTY-ACIDS IN THIOESTER LINKAGE SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 HOSP ST LOUIS,INSERM,UNIT 353,PARIS,FRANCE. LAJOS KOSSUTH UNIV,SCH MED,DEPT CLIN CHEM,H-4010 DEBRECEN,HUNGARY. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1995 VL 73 IS 6 BP 1199 EP 1199 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RP385 UT WOS:A1995RP38501144 ER PT J AU FRENETTE, PS JOHNSON, RC HYNES, RO WAGNER, DD AF FRENETTE, PS JOHNSON, RC HYNES, RO WAGNER, DD TI PLATELETS ROLL ON ACTIVATED VASCULAR ENDOTHELIUM IN-VIVO - AN INTERACTION MEDIATED PRIMARILY BY ENDOTHELIAL P-SELECTIN SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 MIT,CTR CANC RES,CAMBRIDGE,MA 02139. HOWARD HUGHES MED INST,COCONUT GROVE,FL 33133. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RI Frenette, Paul/J-8272-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 1995 VL 73 IS 6 BP 1355 EP 1355 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RP385 UT WOS:A1995RP38501739 ER PT J AU LEWIS, CB AF LEWIS, CB TI UNTITLED 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, 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 1995 VL 10 IS 4 BP R5 EP R5 PG 1 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA QY195 UT WOS:A1995QY19500001 ER PT J AU PISCIOTTO, PT BENSON, K HUME, H GLASSMAN, AB OBERMAN, H POPOVSKY, M HINES, D ANDERSON, K AF PISCIOTTO, PT BENSON, K HUME, H GLASSMAN, AB OBERMAN, H POPOVSKY, M HINES, D ANDERSON, K TI PROPHYLACTIC VERSUS THERAPEUTIC PLATELET TRANSFUSION PRACTICES IN HEMATOLOGY AND/OR ONCOLOGY PATIENTS SO TRANSFUSION LA English DT Article ID ACUTE-LEUKEMIA; CONTROVERSIES; MEDICINE AB Background: Platelet utilization has steadily increased throughout the past three decades. At the same time, there has been very little study of the current transfusion practices. Study Design and Methods: A survey was conducted of institutional members of the American Association of Blood Banks (hospitals) that were actively involved in the care of pediatric and/or adult hematology and/or oncology patients, Inquiries were made relating to the extent of prophylactic versus therapeutic use of platelets, criteria used for prophylactic transfusion of platelets and type, and dose of platelets used, Data were analyzed according to patient age and type of hospital. Results: Of 786 responding hospitals, 630 (80.2%) provided sufficient data for analysis; 126 of that 630 provided care for pediatric patients, The majority (60.9%) of responding hospitals had a minimum of four hematologists and/or oncologists, Eighty-four percent of hospitals reported transfusing some apheresis platelets, The dose of platelet concentrates most frequently used for adults ranged from 6 to 10, with pools of 10 more commonly used in community hospitals, More than 70 percent of hospitals reported transfusing platelets primarily for prophylaxis: 60 percent of hospitals set the threshold platelet count for prophylactic platelet transfusion at 20,000 per mu L, with approximately 20 percent each transfusing at higher and lower levels. A platelet count of 50,000 per mu L was most frequently required for performance of a minor invasive procedure. Conclusion: The data from this study show that the majority of institutions use prophylactic platelet transfusion in both pediatric and adult hematology and/or oncology patients. However, there is considerable variation in platelet transfusion practice. C1 UNIV S FLORIDA,COLL MED,H LEE MOFFITT CANC CTR,BLOOD BANK,TAMPA,FL. UNIV S FLORIDA,COLL MED,H LEE MOFFITT CANC CTR,HLA LABS,TAMPA,FL. UNIV S FLORIDA,COLL MED,DEPT PATHOL & LAB MED,TAMPA,FL. HOP ST JUSTINE,MONTREAL,PQ H3T 1C5,CANADA. MD ANDERSON CANC CTR,DEPT LAB MED,HOUSTON,TX. MD ANDERSON CANC CTR,OLLEE S STRIBLING CHAIR CANC RES,HOUSTON,TX. UNIV MICHIGAN HOSP,DEPT PATHOL,ANN ARBOR,MI 48109. AMER RED CROSS,BLOOD SERV,NE REG,DEDHAM,MA. AMER ASSOC BLOOD BANKS,NATL OFF,TECH SERV,BETHESDA,MD. DANA FARBER CANC INST,DIV MED ONCOL & HEMATOL MALIGNANCIES,BLOOD COMPONENT LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP PISCIOTTO, PT (reprint author), UNIV CONNECTICUT,CTR HLTH,DEPT LAB MED,FARMINGTON,CT 06030, USA. NR 14 TC 78 Z9 85 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 1995 VL 35 IS 6 BP 498 EP 502 DI 10.1046/j.1537-2995.1995.35695288769.x PG 5 WC Hematology SC Hematology GA RB832 UT WOS:A1995RB83200009 PM 7770901 ER PT J AU CHEEK, RF HARMON, JV STOWELL, CP AF CHEEK, RF HARMON, JV STOWELL, CP TI RED-CELL ALLOIMMUNIZATION AFTER A BONE ALLOGRAFT SO TRANSFUSION LA English DT Note ID PLASMA-EXCHANGE; IMMUNIZATION; TRANSFUSION AB Background: Alloimmunization to blood group antigens other than ABH after bone allografting is uncommon,To date, examples of alloimmunization to blood group antigens other than ABH have been limited to the Rh system. Case Report: A 20-year-old woman received an allogeneic bone graft following resection of an osteosarcoma, The patient had received no blood components and denied any pregnancies, Alloimmunization was detected and alloantibodies were identified by standard serologic techniques; Fourteen months after the bone graft, anti-Fy(a) and anti-Jk(b) were identified in her serum. Conclusion: Alloimmunization to blood group antigens other than ABO and Rh may follow bone allografting. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV CLIN LABS,BLOOD TRANSFUS SERV,BOSTON,MA 02114. NR 21 TC 3 Z9 3 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 1995 VL 35 IS 6 BP 507 EP 509 DI 10.1046/j.1537-2995.1995.35695288771.x PG 3 WC Hematology SC Hematology GA RB832 UT WOS:A1995RB83200011 PM 7770903 ER PT J AU FOWLER, FJ BARRY, MJ LUYAO, G WASSON, J ROMAN, A WENNBERG, J AF FOWLER, FJ BARRY, MJ LUYAO, G WASSON, J ROMAN, A WENNBERG, J TI EFFECT OF RADICAL PROSTATECTOMY FOR PROSTATE-CANCER ON PATIENT QUALITY-OF-LIFE - RESULTS FROM A MEDICARE SURVEY SO UROLOGY LA English DT Article ID HEALTH AB Objectives. To assess patient responses to radical prostatectomy and its effects. Methods. A national sample was taken of 1072 Medicare patients who underwent radical prostatectomy for prostate cancer (1988 through 1990) by mail, telephone, and personal interviews. The effects of the surgery and its complications On these patients' lives were studied through: (1) patient ratings of the extent to which sexual and urinary dysfunctions were ''problems'' in their lives; (2) two general measures of quality of life, the Mental Health Index and the General Health Index; (3) patient reports of how they felt about the results of treatment and whether they would choose surgery again. Results. On average, dripping urine, particularly to the point where subjects were wearing pads, had a more significant effect on patients than loss of sexual function; incontinence had significant adverse effects on the measures of quality of life and self-reported results of surgery. Overall, postsurgical patients scored comparatively high on the quality of life measures (similar to a cohort of patients with benigh prostatic hyperplasia who had undergone transurethral resection of the prostate), reported feeling positive about the results (81%), and would choose surgical treatment again (89%). Nonetheless, there was variability in patient response to the effects of surgery. Conclusions. The results demonstrate the ability of many Medicare patients to adapt to adverse outcomes, such as loss of sexual function and incontinence. They also provide evidence of the variability of individual patients' responses to surgical results and reinforce the importance of individualized decision making for patients facing a decision about radical prostatectomy for prostate cancer. C1 MASSACHUSETTS GEN HOSP,CTR MED PRACTICE EVALUAT,BOSTON,MA 02114. DARTMOUTH COLL,SCH MED,CTR EVALUAT CLIN SCI,HANOVER,NH 03755. RP FOWLER, FJ (reprint author), UNIV MASSACHUSETTS,CTR SURVEY RES,100 MORRISSEY BLVD,BOSTON,MA 02125, USA. FU AHRQ HHS [HS08397, HS06336] NR 12 TC 255 Z9 260 U1 0 U2 4 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUN PY 1995 VL 45 IS 6 BP 1007 EP 1013 DI 10.1016/S0090-4295(99)80122-8 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA RB568 UT WOS:A1995RB56800017 PM 7771002 ER PT J AU YOUNG, RH AF YOUNG, RH TI URACHAL ADENOCARCINOMA METASTATIC TO THE OVARY SIMULATING PRIMARY MUCINOUS CYSTADENOCARCINOMA OF THE OVARY - REPORT OF A CASE SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY LA English DT Note DE URACHUS; ADENOCARCINOMA; OVARY; METASTASIS ID CELL-CARCINOMA; URINARY-BLADDER; CLINICOPATHOLOGICAL ANALYSIS; TUMORS AB A 56-year-old woman had a large multicystic ovarian tumour 4 years after undergoing partial cystectomy for a deeply invasive urachal adenocarcinoma. On microscopic examination the ovarian tumour was a moderately differentiated mucinous cystadenocarcinoma similar to the urachal tumour. Several peritoneal biopsies and the omentum were positive for metastatic adenocarcinoma. Although initially interpreted as representing primary mucinous adenocarcinoma of the ovary with peritoneal spread, subsequent comparison with the previous urachal adenocarcinoma led to re-interpretation of the ovarian tumour as metastatic urachal carcinoma. Metastatic mucinous adenocarcinomas involving the ovary may be misinterpreted as primary ovarian carcinomas and the urinary bladder is a potential source of these neoplasms. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. RP YOUNG, RH (reprint author), MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 21 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. Int. J. Pathol. PD JUN PY 1995 VL 426 IS 5 BP 529 EP 532 PG 4 WC Pathology SC Pathology GA RL401 UT WOS:A1995RL40100015 PM 7633664 ER PT J AU ADAMI, C POOLEY, J GLOMB, J STECKER, E FAZAL, F FLEMING, JO BAKER, SC AF ADAMI, C POOLEY, J GLOMB, J STECKER, E FAZAL, F FLEMING, JO BAKER, SC TI EVOLUTION OF MOUSE HEPATITIS-VIRUS (MHV) DURING CHRONIC INFECTION - QUASI-SPECIES NATURE OF THE PERSISTING MHV RNA SO VIROLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; SUBACUTE SCLEROSING PANENCEPHALITIS; MURINE CORONAVIRUS JHM; BIASED HYPERMUTATION; UNWINDING ACTIVITY; MEASLES-VIRUS; C VIRUS; VIRAL PERSISTENCE; SEQUENCE-ANALYSIS; RAPID EVOLUTION AB Coronavirus infection of mice has been used extensively as a model for the study of acute encephalitis and chronic demyelination. To examine the evolution of coronavirus RNA during chronic demyelinating infection, we isolated RNA from intracerebrally inoculated mice at 4, 6, 8, 13, 20, and 42 days postinfection and used reverse transcription-polymerase chain reaction amplification methods (RT-PCR) to detect viral sequences. RNA sequences from two viral structural genes, the spike gene and the nucleocapsid gene, were detected throughout the chronic infection. In contrast, infectious virus was not detectable from brain homongenates beyond 13 days postinfection. These results indicate that coronavirus RNA persists in the brain at times when infectious virus is not detected. To determine if genetic changes were occurring during viral replication in the host, we cloned and sequenced the RT-PCR products from the spike and nucleocapsid regions and analyzed the sequences for mutation's. Sequencing of the cloned products revealed that a variety of mutant forms of viral RNA persisted in the CNS, including point mutants, deletion mutants, and termination mutants. The mutations accumulated during persistent infection in both the spike and the nucleocapsid sequences, with greater than 65% of the mutations encoding amino acid changes. These results show that a diverse population or quasispecies consisting of mutant and deletion variant Viral RNAs (which may not be capable of producing infectious virus particles) persists in the central nervous system of mice during chronic demyelinating infection. The implications of these results for the role of persistent viral genetic information in the pathogenesis of chronic demyelination are discussed. (C) 1995 Academic Press, Inc. C1 LOYOLA UNIV,STRITCH SCH MED,DEPT MICROBIOL & IMMUNOL,MAYWOOD,IL 60153. UNIV WISCONSIN,DEPT NEUROL,MADISON,WI 53792. UNIV WISCONSIN,DEPT MED MICROBIOL,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53792. FU NIAID NIH HHS [AI32065] NR 37 TC 73 Z9 75 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 1 PY 1995 VL 209 IS 2 BP 337 EP 346 DI 10.1006/viro.1995.1265 PG 10 WC Virology SC Virology GA RC351 UT WOS:A1995RC35100007 PM 7778268 ER PT J AU RAWSON, NE BRAND, JG COWART, BJ LOWRY, LD PRIBITKIN, EA RAO, VM RESTREPO, D AF RAWSON, NE BRAND, JG COWART, BJ LOWRY, LD PRIBITKIN, EA RAO, VM RESTREPO, D TI FUNCTIONALLY MATURE OLFACTORY NEURONS FROM 2 ANOSMIC PATIENTS WITH KALLMANN-SYNDROME SO BRAIN RESEARCH LA English DT Article DE OLFACTION; CALCIUM; HYPOGONADOTROPIC HYPOGONADISM ID 2ND MESSENGER PATHWAYS; BULBECTOMY; RECEPTOR; CILIA; CONNECTIONS; ODORANTS; HYPOGONADISM; STIMULATION; RESPONSES; FOREBRAIN AB Patients with Kallmann syndrome (KS) exhibit hypogonadotropic hypogonadism and anosmia [Kallmann et al., Am. J. Mental Def., 48 (1944) 203-236] secondary to failure of gonadotropin-releasing hormone (GnRH)-producing neurons to migrate from the olfactory placode to the brain, and to agenesis of the olfactory bulbs. It has been hypothesized that olfactory neurons (ON) from individuals with KS are immature partly on the basis of studies in animals showing that lack of synaptic connection of ON with the olfactory bulb results in expression of immature ON [Schwob et al., J. Neurosci, 12 (1979) 880-883]. To test this assumption, we obtained olfactory tissue samples from two males diagnosed with KS on the basis of medical history and MRI studies. Both patients were anosmic. The functioning of cells isolated from biopsies taken from the upper middle turbinate and septum was studied by measuring changes in intracellular Ca2+ concentration ([Ca-i]) using dual excitation fluorescence microscopy. Biopsies from both patients yielded cells that morphologically appeared to be ON. Seven of 16 cells that morphologically resembled ON responded with a change in [Ca-i] upon stimulation with an odorant mixture. These studies show that at least some ON in KS individuals are functionally mature and suggest that complete development of the olfactory bulbs is not required for differentiation of mature human ON. C1 THOMAS JEFFERSON UNIV, PHILADELPHIA, PA 19107 USA. VET AFFAIRS MED CTR, PHILADELPHIA, PA USA. UNIV PENN, PHILADELPHIA, PA 19104 USA. RP MONELL CHEM SENSES CTR, 3500 MARKET ST, PHILADELPHIA, PA 19104 USA. FU NIDCD NIH HHS [DC-00566, DC-00214, DC-00014] NR 43 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD MAY 29 PY 1995 VL 681 IS 1-2 BP 58 EP 64 DI 10.1016/0006-8993(95)00283-V PG 7 WC Neurosciences SC Neurosciences & Neurology GA RD895 UT WOS:A1995RD89500007 PM 7552292 ER PT J AU MAYER, U POSCHL, E GERECKE, DR WAGMAN, DW BURGESON, RE TIMPL, R AF MAYER, U POSCHL, E GERECKE, DR WAGMAN, DW BURGESON, RE TIMPL, R TI LOW NIDOGEN AFFINITY OF LAMININ-5 CAN BE ATTRIBUTED TO 2 SERINE RESIDUES IN EGF-LIKE MOTIF GAMMA-2III4 SO FEBS LETTERS LA English DT Article DE BASEMENT MEMBRANE; LAMININ GAMMA-2 CHAIN; NIDOGEN BINDING; SITE-DIRECTED MUTAGENESIS ID COLLAGEN TYPE-IV; B2 CHAIN; BINDING; COMPLEX; EXPRESSION; DOMAINS; KALININ AB High affinity nidogen binding of laminin-1 (chain composition alpha 1 beta 1 gamma 1) has been previously mapped to a single EGF-like motif gamma 1III4 of its gamma 1 chain, Two more isoforms, laminin-5 (alpha 3 beta 3 gamma 2) and laminin-7 (alpha 3 beta 2 gamma 1), show low and high binding activity, respectively, indicating that the gamma 2 chain is of low affinity, This was confirmed by recombinant production of the homologous EGF-like motif gamma 2III4 of the gamma 2 chain, which has a 100,000-fold lower binding activity than gamma 1III4, The crucial heptapeptide binding sequence Asn-lle-Asp-Pro-Asn-Ala-Val of gamma 1III4 is modified in gamma 2III4 by replacing both the central Asn and Val by Ser, Changing these replacements to Asn and Val by site-directed mutagenesis enhanced the activity of gamma 2III4 to a level which was only 5-fold lower than that of gamma 1III4. Despite their high sequence identity (77%) motifs gamma 1III4 and gamma 2III4 were also shown to differ considerably in immunological epitopes, This indicates distinctly different functions for laminins which differ in the gamma chain isoform. C1 MAX PLANCK CONNECT TISSUE CLIN RES GRP RHEUMATOL,D-91054 ERLANGEN,GERMANY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. RP MAYER, U (reprint author), MAX PLANCK INST BIOCHEM,D-82152 MARTINSRIED,GERMANY. RI Poschl, Ernst /E-2103-2011 FU NIAMS NIH HHS [AR35689] NR 30 TC 66 Z9 66 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 29 PY 1995 VL 365 IS 2-3 BP 129 EP 132 DI 10.1016/0014-5793(95)00438-F PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA RB216 UT WOS:A1995RB21600006 PM 7781764 ER PT J AU TEICHER, BA HOLDEN, SA ARA, G DUPUIS, NP LIU, F YUAN, J IKEBE, M KAKEJI, Y AF TEICHER, BA HOLDEN, SA ARA, G DUPUIS, NP LIU, F YUAN, J IKEBE, M KAKEJI, Y TI INFLUENCE OF AN ANTI-ANGIOGENIC TREATMENT ON 9L GLIOSARCOMA - OXYGENATION AND RESPONSE TO CYTOTOXIC THERAPY SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TUMOR-GROWTH; INHIBITOR AGM-1470; RADIATION-THERAPY; CANCER THERAPIES; IN-VITRO; AGENTS; CHEMOTHERAPY; MINOCYCLINE; CARCINOMA; TNP-470 AB Tissue oxygen tensions were measured in subcutaneously growing rat 9L gliosarcoma under normal air and carbogen breathing conditions prior to and after i.v. administration of a perflubron emulsion. When these animals were treated with the anti-angiogenic agents TNP-470 and minocycline for 5 days prior to oxygen measurement, tumor hypoxia was decreased compared with untreated tumors. Hypoxia, defined as the percent of pO(2) readings less than or equal to 5 mm Hg, was decreased from 71% in untreated air-breathing controls to 34% in animals treated with the anti-angiogenic agents, the perflubron emulsion and carbogen breathing. These effects were manifest in the increased response of the tumor to single-dose (10, 20 and 30 Gy) radiation therapy. Twenty-four hours after treatment with BCNU oxygenation of the tumors was not altered; however, 24 hr after administration of adriamycin oxygenation of the tumors was increased such that hypoxia in adriamycin-treated tumors in animals receiving the perflubron emulsion and carbogen was reduced to 21%. Tumor growth delay in the s.c. tumors was increased by the addition of treatment with the anti-angiogenic agents from day 4 through day 18 post-tumor cell implantation along with BCNU or adriamycin on days 7-11. Administration of the perflubron emulsion and carbogen breathing resulted in increased tumor growth delay with the chemotherapeutic agents alone and in combination with the anti-angiogenic agents. Life span in animals bearing intracranially implanted 9L gliosarcoma progressively increased with administration of the anti-angiogenic agents and then the anti-angiogenic agents and perflubron emulsion/carbogen compared to treatment with BCNU or adriamycin. (C) 1995 Wiley-Liss, Inc. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP TEICHER, BA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01-CA19589, R01-CA56501]; NINDS NIH HHS [NS-31-110-03] NR 37 TC 82 Z9 90 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 29 PY 1995 VL 61 IS 5 BP 732 EP 737 DI 10.1002/ijc.2910610523 PG 6 WC Oncology SC Oncology GA RB283 UT WOS:A1995RB28300022 PM 7768649 ER PT J AU CHEN, GA WAXMAN, DJ AF CHEN, GA WAXMAN, DJ TI IDENTIFICATION OF GLUTATHIONE-S-TRANSFERASE AS A DETERMINANT OF 4-HYDROPEROXYCYCLOPHOSPHAMIDE RESISTANCE IN HUMAN BREAST-CANCER CELLS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE CYCLOPHOSPHAMIDE RESISTANCE; GLUTATHIONE S-TRANSFERASE; ALDEHYDE DEHYDROGENASE; ETHACRYNIC ACID ID ALKYLATING AGENT RESISTANCE; HUMAN-LEUKEMIA-CELLS; ALDEHYDE DEHYDROGENASE; CELLULAR GLUTATHIONE; ETHACRYNIC-ACID; PHOSPHORAMIDE MUSTARD; ACQUIRED-RESISTANCE; MASS-SPECTROMETRY; NITROGEN MUSTARDS; CYTO-TOXICITY AB Aldehyde dehydrogenase (ALDH) is well known for its involvement in the resistance of tumor cells to cyclophosphamide (CPA) and its activated derivatives, such as 4-hydroperoxy-CPA (4HC). The role of other drug-metabolizing enzymes such as glutathione S-transferase (GST) in CPA resistance is, however, less certain. In the present study of a human breast cancer cell line (MCF-7) exhibiting about 6-fold resistance to 4HC (MCF/HC), cellular levels of glutathione (GSH) were increased 1.4-fold, while cytosolic GST and ALDH activities were increased 2.7- and 7.2-fold, respectively, relative to the MCF-7 parental line. No significant changes in glutathione peroxidase and NADPH cytochrome P450 reductase activity, and no increase in microsomal GST and GST pi mRNAs were found in the resistant cells. Treatment with the ALDH substrate octanal sensitized the cells to the cytotoxic effects of 4HC to a modest extent in both MCF-7 and MCF/HC cells [dose modification factor (DMF) of 1.4 and 1.6, respectively]. Depletion of GSH by treatment with the GSH synthesis inhibitor buthionine sulfoximine (BSO) enhanced the cytotoxic effect of 4HC to a similar extent in both cell lines. By contrast, ethacrynic acid, which inhibited GST activity by > 85% in MCF-7 and MCF/HC cell extracts without depletion of GSH, sensitized the resistant but not the parental cells to 4HC cytotoxicity, indicating the importance of GST as a determinant of 4HC resistance in these cells. This conclusion is supported by the observation that in MCF/HC cells, ethacrynic acid in combination with BSO increased the DMF 3-fold higher than did BSO or EA alone, while in the parental MCF-7 cells ethacrynic acid with BSO had no significant chemosensitization effect over BSO alone. These studies establish that in addition to ALDH, GST overexpression can contribute to acquired resistance of tumor cells to IHC and, furthermore, suggest that modulators that target the GSH/GST system could be useful in overcoming CPA resistance in the clinic. C1 BOSTON UNIV,DEPT BIOL,DIV CELL & MOLEC BIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA49248] NR 55 TC 40 Z9 40 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 26 PY 1995 VL 49 IS 11 BP 1691 EP 1701 DI 10.1016/0006-2952(95)00079-F PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RB853 UT WOS:A1995RB85300019 PM 7786310 ER PT J AU SU, W LIU, W SCHAFFHAUSEN, BS ROBERTS, TM AF SU, W LIU, W SCHAFFHAUSEN, BS ROBERTS, TM TI ASSOCIATION OF POLYOMAVIRUS MIDDLE TUMOR-ANTIGEN WITH PHOSPHOLIPASE-C-GAMMA-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID PROTEIN-KINASE-C; T-ANTIGEN; TYROSINE PHOSPHORYLATION; VIRUS; TRANSFORMATION; PP60C-SRC; ACTIVATION; COMPLEX; INVITRO; SITES AB Middle tumor antigen (MT) is the primary transforming protein of murine Polyomavirus. MT transforms by associating with and modulating the activities of cellular proteins involved in control of cell proliferation. MT binds to and is phosphorylated by cellular tyrosine kinases. The phosphorylated tyrosines become docking sites for SH2 (Src homology 2) domain-containing molecules. Tyrosine 322 of MT is known to be phosphorylated but has no known binding protein. We have found that phospholipase C-gamma 1 (PLC-gamma 1), a SH2 domain containing protein, coimmunoprecipitates with MT. Tyrosine phosphorylation of PLC-gamma 1 is elevated in cells expressing MT, suggesting activation of this enzyme by MT. A Tyr-322 --> Phe mutation in MT renders it defective in MT-PLC-gamma 1 interaction and in transformation. From the correlation between transformation and MT-PLC-gamma 1 interaction, we suggest that PLC-gamma 1 may play a role in transformation. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. RP SU, W (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,M857,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA30002] NR 33 TC 73 Z9 76 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 MAY 26 PY 1995 VL 270 IS 21 BP 12331 EP 12334 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QZ711 UT WOS:A1995QZ71100002 PM 7759472 ER PT J AU CHANG, PY GOODYEAR, LJ BENECKE, H MARKUNS, JS MOLLER, DE AF CHANG, PY GOODYEAR, LJ BENECKE, H MARKUNS, JS MOLLER, DE TI IMPAIRED INSULIN SIGNALING IN SKELETAL-MUSCLES FROM TRANSGENIC MICE EXPRESSING KINASE-DEFICIENT INSULIN-RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; TYROSINE KINASE; MONOCLONAL-ANTIBODIES; SUBSTRATE PHOSPHORYLATION; TRANSFECTED CELLS; OBESE MICE; STIMULATION; PROTEIN; RAT AB Transgenic mice which overexpress kinase-deficient human insulin receptors in muscle were used to study the relationship between insulin receptor tyrosine kinase and the in vivo activation of several downstream signaling pathways. Intravenous insulin stimulated insulin receptor tyrosine kinase activity by 7-fold in control muscle versus less than or equal to 1.5-fold in muscle from transgenic mice. Similarly, insulin failed to stimulate tyrosyl phosphorylation of receptor beta-subunits or insulin receptor substrate 1 (IRS-1) in transgenic muscle, Insulin substantially stimulated IRS-1 associated phosphatidylinositol (PI) 3-kinase in control versus absent stimulation in transgenic muscles. In contrast, insulin-like growth factor 1 modestly stimulated PI 3-kinase in both control and transgenic muscle, The effects of insulin to stimulate p42 mitogen activated protein kinase and c-fos mRNA expression were also markedly impaired in transgenic muscle. Specific immunoprecipitation of human receptors followed by measurement of residual insulin receptors suggested the presence of hybrid mouse-human heterodimers, In contrast, negligible hybrid formation involving insulin-like growth factor 1 receptors was evident, We conclude that (i) transgenic expression of kinase-defective insulin receptors exerts dominant-negative effects at the level of receptor autophosphorylation and kinase activation; (ii) insulin receptor tyrosine kinase activity is required for in vivo insulin-stimulated IRS-1 phosphorylation, IRS-1-associated PI 3-kinase activation, phosphorylation of mitogen-activated protein kinase, and c-fos gene induction in skeletal muscle; (iii) hybrid receptor formation is likely to contribute to the in vivo dominant-negative effects of kinase-defective receptor expression. C1 BETH ISRAEL HOSP,DEPT MED,CHARLES A DANA RES INST,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,HARVARD THORNDIKE LAB,BOSTON,MA 02215. JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. FU NIAMS NIH HHS [R29-AR42238]; PHS HHS [R01 45874-01] NR 58 TC 31 Z9 31 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 MAY 26 PY 1995 VL 270 IS 21 BP 12593 EP 12600 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QZ711 UT WOS:A1995QZ71100042 PM 7759507 ER PT J AU LIEVENS, PMJ DONADY, JJ TUFARELLI, C NEUFELD, EJ AF LIEVENS, PMJ DONADY, JJ TUFARELLI, C NEUFELD, EJ TI REPRESSOR ACTIVITY OF CCAAT DISPLACEMENT PROTEIN IN HL-60 MYELOID-LEUKEMIA CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SENSORY ORGAN IDENTITY; GAMMA-GLOBIN GENE; DNA-BINDING; CUT LOCUS; DROSOPHILA; EXPRESSION; PROMOTER; REGION; ACTIVATION; ACID AB CCAAT displacement protein (CDP)/cut is implicated in several systems as a transcriptional repressor of developmentally regulated genes. In myeloid leukemia cells, CDP/cut binding activity as assayed on the promoter of the phagocyte-specific cytochrome heavy chain gene gp91-phox varies inversely with expression of gp91-phox mRNA. We used two approaches to ascertain whether CDP/cut serves as a repressor of gp91-phox gene expression, First, we used transient transfection assays in 3T3 cells to demonstrate that the CDP/cut binding site from the gp91-phox promoter acts as a negative regulatory element in artificial promoter constructs, Second, we isolated a stable transformant of HL-60 myeloid cells constitutively expressing transfected CDP/cut cDNA, Stable transformants carrying expression vector alone or expressing CDP/cut mRNA were induced to differentiate along the macrophage lineage with phorbol ester or along the neutrophil lineage with dimethyl sulfoxide or retinoic acid/dimethylformamide, Northern blot analysis was used to assess induction of mRNAs encoding gp91-phox, and the myeloid oxidase cytosolic components, p47 and p67, In the stable transformant expressing transfected CDP/cut cDNA, gp91-phox induction was selectively reduced, whereas morphologic differentiation and induction of mRNA for myeloid oxidase components p47 and p67 were unaffected, These data provide persuasive evidence that CDP/cut acts to repress the gp91-phox gene. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Neufeld, Ellis/F-9331-2011 FU NHLBI NIH HHS [HL49196]; NIDDK NIH HHS [DK01977] NR 29 TC 97 Z9 99 U1 0 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 MAY 26 PY 1995 VL 270 IS 21 BP 12745 EP 12750 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QZ711 UT WOS:A1995QZ71100065 PM 7759529 ER PT J AU WANG, J AUGER, KR JARVIS, L SHI, Y ROBERTS, TM AF WANG, J AUGER, KR JARVIS, L SHI, Y ROBERTS, TM TI DIRECT ASSOCIATION OF GRB2 WITH THE P85 SUBUNIT OF PHOSPHATIDYLINOSITOL 3-KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR TYROSINE KINASES; MIDDLE T-ANTIGEN; PHOSPHOINOSITIDE 3-KINASE; SIGNAL TRANSDUCTION; INTACT-CELLS; PROTEIN; TRANSFORMATION; POLYOMAVIRUS; ACTIVATION; BIND AB Phosphatidylinositol 3-kinase (PI 3-kinase) has been shown to play a key role in growth factor signaling pathways, although its signaling mechanism has not been fully elucidated. Using the yeast interaction trap system, we have identified Grb2 as a PI 3-kinase interacting protein. Our experiments demonstrate that p85, the regulatory subunit of PI 3-kinase, interacts with Grb2 in vivo, and this interaction is independent of growth factor stimulation. The direct association between Grb2 and p85 was reconstituted in vitro with glutathione S-transferase fusion proteins. Domain analyses and peptide competition indicate that the association is mediated by the SH3 domains of Grb2 and the proline-rich motifs of p85 and that only one SH3 domain is required for minimal binding. The interaction does not displace the catalytic subunit of PI 3-kinase but is exclusive of Sos. Signaling through PI 3-kinase, therefore, may involve the ubiquitous adapter Grb2, which serves as a convergence point for multiple pathways. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV CELL & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA30002] NR 48 TC 98 Z9 99 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 MAY 26 PY 1995 VL 270 IS 21 BP 12774 EP 12780 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QZ711 UT WOS:A1995QZ71100068 PM 7759531 ER PT J AU PERKINS, AC SHARPE, AH ORKIN, SH AF PERKINS, AC SHARPE, AH ORKIN, SH TI LETHAL BETA-THALASSEMIA IN MICE LACKING THE ERYTHROID CACCC-TRANSCRIPTION FACTOR EKLF SO NATURE LA English DT Article ID HUMAN GAMMA-GLOBIN; TARGETED MUTATION; MAMMALIAN-CELLS; TRANSGENIC MICE; FACTOR GATA-1; GENE; BINDING; EXPRESSION; EXTRACTION; PROMOTER AB GLOBIN genes are regulated in a tissue-specific and developmental stage-specific manner, with the beta-globin gene being the last to be activated in the beta-gene cluster(1). CACCC-nucleotide sequences, which bind multiple nuclear proteins, including ubiquitously expressed Sp1 and erythroid Kruppel-like factor (EKLF), are among the cis-regulatory sequences critical for transcription of globin and non-globin erythroid-expressed genes(2-5). To determine the function of EKLF in vivo, we created mice deficient in EKLF by gene targeting(6). These embryos die of anaemia during fetal liver erythropoiesis and show the molecular and haematological features of beta-globin deficiency, found in beta-thalassaemia. Although it is expressed at all stages, EKLF is not required for yolk sac erythropoiesis, erythroid commitment or expression of other potential target genes. Its stage-specific and beta-globin-gene-specific requirement suggests that EKLF may facilitate completion of the fetal-to-adult (haemoglobin gamma to beta) switch in humans. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Brugnara, Carlo/A-8041-2010; Perkins, Andrew/M-3216-2014 OI Brugnara, Carlo/0000-0001-8192-8713; Perkins, Andrew/0000-0003-3644-7093 NR 29 TC 460 Z9 468 U1 0 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAY 25 PY 1995 VL 375 IS 6529 BP 318 EP 322 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RA030 UT WOS:A1995RA03000051 PM 7753195 ER PT J AU MA, A PENA, JC CHANG, B MARGOSIAN, E DAVIDSON, L ALT, FW THOMPSON, CB AF MA, A PENA, JC CHANG, B MARGOSIAN, E DAVIDSON, L ALT, FW THOMPSON, CB TI BCLX REGULATES THE SURVIVAL OF DOUBLE-POSITIVE THYMOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID APOPTOTIC CELL-DEATH; FOLLICULAR LYMPHOMA; NEGATIVE SELECTION; T-CELLS; GENE; MICE; LYMPHOCYTES; RECEPTOR; PROTEIN; ANTIBODIES AB The bclx gene has been shown to regulate programmed cell death in vitro. We now show that Bclx expression increases dramatically when T cells differentiate from CD4(-) CD8(-) (double negative) thymocytes to CD4(+) CD8(+) [double positive (DP)] thymocytes, In contrast single-positive (SP) thymocytes express negligible amounts of Bclx protein. This expression pattern contrasts with that of Bcl2, which is present in double-negative thymocytes, downregulated in DP thymocytes, and reinduced upon maturation to SP thymocytes. Elimination of Bclx by gene targeting dramatically shortens the survival of DP thymocytes but not the survival of SP thymocytes or peripheral SP T cells, These data suggest that the induction of Bclx during thymic maturation plays a critical role in regulating the length of time DP thymocytes survive in the absence of selection. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT GENET,BOSTON,MA 02115. UNIV CHICAGO,HOWARD HUGHES MED INST,COMM IMMUNOL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT MED,GWEN KNAPP CTR LUPUS & IMMUNOL RES,CHICAGO,IL 60637. UNIV CHICAGO,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. FU NCI NIH HHS [CA-42335]; NIAID NIH HHS [AI-20047, AI-35294] NR 26 TC 200 Z9 200 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 MAY 23 PY 1995 VL 92 IS 11 BP 4763 EP 4767 DI 10.1073/pnas.92.11.4763 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RA150 UT WOS:A1995RA15000010 PM 7761398 ER PT J AU GOLUB, TR BARKER, GF BOHLANDER, SK HIEBERT, SW WARD, DC BRAYWARD, P MORGAN, E RAIMONDI, SC ROWLEY, JD GILLILAND, DG AF GOLUB, TR BARKER, GF BOHLANDER, SK HIEBERT, SW WARD, DC BRAYWARD, P MORGAN, E RAIMONDI, SC ROWLEY, JD GILLILAND, DG TI FUSION OF THE TEL GENE ON 12P13 TO THE AML1 GENE ON 21Q22 IN ACUTE LYMPHOBLASTIC-LEUKEMIA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRANSCRIPTION FACTORS; ETS; TRANSLOCATION; CHROMOSOME 12; CHROMOSOME 21 ID TRANSCRIPTION FACTORS; FAMILY; RUNT AB Chromosomal rearrangements involving band 12p13 are found in a wide variety of human leukemias but are particularly common in childhood acute lymphoblastic leukemia, The genes involved in these rearrangements, however, have not been identified. We now report the cloning of a t(12;21) translocation breakpoint involving 12p13 and 21q22 in two cases of childhood pre-B acute lymphoblastic leukemia, in which t(12;21) rearrangements were not initially apparent, The consequence of the translocation is fusion of the helix-loop-helix domain of TEL, an ETS-like putative transcription factor, to the DNA-binding and transactivation domains of the transcription factor AML1, These data show that TEL, previously shown to be fused to the platelet-derived growth factor receptor beta in chronic myelomonocytic leukemia, can be implicated in the pathogenesis of leukemia through its fusion to either a receptor tyrosine kinase or a transcription factor. The TEL-AML1 fusion also indicates that translocations affecting the AML1 gene can be associated with lymphoid, as well as myeloid, malignancy. C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, CHILDRENS HOSP, SCH MED, DIV PEDIAT HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. UNIV CHICAGO, HEMATOL ONCOL SECT, CHICAGO, IL 60637 USA. ST JUDE CHILDRENS RES HOSP, DEPT TUMOR CELL BIOL, MEMPHIS, TN 38105 USA. ST JUDE CHILDRENS RES HOSP, DEPT LAB MED & PATHOL, MEMPHIS, TN 38105 USA. YALE UNIV, DEPT GENET, NEW HAVEN, CT 06520 USA. CHILDRENS MEM HOSP, HEMATOL ONCOL SECT, CHICAGO, IL 60614 USA. OI Bohlander, Stefan/0000-0002-2202-9088 FU NCI NIH HHS [CA 20180, CA 21765, R01-CA 64140] NR 23 TC 606 Z9 611 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 23 PY 1995 VL 92 IS 11 BP 4917 EP 4921 DI 10.1073/pnas.92.11.4917 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RA150 UT WOS:A1995RA15000041 PM 7761424 ER PT J AU CASINI, G RICKMAN, DW BRECHA, NC AF CASINI, G RICKMAN, DW BRECHA, NC TI AII AMACRINE CELL-POPULATION IN THE RABBIT RETINA - IDENTIFICATION BY PARVALBUMIN IMMUNOREACTIVITY SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE NARROW-FIELD AMACRINE CELL; CALCIUM-BINDING PROTEIN; ROD PATHWAY; DOPAMINERGIC AMACRINE CELL ID INNER PLEXIFORM LAYER; CALCIUM-BINDING PROTEINS; CAT RETINA; MAMMALIAN RETINA; RAT RETINA; QUANTITATIVE-ANALYSIS; POSTNATAL-DEVELOPMENT; ACCUMULATING NEURONS; SYNAPTIC CONNECTIONS; VERTEBRATE RETINA AB Parvalbumin (PV) is a calcium-binding protein localized to selected neurons in the nervous system, including the retina. This investigation evaluated the distribution of PV immunoreactivity in the rabbit retina using immunohistochemistry with a monoclonal antibody directed to carp PV. In the inner nuclear layer (INL), PV immunoreactivity was present in horizontal and amacrine cells. In the ganglion cell layer, PV immunostaining was confined to somata that are likely to be both displaced amacrine cells and ganglion cells. PV-immunoreactive (IR) amacrine cells were positioned in the proximal INL adjacent to the inner plexiform layer (IPL). These cells usually gave rise to a single primary process, which arborized into two distinct bands in the IPL. In sublamina a, the processes were thin and had large, irregular endings. In sublamina b, multiple processes branched from the primary process and were characterized by varicosities and spines. PV-IR amacrine cell bodies measured from 8 to 10 mu m in diameter. Their density was highest in the visual streak and lowest in the periphery of the superior retina. The average number of PV-IR amacrine cells was 464,045 cells per retina (N = 3), and the average regularity index of the PV-IR cell mosaic was 3.23. PV-IR amacrine cells were further characterized by double-label immunofluorescence experiments using antibodies to PV and tyrosine hydroxylase (TH). Varicose TH-IR processes were in close apposition to many PV-IR amacrine cells and often formed ''ring structures'' around them. Together, these morphological, quantitative, and histochemical observations indicate that PV immunoreactivity in the INL is localized predominantly to AII amacrine cells, and therefore it is a valuable marker for the identification of this cell type. (C) 1995 Wiley-Liss, Inc. C1 W LOS ANGELES VET AFFAIRS MED CTR,CURE,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,VA,CURE,CTR GASTROENTER BIOL,BRAIN RES INST,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,VA,CURE,CTR GASTROENTER BIOL,BRAIN RES INST,DEPT ANAT & CELL BIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,JULES STEIN EYE INST,LOS ANGELES,CA 90024. FU NEI NIH HHS [EY 04067, R01 EY004067] NR 47 TC 54 Z9 55 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 22 PY 1995 VL 356 IS 1 BP 132 EP 142 DI 10.1002/cne.903560109 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA RA886 UT WOS:A1995RA88600008 PM 7629307 ER PT J AU SCHAEFER, BC AF SCHAEFER, BC TI REVOLUTIONS IN RAPID AMPLIFICATION OF CDNA ENDS - NEW STRATEGIES FOR POLYMERASE CHAIN-REACTION CLONING OF FULL-LENGTH CDNA ENDS SO ANALYTICAL BIOCHEMISTRY LA English DT Review ID T4 RNA LIGASE; SINGLE-SIDED SPECIFICITY; PCR PRODUCTS; MESSENGER-RNA; REVERSE TRANSCRIPTION; LIBRARY CONSTRUCTION; EFFICIENT METHOD; DNA; LIGATION; ACID AB Rapid amplification of cDNA ends (RACE) is a polymerase chain reaction (PCR)-based technique which was developed to facilitate the cloning of full-length cDNA 5'- and 3'-ends after a partial cDNA sequence has been obtained by other methods, While RACE can yield complete sequences of cDNA ends in only a few days, the RACE procedure frequently results in the exclusive amplification of truncated cDNA ends, undermining efforts to generate full-length clones, Many investigators have suggested modifications to the RACE protocol to improve the effectiveness of the technique, Based on first-hand experience with RACE, a critical review of numerous published variations of the hey steps in the RACE method is presented. Also included is a detailed, effective protocol based on RNA ligase-mediated RACE/reverse ligation-mediated PCR, as well as a demonstration of its utility, (C) 1995 Academic Press, Inc. RP SCHAEFER, BC (reprint author), DANA FARBER CANC INST,DIV TUMOR VIROL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Marion-Poll, Frederic/D-8882-2011; OI Marion-Poll, Frederic/0000-0001-6824-0180; Schaefer, Brian C/0000-0001-8877-3507 FU NCI NIH HHS [CA47554, CA43143] NR 79 TC 230 Z9 260 U1 1 U2 33 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 20 PY 1995 VL 227 IS 2 BP 255 EP 273 DI 10.1006/abio.1995.1279 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RC014 UT WOS:A1995RC01400001 PM 7573945 ER PT J AU SLAUGENHAUPT, SA ROCA, AL LIEBERT, CB ALTHERR, MR GUSELLA, JF REPPERT, SM AF SLAUGENHAUPT, SA ROCA, AL LIEBERT, CB ALTHERR, MR GUSELLA, JF REPPERT, SM TI MAPPING OF THE GENE FOR THE MEL(1A)-MELATONIN RECEPTOR TO HUMAN-CHROMOSOME-4 (MTNR1A) AND MOUSE CHROMOSOME-8 (MTNR1A) SO GENOMICS LA English DT Note ID MELATONIN AB The pineal hormone melatonin elicits potent circadian and reproductive effects in mammals. We report the chromosomal location of the gene for the Mel(1a)-melatonin receptor that likely mediates these circadian and reproductive actions, PCR analysis of human-rodent somatic cell hybrids showed that the receptor gene (MTNR1A) maps to human chromosome 4q35.1. An interspecific backcross analysis revealed that the mouse gene (Mtnr1a) maps to the proximal portion of chromosome 8. These loci may be involved in genetically based circadian and neuroendocrine disorders. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEV CHRONOBIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. LOS ALAMOS NATL LAB,GENOM & STRUCT BIOL GRP,LOS ALAMOS,NM 87545. FU NHGRI NIH HHS [HG00169, F32-HG00073]; NIDDK NIH HHS [DK42125] NR 14 TC 63 Z9 71 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 20 PY 1995 VL 27 IS 2 BP 355 EP 357 DI 10.1006/geno.1995.1056 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RD687 UT WOS:A1995RD68700022 PM 7558006 ER PT J AU STANGER, BZ LEDER, P LEE, TH KIM, E SEED, B AF STANGER, BZ LEDER, P LEE, TH KIM, E SEED, B TI RIP - A NOVEL PROTEIN CONTAINING A DEATH DOMAIN THAT INTERACTS WITH FAS/APO-1 (CD95) IN YEAST AND CAUSES CELL-DEATH SO CELL LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR RECEPTOR SUPERFAMILY; FAS ANTIGEN; MONOCLONAL-ANTIBODY; SURFACE ANTIGEN; CONSERVED FEATURES; DNA FRAGMENTATION; CROSS-LINKING; KINASE FAMILY; TNF RECEPTOR AB Ligation of the extracellular domain of the cell surface receptor Fas/APO-1 (CD95) elicits a characteristic programmed death response in susceptible cells. Using a genetic selection based on protein-protein interaction in yeast, we have identified two gene products that associate with the intracellular domain of Pas: Pas itself, and a novel 74 kDa protein we have named RIP, for receptor interacting protein. RIP also interacts weakly with the p55 tumor necrosis factor receptor (TNFR1) intracellular domain, but not with a mutant version of Pas corresponding to the murine lpr(cg) mutation. RIP contains an N-terminal region with homology to protein kinases and a C-terminal region containing a cytoplasmic motif (death domain) present in the Pas and TNFR1 intracellular domains. Transient overexpression of RIP causes transfected cells to undergo the morphological changes characteristic of apoptosis. Taken together, these properties indicate that RIP is a novel form of apoptosis-inducing protein. C1 HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02114 USA. RP HARVARD UNIV, SCH MED, HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. FU NIDDK NIH HHS [DK43031] NR 56 TC 738 Z9 755 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD MAY 19 PY 1995 VL 81 IS 4 BP 513 EP 523 DI 10.1016/0092-8674(95)90072-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QZ710 UT WOS:A1995QZ71000008 PM 7538908 ER PT J AU VANETTEN, RA DEBNATH, J ZHOU, H CASASNOVAS, JM AF VANETTEN, RA DEBNATH, J ZHOU, H CASASNOVAS, JM TI INTRODUCTION OF A LOSS-OF-FUNCTION POINT MUTATION FROM THE SH3 REGION OF THE CAENORHABDITIS-ELEGANS SEM-5 GENE ACTIVATES THE TRANSFORMING ABILITY OF C-ABL IN-VIVO AND ABOLISHES BINDING OF PROLINE-RICH LIGANDS IN-VITRO SO ONCOGENE LA English DT Article DE ONCOGENES; ABELSON MURINE LEUKEMIA VIRUS; TYROSINE KINASE; CELL TRANSFORMATION; SRC HOMOLOGY REGION ID TYROSINE-PHOSPHORYLATED PEPTIDES; GUANINE-NUCLEOTIDE EXCHANGE; ONCOGENIC ACTIVATION; CRYSTAL-STRUCTURE; ADAPTER PROTEIN; KINASE-ACTIVITY; DOMAIN; GRB2; SRC; RAS AB We have introduced two loss-of-function point mutations from highly conserved regions of the src homology 3 (SH3) domains of the Caenorhabditis elegans sem-5 gene into the SH3 domain of the murine type IV c-abl tyrosine kinase proto-oncogene. One of the mutations, P131L, activated abl to transform fibroblasts while tbe other, G128R, did not. When combined with independent activating mutations in the c-abl kinase domain or NH,terminus, the G128R mutation blocked transformation by the double mutant, suggesting that the G128R mutant was unable to transform cells for trivial reasons. The c-Abl G128R mutant, like wild type c-Abi protein, was localized to the nucleus and actin cytoskeleton and had normal tyrosine kinase activity in vitro, while the transforming c-Abl P131L protein was localized exclusively to the cytoplasm and exhibited decreased in vitro kinase activity. By real-time biospecific interaction analysis, the wild type Abl SH3 domain bound to two proteins containing proline-rich motifs with dissociation constants of 0.2 and 17 mu M; the G128R mutant bound with 50-fold lower affinity, and no binding was detected by the P131L mutant. Both mutations completely abolished binding of the Abl SH3 domain to proline-rich target proteins in a filter-binding assay, These results suggest that the transforming activity of Abl is regulated in vivo by an inhibitor protein which associates with the SH3 domain via a proline-rich sequence. C1 HARVARD UNIV, SCH MED, CTR BLOOD RES, DEPT PATHOL, BOSTON, MA 02115 USA. RP VANETTEN, RA (reprint author), HARVARD UNIV, SCH MED, CTR BLOOD RES, DEPT GENET, 200 LONGWOOD AVE, BOSTON, MA 02115 USA. RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 FU NIAID NIH HHS [AI 39121] NR 70 TC 48 Z9 49 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 18 PY 1995 VL 10 IS 10 BP 1977 EP 1988 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA QZ926 UT WOS:A1995QZ92600012 PM 7539119 ER PT J AU LI, JJ OBERLEY, LW STCLAIR, DK RIDNOUR, LA OBERLEY, TD AF LI, JJ OBERLEY, LW STCLAIR, DK RIDNOUR, LA OBERLEY, TD TI PHENOTYPIC CHANGES INDUCED IN HUMAN BREAST-CANCER CELLS BY OVEREXPRESSION OF MANGANESE-CONTAINING SUPEROXIDE-DISMUTASE SO ONCOGENE LA English DT Article DE BREAST; CANCER; MNSOD; TRANSFECTION; SOFT AGAR; NUDE MICE ID SYRIAN-HAMSTER TISSUES; GLUTATHIONE-PEROXIDASE; ANTIOXIDANT ENZYMES; IMMUNOHISTOCHEMICAL LOCALIZATION; KIDNEY DEVELOPMENT; TRANSFECTED CELLS; EXPRESSION VECTOR; TRANSGENIC MICE; MAMMALIAN-CELLS; DOWNS-SYNDROME AB Human manganese containing superoxide dismutase (MnSOD) cDNA was transfected into a human breast cancer cell line (MCF-7) in order to examine the effect of increased functional MnSOD on the cellular phenotype. A MnSOD-overexpressing clone was compared to control vector-transfected cells and to wild type MCF-7 cells. Southern blotting indicated incorporation of MnSOD cDNA into genomic DNA in the MnSOD overexpressing cell line. The MnSOD overexpressing cell line showed a 5.7-fold increase in MnSOD activity compared to wild type MCF-7 cells. Similar increases in MnSOD immunoreactive protein and mRNA levels were observed by Western and Northern blotting as well as using RT-PCR, The plating efficiency of cells grown in different concentrations of serum (1 to 20%) was decreased in the MnSOD overexpressing cell line. The fraction in soft agar culture was also after MnSOD cDNA transfection. When inoculated in nude mice, tumor growth was markedly inhibited in MnSOD overexpressing cells compared to wild type MCF-7 cells or plasmid control cells, These results support the hypothesis that increased MnSOD expression suppresses the malignant phenotype of human breast cancer cells and suggests that the MnSOD gene is a tumor suppressor gene in human breast cancer. C1 UNIV IOWA,RADIAT RES LAB,MED LABS 14,IOWA CITY,IA 52242. UNIV KENTUCKY,GRAD CTR TOXICOL,LEXINGTON,KY 40506. WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL SERV,MADISON,WI 53705. FU NCI NIH HHS [CA 41267, CA 49797] NR 49 TC 229 Z9 233 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 18 PY 1995 VL 10 IS 10 BP 1989 EP 2000 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA QZ926 UT WOS:A1995QZ92600013 PM 7761099 ER PT J AU NASH, IS PASTERNAK, RC AF NASH, IS PASTERNAK, RC TI PHYSICIAN, EDUCATE THYSELF SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MEDICAL-EDUCATION; COMMISSION; REFORM C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 10 TC 1 Z9 1 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 MAY 17 PY 1995 VL 273 IS 19 BP 1533 EP 1534 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QX418 UT WOS:A1995QX41800037 PM 7739081 ER PT J AU NIERENBERG, AA GROSSBARD, SJ FAVA, M ROSENBAUM, JF AF NIERENBERG, AA GROSSBARD, SJ FAVA, M ROSENBAUM, JF TI SOCIAL-ADJUSTMENT DOES NOT PREDICT DEPRESSIVE RELAPSE DURING CONTINUATION FLUOXETINE THERAPY SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE SOCIAL ADJUSTMENT; DEPRESSIVE RELAPSE; FLUOXETINE; CONTINUATION TREATMENT ID MAINTENANCE THERAPIES; RECURRENT DEPRESSION AB The purpose of this study was to assess the relationship between social adjustment and the risk of depressive relapse during continuation antidepressant treatment. The Social Adjustment Scale-Self Report Version (SAS-SR) was used to assess a broad range of social functioning before and after acute treatment in 41 outpatients with unipolar depression who responded to fluoxetine and then continued on this antidepressant. No differences were detected between those who relapsed and those who stayed well with regard to pre- and posttreatment SAS-SR total or subscale scores. These data suggest that social functioning does not affect the risk of relapse while depressed patients are taking fluoxetine continuation treatment. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. RP NIERENBERG, AA (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,WACC-815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 8 TC 8 Z9 8 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 MAY 17 PY 1995 VL 34 IS 2 BP 73 EP 77 DI 10.1016/0165-0327(94)00100-N PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RA226 UT WOS:A1995RA22600001 PM 7665807 ER PT J AU FRYXELL, D LI, BY MOHANRAJ, D JOHNSON, B RAMAKRISHNAN, S AF FRYXELL, D LI, BY MOHANRAJ, D JOHNSON, B RAMAKRISHNAN, S TI GENETIC CONSTRUCTION OF A PHOSPHORYLATION SITE IN RICIN A CHAIN - SPECIFIC RADIOLABELING OF RECOMBINANT PROTEINS FOR LOCALIZATION AND DEGRADATION STUDIES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID A CHAIN; IMMUNOTOXINS; PURIFICATION; CHEMISTRY AB Ricin A chain was modified by the addition of the heptapeptide LRRASLG (Kemptide) and a histidine rag for bacterial expression. The mutagenized toxin was as demonstrated by labeling with [gamma-P-32] ATP. Kemptide-A chain could be labeled even after reassociation with ricin B chain or disulfide linkage to antibody to form an immunotoxin. The P-32 label in all cases was associated only with the A chain; ricin B chain and antibody were not kinase substrates alone or after conjugation. Kemptide-immunotoxin was tested in cytotoxicity assays and used to monitor internalization of the toxin moiety after [P-32] phosphorylation. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. RP UNIV MINNESOTA, DEPT PHARMACOL, MINNEAPOLIS, MN 55455 USA. FU NCI NIH HHS [CA48068] NR 13 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 16 PY 1995 VL 210 IS 2 BP 253 EP 259 DI 10.1006/bbrc.1995.1654 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QX870 UT WOS:A1995QX87000003 PM 7755598 ER PT J AU KUTER, DJ ROSENBERG, RD AF KUTER, DJ ROSENBERG, RD TI THE RECIPROCAL RELATIONSHIP OF THROMBOPOIETIN (C-MPL LIGAND) TO CHANGES IN THE PLATELET MASS DURING BUSULFAN-INDUCED THROMBOCYTOPENIA IN THE RABBIT SO BLOOD LA English DT Article ID MEGAKARYOCYTE STIMULATORY FACTOR; BONE-MARROW; GROWTH-FACTOR; ERYTHROPOIETIN GENE; PLASMA; INVIVO; CELLS; RAT; INTERLEUKIN-6; PURIFICATION AB Thrombopoietin (c-Mpl ligand) has recently been purified and is considered to be the humoral regulator of platelet production. To see whether this molecule possessed the physiologic characteristics necessary to mediate the feedback loop between blood platelets and the bone marrow megakaryocytes, we determined the relationship between blood levels of thrombopoietin and changes in the circulating platelet mass. We developed a model of nonimmune thrombocytopenia in rabbits by the subcutaneous administration of busulfan. Compared with pretreatment plasma, plasma taken from all thrombocytopenic rabbits at their platelet nadir contained increased amounts of thrombopoietin. All of this activity was neutralized by soluble c-Mpl receptor. We subsequently measured the level of thrombopoietin in the circulation over the entire time course after the administration of busulfan. As the platelet mass declined, levels of thrombopoietin increased inversely and proportionally and peaked during the platelet nadir, With return of the platelet mass toward normal, thrombopoietin levels decreased accordingly. When platelets were transfused into thrombocytopenic rabbits near the time of their platelet count nadir, the elevated levels of thrombopoietin decreased. In addition, platelets were observed to remove thrombopoietin from thrombocytopenic plasma in vitro. These results confirm that thrombopoietin is the humoral mediator of megakaryocytopoiesis and suggest that the platelet mass may directly play a role in regulating the circulating levels of this factor, (C) 1995 by The American Society of Hematology. C1 MIT,DEPT BIOL,CAMBRIDGE,MA. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. RP KUTER, DJ (reprint author), MASSACHUSETTS GEN HOSP,HEMATOL UNIT,COX 235,FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL 39753] NR 67 TC 309 Z9 313 U1 1 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 MAY 15 PY 1995 VL 85 IS 10 BP 2720 EP 2730 PG 11 WC Hematology SC Hematology GA QX866 UT WOS:A1995QX86600011 PM 7742532 ER PT J AU LEE, C WU, SS CHEN, LB AF LEE, C WU, SS CHEN, LB TI PHOTOSENSITIZATION BY 3,3'-DIHEXYLOXACARBOCYANINE IODIDE - SPECIFIC DISRUPTION OF MICROTUBULES AND INACTIVATION OF ORGANELLE MOTILITY SO CANCER RESEARCH LA English DT Article ID ENDOPLASMIC-RETICULUM; PHOTODYNAMIC THERAPY; SINGLET OXYGEN; CARCINOMA-CELLS; LIVING CELLS; RHODAMINE-123; PHTHALOCYANINES; IDENTIFICATION; LOCALIZATION; INVITRO AB Photodynamic therapy is a useful new direction for cancer treatment. However, relatively little is currently known about the cellular targets and processes underlying the efficacy of these therapies. In this study, we report evidence of specific photosensitization of a novel intracellular target, cytoskeletal microtubules, that has great importance for cancer treatment. Photosensitization destroys microtubules, halts intracellular organelle motility processes, and leads to rapid cell death, We have examined the cell biological effects of photosensitization with the carbocyanine dye 3,3'-dihexyloxacarbocyanine iodide, which concentrates in mitochondria and the endoplasmic reticulum. Exposure of stained CV-1 kidney epithelial cells to as little as 30-120 s standard fluorescence excitation light caused disruption of the interphase microtubule network and complete inhibition of motility of the endoplasmic reticulum and all phase-contrast visible organelles, as specific effects of dye photoexcitation. Photoexcitation of rhodamine 123 or Hoechst produced neither of these effects. Furthermore, 3,3'-dihexyloxacarbocyanine iodide-mediated photodamage was specific to microtubules; other elements of the cytoskeleton, including vimentin intermediate filaments and actin stress fibers, were unaffected, We have reproduced the photoinactivation of microtubules in vitro with purified microtubule proteins. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA19589]; NICHD NIH HHS [HD24926]; NIGMS NIH HHS [GM38318] NR 43 TC 40 Z9 41 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 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1995 VL 55 IS 10 BP 2063 EP 2069 PG 7 WC Oncology SC Oncology GA QX367 UT WOS:A1995QX36700014 PM 7743503 ER PT J AU RODABAUGH, KJ BLANCHARD, G WELCH, WR BELL, DA BERKOWITZ, RS MOK, SC AF RODABAUGH, KJ BLANCHARD, G WELCH, WR BELL, DA BERKOWITZ, RS MOK, SC TI DETAILED DELETION MAPPING OF CHROMOSOME 6Q IN BORDERLINE EPITHELIAL OVARIAN-TUMORS SO CANCER RESEARCH LA English DT Article ID FREQUENT LOSS; ALLELE LOSS; HETEROZYGOSITY; CANCER; CARCINOMAS; MALIGNANCY; LOCUS; GENE AB We have used PCR amplification of tandem repeats and Southern blot analysis to study the pattern of allelic loss at chromosome 6q in borderline ovarian tumors and compared that with invasive ovarian carcinomas. DNA from 46 borderline ovarian tissues, 20 invasive ovarian tumor tissues, together with corresponding uninvolved (control) tissues was used. The invasive tumors demonstrated the highest percentage of loss of heterozygosity (13 of 45 informative cases, 29%) at the 6q25-27 locus site. In contrast, the borderline ovarian tumors showed only an 11% frequency of loss of heterozygosity (3 of 26). Our results display a sharp contrast in the pattern of loss of heterozygosity between invasive and borderline ovarian tumors and suggest that allelic loss at chromosome 6q may not be involved in the development of borderline ovarian tumors. C1 HARVARD UNIV,SCH MED,DEPT OBSTET GYNECOL & REPROD BIOL,GYNECOL ONCOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [R01CA63381] NR 20 TC 43 Z9 43 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 MAY 15 PY 1995 VL 55 IS 10 BP 2169 EP 2172 PG 4 WC Oncology SC Oncology GA QX367 UT WOS:A1995QX36700031 PM 7743519 ER PT J AU LEE, JS GALVIN, KM SEE, RH ECKNER, R LIVINGSTON, D MORAN, E SHI, Y AF LEE, JS GALVIN, KM SEE, RH ECKNER, R LIVINGSTON, D MORAN, E SHI, Y TI RELIEF OF YY1 TRANSCRIPTIONAL REPRESSION BY ADENOVIRUS E1A IS MEDIATED BY E1A-ASSOCIATED PROTEIN P300 SO GENES & DEVELOPMENT LA English DT Article DE TRANSCRIPTIONAL REPRESSION; ADENOVIRUS E1A; YY1; P300; COFACTOR ID RETINOBLASTOMA GENE-PRODUCT; CELLULAR PROTEINS; POLYMERASE-II; VIRAL GENES; ACTIVATION; BINDING; SITE; POLYPEPTIDES; PROMOTER; REGION AB YY1 represses transcription when bound upstream of transcriptional initiation sites. This repression can be relieved by adenovirus E1A. Here, we present genetic evidence that the ability of E1A to relieve YY1 repression was impaired by mutations that affect E1A binding to its associated protein p300. This suggests that E1A may modulate the repressor activity of YY1 by binding to p300, which may be physically complexed with YY1. A YY1/p300 protein complex in vivo was demonstrated by several independent approaches, and the YY1-interacting domain was mapped to the carboxy-terminal region of p300, distinct from the E1A-binding site. Unlike E2F/RB, the YY1/p300 complex is not disrupted by E1A. functional studies using recombinant p300 demonstrated unequivocally that p300 is capable of mediating E1A-induced transcriptional activation through YY1. Taken together, these results reveal, for the first time, a YY1/p300 complex that is targeted by E1A and demonstrate a function for p300 in mediating interactions between YY1 and E1A. Our data thus identify YY1 as a partner protein for p300 and uncover a molecular mechanism for the relief of YY1-mediated repression by E1A. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,COMM VIROL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. TEMPLE UNIV,SCH MED,FELS INST CANC RES & MOLEC BIOL,PHILADELPHIA,PA 19140. FU NCI NIH HHS [CA58997] NR 55 TC 216 Z9 221 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 MAY 15 PY 1995 VL 9 IS 10 BP 1188 EP 1198 DI 10.1101/gad.9.10.1188 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA RA031 UT WOS:A1995RA03100004 PM 7758944 ER PT J AU ZIETMAN, AL COEN, JJ DALLOW, KC SHIPLEY, WU AF ZIETMAN, AL COEN, JJ DALLOW, KC SHIPLEY, WU TI THE TREATMENT OF PROSTATE-CANCER BY CONVENTIONAL RADIATION-THERAPY - AN ANALYSIS OF LONG-TERM OUTCOME SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE PROSTATE CANCER; RADIATION THERAPY ID ANTIGEN; RADIOTHERAPY; PSA AB Purpose: To assess the long-term outcome of conventional external beam radiation therapy in the management of clinically confined prostate cancer and to examine the proposition that radiation accelerates tumor growth in those who fail treatment. Methods and Materials: One thousand and forty-four men with T1-4NxMO prostate cancer treated by conventional external beam radiation therapy at the Massachusetts General Hospital between 1977 and 1991 were analyzed. Median follow-up was 49 months, Failure was defined as: two sequential rises in serum prostate specific antigen (PSA) level; or a PSA >1 ng/ml 2 or more years after radiation; or any clinical failure. Kaplan-Meier actuarial analyses were used to assess outcome. Results: At 10 years only 40% of the T1-2 group remained disease free. subdivided by grade, the well-differentiated tumors (Gleason 1-2) exhibited a 53% actuarial 10-year disease-free survival, moderately differentiated (Gleason 3) 42%, and poorly differentiated (Gleason 4-5) 20%. The corresponding values for the T3-4 men were 33% for Gleason 1-2, 20% for Gleason 3, and 10% for Gleason 4-5. Overall the value for T3-4 tumors was 18% at 10 years. On relapse the median PSA doubling times for the T1-2 patients were predicted by histology: 18.8 months for Gleason 1-2 patients; 11.1 months for Gleason 3; and 9.6 months for Gleason 5. Significant differences were found between the Gleason 3 and the Gleason 4-5 groups (p = 0.04) and the Gleason 1-2 and the Gleason 4-5 groups (p = 0.03). A wide range of doubling times was seen within each grade group. When compared with recently reported data on selected T1-2 patients who were managed by expectant observation there was no advantage over the first decade (and certainly no disadvantage) in terms of metastasis-free survival or disease-specific survival for the irradiated Gleason 1-3 patients. However, a gain was seen for those with Gleason 4-5 tumors. Conclusion: Less than half of the T1-2NxMO and less than one-fifth of the T3-4NxMO patients receiving conventional radiation therapy were biochemically disease free at 10 years. The PSA doubling times on relapse show a wide variation. Grade was important in determining the rate of relapse suggesting that radiation does not induce a homogeneous acceleration of prostate turners. A metastasis-free and disease-specific survival advantage was found for the poorly differentiated tumors when compared with similar patients reported in the literature who were managed initially by observation. RP ZIETMAN, AL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,GENITOURINARY ONCOL UNIT,BOSTON,MA 02114, USA. NR 17 TC 111 Z9 113 U1 0 U2 2 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 MAY 15 PY 1995 VL 32 IS 2 BP 287 EP 292 DI 10.1016/0360-3016(95)00123-G PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA RA038 UT WOS:A1995RA03800001 PM 7751173 ER PT J AU HEALEY, EA SHAMBERGER, RC GRIER, HE LOEFFLER, JS TARBELL, NJ AF HEALEY, EA SHAMBERGER, RC GRIER, HE LOEFFLER, JS TARBELL, NJ TI A 10-YEAR EXPERIENCE OF PEDIATRIC BRACHYTHERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Note DE BRACHYTHERAPY; PEDIATRIC; SARCOMA; BRAIN TUMORS ID MALIGNANCIES; MANAGEMENT; GLIOMAS AB Purpose: The purpose of this project was to review the brachytherapy experience in the pediatric population at the Joint Center for Radiation Therapy (JCRT) with respect to efficacy and morbidity. Methods and Materials: Treatment outcome was reviewed for 18 children between the ages of 6 months and 23 years who received 19 implants between 1982 and 1992 at JCRT. Fourteen children received permanent Iodine-125 seed implants placed in the operative tumor bed at the time of resection. Two children received stereotactically placed afterloaded high-activity I-125 seed brain implants, and one child received a high-activity I-125 brain implant followed by a permanent I-125 seed brain implant 3 years later. One girl received a temporary Iridium-192 volume implant for a vulvar rhabdomyosarcoma. Among the 15 permanent I-125 implants, the cases included five primary brain tumors, one metastatic brain tumor, six sarcomas, and one each of the following: suprarenal neuroblastoma, hepatoblastoma, and adenocarcinoma of the pancreas. All patients underwent surgery and most patients (15 out of 18) received external beam radiotherapy to a field that included the implant. Results: The median follow-up from the time of diagnosis for patients who remain alive is 55 months (range 24 to 119 months), and the median follow-up from the time of implant is 46 months (15 to 60 months). Disease was controlled in the area of the implant in 13 of 17 evaluable cases. Two patients experienced treatment-related morbidity; one patient developed severe desquamation related to an ''adriamycin recall reaction,'' and one patient died of postoperative complications. Conclusion: Despite the heterogeneous mix of cases, the use of brachytherapy in this pediatric population resulted in several cases of long-term disease control, and the overall morbidity was very low. Therefore, in properly selected pediatric cases, brachytherapy appears to be an efficacious adjunct to multimodality cancer management. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP HEALEY, EA (reprint author), HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,50 BINNEY ST,BOSTON,MA 02115, USA. NR 12 TC 25 Z9 26 U1 0 U2 1 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 MAY 15 PY 1995 VL 32 IS 2 BP 451 EP 455 DI 10.1016/0360-3016(95)00520-9 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA RA038 UT WOS:A1995RA03800019 PM 7772200 ER PT J AU KUCHROO, VK BYRNE, MC GREENFIELD, E WHITTERS, MJ NALEFSKY, EA RAO, A COLLINS, M DORF, ME AF KUCHROO, VK BYRNE, MC GREENFIELD, E WHITTERS, MJ NALEFSKY, EA RAO, A COLLINS, M DORF, ME TI TRANSFECTION OF TCR ALPHA-CHAINS INTO SUPPRESSOR AND T-HELPER CELL HYBRIDOMAS - PRODUCTION OF SUPPRESSOR FACTORS WITH PREDICTED ANTIGEN-SPECIFICITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMPLEMENTARITY-DETERMINING REGION; BETA-CHAIN; MONOCLONAL-ANTIBODY; GENETIC RESTRICTION; IMMUNE-RESPONSES; BINDING FACTORS; I-J; RECEPTOR; EXPRESSION; RECOGNITION AB Conditioned medium from Ag-specific suppressor T cell hybridomas contains soluble factors (TsF) that modulate immune responses in an Ag-specific manner. We previously generated a series of TCR-alpha(-) and TCR-beta(-) expression variants from a 4-hydroxy-3-nitrophenyl acetyl (NP)-specific inducer suppressor T cell hybridoma and demonstrated that loss of TCR alpha-chain mRNA, but not TCR-beta chain mRNA, was accompanied by concomitant loss of suppressor bioactivity. Suppressor factor bioactivity was restored by expression of TCR alpha-chain cDNA, suggesting that the TCR alpha-chain plays a critical role in Ag-specific suppressor cell function. We have now transfected TCR alpha-chain from a Th cell clone specific for arsanylated peptides plus I-A(d) into a TCR-alpha(-) derivative of an NP-specific inducer suppressor T cell hybridoma. The transfectants expressed a new hybrid TCR-alpha beta complex and produced soluble factors that suppressed azobenzenearsonate hapten (ABA) but not NP delayed-type hypersensitivity responses. These supernatants mediated suppression of the induction, but not the effector phase of the delayed-type hypersensitivity reaction. In reciprocal experiments we transfected a TCR alpha-chain from an NP-specific suppressor T cell hybridoma into a TCR-alpha(-) hybridoma derived from the ABA-specific Th cell hybridoma. The NP-specific TCR alpha-chain was expressed in the Th cell hybridoma, but the supernatant from this transfectant did not suppress DTH responses to either NP or ABA. However, the latter supernatants, when combined with cell lysates derived from a TCR-alpha(-) Ts hybridoma, specifically suppress NP DTH responses. These data are consistent with the interpretation that TCR alpha-chain imparts Ag specificity to the suppressor molecule and a second, yet undefined, component produced by the Ts hybridoma controls the immunoregulatory bioactivity. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. GENET INST INC,CAMBRIDGE,MA 02140. DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA 56057]; NINDS NIH HHS [NS 30843] NR 48 TC 9 Z9 9 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 MAY 15 PY 1995 VL 154 IS 10 BP 5030 EP 5038 PG 9 WC Immunology SC Immunology GA QW901 UT WOS:A1995QW90100014 PM 7730610 ER PT J AU ALON, R FEIZI, T YUEN, CT FUHLBRIGGE, RC SPRINGER, TA AF ALON, R FEIZI, T YUEN, CT FUHLBRIGGE, RC SPRINGER, TA TI GLYCOLIPID LIGANDS FOR SELECTINS SUPPORT LEUKOCYTE TETHERING AND ROLLING UNDER PHYSIOLOGICAL FLOW CONDITIONS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTE HOMING RECEPTOR; O-LINKED OLIGOSACCHARIDES; MOLECULE E-SELECTIN; MYELOID CELLS; P-SELECTIN; GLYCOPROTEIN LIGAND; ADHESION MOLECULE-1; SIALYL-LEX; CARBOHYDRATE LIGANDS; ENDOTHELIAL LIGAND AB Selectin interactions with glycolipids have been examined previously under static conditions, whereas physiologic interactions mediated by selectins take place under flow. We find that under physiologic flow conditions, sialyl Lewis(x) (sLe(x)) glycolipid and sialyl Lewis(a) (sLe(a)) neoglycolipid support tethering and rolling adhesions of Chinese hamster ovary (CHO) cells expressing E-selectin and lymphoid and myeloid cells expressing L-selectin. These selectin-mediated adhesions persist at the highest shear stresses that occur in postcapillary venules in vivo and occur at lower site densities than found for sLe(x) on neutrophils. The interactions are Ca2+-dependent and can be specifically and completely blocked with anti-selectin mAbs. Asialo nonfucosylated glycolipids are inactive, and sulfatide supports weak tethering, but not rolling, of L-selectin-expressing cells. Rolling velocities and resistance to detachment are related to the glycolipid site density and fall within the range measured for neutrophil and myeloid cell rolling on substrates containing purified selectins. These observations are the first indication that glycolipids can interact with selectins in physiologic flow conditions, and can contribute to rolling adhesions. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NORTHWICK PK HOSP & CLIN RES CTR,GLYCOSCI LAB,HARROW,MIDDX,ENGLAND. FU NHLBI NIH HHS [HL48675] NR 56 TC 115 Z9 116 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 MAY 15 PY 1995 VL 154 IS 10 BP 5356 EP 5366 PG 11 WC Immunology SC Immunology GA QW901 UT WOS:A1995QW90100049 PM 7537307 ER PT J AU BERG, J WEINSTEIN, MJ SPRINGFIELD, DS RAND, WM AF BERG, J WEINSTEIN, MJ SPRINGFIELD, DS RAND, WM TI RESULTS OF SURGERY AND DOXORUBICIN CHEMOTHERAPY IN DOGS WITH OSTEOSARCOMA SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article DE CANINE SPECIES; DOXORUBICIN; OSTEOSARCOMA; SURGERY ID OSTEOGENIC-SARCOMA; APPENDICULAR OSTEOSARCOMA; CANINE OSTEOSARCOMA; MALIGNANT-TUMORS; CISPLATIN; AMPUTATION; THERAPY AB Thirty-five dogs with appendicular osteosarcoma were treated with 5 doses of doxorubicin (30 mg/m(2) of body surface, IV, every 2 weeks). Surgical excision of the primary tumor was performed 13 days after the second in = 18) or third in = 17) treatment, and the subsequent doxorubicin treatment was given the day following surgery. Resected tumors were evaluated histologically to determine response to preoperative chemotherapy (ie, percentage of the tumor that was necrotic). Survival data for the 35 dogs were compared with survival data for a historical control group, consisting of 162 dogs with appendicular osteosarcoma treated by amputation alone. Administration of doxorubicin at 2 week intervals was well tolerated. Three dogs were alive and did not have evidence of disease at the time of reporting. Of the remaining 32 dogs, 3 died or were euthanatized be cause of cardiomyopathy presumably caused by doxorubicin; 1 died suddenly 116 weeks after initiation of treatment, and the remaining 28 were euthanatized because of problems documented to be related to distant metastases. Thirteen dogs (40.6%) were euthanatized because of pulmonary metastases, 10 dogs (31.3%) were euthanatized because of bone metastases, and 5 dogs (15.6%) were euthanatized because of metastases in other sites. The proportion of dogs euthanatized be cause of bone metastases was significantly (P < 0.001) higher for the study group than for the control group. Median survival time for the 35 dogs that received doxorubicin was estimated to be 52.3 weeks, and 1- and 2-year survival rates were estimated to be 50.5 and 9.7%, respectively Survival time was significantly (P < 0.0001) longer for these dogs than for control dogs. Percentage of the resected primary tumor that was necrotic ranged from 0 to 87% (mean, 24.9%). There was a significant (r = 0.39; P < 0.05) direct correlation between survival time and percentage of the tumor that was necrotic. C1 MASSACHUSETTS GEN HOSP,ORTHOPED ONCOL UNIT,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT COMMUNITY HLTH,BOSTON,MA 02111. RP BERG, J (reprint author), TUFTS UNIV,SCH VET MED,DEPT SURG,200 WESTBORO RD,N GRAFTON,MA 01536, USA. NR 31 TC 86 Z9 86 U1 0 U2 7 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1995 VL 206 IS 10 BP 1555 EP 1560 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA QX382 UT WOS:A1995QX38200014 PM 7775232 ER PT J AU HOOPER, DC AF HOOPER, DC TI FROM FLUOROQUINOLONES TO 2-PYRIDONES SO LANCET LA English DT Editorial Material ID NALIDIXIC-ACID; DNA GYRASE RP HOOPER, DC (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114, USA. NR 12 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD MAY 13 PY 1995 VL 345 IS 8959 BP 1192 EP 1193 DI 10.1016/S0140-6736(95)91986-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QX861 UT WOS:A1995QX86100004 PM 7739303 ER PT J AU DAVAR, G WAIKAR, S EISENBERG, E HATTORI, M THALHAMMER, JG AF DAVAR, G WAIKAR, S EISENBERG, E HATTORI, M THALHAMMER, JG TI BEHAVIORAL EVIDENCE OF THERMAL HYPERALGESIA IN NONOBESE DIABETIC MICE WITH AND WITHOUT INSULIN-DEPENDENT DIABETES SO NEUROSCIENCE LETTERS LA English DT Article DE PAIN; DIABETES; NEUROPATHY ID MOUSE; RATS; PAIN; NEUROPATHY; NEURONS AB The non-obese diabetic (NOD) mouse, a model of Type 1 diabetes in humans, has proven useful for the study of genetic, immunologic and epidemiologic aspects of inherited diabetes. Behavioral evidence of hyperalgesia may also be present in the NOD mouse but has not been described. This study examined NOD mice with (NOD+) and without (NOD-) insulin-dependent diabetes, and control strain (ILI) mice for evidence of hyperalgesia to a noxious thermal stimulus. Interestingly, both NOD+ and NOD- mice showed reduced mean hindpaw withdrawal latencies when compared with non-diabetic ILI mice. NOD+ and NOD- mice were also abnormal in their general appearance, activity level, posture, gait and muscle bulk when compared with ILI mice. These findings raise the possibility that hyperalgesia in insulin-dependent NOD mice, or insulin-dependent humans with Type 1 diabetes, may be independent of diabetes and due to a primary disturbance within sensory pathways. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. RP DAVAR, G (reprint author), BRIGHAM & WOMENS HOSP,MOLEC NEUROBIOL PAIN LAB,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIADDK NIH HHS [1P30AM36836]; NIDDK NIH HHS [R01DK43613]; NINDS NIH HHS [1KO8NS01497] NR 16 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 12 PY 1995 VL 190 IS 3 BP 171 EP 174 DI 10.1016/0304-3940(95)11532-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA QZ773 UT WOS:A1995QZ77300007 PM 7637886 ER PT J AU SERENO, MI DALE, AM REPPAS, JB KWONG, KK BELLIVEAU, JW BRADY, TJ ROSEN, BR TOOTELL, RBH AF SERENO, MI DALE, AM REPPAS, JB KWONG, KK BELLIVEAU, JW BRADY, TJ ROSEN, BR TOOTELL, RBH TI BORDERS OF MULTIPLE VISUAL AREAS IN HUMANS REVEALED BY FUNCTIONAL MAGNETIC-RESONANCE-IMAGING SO SCIENCE LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; HUMAN STRIATE CORTEX; HUMAN BRAIN; RETINOTOPIC ORGANIZATION; CORTICAL AREAS; MACAQUE MONKEY; TOPOGRAPHY; MRI; REPRESENTATION; CONNECTIONS AB The borders of human visual areas V1, V2, VP, V3, and V4 were precisely and noninvasively determined. Functional magnetic resonance images were recorded during phase-encoded retinal stimulation. This volume data set was then sampled with a cortical surface reconstruction, making it possible to calculate the local visual field sign (mirror image Versus non-mirror image representation). This method automatically and objectively outlines area borders because adjacent areas often have the opposite field sign. Cortical magnification factor curves for striate and extrastriate cortical areas were determined, which showed that human visual areas have a greater emphasis on the center-of-gaze than their counterparts in monkeys. Retinotopically organized visual areas in humans extend anteriorly to overlap several areas previously shown to be activated by written words. C1 UNIV OSLO,DEPT NEUROPHYSIOL,N-0316 OSLO,NORWAY. HARVARD MIT DIV HLTH SCI & TECHNOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,BOSTON,MA 02129. RP SERENO, MI (reprint author), UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093, USA. RI Dale, Anders/A-5180-2010; Sereno, Martin/F-7657-2012 OI Sereno, Martin/0000-0002-7598-7829 FU NEI NIH HHS [EY07980]; NICHD NIH HHS [NICHD22614]; NIMH NIH HHS [MH47035] NR 49 TC 1574 Z9 1595 U1 7 U2 78 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 12 PY 1995 VL 268 IS 5212 BP 889 EP 893 DI 10.1126/science.7754376 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QX850 UT WOS:A1995QX85000043 PM 7754376 ER PT J AU TOOTELL, RBH REPPAS, JB DALE, AM LOOK, RB SERENO, MI MALACH, R BRADY, TJ ROSEN, BR AF TOOTELL, RBH REPPAS, JB DALE, AM LOOK, RB SERENO, MI MALACH, R BRADY, TJ ROSEN, BR TI VISUAL-MOTION AFTEREFFECT IN HUMAN CORTICAL AREA MT REVEALED BY FUNCTIONAL MAGNETIC-RESONANCE-IMAGING SO NATURE LA English DT Article ID HUMAN BRAIN; SENSORY STIMULATION; CORTEX; INFORMATION; ACTIVATION; ADAPTATION; MOVEMENT AB FUNCTIONAL magnetic resonance imaging (fMRI)(1-3) was used to measure local haemodynamic changes (reflecting electrical activity) in human visual cortex during production of the visual motion aftereffect, also known as the waterfall illusion(4,5). As in previous studies(6-9), human cortical area MT (V5) responded much better to moving than to stationary visual stimuli. Here we demonstrate a clear increase in activity in MT when subjects viewed a stationary stimulus undergoing illusory motion, following adaptation to stimuli moving in a single local direction. Control stimuli moving in reversing, opposed directions produced neither a perceptual motion aftereffect nor elevated fMRI levels postadaptation. The time course of the motion aftereffect (measured in parallel psychophysical tests) was essentially identical to the time course of the fMRI motion aftereffect. Because the motion aftereffect is direction specific, this indicates that cells in human area MT are also direction specific. In five other retinotopically defined cortical areas, similar motion-specific aftereffects were smaller than those in MT or absent. C1 UNIV CALIF SAN DIEGO,DEPT COGNIT SCI,LA JOLLA,CA 92093. UNIV OSLO,DEPT NEUROPHYSIOL,OSLO,NORWAY. RP TOOTELL, RBH (reprint author), MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,149 13TH ST,BOSTON,MA 02129, USA. RI Dale, Anders/A-5180-2010; Sereno, Martin/F-7657-2012 OI Sereno, Martin/0000-0002-7598-7829 NR 30 TC 387 Z9 391 U1 3 U2 24 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAY 11 PY 1995 VL 375 IS 6527 BP 139 EP 141 DI 10.1038/375139a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QX741 UT WOS:A1995QX74100049 PM 7753168 ER PT J AU FUCHS, CS STAMPFER, MJ COLDITZ, GA GIOVANNUCCI, EL MANSON, JE KAWACHI, I HUNTER, DJ HANKINSON, SE HENNEKENS, CH ROSNER, B SPEIZER, FE WILLETT, WC AF FUCHS, CS STAMPFER, MJ COLDITZ, GA GIOVANNUCCI, EL MANSON, JE KAWACHI, I HUNTER, DJ HANKINSON, SE HENNEKENS, CH ROSNER, B SPEIZER, FE WILLETT, WC TI ALCOHOL-CONSUMPTION AND MORTALITY AMONG WOMEN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; SELF-ADMINISTERED QUESTIONNAIRE; U-SHAPED CURVE; BREAST-CANCER; RISK-FACTORS; COHORT; MEN; REPRODUCIBILITY; FREQUENCY; DRINKING AB Background. Studies in men suggest that light-to-moderate alcohol intake is associated with a reduction in overall mortality, due primarily to a reduced risk of coronary heart disease. Among women with similar levels of alcohol consumption, an increased risk of breast cancer has been noted that complicates the balance of risks and benefits. Methods. We conducted a prospective study among 85,709 women, 34 to 59 years of age and without a history of myocardial infarction, angina, stroke, or cancer, who completed a dietary questionnaire in 1980. During the 12-year follow-up period, 2658 deaths were documented. Results. The relative risks of death in drinkers as compared with nondrinkers were 0.83 (95 percent confidence interval, 0.74 to 0.93) for women who consumed 1.5 to 4.9 g of alcohol per day (one to three drinks per week), 0.88 (95 percent confidence interval, 0.80 to 0.98) for those who consumed 5.0 to 29.9 g per day, and 1.19 (95 percent confidence interval, 1.02 to 1.38) for those who consumed 30 g or more per day, after adjustment for other predictors of mortality. Light-to-moderate drinking (1.5 to 29.9 g per day) was associated with a decreased risk of death from cardiovascular disease; heavier drinking was associated with an increased risk of death from other causes, particularly breast cancer and cirrhosis. The benefit associated with light-to-moderate drinking was most apparent among women with risk factors for coronary heart disease and those 50 years of age or older. Conclusions. Among women, light-to-moderate alcohol consumption is associated with a reduced mortality rate, but this apparent survival benefit appears largely confined to women at greater risk for coronary heart disease. C1 BRIGHAM & WOMENS HOSP,CHANNING LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV PREVENT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH & SOCIAL BEHAV,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RP FUCHS, CS (reprint author), HARVARD UNIV,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 40356]; NHLBI NIH HHS [HL 34594] NR 44 TC 467 Z9 474 U1 2 U2 14 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 MAY 11 PY 1995 VL 332 IS 19 BP 1245 EP 1250 DI 10.1056/NEJM199505113321901 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QW600 UT WOS:A1995QW60000001 PM 7708067 ER PT J AU KROLEWSKI, AS LAFFEL, LMB KROLEWSKI, M QUINN, M WARRAM, JH AF KROLEWSKI, AS LAFFEL, LMB KROLEWSKI, M QUINN, M WARRAM, JH TI GLYCOSYLATED HEMOGLOBIN AND THE RISK OF MICROALBUMINURIA IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STATISTICAL-METHOD; GLUCOSE CONTROL; COMPLICATIONS; NEPHROPATHY; DISEASE AB Background. The risk of microalbuminuria in patients with insulin-dependent diabetes mellitus (IDDM) is thought to depend on the degree of hyperglycemia, but the relation between the degree of hyperglycemia and urinary albumin excretion has not been defined. Methods. We measured urinary albumin excretion in three random urine samples obtained at least one month apart from 1613 patients with IDDM. Microalbuminuria or overt albuminuria was considered to be present if the ratio of albumin (in micrograms) to creatinine (in milligrams) was 17 to 299 or greater than or equal to 300, respectively, for men and 25 to 299 or greater than or equal to 300, respectively, for women. Measurements of glycosylated hemoglobin (hemoglobin A(1)) obtained up to four years before the urine testing were used as an index of hyperglycemia. Twelve percent of the patients had overt albuminuria and were excluded from subsequent analyses. Results. The prevalence of microalbuminuria was 18 percent in patients with IDDM. It increased with increasing postpubertal duration of diabetes and, within each six-year interval of disease duration, it increased nonlinearly with the hemoglobin A(1) value. For hemoglobin A(1) values below 10.1 percent, the slope of the relation was almost flat, whereas for values above 10.1 percent, the prevalence of microalbuminuria rose steeply (P<0.001). For example, as the hemoglobin A(1) value increased from 8.1 to 10.1 percent, the odds of microalbuminuria increased by a factor of 1.3, but as the value increased from 10.1 to 12.1 percent, the odds were increased by a factor of 2.4. Conclusions. The risk of microalbuminuria in patients with IDDM increases abruptly above a hemoglobin A(1) value of 10.1 percent (equivalent to a hemoglobin A(1c) value of 8.1 percent), suggesting that efforts to reduce the frequency of diabetic nephropathy should be focused on reducing hemoglobin A(1) values that are above this threshold. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT EPIDEMIOL, BOSTON, MA 02115 USA. RP KROLEWSKI, AS (reprint author), JOSLIN DIABET CTR, EPIDEMIOL & GENET SECT, 1 JOSLIN PL, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [R01-DK41526] NR 33 TC 358 Z9 366 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 11 PY 1995 VL 332 IS 19 BP 1251 EP 1255 DI 10.1056/NEJM199505113321902 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA QW600 UT WOS:A1995QW60000002 PM 7708068 ER PT J AU GOLDFELD, AE LIU, PF LIU, SF FLEMINGTON, EK STROMINGER, JL SPECK, SH AF GOLDFELD, AE LIU, PF LIU, SF FLEMINGTON, EK STROMINGER, JL SPECK, SH TI CYCLOSPORINE-A AND FK506 BLOCK INDUCTION OF THE EPSTEIN-BARR-VIRUS LYTIC CYCLE BY ANTIIMMUNOGLOBULIN SO VIROLOGY LA English DT Note ID SWITCH GENE BZLF1; FACTOR-ALPHA GENE; LYMPHOCYTES-T; TRANSCRIPTION; PROMOTER; CELLS; ACTIVATION; IDENTIFICATION; DNA; CALCINEURIN AB The Epstein-Barr virus (EBV) BZLF1 gene is expressed early upon induction of the viral lytic cycle and its protein product is unique in its ability to disrupt viral latency in some latently infected cell lines. Anti-immunoglobulin (anti-Ig) treatment of the Burkitt's lymphoma cell line Akata, which bears surface IgG, has previously been shown to synchronously induce transcription of the BZLF1 gene (K. Takada and Y. One, 1989, J. Virol. 63, 445-449). We have previously shown that anti-Ig induction of Akata cells activates expression of the tumor necrosis factor alpha (TNF-alpha) gene via a calcineurin-dependent mechanism (Goldfeld et al., 1992, Proc. Natl. Acad. Sci. USA 89, 12198-12201). Here, we report that anti-Ig induction of the EBV lytic cycle in Akata cells can be blocked by the immunosuppressants cyclosporin A and FK506. Furthermore, we demonstrate that synergistic induction by phorbol ester and calcium ionophore of a BZLF1 promoter-driven reporter construct in an EBV-negative BL cell line can be inhibited by addition of cyclosporin A. Thus, analogous to activation of TNF-alpha gene in Akata cells, anti-Ig induction of the BZLF1 promoter is most likely mediated by calcineurin and probably involves translocation to the nucleus of a transcription factor sequestered in the cytoplasm. As such, immunosuppressants may be useful probes for dissecting a cell activation pathways involved in regulating EBV gene transcription. (C) 1995 Academic Press, Inc. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOLEC MICROBIOL,ST LOUIS,MO 63110. DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA52004, CA58735] NR 46 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 10 PY 1995 VL 209 IS 1 BP 225 EP 229 DI 10.1006/viro.1995.1247 PG 5 WC Virology SC Virology GA QY819 UT WOS:A1995QY81900024 PM 7538254 ER PT J AU AUSUBEL, FM KATAGIRI, F MINDRINOS, M GLAZEBROOK, J AF AUSUBEL, FM KATAGIRI, F MINDRINOS, M GLAZEBROOK, J TI USE OF ARABIDOPSIS-THALIANA DEFENSE-RELATED MUTANTS TO DISSECT THE PLANT-RESPONSE TO PATHOGENS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Self-Defense by Plants: Induction and Signalling Pathways CY SEP 15-17, 1994 CL IRVINE, CA SP NATL ACAD SCI ID CAMPESTRIS PV CAMPESTRIS; MEMBRANE-SPANNING PROTEINS; AVIRULENCE GENE AVRRPT2; TURNIP CRINKLE VIRUS; LEUCINE-RICH REPEATS; DISEASE RESISTANCE; XANTHOMONAS-CAMPESTRIS; NICOTIANA-SYLVESTRIS; ACIDIC CHITINASE; SYNTHASE GENES AB The plant defense response to microbial pathogens had been studied primarily by using biochemical and physiological techniques, Recently, several laboratories have developed a variety of pathosystems utilizing Arabidopsis thaliana as a model host so that genetic analysis could also be used to study plant defense responses. Utilizing a pathosystem that involves the infection of Arabidopsis with pathogenic pseudomonads, we have cloned the Arabidopsis disease-resistance gene RPS2, which corresponds to the avirulence gene avrRpt2 in a gene-for-gene relationship. RPS2 encodes a 105-kDa protein containing a leucine zipper, a nucleotide binding site, and 14 imperfect leucine-rich repeats. The RPS2 protein is remarkably similar to the product of the tobacco N gene, which confers resistance to tobacco mosaic virus. We have also isolated a series of Arabidopsis mutants that synthesize decreased levels of an Arabidopsis phytoalexin called camalexin. Analysis of these mutants indicated that camalexin does not play a significant role in limiting growth of avirulent Pseudomonas syringae strains during the hypersensitive defense response but that it may play a role in limiting the growth of virulent strains. More generally, we have shown that we can utilize Arabidopsis to systematically dissect the defense response by isolation and characterization of appropriate defense-related mutants. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP AUSUBEL, FM (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114, USA. OI Glazebrook, Jane/0000-0001-5167-736X FU NIGMS NIH HHS [GM48707] NR 68 TC 39 Z9 40 U1 0 U2 5 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 MAY 9 PY 1995 VL 92 IS 10 BP 4189 EP 4196 DI 10.1073/pnas.92.10.4189 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QX876 UT WOS:A1995QX87600022 PM 7753782 ER PT J AU BAMEZAI, A ROCK, KL AF BAMEZAI, A ROCK, KL TI OVEREXPRESSED LY-6A.2 MEDIATES CELL-CELL ADHESION BY BINDING A LIGAND EXPRESSED ON LYMPHOID-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LY-6 PROTEIN; THYMUS ID MULTIGENE FAMILY; LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; ACTIVATING PROTEIN; SURFACE MOLECULES; INTERFERON-GAMMA; TAP MOLECULE; ANTIGEN; STIMULATION; RECEPTOR AB The Ly-6 locus encodes several cell surface proteins whose functions are unknown, Although it is hypothesized that these proteins may be receptors, there is no direct evidence that they bind a ligand, Herein we present evidence that Ly-6A.2, a Ly-6 protein expressed on T lymphocytes, binds a ligand expressed on normal thymocytes and splenic B and T cells, We find that transgenic thymocytes that overexpress Ly-6A.2 spontaneously aggregate in culture, This homotypic adhesion requires the overexpression of Ly-6A.2 because it is not observed in cultures of nontransgenic thymocytes, The aggregation of Ly-6A.2 transgenic thymocytes is inhibited by phosphatidylinositol specific phospholipase C (which removes Ly-6A.2 and other glycosylphosphatidylinositol-anchored proteins from the membrane). Some anti-Ly-6A.2 monoclonal antibodies, including nonactivating ones and Fab' fragments, inhibit this aggregation, In contrast, other anti-Ly-6A.2 monoclonal antibodies increase the aggregation of transgenic but not nontransgenic thymocytes, To further examine whether Ly-6A.2 mediates adhesion (versus inducing another adhesion pathway) reaggregation assays were performed with paraformaldehyde-fixed Tg(+) thymocytes, Paraformaldehyde-fixed Tg(+) thymocytes reaggregate in culture and this aggregation is also blocked by phosphatidylinositol-specific phospholipase C and anti-Ly-6A.2 monoclonal antibodies, These results indicate that the homotypic adhesion of cultured Ly-6A.2 transgenic thymocytes is directly mediated by Ly-6A.2 and, more importantly, strongly suggests that Ly-6A.2 binds a ligand that is expressed on thymocytes. Tg(+) thymocytes also bind to nontransgenic thymocytes, B cells, and T cells, indicating that normal cells naturally express the Ly-6A.2 ligand. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BAMEZAI, A (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIGMS NIH HHS [GM 38515] NR 27 TC 62 Z9 62 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 MAY 9 PY 1995 VL 92 IS 10 BP 4294 EP 4298 DI 10.1073/pnas.92.10.4294 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QX876 UT WOS:A1995QX87600043 PM 7753800 ER PT J AU SWISSHELM, K RYAN, K TSUCHIYA, K SAGER, R AF SWISSHELM, K RYAN, K TSUCHIYA, K SAGER, R TI ENHANCED EXPRESSION OF AN INSULIN GROWTH FACTOR-LIKE BINDING-PROTEIN (MAC25) IN SENESCENT HUMAN MAMMARY EPITHELIAL-CELLS AND INDUCED EXPRESSION WITH RETINOIC ACID SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BREAST CANCER; RETINOIDS; INSULIN GROWTH FACTOR-BINDING PROTEIN; SENESCENCE; DIFFERENTIAL DISPLAY ID HUMAN-BREAST-CANCER; ESTROGEN-RECEPTOR STATUS; DIFFERENTIAL DISPLAY; GENE-EXPRESSION; IGF-I; MODULATION; IDENTIFICATION; PROLIFERATION; INHIBITOR; IGFBP-1 AB mac25, the subject of this report, was selected by the differential display of mRNA method in a search for genes overexpressed in senescent human mammary epithelial cells. mac25 had previously been cloned as a discrete gene, preferentially expressed in normal, leptomeningial cells compared with meningioma tumors. mac25 is another member of the insulin growth factor-binding protein (IGFBP) family. Insulin-like growth factors are potent mitogens for mammary epithelial cells, and the IGFBPs have been shown to modulate this mitogenic activity. We report here that mac25, unlike most IGFBPs, is down-regulated at the transcription level in mammary carcinoma cell lines, suggesting a tumor-suppressor role. The gene was mapped to chromosome 4q12. We found that mac25 accumulates in senescent cells and is up-regulated in normal, growing mammary epithelial cells by all-trans-retinoic acid or the synthetic retinoid fenretinide. These findings suggest that mac25 may be a downstream effector of retinoid chemoprevention in breast epithelial cells and that its tumor-suppressive role may involve a senescence pathway. C1 DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. FU NCI NIH HHS [T32 CA-09361]; NIA NIH HHS [AG-10819] NR 41 TC 179 Z9 185 U1 1 U2 1 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 MAY 9 PY 1995 VL 92 IS 10 BP 4472 EP 4476 DI 10.1073/pnas.92.10.4472 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QX876 UT WOS:A1995QX87600079 PM 7538673 ER PT J AU DOLIN, R AMATO, DA FISCHL, MA PETTINELLI, C BELTANGADY, M LIOU, SH BROWN, MJ CROSS, AP HIRSCH, MS HARDY, WD MILDVAN, D BLAIR, DC POWDERLY, WG PARA, MF FIFE, KH STEIGBIGEL, RT SMALDONE, L CRUMPACKER, CS COOLEY, T MITSUYASO, RT JOHN, R SANDERS, C REITMAN, D HEWITT, R REICHMAN, RC GELB, LD MCGUIRE, ML JONES, M NEIDIG, JL ZWICKL, B HARTMAN, PB ROARKE, ME BURK, RA FUHRER, J SOMOGYI, KA SEPKOWITZ, K TELZAK, EE MCAULIFFE, VJ VALENTINE, FT VASQUEZ, M MERIGAN, TC KATZENSTEIN, D FESSELL, J HAVLIR, DV RICHMAN, DD SPECTOR, SA KAHN, JO JOHNSON, L COLEMAN, R HO, M MCMAHON, D PAZIN, G ANTONISKIS, D MCNAMARA, B DIAMOND, D COLLIER, AC PARADISE, MA WALD, A DEPAOLISJONES, A HENRY, K WASKIN, HA HYSLOP, NE MUSHATT, DM ZACHARY, JA SOEIRO, R HARRIS, C ZINGMAN, B GIORDANO, MF SLEDZ, S MURRAY, HW CAREY, JT DAVIS, TL BAGBY, B KESSLER, HA MURPHY, RL HIRSCHTICK, RE CHEESEMAN, SH LAI, KK FAIRCHILD, PG EHMANN, WC ZURLO, JJ MILLARD, R TROIANI, L HEGGEN, AA VANDERHORST, CM MCKINLEY, GF GRIECO, MH KOLATCH, BR GOLDSMITH, JC GOMPERTS, ED WOODS, LM GRUE, L MAYJO, K BECKER, RL JAYAWEERA, DT ROLFE, L COLE, J JERMANO, J AF DOLIN, R AMATO, DA FISCHL, MA PETTINELLI, C BELTANGADY, M LIOU, SH BROWN, MJ CROSS, AP HIRSCH, MS HARDY, WD MILDVAN, D BLAIR, DC POWDERLY, WG PARA, MF FIFE, KH STEIGBIGEL, RT SMALDONE, L CRUMPACKER, CS COOLEY, T MITSUYASO, RT JOHN, R SANDERS, C REITMAN, D HEWITT, R REICHMAN, RC GELB, LD MCGUIRE, ML JONES, M NEIDIG, JL ZWICKL, B HARTMAN, PB ROARKE, ME BURK, RA FUHRER, J SOMOGYI, KA SEPKOWITZ, K TELZAK, EE MCAULIFFE, VJ VALENTINE, FT VASQUEZ, M MERIGAN, TC KATZENSTEIN, D FESSELL, J HAVLIR, DV RICHMAN, DD SPECTOR, SA KAHN, JO JOHNSON, L COLEMAN, R HO, M MCMAHON, D PAZIN, G ANTONISKIS, D MCNAMARA, B DIAMOND, D COLLIER, AC PARADISE, MA WALD, A DEPAOLISJONES, A HENRY, K WASKIN, HA HYSLOP, NE MUSHATT, DM ZACHARY, JA SOEIRO, R HARRIS, C ZINGMAN, B GIORDANO, MF SLEDZ, S MURRAY, HW CAREY, JT DAVIS, TL BAGBY, B KESSLER, HA MURPHY, RL HIRSCHTICK, RE CHEESEMAN, SH LAI, KK FAIRCHILD, PG EHMANN, WC ZURLO, JJ MILLARD, R TROIANI, L HEGGEN, AA VANDERHORST, CM MCKINLEY, GF GRIECO, MH KOLATCH, BR GOLDSMITH, JC GOMPERTS, ED WOODS, LM GRUE, L MAYJO, K BECKER, RL JAYAWEERA, DT ROLFE, L COLE, J JERMANO, J TI ZIDOVUDINE COMPARED WITH DIDANOSINE IN PATIENTS WITH ADVANCED HIV TYPE-1 INFECTION AND LITTLE OR NO PREVIOUS EXPERIENCE WITH ZIDOVUDINE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; PLACEBO-CONTROLLED TRIAL; PHASE-I TRIAL; DOUBLE-BLIND; 2',3'-DIDEOXYINOSINE DDI; AZIDOTHYMIDINE AZT; TOXICITY; DISEASE; EFFICACY AB Background: We conducted a trial to compare treatment with zidovudine or didanosine in patients with advanced human immunodeficiency virus type 1 (HIV-1) infection who had received little or no previous therapy with zidovudine. Methods: Six hundred seventeen patients with acquired immunodeficiency syndrome (AIDS), advanced AIDS-related complex (CD4 cell count, less than or equal to 0.03x10(9)/L [300/mu L]), or asymptomatic HIV (CD4 cell count, less than or equal to 0.20x10(9)/L) received zidovudine, 500 mg/d of didanosine, or 750 mg/d of didanosine in a randomized, double-blind allocation, with cross-over to alternative medication after development of an end point or serious toxic effect. To be eligible, patients must have received either no or up to 16 weeks of zidovudine therapy before entry into the study. Primary end points were development of a new AIDS-defining event or death. Secondary clinical end points were new or recurrent AIDS-defining events, or death, and survival. Results: In the study as a whole, there were no differences in the relative risks (RRs) of the development of end points between treatment groups. However, there was a strong interaction between the relative efficacies of zidovudine and didanosine and previous experience with zidovudine. Among 380 patients with no previous zidovudine therapy, zidovudine was more effective than 750 mg/d of didanosine (RR, 1.43; 90% confidence interval [CI], 1.02 to 2.00), with a similar trend for zidovudine compared with 500 mg/d of didanosine (RR, 1.21;90% CI, 0.86 to 1.71). However, among 118 patients with more than 8 weeks but no more than 16 weeks of previous zidovudine therapy, 500 mg/d of didanosine was more effective than zidovudine (RR, 0.48; 90% CI, 0.27 to 0.86); there was a similar trend for increased effectiveness of 750 mg/d of didanosine compared with zidovudine (RR, 0.61;90% CI, 0.36 to 1.03). Among 119 patients who had some but no more than 8 weeks of previous zidovudine therapy, there were no significant differences among the treatment arms. Similar findings were noted in the analysis of the two secondary clinical end points. No significant differences were found in efficacy between the groups receiving 500 and 750 mg/d of didanosine. The major toxic effect associated with zidovudine was hematopoietic (granulocytopenia) and that associated with didanosine was pancreatitis (dosage, 750 mg/d). Conclusions: In patients with advanced HIV disease, zidovudine appears to be more effective than didanosine as initial therapy; however, some patients with advanced HIV disease may benefit from a change to didanosine therapy after as little as 8 to 16 weeks of therapy with zidovudine. C1 UNIV ROCHESTER,SCH MED & DENT,DEPT MED,ROCHESTER,NY 14642. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. UNIV MIAMI,SCH MED,DEPT MED,MIAMI,FL. NIAID,DIV AIDS,BETHESDA,MD 20892. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,WALLINGFORD,CT. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,BOSTON,MA. UNIV CALIF LOS ANGELES,CTR CARE,DEPT MED,LOS ANGELES,CA. BETH ISRAEL MED CTR,DIV INFECT DIS,NEW YORK,NY 10003. SUNY SYRACUSE,DEPT MED,SYRACUSE,NY. UNIV WASHINGTON,DIV INFECT DIS,ST LOUIS,MO. OHIO STATE UNIV,COLL MED,DEPT INTERNAL MED,COLUMBUS,OH 43210. INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN. SUNY STONY BROOK,DIV INFECT DIS,STONY BROOK,NY 11794. RI Wald, Anna/B-6272-2012 OI Wald, Anna/0000-0003-3486-6438 NR 30 TC 56 Z9 56 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern Med. PD MAY 8 PY 1995 VL 155 IS 9 BP 961 EP 974 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA QW172 UT WOS:A1995QW17200010 PM 7726705 ER PT J AU MASHIMO, H PODOLSKY, DK FISHMAN, MC AF MASHIMO, H PODOLSKY, DK FISHMAN, MC TI STRUCTURE AND EXPRESSION OF MURINE INTESTINAL TREFOIL FACTOR - HIGH EVOLUTIONARY CONSERVATION AND POSTNATAL EXPRESSION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PANCREATIC SPASMOLYTIC POLYPEPTIDE; MUCOSAL ULCERATION; GROWTH-FACTOR; CELL LINEAGE; DNA; SECRETION; IDENTIFICATION; INDUCTION; PEPTIDES; PROTEIN AB Intestinal Trefoil Factor (ITF) is a member of a family of gastrointestinal tract peptides with region-specific expression which are enhanced at sites of injury and repair. In the present study, the murine homologue gene of ITF was molecularly cloned in order to characterize the structure and expression of this peptide in mice. Murine ITF exhibited 78, 95 and 94% nucleotide homology respectively in exons I, II and III, with overall 90% predicted amino acid identity when compared to the rat ITF. Murine ITF exhibited 70% inferred amino acid identity compared with human ITF. Northern blot analysis of various adult mouse tissues demonstrated that ITF is expressed abundantly in the intestine and colon, and minimally in stomach, but not in brain, lung, spleen, kidney, uterus, pancreas, liver, heart or thymus tissues. Expression of ITF appeared to occur as a post-natal event: antibody specific for ITF stains intensely goblet cells in the intestine and colon of three-day old and older mice, but not in the gastrointestinal tract of younger mice or embryos. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. FU NIDDK NIH HHS [P30DK43351, T32DK07191, R01DK46906] NR 25 TC 42 Z9 44 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 5 PY 1995 VL 210 IS 1 BP 31 EP 37 DI 10.1006/bbrc.1995.1623 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QW693 UT WOS:A1995QW69300005 PM 7741746 ER PT J AU SALEEM, A KHARBANDA, S YUAN, ZM KUFE, D AF SALEEM, A KHARBANDA, S YUAN, ZM KUFE, D TI MONOCYTE COLONY-STIMULATING FACTOR STIMULATES BINDING OF PHOSPHATIDYLINOSITOL 3-KINASE TO GRB2-CENTER-DOT-SOS COMPLEXES IN HUMAN MONOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID GUANINE-NUCLEOTIDE EXCHANGE; RECEPTOR TYROSINE KINASES; FMS PROTO-ONCOGENE; SIGNAL-TRANSDUCTION; CSF-1 RECEPTOR; FACTOR-I; INSULIN STIMULATION; GROWTH-FACTOR; SH3 DOMAIN; RAS AB Monocyte colony-stimulating factor (M-CSF) is required for the proliferation of mononuclear phagocytes. The activated M-CSF receptor associates with phosphatidylinositol 3-kinase (PI 3-kinase). In the present studies, we demonstrate that M-CSF also induces direct interaction of PI 3-kinase (p85 alpha subunit) with the SH2/SH3 adaptor protein Grb2. Tyrosine-phosphorylated PI 3-kinase interacts with the SH2 domain of Grb2. A pYRNE (pY408) site in PI 3-kinase is potentially involved in this interaction. The results also demonstrate that the PI 3-kinase . Grb2 complex associates with the guanine nucleotide exchange protein Sos. Since Sos binds to the SH3 domains of Grb2 and thereby associates with Pas at the cell membrane, formation of the PI 3-kinase . Grb2 . Sos complex provides a potential mechanism for growth factor-induced interactions of PI 3-kinase and Pas. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA42802] NR 32 TC 27 Z9 27 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 MAY 5 PY 1995 VL 270 IS 18 BP 10380 EP 10383 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QW601 UT WOS:A1995QW60100006 PM 7737969 ER PT J AU REDDY, JC MORRIS, JC WANG, J ENGLISH, MA HABER, DA SHI, Y LICHT, JD AF REDDY, JC MORRIS, JC WANG, J ENGLISH, MA HABER, DA SHI, Y LICHT, JD TI WT1-MEDIATED TRANSCRIPTIONAL ACTIVATION IS INHIBITED BY DOMINANT-NEGATIVE MUTANT PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR GENE-PRODUCT; ZINC FINGER PROTEIN; DNA-BINDING SITE; WILMS-TUMOR; KIDNEY DEVELOPMENT; PROMOTER ACTIVITY; POINT MUTATIONS; WT1 GENE; LOCUS; EXPRESSION AB The WT1 tumor suppressor gene encodes four isoforms of a zinc finger transcription factor with both activation and repression functions which are dependent upon promoter architecture, Using a simple HSV-tk promoter containing 5'-Egr-1/WT1-binding sites, we found that WT1 isoforms (A) and (B) strongly activated transcription, WT1(A) and (B) bound equally well to the Egr-1/WT1 binding site, but WT1(B), which contains a 17 amino acid insertion compared to WT1(A), was a consistently stronger activator of transcription than WT1(A), Transcriptional activation by wild-type WT1 was inhibited by coexpression of WT(PM) or WT(AR), genetically defined dominant negative alleles of WT1, In vitro, as well as in the yeast two-hybrid system, WT1 protein associated with itself and with dominant negative mutant proteins, The major domain required for self-association and inhibition of transcriptional activation mapped to the first 182 amino acids of WT1, Dominant negative WT1 alleles may play a role in tumorigenesis by associating with wild-type WT1 proteins and decreasing their transcriptional activity. C1 CUNY MT SINAI SCH MED,BROOKDALE CTR MOLEC BIOL,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT MED,DIV MOLEC MED,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DERALD H RUTTENBERG CANC CTR,DIV NEOPLAST DIS,NEW YORK,NY 10029. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. FU NCI NIH HHS [CA58596, CA58997, CA59998] NR 43 TC 130 Z9 131 U1 1 U2 5 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 MAY 5 PY 1995 VL 270 IS 18 BP 10878 EP 10884 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QW601 UT WOS:A1995QW60100075 PM 7738027 ER PT J AU RUTAN, KJ HELDRICH, FJ BORGES, LF AF RUTAN, KJ HELDRICH, FJ BORGES, LF TI ON THE PREPARATION OF ARYL NITRILES USING TOSYL CYANIDE SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Note ID CYANATION; HALIDES C1 COLL CHARLESTON,DEPT CHEM,CHARLESTON,SC 29424. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. NR 25 TC 15 Z9 15 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAY 5 PY 1995 VL 60 IS 9 BP 2948 EP 2950 DI 10.1021/jo00114a060 PG 3 WC Chemistry, Organic SC Chemistry GA QX165 UT WOS:A1995QX16500060 ER PT J AU STASKAWICZ, BJ AUSUBEL, FM BAKER, BJ ELLIS, JG JONES, JDG AF STASKAWICZ, BJ AUSUBEL, FM BAKER, BJ ELLIS, JG JONES, JDG TI MOLECULAR-GENETICS OF PLANT-DISEASE RESISTANCE SO SCIENCE LA English DT Article ID NF-KAPPA-B; PROTEIN-KINASE; TRANSMEMBRANE PROTEIN; ELEMENT ACTIVATOR; DROSOPHILA EMBRYO; GENES; TOMATO; MAIZE; ARABIDOPSIS; PHENOTYPE AB Plant breeders have used disease resistance genes (R genes) to control plant disease since the turn of the century, Molecular cloning of R genes that enable plants to resist a diverse range of pathogens has revealed that the proteins encoded by these genes have several features in common. These findings suggest that plants may have evolved common signal transduction mechanisms for the expression of resistance to a wide range of unrelated pathogens. Characterization of the molecular signals involved in pathogen recognition and of the molecular events that specify the expression of resistance may lead to novel strategies for plant disease control. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT BIOL MOLEC,BOSTON,MA 02114. USDA ARS,CTR PLANT GENE EXPRESS,ALBANY,CA 94710. CSIRO,DIV PLANT IND,CANBERRA,ACT,AUSTRALIA. CSIRO,COOPERAT RES CTR PLANT SCI,CANBERRA,ACT,AUSTRALIA. JOHN INNES CTR PLANT SCI RES,SAINSBURY LAB,NORWICH NR4 7UH,NORFOLK,ENGLAND. RP STASKAWICZ, BJ (reprint author), UNIV CALIF BERKELEY,DEPT PLANT BIOL,BERKELEY,CA 94720, USA. RI Ellis, Jeffrey/A-1999-2010; Baker, Barbara/L-7198-2016; Jones, Jonathan/J-5129-2012 OI Baker, Barbara/0000-0002-1276-971X; Jones, Jonathan/0000-0002-4953-261X NR 79 TC 644 Z9 698 U1 2 U2 40 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 5 PY 1995 VL 268 IS 5211 BP 661 EP 667 DI 10.1126/science.7732374 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QW603 UT WOS:A1995QW60300034 PM 7732374 ER PT J AU PROVINCE, MA HADLEY, EC HORNBROOK, MC LIPSITZ, LA MULROW, CD ORY, MG SATTIN, RW TINETTI, ME WOLF, SL AF PROVINCE, MA HADLEY, EC HORNBROOK, MC LIPSITZ, LA MULROW, CD ORY, MG SATTIN, RW TINETTI, ME WOLF, SL TI THE EFFECTS OF EXERCISE ON FALLS IN ELDERLY PATIENTS - A PREPLANNED METAANALYSIS OF THE FICSIT TRIALS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FUNCTIONAL STATUS; OLDER PERSONS; RISK-FACTORS; POPULATION; FRAILTY; PREDICTORS; COMMUNITY; INJURIES; BALANCE; PEOPLE AB Objective.-To determine if short-term exercise reduces falls and fall-related injuries in the elderly. Design.-A preplanned meta-analysis of the seven Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT)-independent, randomized, controlled clinical trials that assessed intervention efficacy in reducing falls and frailty in elderly patients. All included an exercise component for 10 to 36 weeks. Fall and injury follow-up was obtained for up to 2 to 4 years. Setting.-Two nursing home and five community-dwelling (three health maintenance organizations) sites. Six were group and center based; one was conducted at home. Participants.-Numbers of participants ranged from 100 to 1323 per study. Subjects were mostly ambulatory and cognitively intact, with minimum ages of 60 to 75 years, although some studies required additional deficits, such as functionally dependent in two or more activities of daily living, balance deficits or lower extremity weakness, or high risk of falling. Interventions.-Exercise components varied across studies in character, duration, frequency, and intensity. Training was performed in one area or more of endurance, flexibility, balance platform, Tai Chi (dynamic balance), and resistance. Several treatment arms included additional nonexercise components, such as behavioral components, medication changes, education, functional activity, or nutritional supplements. Main Outcome Measures.-Time to each fall (fall-related injury) by self-report and/or medical records. Results.-Using the Andersen-Gill extension of the Cox model that allows multiple fall outcomes per patient, the adjusted fall incidence ratio for treatment arms including general exercise was 0.90 (95% confidence limits [CL], 0.81, 0.99) and for those including balance was 0.83 (95% CL, 0.70, 0.98). No exercise component was significant for injurious falls, but power was low to detect this outcome. Conclusions.-Treatments including exercise for elderly adults reduce the risk of falls. C1 NIA,BETHESDA,MD 20892. KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR. HARVARD UNIV,BETH ISRAEL HOSP,HEBREW REHABIL CTR AGED,BOSTON,MA 02215. AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,SAN ANTONIO,TX. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. YALE UNIV,SCH MED,PROGRAM AGING,NEW HAVEN,CT. EMORY UNIV,SCH MED,DEPT REHABIL MED,ATLANTA,GA. RP PROVINCE, MA (reprint author), WASHINGTON UNIV,SCH MED,DIV BIOSTAT,BOX 8067,600 S EUCLID ST,ST LOUIS,MO 63110, USA. RI Wolf, Steven/F-6588-2010; OI Wolf, Steven/0000-0002-9446-8995; Miller, J Philip/0000-0003-4568-6846 NR 44 TC 643 Z9 658 U1 28 U2 81 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 MAY 3 PY 1995 VL 273 IS 17 BP 1341 EP 1347 DI 10.1001/jama.273.17.1341 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA QV307 UT WOS:A1995QV30700018 PM 7715058 ER PT J AU HEBERT, LE SCHERR, PA BECKETT, LA ALBERT, MS PILGRIM, DM CHOWN, MJ FUNKENSTEIN, HH EVANS, DA AF HEBERT, LE SCHERR, PA BECKETT, LA ALBERT, MS PILGRIM, DM CHOWN, MJ FUNKENSTEIN, HH EVANS, DA TI AGE-SPECIFIC INCIDENCE OF ALZHEIMERS-DISEASE IN A COMMUNITY POPULATION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DEMENTING ILLNESSES; SENILE DEMENTIA; UNITED-STATES; PREVALENCE; PERIODS; LUNDBY; RATES AB Objective.-To determine age-specific incidence rates of clinically diagnosed Alzheimer's disease. Design.-Cohort, followed a mean of 4.3 years. Setting.-East Boston, Mass. Participants.-Of 2313 persons aged 65 years and older who were initially free of Alzheimer's disease, 1601 participated in the ascertainment of incident disease (80% of survivors), 409 declined participation, and 303 died before the end of the follow-up period. A stratified sample of 642 persons received detailed clinical evaluation. Outcome Measure.-Diagnosis of new probable Alzheimer's disease through structured clinical evaluation including neurologic, neuropsychological, and psychiatric examination. Community incidence rates were computed by 5-year age groups, adjusted for gender, single year of age, length of follow-up interval, and sampling design. Results.-The estimated annual incidence of Alzheimer's disease in the population was 0.6% (95% confidence interval [CI], 0.3% to 0.9%) for persons aged 65 to 69 years, 1.0% (95% CI, 0.6% to 1.4%) for persons aged 70 to 74 years, 2.0% (95% CI, 1.3% to 2.7%) for persons aged 75 to 79 years, 3.3% (95% CI, 2.2% to 4.4%) for persons aged 80 to 84 years, and 8.4% (95% CI, 3.7% to 13.1%) for persons aged 85 years and older. Conclusions.-The incidence of Alzheimer's disease is substantial and is approximately 14 times higher among persons older than 85 years compared with those between 65 and 69 years of age. C1 RUSH UNIV,RUSH ALZHEIMERS DIS CTR,CHICAGO,IL 60612. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. CTR DIS CONTROL & PREVENT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,AGING STUDIES BRANCH,ATLANTA,GA 30341. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD COMMUNITY HLTH PLAN,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP HEBERT, LE (reprint author), RUSH INST AGING,1645 W JACKSON BLVD,SUITE 675,CHICAGO,IL 60612, USA. FU NIA NIH HHS [AG06789, AG05362, AG10161] NR 36 TC 249 Z9 255 U1 0 U2 6 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 MAY 3 PY 1995 VL 273 IS 17 BP 1354 EP 1359 DI 10.1001/jama.273.17.1354 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QV307 UT WOS:A1995QV30700020 PM 7715060 ER PT J AU KOSOWER, E AF KOSOWER, E TI AN ASSESSMENT AND TEACHING TOOL FOR INTERPERSONAL-COMMUNICATION SKILLS SO ACADEMIC MEDICINE LA English DT Note C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VAMC,LOS ANGELES,CA 90024. NR 0 TC 3 Z9 3 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAY PY 1995 VL 70 IS 5 BP 452 EP 453 DI 10.1097/00001888-199505000-00056 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA QZ280 UT WOS:A1995QZ28000062 PM 7748425 ER PT J AU KINNEY, TB LEE, MJ MULLER, PR WALTMAN, AC AF KINNEY, TB LEE, MJ MULLER, PR WALTMAN, AC TI A THEORETICAL-MODEL USING MECHANICAL PRINCIPLES TO QUANTIFY THE PHYSICAL PRINCIPLES OF BALLOON DILATATION SO ACADEMIC RADIOLOGY LA English DT Article DE BALLOON DILATATION; BALLOON ANGIOPLASTY; BALLOON PRESSURES; STRESSES; LAPLACES LAW ID TRANS-LUMINAL ANGIOPLASTY; CORONARY; ARTERIES; DISEASE AB Rationale and. Objectives. Balloon dilatation is a mechanical form of controlled injury used to alleviate vascular stenoses. Several factors influence successful angioplasty. Few mechanical models exist to illustrate the physical principles of balloon dilatation. Methods. We used mechanical analysis of membrane stresses, along with Laplace's law, to determine a relation between balloon inflation and dilating pressures exerted by balloons in stenoses of varying severity, length, and eccentricity. The balloons were assumed to be perfectly inelastic and flexible. We also examined the resultant stresses in the lesion wall of concentric and eccentric stenoses from exertion of dilating pressures. Results. Dilating pressures depend directly on maximal balloon inflation pressure and balloon diameter. Short, focal stenoses experience greater dilating pressures, which often are several multiples of the inflation pressure, than similarly narrowed longer lesions. Conclusion. Dilating pressures depend on inflation pressure, balloon diameter, and lesion severity. C1 UNIV CALIF SAN DIEGO,MED CTR,DEPT RADIOL,SAN DIEGO,CA 92103. BEAUMONT HOSP,DUBLIN 9,IRELAND. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 21 TC 4 Z9 4 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 1995 VL 2 IS 5 BP 385 EP 391 DI 10.1016/S1076-6332(05)80340-X PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QV254 UT WOS:A1995QV25400005 PM 9419580 ER PT J AU GOLDBERG, SN GAZELLE, GS DAWSON, SL RITTMAN, WJ MUELLER, PR ROSENTHAL, DI AF GOLDBERG, SN GAZELLE, GS DAWSON, SL RITTMAN, WJ MUELLER, PR ROSENTHAL, DI TI TISSUE ABLATION WITH RADIOFREQUENCY - EFFECT OF PROBE SIZE, GAUGE, DURATION, AND TEMPERATURE ON LESION VOLUME SO ACADEMIC RADIOLOGY LA English DT Article DE RADIOFREQUENCY; ABLATION; COAGULATION NECROSIS ID ELECTRODE; LIVER; PIG AB Rationale and Objectives. We evaluated the parameters affecting the size and distribution of thermal tissue damage produced by radiofrequency electrodes. Methods. Thermal lesions were produced by electrodes connected to a radiofrequency generator in specimens of liver (n = 143) and muscle (n = 20). Various combinations of probe tip exposure (0.5-8 cm), gauge (12-24 gauge), duration of treatment (0.5-12 min), and temperature (80-90 degrees C) were studied. The resulting volumes of tissue coagulation were measured and compared. Results. Lesions equal to or less than 1.6 cm in diameter were symmetrically distributed around the electrode. Lesion diameter (but not length) increased with probe gauge and duration of treatment to a maximum of 6 min. However, lesions with mean diameters larger than 1.6 cm could not be produced using a single probe with any technique. Lesion length correlated with probe tip exposure from 1 to 8 cm (r(2) = .996). Over the limited; range investigated, increased temperature had minimal effects, except for tip exposures greater than 5 cm, in which larger and more uniform lesions resulted, Lesions varied equal to or less than 3 mm in diameter and equal to or less than 5 mm in length for each combination of variables. Conclusion. Radiofrequency ablation can accurately and reproducibly cause coagulative tissue necrosis. Necrosed tissue volume increases with length of exposed probe tip, larger probes, and sessions lasting at least 6 min. C1 RADION INC,BURLINGTON,MA. RP GOLDBERG, SN (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 13 TC 257 Z9 273 U1 3 U2 6 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 1995 VL 2 IS 5 BP 399 EP 404 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QV254 UT WOS:A1995QV25400007 PM 9419582 ER PT J AU TORRES, FW ACQUATELLA, H CONDADO, JA DINSMORE, R PALACIOS, IF AF TORRES, FW ACQUATELLA, H CONDADO, JA DINSMORE, R PALACIOS, IF TI CORONARY VASCULAR REACTIVITY IS ABNORMAL IN PATIENTS WITH CHAGAS HEART-DISEASE SO AMERICAN HEART JOURNAL LA English DT Article ID NEUROGENIC PATHOGENESIS CONCEPT; ACUTE MYOCARDIAL-INFARCTION; HUMAN-ENDOTHELIAL CELLS; BLOOD-FLOW VELOCITY; TRYPANOSOMA-CRUZI; SUBSELECTIVE MEASUREMENT; SMOOTH-MUSCLE; ACETYLCHOLINE; CARDIOMYOPATHY; ARTERIES AB Symptoms of myocardial ischemia, such as chest pain (sometimes with anginal features), acute myocardial infarction, and segmental wall motion abnormalities (including left ventricular apical aneurysm), frequently occur in patients with Chagas' heart disease, Because these clinical findings occur in the presence of normal coronary arteries, it is possible that an abnormality of the coronary vascular reactivity could be present in these patients. Therefore the current study was undertaken to determine whether endothelium-dependent coronary vasodilation is abnormal in Chagas' heart disease, Coronary endothelial function was assessed by infusing the endothelium-dependent vasodilator acetylcholine (10(-8) to 10(-6) mol/L) and the endothelium-independent vasodilator adenosine (10(-4) mol/L) into the left anterior descending coronary artery of nine patients (age 43 +/- 4 years) with Chagas' heart disease, Coronary blood flow was measured with a Doppler flow velocity catheter and by quantitative coronary cineangiography. The left ventricular ejection fraction was 39% +/- 5%; eight patients had a left ventricular apical aneurysm; and one had an area of anteroapical hypokinesis, An impairment of the endothelium-dependent coronary vasodilation was demonstrated by a reduction in coronary blood flow of 41.2% +/- 12.8% produced by the infusion of acetylcholine at 10(-6) mol/L and by a blunted but preserved increase in coronary blood flow of 114.6% +/- 65.0% with the infusion of adenosine at 10(-4) mol/L (p = 0.03). In conclusion, patients with Chagas' heart disease have an abnormality of the coronary endothelium-dependent vasodilation, and this abnormality may play a role in their chest pain syndrome and in the development of segmental wall motion abnormalities, C1 UNIV HOSP CARACAS,MINIST HLTH VENEZUALA,CTR JOSE FRANCISCO TORREALBA,CARACAS,VENEZUELA. MED CTR,CARACAS,VENEZUELA. RP TORRES, FW (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA 02114, USA. OI Acquatella, Harry/0000-0002-5115-8495 NR 46 TC 29 Z9 34 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 1995 VL 129 IS 5 BP 995 EP 1001 DI 10.1016/0002-8703(95)90122-1 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QX023 UT WOS:A1995QX02300021 PM 7732990 ER PT J AU CHAN, JKC BANKS, PM CLEARY, ML DELSOL, G DEWOLFPEETERS, C FALINI, B GATTER, KC GROGAN, TM HARRIS, NL ISAACSON, PG JAFFE, ES KNOWLES, DM MASON, DY MULLERHERMELINK, HK PILERI, SA PIRIS, MA RALFKIAER, E STEIN, H WARNKE, RA AF CHAN, JKC BANKS, PM CLEARY, ML DELSOL, G DEWOLFPEETERS, C FALINI, B GATTER, KC GROGAN, TM HARRIS, NL ISAACSON, PG JAFFE, ES KNOWLES, DM MASON, DY MULLERHERMELINK, HK PILERI, SA PIRIS, MA RALFKIAER, E STEIN, H WARNKE, RA TI A REVISED EUROPEAN-AMERICAN CLASSIFICATION OF LYMPHOID NEOPLASMS PROPOSED BY THE INTERNATIONAL LYMPHOMA STUDY-GROUP - A SUMMARY VERSION SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article C1 UNIV TEXAS, HLTH SCI CTR, DEPT PATHOL, SAN ANTONIO, TX 78284 USA. STANFORD UNIV, SCH MED, DEPT PATHOL, STANFORD, CA 94305 USA. UNIV TOULOUSE 3, FAC MED PURPAN, DEPT PATHOL, F-31062 TOULOUSE, FRANCE. CATHOLIC UNIV LEUVEN, DEPT PATHOL, B-3000 LOUVAIN, BELGIUM. UNIV PERUGIA, INST HEMATOL, DEPT PATHOL, I-06100 PERUGIA, ITALY. UNIV OXFORD, JOHN RADCLIFFE HOSP, DEPT PATHOL, OXFORD OX3 9DU, ENGLAND. UNIV ARIZONA, SCH MED, DEPT PATHOL, TUCSON, AZ 85721 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA. NCI, DEPT PATHOL, BETHESDA, MD 20892 USA. CORNELL UNIV, MED CTR, NEW YORK HOSP, DEPT PATHOL, NEW YORK, NY 10021 USA. UNIV WURZBURG, DEPT PATHOL, W-8700 WURZBURG, GERMANY. UNIV BOLOGNA, DEPT PATHOL, BOLOGNA, ITALY. HOSP VIRGEN SALUD, DEPT PATHOL, TOLEDO, SPAIN. UNIV COPENHAGEN, DEPT PATHOL, HERLEV, DENMARK. FREE UNIV BERLIN, KLINIKUM BENJAMIN FRANKLIN, DEPT PATHOL, W-1000 BERLIN, GERMANY. UCL HOSP, DEPT PATHOL, LONDON, ENGLAND. MIDDLESEX HOSP, DEPT PATHOL, LONDON, ENGLAND. RP CHAN, JKC (reprint author), QUEEN ELIZABETH HOSP, DEPT PATHOL, WYLIE RD, KOWLOON, HONG KONG. OI Piris, Miguel A/0000-0001-5839-3634 NR 15 TC 94 Z9 98 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 1995 VL 103 IS 5 BP 543 EP 560 PG 18 WC Pathology SC Pathology GA QX171 UT WOS:A1995QX17100003 PM 7741099 ER PT J AU DAYA, D YOUNG, RH AF DAYA, D YOUNG, RH TI FLORID DEEP GLANDS OF THE UTERINE CERVIX - ANOTHER MIMIC OF ADENOMA MALIGNUM SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE UTERINE CERVIX; FLORID DEEP GLANDS ID MINIMAL-DEVIATION ADENOCARCINOMA; ENDOCERVICAL ADENOCARCINOMA; HYPERPLASIA; NEOPLASIA; LESIONS AB Two cases of florid deep glands of the uterine cervix, a lesion which mimics adenoma malignum are reported. One case was misdiagnosed as adenoma malignum, and the patient was treated with adjuvant radiotherapy. In contrast to the majority of cases of adenoma malignum in which there is preoperative evidence of a cervical abnormality, the lesion described in both cases was an incidental microscopic finding in hysterectomy specimens. The architectural pattern in both these cases was strikingly similar, showing diffusely scattered endocervical glands within the endocervical stroma extending to the outer third of the cervical wall. However, the variability in size and shape of the glands, which were typically round to oval, was less than observed in adenoma malignum. Additionally, there was no cytologic atypia, which is observed focally in most cases of deeply invasive adenoma malignum. The lack of a desmoplastic stromal reaction, vascular and perineural invasion also mag. help distinguish florid deep glands from adenoma malignum, Finally, in both cases of florid deep glands, there was no cytoplasmic immunoreactivity for carcinoembryonic antigen, which is in contrast to what is seen in adenoma malignum. C1 MCMASTER UNIV,DEPT PATHOL,HAMILTON,ON,CANADA. MCMASTER UNIV,DEPT OBSTET & GYNECOL,HAMILTON,ON,CANADA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA. RP DAYA, D (reprint author), HENDERSON GEN HOSP,DEPT PATHOL,711 CONCESS ST,HAMILTON,ON L8V 1C3,CANADA. NR 16 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 1995 VL 103 IS 5 BP 614 EP 617 PG 4 WC Pathology SC Pathology GA QX171 UT WOS:A1995QX17100013 PM 7741109 ER PT J AU OLIVA, E CLEMENT, PB YOUNG, RH AF OLIVA, E CLEMENT, PB YOUNG, RH TI TUBAL AND TUBO-ENDOMETRIOID METAPLASIA OF THE UTERINE CERVIX - UNEMPHASIZED FEATURES THAT MAY CAUSE PROBLEMS IN DIFFERENTIAL-DIAGNOSIS - A REPORT OF 25 CASES SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE CERVIX; TUBAL METAPLASIA; TUBO-ENDOMETRIOID METAPLASIA ID ADENOCARCINOMA; PREVALENCE; DYSPLASIA; SMEARS AB Twenty-five cases of tubal or tubo-endometrioid metaplasia that occurred in patients from 21 to 51 years of age (mean 39 years) are described. The majority of the cases were seen in consultation. They were referred because of diagnostic problems resulting from features that have received little emphasis, The metaplasia was typically an incidental microscopic finding, although in one case metaplastic cystic glands resulted in a gross abnormality. The involved glands were usually confined to the superficial third of the cervical wall, However, in seven cases they extended more deeply. In three cases, the outer third of the wall was involved. The involved glands showed only slight variation in size and shape in 12 of the cases, but in the remainder some branching was present. Prominent cystic dilatation of the glands was seen in nine cases, The glands were typically evenly spaced, but in four cases they were focally crowded. In 22 cases, the stroma surrounding the metaplastic glands was abnormal. In 16 cases, it consisted of hypercellular endocervical stroma, and in five of these cases, the cellularity was pronounced. Four of these cases and six others focally had a loose edematous or myxoid stroma, which was pronounced in three cases. In addition to the diagnostic problems inherently associated with tubal and tubo-endometrioid metaplasia, the findings in this study, including deep glands, irregularity of gland size and shape (including cystic glands), and periglandular stromal alterations, often raised the suspicion of a premalignant or malignant glandular abnormality, Awareness that these features may be seen, as well as the often prominent ciliation of the cells, their bland cytologic features, their mitotic inactivity, and lack of an unequivocal desmoplastic stromal reaction, facilitate the differential diagnosis. C1 VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,VANCOUVER,BC,CANADA. UNIV BRITISH COLUMBIA,VANCOUVER,BC,CANADA. RP OLIVA, E (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 13 TC 37 Z9 38 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 1995 VL 103 IS 5 BP 618 EP 623 PG 6 WC Pathology SC Pathology GA QX171 UT WOS:A1995QX17100014 PM 7741110 ER PT J AU DAVEY, FR ABRAHAM, N BRUNETTO, VL MACCALLUM, JM NELSON, DA BALL, ED GRIFFIN, JD BAER, MR WURSTERHILL, D MAYER, RJ SCHIFFER, CA BLOOMFIELD, CD AF DAVEY, FR ABRAHAM, N BRUNETTO, VL MACCALLUM, JM NELSON, DA BALL, ED GRIFFIN, JD BAER, MR WURSTERHILL, D MAYER, RJ SCHIFFER, CA BLOOMFIELD, CD TI MORPHOLOGIC CHARACTERISTICS OF ERYTHROLEUKEMIA (ACUTE MYELOID-LEUKEMIA FAB-M6) - A CALGB STUDY SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE ACUTE MYELOID LEUKEMIA; FAB-M6; ERYTHROLEUKEMIA ID ACUTE NONLYMPHOCYTIC LEUKEMIA; INTENSIVE POSTREMISSION THERAPY; PHASE-III TRIAL; MYELODYSPLASTIC SYNDROMES; MONOCLONAL-ANTIBODIES; COOPERATIVE GROUP; ARA-C; CLASSIFICATION; CRITERIA; ANTIGENS AB We have reviewed the clinical, morphologic, immunophenotypic, and cytogenetic features of 52 patients with erythroleukemia (FAB Cooperative Group; AML-M6) studied by the Cancer and Leukemia Group B (CALGB). The purpose of this study was to correlate morphology with the clinical features, immunophenotypes, and karyotypes of neoplastic cells, and with the response to therapy of patients with AML-M6. Thirty-three patients (63%) were male, median age 59 (range 16-81) years, 47 patients (90%) were white, and 42 patients (81%) had a performance status of <2. Myelodysplastic changes were observed in at least 1 cell lineage in all cases, and in 2 cell lineages in 45 of 52 (86%) cases. Fifty percent or more of cases studied were positive for CD11b, CD13, CD15, CD33, glycophorin-CI, and HLA-DR markers, Fourteen of 27 cases (52%) in whom karyotypic analyses were conducted had cytogenetic abnormalities. Five (19%) were simple (<3 karyotypic abnormalities), while 9 (33%) were complex (greater than or equal to 3 abnormalities). We observed either a complete or partial loss of chromosomes 5, 7, or 12p, or the presence of trisomy 8, in 11 of 27 (41%) patients. Cases of AML-MG were divided into group 1 (14 patients with bone marrow proerythroblasts and basophilic erythroblasts >25% of all erythroblasts) and group 2 (38 patients with proerythroblasts and basophile erythroblasts less than or equal to 25% of all erythroblasts). We observed no significant differences between groups 1 and 2 in regard to sex, age, race, performance status, percentage of blood erythroblasts or myeloblasts, percentage of bone marrow erythroblasts, and periodic acid-Schiff (PAS) or myelodysplasia scores. Six of 6 (100%) patients of group 1, and 7 of 21 (33%) patients of group 2, had normal karyotypes (P = .006). Nine of 13 (69%) patients of group 1 and 15 of 33 (45%) patients of group 2 had a complete remission (CR) (P = .2). Eight of 11 (73%) cytogenetically normal patients achieved CR: 5 of 6 (83%) in group 1, and 3 of 5 (60%) in group 2. Five of 12 (42%) cytogenetically abnormal patients achieved CR. No difference in duration of survival (group 1, median = 4.6 months vs. group 2, median = 10.2 months; P = .93) was observed between the 2 groups. We conclude that AML-MI is typified by multilineage involvement of hematopoietic cells, The morphology of erythroblasts in patients with AML-M6 may correlate with cytogenetic abnormalities and rate of CR. (C) 1995 Wiley-Liss, Inc. C1 ROSWELL PK CANC INST,BUFFALO,NY 14263. UNIV PITTSBURGH,PITTSBURGH,PA 15260. DANA FARBER CANC INST,BOSTON,MA 02115. DARTMOUTH COLL,SCH MED,HANOVER,NH 03755. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. CALGB,LEBANON,NH. RP DAVEY, FR (reprint author), SUNY HLTH SCI CTR,DEPT PATHOL,750 E ADAMS ST,SYRACUSE,NY 13210, USA. FU NCI NIH HHS [CA-03927, CA-12011, CA-47545] NR 47 TC 37 Z9 40 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 1995 VL 49 IS 1 BP 29 EP 38 DI 10.1002/ajh.2830490106 PG 10 WC Hematology SC Hematology GA QV722 UT WOS:A1995QV72200005 PM 7741135 ER PT J AU MATSUMOTO, K LO, EH PIERCE, AR WEI, HR GARRIDO, L KOWALL, NW AF MATSUMOTO, K LO, EH PIERCE, AR WEI, HR GARRIDO, L KOWALL, NW TI ROLE OF VASOGENIC EDEMA AND TISSUE CAVITATION IN ISCHEMIC EVOLUTION ON DIFFUSION-WEIGHTED IMAGING - COMPARISON WITH MULTIPARAMETER MR AND IMMUNOHISTOCHEMISTRY SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE BRAIN, EDEMA; BRAIN, ISCHEMIA; MAGNETIC RESONANCE, DIFFUSION-WEIGHTED; ANIMAL STUDIES ID NUCLEAR-MAGNETIC-RESONANCE; MIDDLE CEREBRAL-ARTERY; BRAIN EDEMA; T2-WEIGHTED MRI; RAT-BRAIN; OCCLUSION; STROKE; INFARCTION; LESIONS; PROTEIN AB PURPOSE: To examine the mechanisms of further evolution that occurs from the early to late phase after initial changes in diffusion-weighted imaging after cerebral ischemia. METHODS: Sprague-Dawley rats were subjected to middle cerebral artery occlusion. Diffusion-, proton density-, T1- and T2-weighted imaging were performed on days 0, 2, and 6. Histologic examination (IgG, glial fibrillary acidic protein, and cresyl violet staining) was done after scanning. RESULTS: Apparent diffusion coefficients (ADCs) in the ischemic hemisphere were significantly decreased on day 0. Thereafter, ADCs increased over time and became significantly higher than the contralateral side by day 6. Changes in basal ganglia occurred more rapidly than in cortex. Proton density-, T1-, and T2-weighted scans showed maximal changes on day 2. From day 0 to day 2, there are significant correlations between changes in ADC and changes in T1-weighted signals and T2-weighted signals. Histologic exam showed early neuronal injury on day 0, intense gliotic activity and protein leakage associated with infarction and edema on day 2, and cavitation in severely infarcted areas on day 6. CONCLUSION: After initial reduction of ADC, the subsequent increase in ADC values on day 2 may be associated with vasogenic edema and cell lysis. Later elevations in ADC may be related to cavitation of infarcted tissue. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR NMR,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR IMAGING & PHARMACEUT RES,BOSTON,MA. KYOTO PREFECTURAL UNIV MED,DEPT NEUROSURG,KYOTO 602,JAPAN. VET ADM MED CTR,GERIATR RES INST,BEDFORD,ENGLAND. RI Kowall, Neil/G-6364-2012; Garrido, Leoncio/K-3092-2014 OI Kowall, Neil/0000-0002-6624-0213; Garrido, Leoncio/0000-0002-7587-1260 NR 30 TC 81 Z9 84 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 1995 VL 16 IS 5 BP 1107 EP 1115 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA QX578 UT WOS:A1995QX57800017 PM 7639135 ER PT J AU BROWN, E AUGUST, M PILCH, BZ WEBER, A AF BROWN, E AUGUST, M PILCH, BZ WEBER, A TI POLYCYSTIC DISEASE OF THE PAROTID-GLANDS SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE SALIVARY GLANDS; NECK, CYSTS AB A 31-year-old woman had bilateral swelling of the parotid glands at 4 months of pregnancy, MR imaging showed marked enlargement of the parotid glands with increased signal on images with long repetition times. A diagnosis of polycystic disease of the parotid gland was made after biopsy and histologic examination. The radiographic and histologic features of this rare disease are discussed. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114. RP BROWN, E (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,234 CHARLES ST,BOSTON,MA 02114, USA. NR 6 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 1995 VL 16 IS 5 BP 1128 EP 1131 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA QX578 UT WOS:A1995QX57800020 PM 7639138 ER PT J AU WRAY, SH PROVENZALE, JM JOHNS, DR THULBORN, KR AF WRAY, SH PROVENZALE, JM JOHNS, DR THULBORN, KR TI MR OF THE BRAIN IN MITOCHONDRIAL MYOPATHY SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE MUSCLES, DISEASES; DEGENERATIVE DISEASE; BRAIN, MAGNETIC RESONANCE ID KEARNS-SAYRE SYNDROME; RAGGED-RED FIBERS; OCULOCRANIOSOMATIC NEUROMUSCULAR DISEASE; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; DNA DELETIONS; MELAS SYNDROME; ENCEPHALOMYOPATHY; LEUKOENCEPHALOPATHY; ABNORMALITIES; TOMOGRAPHY AB PURPOSE: To determine the spectrum of MR findings in patients with mitochondrial myopathy and correlate them with central nervous system symptoms and signs, METHODS: We performed a prospective evaluation of the MR findings of eight patients with mitochondrial myopathy (three with Kearns-Sayre syndrome and five with chronic progressive external ophthalmoplegia), six of whom had central nervous system symptoms or signs (ataxia, sensorineural hearing loss, or cognitive dysfunction). RESULTS: All six patients with neurologic symptoms or signs had multiple abnormal MR findings, whereas patients without neurologic symptoms had either normal MR findings (one patient) or the solitary finding of cortical atrophy (one patient), Abnormal MR findings consisted of cerebral cortical atrophy (seven patients), cerebellar atrophy (six patients), and hyperintense signal abnormalities on T2-weighted images within the cerebral white matter (three patients), cerebellar white matter (one patient), basal ganglia (three patients), brain stem (one patient), and thalamus (one patient), In two patients, the cerebral white matter signal abnormalities were primarily peripheral and involved the arcuate fibers. All patients with ataxia had abnormal cerebellar findings on MR imaging, but there was poor correlation between other neurologic features and MR findings. CONCLUSIONS: Cerebral and cerebellar atrophy are the most common MR findings in Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia. White matter and deep gray nuclei abnormalities, presumed to result from the diffuse spongiform encephalopathy reported in these patients, can also be seen. Patients with abnormal neurologic findings typically have multiple abnormalities on MR imaging, which frequently do not correlate with specific symptoms. C1 DUKE UNIV,MED CTR,DEPT RADIOL,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA 02215. UNIV PITTSBURGH,DEPT RADIOL,DIV MR RES,PITTSBURGH,PA 15260. RI Thulborn, Keith/D-9183-2015 OI Thulborn, Keith/0000-0001-6197-4296 NR 40 TC 45 Z9 46 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 1995 VL 16 IS 5 BP 1167 EP 1173 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA QX578 UT WOS:A1995QX57800030 PM 7639148 ER PT J AU BAUM, J CHATURVEDI, N NETLAND, PA DREYER, EB AF BAUM, J CHATURVEDI, N NETLAND, PA DREYER, EB TI ASSESSMENT OF INTRAOCULAR-PRESSURE BY PALPATION SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Note AB PURPOSE/METHODS: Corneal specialists may as sess the intraocular pressure by palpation although this technique has never been validated. We explored the reliability of a tactile assessment of the intraocular pressure in comparison to Goldmann tonometry. RESULTS/CONCLUSION: There was little correlation between tactile assessment of the intraocular pressure and tonometry. However, palpation was moderately successful in identifying most eyes (five of seven eyes) with an intraocular pressure greater than 30 mm Hg. Although palpation was generally inaccurate, it may serve as a warning for marked increases in intraocular pressure exceeding 39 mm Hg. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,GLAUCOMA CONSULTAT SERV,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02111. FU NEI NIH HHS [R01-EY10009] NR 5 TC 26 Z9 28 U1 1 U2 1 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY PY 1995 VL 119 IS 5 BP 650 EP 651 PG 2 WC Ophthalmology SC Ophthalmology GA QW578 UT WOS:A1995QW57800013 PM 7733191 ER PT J AU YUZAWA, Y BRETT, J FUKATSU, A MATSUO, S CALDWELL, PRB NIESEN, N MILGROM, F GODMAN, G STERN, D ANDRES, G AF YUZAWA, Y BRETT, J FUKATSU, A MATSUO, S CALDWELL, PRB NIESEN, N MILGROM, F GODMAN, G STERN, D ANDRES, G TI INTERACTION OF ANTIBODY WITH FORSSMAN ANTIGEN IN GUINEA-PIGS - A MECHANISM OF ADAPTATION TO ANTIBODY-MEDIATED AND COMPLEMENT-MEDIATED INJURY SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID VISCERAL EPITHELIAL-CELLS; ENDOTHELIAL-CELLS; RENAL-TRANSPLANTATION; SURFACE-ANTIGENS; IMMUNE DEPOSITS; HLA ANTIBODIES; RABBIT; LUNG; XENOGRAFTS; GLOMERULONEPHRITIS AB Forssman antigen is a glycosphingolipid with antigenic specificity determined by extra-membrane haptenic sugars similar to blood group antigens and antigens that are the main barrier to xeno-geneic organ transplantation. Herein, we describe the localization of Forssman antigen in guinea pig lungs and kidneys and the consequences of its interaction with antibodies in vitro and in vivo (Forssmas reaction). Exposure of cultured guinea Pig aortic endothelial cells to Forssman antibodies induced rapid redistribution of antigen-antibody complexes at the cell surface, followed by shedding that occurred by blebbing of plasma membrane as vesicles or fragments, and was associated with disappearance of antigen from the cell surface (antigenic modulation). Guinea pigs surviving frequent intravenous injections of increasing amounts of antibodies, for a total of 20 to 40 lethal doses, developed a partial or complete adaptation to generalized Forssman reaction, and adaptation was associated with partial or complete modulation of Forssman antigen at the surface of the pulmonary and in minor degree, renal endothelial and epithelial cells. These findings support the hypothesis that modulation of endothelial carbohydrate antigens contributes to adaptation of highly vascularized organs exposed to tolerable levels of allo- or xeno-antibodies. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02129. SUNY BUFFALO,DEPT MICROBIOL,BUFFALO,NY. NAGOYA UNIV,SCH MED,DEPT INTERNAL MED 3,NAGOYA,AICHI 466,JAPAN. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PHYSIOL,NEW YORK,NY. COLUMBIA UNIV,COLL PHYS & SURG,DEPT MED,NEW YORK,NY. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY. RI Caldwell, Peter/E-2968-2015 OI Caldwell, Peter/0000-0001-8227-3771 FU NHLBI NIH HHS [HL-21006, HL-42833]; NIDDK NIH HHS [DK-36807] NR 52 TC 26 Z9 26 U1 0 U2 3 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 MAY PY 1995 VL 146 IS 5 BP 1260 EP 1272 PG 13 WC Pathology SC Pathology GA QX871 UT WOS:A1995QX87100025 PM 7747818 ER PT J AU GOODYEAR, LJ GIORGINO, F BALON, TW CONDORELLI, G SMITH, RJ AF GOODYEAR, LJ GIORGINO, F BALON, TW CONDORELLI, G SMITH, RJ TI EFFECTS OF CONTRACTILE ACTIVITY ON TYROSINE PHOSPHOPROTEINS AND PI 3-KINASE ACTIVITY IN RAT SKELETAL-MUSCLE SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE INSULIN RECEPTOR; INSULIN RECEPTOR SUBSTRATE-1; CELL SIGNALING; PHOSPHATIDYLINOSITOL 3-KINASE ID INSULIN-RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; GLUCOSE TRANSPORTERS; KINASE-ACTIVITY; EXERCISE; PROTEIN; PHOSPHORYLATION; SUBSTRATE; BINDING; ACTIVATION AB Insulin stimulates signaling reactions that include insulin receptor autophosphorylation and tyrosine kinase activation, insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, and phosphatidylinositol 3-kinase (PI 3-kinase) activation. Muscle contraction has metabolic effects similar to insulin, and contraction can increase insulin sensitivity, but little is known about the molecular signals that mediate the effects of contraction. To investigate the effects of muscle contraction on insulin signaling, rats were studied after contraction of hindlimb muscles by electrical stimulation, maximal insulin injection in the absence of contraction, or contraction followed by insulin injection. Insulin increased tyrosine phosphorylation of the insulin receptor and IRS-1, whereas contraction alone had no effect. Contraction before insulin injection decreased the insulin effect on receptor and IRS-1 phosphorylation by 20-25%. Increased tyrosine phosphorylation of other proteins by insulin and/or contraction was not observed. Contraction alone had little effect on PI 3-kinase activity, but contraction markedly blunted the insulin-stimulated activation of IRS-1 and insulin receptor-immunoprecipitable PI 3-kinase. In conclusion, skeletal muscle contractile activity does not result in tyrosine phosphorylation of molecules involved in the initial steps of insulin signaling. Although contractile activity increases insulin sensitivity and responsiveness in skeletal muscle, contraction causes a paradoxical decrease in insulin-stimulated tyrosine phosphorylation and PI 3-kinase activity. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. CITY HOPE NATL MED CTR, DEPT DIABET, DUARTE, CA 91010 USA. RP GOODYEAR, LJ (reprint author), BRIGHAM & WOMENS HOSP, DEPT MED, JOSLIN DIABET CTR, DIV RES, 1 JOSLIN PL, BOSTON, MA 02115 USA. RI Giorgino, Francesco/K-7262-2016 OI Giorgino, Francesco/0000-0001-7372-2678 FU NIAMS NIH HHS [AR-42238]; NIDDK NIH HHS [DK-36836]; NIGMS NIH HHS [GM-36428] NR 37 TC 143 Z9 145 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 1995 VL 268 IS 5 BP E987 EP E995 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA QW584 UT WOS:A1995QW58400026 PM 7762655 ER PT J AU CHEN, RYZ GUTH, PH AF CHEN, RYZ GUTH, PH TI INTERACTION OF ENDOGENOUS NITRIC-OXIDE AND CGRP IN SENSORY NEURON-INDUCED GASTRIC VASODILATION SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE GASTRIC MICROCIRCULATION; CAPSAICIN-SENSITIVE SENSORY NERVES; CALCITONIN GENE-RELATED PEPTIDE; HUMAN CALCITONIN GENE-RELATED PEPTIDE-(8-37) ID GENE-RELATED PEPTIDE; ACID BACK-DIFFUSION; MUCOSAL BLOOD-FLOW; INTRAGASTRIC CAPSAICIN; HYPEREMIC RESPONSE; MESENTERIC-ARTERY; NERVOUS-SYSTEM; BINDING-SITES; RAT STOMACH; CALCITONIN AB Stimulation of capsaicin-sensitive sensory nerves induces gastric mucosal hyperemia, which is mediated in part by both calcitonin gene-related peptide (CGRP) and nitric oxide (NO). In the present study, we used in vivo microscopy in anesthetized rats to determine 1) whether these agents were released locally at the submucosal level and, if so, 2) whether CGRP dilates arterioles via release of endothelium-derived NO. Intragastric capsaicin (160 mu M) dilated submucosal arterioles from 25 +/- 3 to 67 +/- 8 mu m. The intragastric capsaicin-induced vasodilation was markedly reversed not only by intravenous administration of the NO synthesis inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) but also by submucosal suffusion of either L-NAME or the CORP receptor antagonist human CGRP-(8-37). The latter findings indicate that both NO and CGRP are released locally at the submucosal level. Submucosal application of CGRP induced dose-dependent dilation of gastric submucosal arterioles, which was significantly attenuated by L-NAME. However, at the same degree of vasodilation (42 mu m), the dilation induced with submucosal CGRP was much less attenuated by NO synthesis inhibition (-28%) compared with that induced with intragastric capsaicin (-79%). This indicates that endothelium-derived NO released by CGRP was not the only source of submucosal NO in the latter response. There must be another as yet undetermined source of submucosal NO, e.g., possibly nitroxidergic nerves. C1 W LOS ANGELES VET AFFAIRS MED CTR, MED SERV, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, RES SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA 90073 USA. RP CHEN, RYZ (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, DEPT ANESTHESIOL W212, ANESTHESIOL SERV, LOS ANGELES, CA 90073 USA. NR 31 TC 27 Z9 28 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 1995 VL 268 IS 5 BP G791 EP G796 PG 6 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA QW835 UT WOS:A1995QW83500009 PM 7762663 ER PT J AU SCHULTZ, JEJ ROSE, E YAO, ZH GROSS, GJ AF SCHULTZ, JEJ ROSE, E YAO, ZH GROSS, GJ TI EVIDENCE FOR INVOLVEMENT OF OPIOID RECEPTORS IN ISCHEMIC PRECONDITIONING IN RAT HEARTS SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Note DE MYOCARDIAL PROTECTION; INFARCTION; NALOXONE ID MYOCARDIAL-ISCHEMIA; POTASSIUM CHANNELS; INFARCTION; MECHANISM; AGONISTS; DOGS AB The purpose of the present study was to investigate a possible role of opioid receptors in ischemic preconditioning (PC). To test this hypothesis, anesthetized, open-chest, male Wistar rats were subjected to five different protocols. In group I, the control group was subjected to 30 min of left coronary artery occlusion and 2 h of reperfusion. In group II, ischemic PC was elicited by three 5-min occlusion periods interspersed with 5 min of reperfusion. In group III, naloxone (NL, 3 mg/kg iv), a nonselective opioid antagonist, was given to nonpreconditioned rats 10 min before the 30-min occlusion period. Finally, NL was administered 10 min before preconditioning (NL + PC, group TV) or immediately after the last 5-min preconditioning period (PC + NL, group V). Infarct size (IS) as a percentage of the area at risk (AAR) (IS/AAR) was determined by 2,3,5-triphenyltetrazolium chloride staining. PC resulted in a marked reduction in myocardial IS from 45 +/- 5 to 8 +/- 1 (P < 0.05). NL treatment before or immediately after PC abolished this protective effect; however, NL had no effect on IS in non-PC rats. These results are the first to support the hypothesis that activation of opioid receptors may play an important role in ischemic PC in the rat myocardium. C1 MED COLL WISCONSIN, DEPT PHARMACOL & TOXICOL, MILWAUKEE, WI 53226 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT ANESTHESIA, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [HL-08311] NR 26 TC 234 Z9 248 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 1995 VL 268 IS 5 BP H2157 EP H2161 PG 5 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA QW850 UT WOS:A1995QW85000045 PM 7771566 ER PT J AU ZILE, MR MUKHERJEE, R CLAYTON, C KATO, S SPINALE, FG AF ZILE, MR MUKHERJEE, R CLAYTON, C KATO, S SPINALE, FG TI EFFECTS OF CHRONIC SUPRAVENTRICULAR PACING TACHYCARDIA ON RELAXATION RATE IN ISOLATED CARDIAC-MUSCLE-CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE DIASTOLE; CARDIOMYOPATHY; ISOLATED CARDIOCYTE ID INDUCED HEART-FAILURE; FORCE-FREQUENCY-RELATIONSHIP; BETA-ADRENERGIC STIMULATION; INDUCED CARDIOMYOPATHY; VENTRICULAR MYOCYTES; DIASTOLIC FUNCTION; MYOCARDIUM; RECOVERY; DOGS; TEMPERATURE AB Chronic supraventricular pacing tachycardia (SVT) causes abnormalities in both ventricular and cellular relaxation. The mechanisms causing these abnormalities have not been fully determined. To examine two of the possible mechanisms, a decrease in restoring force or an impairment of the intrinsic myocardial relaxation process, cardiocytes were enzymatically isolated from the left ventricle of pigs subjected to left atrial pacing at 240 beats/min for 3 wk and normal control pigs. SVT caused a decrease in the extent of cardiocyte shortening and the velocity of cardiocyte lengthening. To determine whether the changes in the relaxation velocity merely reflected a concomitant decrease in the extent of cardiocyte shortening (and a resultant decrease in restoring forces) or, in addition, reflected impairment in intrinsic relaxation properties, the relation between cardiocyte relaxation velocity and cardiocyte shortening extent was examined. There was a direct relation between relaxation velocity and shortening extent in both control and SVT cardiocytes. However, SVT decreased the relaxation velocity at any common extent of shortening and decreased the slope of the direct relation (slope 5.91 in control vs. 3.51 s(-1) in SVT, P < 0.05). Therefore, these data suggested that SVT caused a primary impairment in the intrinsic myocardial relaxation process independently of a decrease in restoring force. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR, CHARLESTON, SC 29425 USA. RP ZILE, MR (reprint author), MED UNIV S CAROLINA, GAZES CARDIAC RES INST, DEPT MED, DEPT SURG, DIV CARDIOL, CHARLESTON, SC 29425 USA. NR 44 TC 19 Z9 19 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 1995 VL 268 IS 5 BP H2104 EP H2113 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA QW850 UT WOS:A1995QW85000040 ER PT J AU RYAN, LK VERMEULEN, MW AF RYAN, LK VERMEULEN, MW TI ALVEOLAR MACROPHAGES FROM C3H/HEJ MICE SHOW SENSITIVITY TO ENDOTOXIN SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; RESPIRATORY-DISTRESS-SYNDROME; LIPOPOLYSACCHARIDE BINDING-PROTEIN; GROWTH-FACTOR-BETA; BONE-MARROW CELLS; TYROSINE PHOSPHORYLATION; MURINE MACROPHAGES; FACTOR-ALPHA; BACTERIAL LIPOPOLYSACCHARIDE; MONONUCLEAR PHAGOCYTES AB Alveolar macrophages (AM) orchestrate the release of several cytokines in the lung, including tumor necrosis factor alpha (TNF). Lipopolysaccharide endotoxin (LPS), one of the most potent stimulators of TNF production in macrophages, often contributes to the development of adult respiratory distress syndrome. The mechanism by which LPS induces TNF production in macrophages is unclear. Many studies have employed murine macrophages lavaged from the peritoneal cavity (PM), either resident cells or those obtained following elicitation with sterile thioglycollate (TGPM), as these cells are readily accessible. LPS does not induce TNF in PM or TGPM from C3H/HeJ mice, and the alteration is thought to reside at the post-transcriptional level of gene regulation. Generalization of results from PM to AM may not be warranted, however. While investigating cytokine production by AM cell lines, we observed that C3HAMSV40, a transformed cell line derived from C3H/HeJ AM, made substantial quantities of TNF when stimulated with 1 mu g/ml LPS, prompting us to study TNF production in primary C3H/HeJ AM. In the present study, readily detectable quantities of biologically active TNF were found in supernatants of C3H/HeJ AM that had been stimulated in vitro with 0.01 to 10 mu g/ml LPS. The amount of TNF produced was not significantly different from that observed with AM from endotoxin-sensitive C3HeB/FeJ mice. LPS induction of TNF in AM from either mouse strain was completely inhibited by polymyxin B, demonstrating that the sensitivity of C3H/HeJ AM was not due to a contaminant in the LPS. This study shows that AM from C3H/HeJ mice have a more normal sensitivity to LPS-induced TNF production, in contrast to the restricted response observed with PM and TGPM from the same animals, These results also suggest that AM regulate TNF production differently than do PM, and that other LPS-responsive pathways may exist in the AM that are not affected by the C3H/HeJ alteration. C1 MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [HL46966] NR 39 TC 13 Z9 13 U1 0 U2 0 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 MAY PY 1995 VL 12 IS 5 BP 540 EP 546 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA QY913 UT WOS:A1995QY91300011 PM 7742017 ER PT J AU DUERINCKX, AJ BOGAERT, J JIANG, H LEWIS, BS AF DUERINCKX, AJ BOGAERT, J JIANG, H LEWIS, BS TI ANOMALOUS ORIGIN OF THE LEFT CORONARY-ARTERY - DIAGNOSIS BY CORONARY MR-ANGIOGRAPHY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID DEFINITION; SINUS C1 UNIV CALIF LOS ANGELES,MED CTR,DEPT RADIOL,LOS ANGELES,CA 90024. CATHOLIC UNIV LEUVEN,DEPT RADIOL,B-3000 LOUVAIN,BELGIUM. W LOS ANGELES VET AFFAIRS MED CTR,CARDIOL SECT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. RP DUERINCKX, AJ (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,SERV RADIOL,MAIL ROUTE W114,MRI,BLDG 507,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. RI bogaert, jan/E-6181-2012 NR 9 TC 28 Z9 29 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 MAY PY 1995 VL 164 IS 5 BP 1095 EP 1097 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QT936 UT WOS:A1995QT93600007 PM 7717210 ER PT J AU GERVAIS, DA WHITMAN, GJ CHEW, FS AF GERVAIS, DA WHITMAN, GJ CHEW, FS TI PNEUMOCYSTIS-CARINII PNEUMONIA SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID CT C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 4 TC 0 Z9 0 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 MAY PY 1995 VL 164 IS 5 BP 1098 EP 1098 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QT936 UT WOS:A1995QT93600008 PM 7717211 ER PT J AU SAINI, S EDELMAN, RR SHARMA, P LI, W MAYOSMITH, W SLATER, GJ EISENBERG, PJ HAHN, PF AF SAINI, S EDELMAN, RR SHARMA, P LI, W MAYOSMITH, W SLATER, GJ EISENBERG, PJ HAHN, PF TI BLOOD-POOL MR CONTRAST MATERIAL FOR DETECTION AND CHARACTERIZATION OF FOCAL HEPATIC-LESIONS - INITIAL CLINICAL-EXPERIENCE WITH ULTRASMALL SUPERPARAMAGNETIC IRON-OXIDE (AMI-227) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID MN-DPDP; AGENTS; TUMORS; MEDIA AB OBJECTIVE, AMI-227 is an ultrasmall superparamagnetic iran oxide colloid known to enhance tissue T1 and T2 relaxation rates, Animal studies show that AMI-227 has an estimated blood half-life of more than 200 min. In this study we evaluated the clinical utility of AMI-227 as an MR contrast agent for detection and characterization of focal hepatic lesions, with MR imaging done while the contrast agent is in the intravascular space (blood-pool phase), SUBJECTS AND METHODS. Twenty-two patients with known or suspected focal hepatic masses underwent T1- and T2-weighted MR imaging of the liver at 1.5 T before and immediately after drip infusion of AMI-227 at doses of 0.8, 1.1, or 1.7 mg Fe/kg. Unenhanced and contrast-enhanced images were analyzed qualitatively (lesion detection and tissue characterization) and quantitatively (lesion-liver contrast-to-noise ratio), RESULTS. AMI-227 enhanced signal in normal liver and blood vessels on T1-weighted images and decreased signal in these tissues on TP-weighted images. Qualitatively and quantitatively, lesion-liver contrast was increased for solid tumors (noncyst and nonhemangioma) at all three doses (p < .02) on both T1- and TS-weighted images, Differentiation between blood vessels and small lesions was easier on contrast-enhanced images, which allowed increased confidence in excluding lesions, Unique enhancement patterns were noted for hemangiomas, solid tumors, and cysts, CONCLUSION, Initial clinical experience suggests that AMI-227 is a useful contrast agent for detection and characterization of focal hepatic lesions. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BETH ISRAEL HOSP,BOSTON,MA 02215. RP SAINI, S (reprint author), HARVARD UNIV,SCH MED,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 15 TC 89 Z9 89 U1 0 U2 3 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 MAY PY 1995 VL 164 IS 5 BP 1147 EP 1152 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QT936 UT WOS:A1995QT93600019 PM 7717222 ER PT J AU BLICKMAN, JG BRAMSON, RT HERRIN, JT AF BLICKMAN, JG BRAMSON, RT HERRIN, JT TI AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY-DISEASE - LONG-TERM SONOGRAPHIC FINDINGS IN PATIENTS SURVIVING THE NEONATAL-PERIOD SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID HEPATIC-FIBROSIS; CHILDREN; LIVER AB OBJECTIVE. We studied the sonographic findings and the changes in renal function seen on long-term follow-up of children who had the initial diagnosis of autosomal recessive polycystic kidney disease made in the neonatal period. MATERIALS AND METHODS. The case records and sonograms of 14 children with biopsy evidence of autosomal recessive polycystic kidney disease were evaluated. Nine children who survived the neonatal period were followed up for a mean of 13 years (range, 5-19 years) after diagnosis and form the basis of this study. Serial changes in renal size, echogenicity, and function were assessed sonographically, The imaging findings were compared with those described in published reports. RESULTS. The sonographic findings showed that five of the nine children had a decrease in renal size, and three had stable renal size over a minimum follow-up period of 5 years, Only one of the nine survivors showed progressive increase in renal size, All had increased cortical echogenicity and large kidneys. Three patients showed a subjective change in renal echogenicity over time, A change in the echogenic pattern to one that resembles autosomal dominant polycystic kidney disease was noted with no evidence of increase in size of the kidneys, None of the surviving children had renal stones or massively enlarged kidneys, The renal function of seven of the nine survivors has remained stable with creatinine clearance nearly normal (>60 ml/min/1.73 m(2)), and there was no correlation between renal size and renal function. CONCLUSION. In patients with autosomal recessive polycystic kidney disease who survive the neonatal period, kidney size as seen on sonograms does not continue to increase despite the patients' linear growth and maintained normal renal function, Rather, a decrease in kidney size and change in echogenicity occurs, producing a pattern that is similar to that seen on sonograms of patients with autosomal dominant polycystic kidney disease but without the marked increase in kidney size that occurs in that entity, This changing cystic pattern on follow-up sonograms may be the reason that previous descriptions of the sonographic findings in cases of autosomal recessive polycystic kidney disease have varied and why a decrease in size may not herald deteriorating renal function. C1 MASSACHUSETTS GEN HOSP,DIV PEDIAT IMAGING,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV PEDIAT NEPHROL,CHILDRENS SERV,BOSTON,MA 02114. NR 16 TC 27 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 MAY PY 1995 VL 164 IS 5 BP 1247 EP 1250 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QT936 UT WOS:A1995QT93600037 PM 7717240 ER PT J AU GIRVIN, GW MATSUMOTO, GH BATES, DM GARCIA, JM CLYDE, JC LIN, PH AF GIRVIN, GW MATSUMOTO, GH BATES, DM GARCIA, JM CLYDE, JC LIN, PH TI TREATING ESOPHAGEAL CANCER WITH A COMBINATION OF CHEMOTHERAPY, RADIATION, AND EXCISION SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 81st Annual Meeting of the North-Pacific-Surgical-Association CY NOV 10-11, 1994 CL COEUR ALENE, ID SP N PACIFIC SURG ASSOC ID TRANSHIATAL ESOPHAGECTOMY; CARCINOMA; THERAPY; CISPLATIN AB BACKGROUND: Treatment of esophageal cancer has been primarily palliative. Recent studies have shown that preoperative combination chemo- and radiation therapy increases the effectiveness of surgical excision. PATIENTS AND METHODS: Beginning in 1990, 29 patients in the Spokane area were treated with preoperative chemo- and radiation therapy. They were 23 men and 6 women whose mean age was 66 years. Twenty-five had adenocarcinoma, of whom 3 had Barrett's esophagitis. Four had squamous cell carcinoma, The chemotherapy included fluorouracil, cisplatin, and vinblastine, Radiation was given concomitantly, BID for 21 days. Surgical excision Tvas performed about 3 weeks after the last radiation session, pending recovery from cytopenia. RESULTS: There was 1 operative death, for an operative mortality of 3.4%. Twenty-three patients (79%) were found to have no residual cancer at the time of resection, Of this group, 8 died of metastatic cancer at a mean of 15 months postoperatively (range 1 to 28), and 15 were alive at a mean of 28 months (range 12 to 46). Six patients (21%) had residual cancer in the resected specimen, either at the primary site or-more often-in adjacent lymph nodes, Five have died at 6, 8, 9, 24, and 28 months postoperatively; 1 remains alive at 14 months, The mean survival among these 6 patients is 15 months. CONCLUSIONS: Combined chemo- and radiation therapy prior to esophagectomy appeared to improve outcome in this small series of patients with esophageal cancer, Local control was excellent, but distant metastasis continues to be a significant problem. C1 SACRED HEART MED CTR,SPOKANE,WA. DEACONESS MED CTR,SPOKANE,WA. NR 15 TC 10 Z9 10 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 1995 VL 169 IS 5 BP 557 EP 559 DI 10.1016/S0002-9610(99)80218-9 PG 3 WC Surgery SC Surgery GA QV629 UT WOS:A1995QV62900023 PM 7747839 ER PT J AU MCCLOSKEY, M MACARUSO, P AF MCCLOSKEY, M MACARUSO, P TI REPRESENTING AND USING NUMERICAL INFORMATION SO AMERICAN PSYCHOLOGIST LA English DT Article ID BRAIN-DAMAGED SUBJECTS; NUMBER-FACT RETRIEVAL; COGNITIVE MECHANISMS; MENTAL CALCULATION; HUMAN INFANTS; MULTIPLICATION; DYSCALCULIA; PERFORMANCE; PERCEPTION; INFERENCES AB Issues of mental representation are central to cognitive psychology and indeed to psychology in general. This article synthesizes recent theoretical and empirical research concerning cognitive representations in one specific domain, that of numbers. First, several forms of cognitive numerical representation are defined, and the roles the various forms may play in numerical processing are considered. Then, two current representational issues that have generated some controversy are examined: In what form are arithmetic table facts (e.g., 4 x 7 = 28) stored in memory, and what forms of representation are involved in converting numerals from one form to another (as in reading 604 aloud as ''six hundred four'')? In the course of the discussion the major current theories of numerical cognition are described, with emphasis on how they differ in their assumptions about numerical representations and how these differences are reflected in the positions taken on various specific issues. C1 MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. RP MCCLOSKEY, M (reprint author), JOHNS HOPKINS UNIV,DEPT COGNIT SCI,BALTIMORE,MD 21218, USA. FU NINDS NIH HHS [NS21047] NR 54 TC 76 Z9 78 U1 2 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD MAY PY 1995 VL 50 IS 5 BP 351 EP 363 DI 10.1037//0003-066X.50.5.351 PG 13 WC Psychology, Multidisciplinary SC Psychology GA QX579 UT WOS:A1995QX57900002 PM 7762888 ER PT J AU GELBER, RD COLE, BF GELBER, S GOLDHIRSCH, A AF GELBER, RD COLE, BF GELBER, S GOLDHIRSCH, A TI COMPARING TREATMENTS USING QUALITY-ADJUSTED SURVIVAL - THE Q-TWIST METHOD SO AMERICAN STATISTICIAN LA English DT Article DE CLINICAL TRIALS, QUALITY OF LIFE; RESTRICTED MEANS; SURVIVAL ANALYSIS; UTILITY ID OPERABLE BREAST-CANCER; OF-LIFE; ADJUVANT THERAPY; CLINICAL-TRIALS; ENDPOINT AB The quality of life of patients is an important component of evaluation of therapies. We present an overview of a statistical method called Q-TWiST (Quality-Adjusted Time Without Symptoms and Toxicity) which incorporates quality-of-life considerations into treatment comparisons. Multivariate censored survival data are used to partition the overall survival time into periods of time spent in a set of progressive clinical health states which may differ in quality of life. Mean health state durations, restricted to the follow-up limits of the clinical trial, are derived from the data and combined with value weights to estimate quality-adjusted survival. The methodology emphasizes treatment comparisons based on threshold utility analyses that highlight trade-offs between different health state durations; it is not intended to provide a unique result combining quality and quantity of life. We also describe three recent extensions of the methodology: covariates can be included using proportional hazards and accelerated failure time regression models, restricted estimates can be projected beyond follow-up limits using parametric models, and meta-analyses can be performed incorporating quality-of-life dimensions. The basic methods are demonstrated in an analysis of data from a clinical trial comparing long versus short duration adjuvant chemotherapy regimens for the treatment of breast cancer. The clinical health states are defined by the following three outcomes: (1) end of treatment toxicity, (2) disease recurrence, and (3) death. The results allow one to evaluate the trade-off between the increased toxic effects and the increased recurrence-free interval associated with the long duration treatment. C1 DANA FARBER CANC INST,BOSTON,MA 02115. BROWN UNIV,DEPT COMMUNITY HLTH,PROVIDENCE,RI 02912. BROWN UNIV,DIV APPL MATH,PROVIDENCE,RI 02912. FRONTIER SCI & TECHNOL RES FDN INC,BROOKLINE,MA 02146. UNIV BERN,CH-3012 BERN,SWITZERLAND. OSPED CIVICO,SERV ONCOL,INT BREAST CANC STUDY GRP,CH-6900 LUGANO,SWITZERLAND. RP GELBER, RD (reprint author), HARVARD UNIV,SCH MED,SCH PUBL HLTH,BOSTON,MA 02115, USA. RI Cole, Bernard/I-3775-2012 NR 24 TC 79 Z9 79 U1 0 U2 4 PU AMER STATIST ASSN PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0003-1305 J9 AM STAT JI Am. Stat. PD MAY PY 1995 VL 49 IS 2 BP 161 EP 169 DI 10.2307/2684631 PG 9 WC Statistics & Probability SC Mathematics GA RN994 UT WOS:A1995RN99400007 ER PT J AU VASSALLO, SA THURSTON, TA KIM, SH TODRES, ID AF VASSALLO, SA THURSTON, TA KIM, SH TODRES, ID TI ALLERGIC REACTION TO LATEX FROM STOPPER OF A MEDICATION VIAL SO ANESTHESIA AND ANALGESIA LA English DT Note AB Latex hypersensitivity is now recognized as a potential cause of intraoperative anaphylaxis (1,2). Patients at risk for latex allergy include children with myelodysplasia or congenital urologic anomalies, sensitized health care personnel, and rubber factory workers (3-5). Latex-sensitive patients can be anesthetized safely if precautions are taken to remove all latex-based products from contact with the patient. In this report we describe a patient with known latex sensitivity who developed an allergic reaction after the administration of a drug from a vial with a latex stopper. C1 MASSACHUSETTS GEN HOSP,DEPT SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02115. RP VASSALLO, SA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,FRUIT ST,BOSTON,MA 02114, USA. NR 7 TC 23 Z9 24 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 MAY PY 1995 VL 80 IS 5 BP 1057 EP 1058 DI 10.1097/00000539-199505000-00039 PG 2 WC Anesthesiology SC Anesthesiology GA QV694 UT WOS:A1995QV69400039 PM 7726409 ER PT J AU NISHIMURA, M HESS, D KACMAREK, RM RITZ, R HURFORD, WE AF NISHIMURA, M HESS, D KACMAREK, RM RITZ, R HURFORD, WE TI NITROGEN-DIOXIDE PRODUCTION DURING MECHANICAL VENTILATION WITH NITRIC-OXIDE IN ADULTS - EFFECTS OF VENTILATOR INTERNAL VOLUME, AIR VERSUS NITROGEN DILUTION, MINUTE VENTILATION, AND INSPIRED OXYGEN FRACTION SO ANESTHESIOLOGY LA English DT Article DE GASES, NITRIC OXIDE NITROGEN DIOXIDE; VENTILATION, MECHANICAL ID EXPOSURE; LUNGS; NO2; HUMANS; RATS AB Background: Inhaled nitric oxide (NO) may be useful in the treatment of adult respiratory distress syndrome and other diseases characterized by pulmonary hypertension and hypoxemia. NO is rapidly converted to nitrogen dioxide (NO2) in oxygen (O-2) environments. We hypothesized that in patients whose lungs are mechanically ventilated and in those with a long residence time for NO in the lungs, a clinically important [NO2] may be present. We therefore determined the rate constants for NO conversion in adult mechanical ventilators and in a test lung simulating prolonged intrapulmonary residence of NO. Methods: NO (800 ppm) was blended with nitrogen (N-2), delivered to the high-pressure air inlet of a Puritan-Bennett 7200ae or Siemens Servo 900C ventilator, and used to ventilate a test lung. The ventilator settings were varied: minute ventilation (V-E) from 5 to 25 1/min, inspired O-2 fraction (FIO2) from 0.24 to 0.87, and [NO] from 10 to 80 ppm. The experiment was then repeated with air instead of N-2 as the dilution gas. The effect of pulmonary residence time on NO2 production was examined at test lung volumes of 0.5-4.01, V-E of 5-25 1/min, FIO2 of 0.24-0.87, and [NO] of 10-80 ppm. The inspiratory gas mixture was sampled 20 cm from the Y-piece and from within the test lung. NO and NO2 were measured by chemiluminescence. The rate constant (k) for the conversion of NO to NO2 was determined from the relation 1/[NO](1) - 1/[NO](0) = k X [O-2] X t) where t = residence time. Results: No NO2 was detected during any trial with V-E 20 or 25 1/min. With N-2 dilution and the Puritan-Bennett 7200ae, NO2 (less than or equal to 1 ppm) was detected only at a V-E of 5 1/min with an FIO2 of 0.87 and [NO] greater than or equal to 70 ppm. In contrast, [NO2] values were greater with the Servo 900C ventilator than with the Puritan-Bennett 7200ae at similar settings. When NO was diluted with air, clinically important [NO2] values were measured with both ventilators at high [NO] and FIO2. Rate constants were 1.46 X 10(-9) ppm(-2).min(-1) when NO was mixed with N-2, 1.17 X 10(-8) ppm(-2).min(-1) when NO was blended with air, and 1.44 X 10(-9) ppm(-2).min(-1) in the test lung. Conclusions: [NO2] increased with increased FIO2 and [NO], decreased V-E, blending with air, and increased lung volumes. Higher [NO2] was produced with the Servo 900C ventilator than the Puritan-Bennett 7200ae because of the greater residence time. With long intrapulmonary residence times for NO, there is a potential for NO2 production within the lungs. The rate constants determined can be used to estimate [NO2] in adult mechanical ventilation systems. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,RESP CARE SERV,BOSTON,MA 02114. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 32 TC 48 Z9 48 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 1995 VL 82 IS 5 BP 1246 EP 1254 DI 10.1097/00000542-199505000-00020 PG 9 WC Anesthesiology SC Anesthesiology GA QW587 UT WOS:A1995QW58700022 PM 7741300 ER PT J AU PENNEY, JB AF PENNEY, JB TI MULTIPLE SYSTEMS ATROPHY AND NONFAMILIAL OLIVOPONTOCEREBELLAR ATROPHY ARE THE SAME DISEASE SO ANNALS OF NEUROLOGY LA English DT Editorial Material RP PENNEY, JB (reprint author), MASSACHUSETTS GEN HOSP,WARREN 408,32 FRUIT ST,BOSTON,MA 02114, USA. NR 16 TC 15 Z9 16 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 MAY PY 1995 VL 37 IS 5 BP 553 EP 554 DI 10.1002/ana.410370502 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RF069 UT WOS:A1995RF06900001 PM 7755347 ER PT J AU COPELAND, PM AF COPELAND, PM TI 2 CASES OF THERAPEUTIC FAILURE ASSOCIATED WITH LEVOTHYROXINE BRAND INTERCHANGE SO ANNALS OF PHARMACOTHERAPY LA English DT Note ID THYROXINE; HYPOTHYROIDISM; PRODUCTS AB OBJECTIVE: To report the loss of therapeutic control in 2 hypothyroid patients and remind clinical pharmacists and other healthcare professionals to remain cognizant of possible product quality differences within or bioequivalency differences between levothyroxine products. CASE SUMMARIES: Two patients with stable hypothyroidism experienced symptoms of hypothyroidism with increased serum thyroid-stimulating hormone (TSH) concentrations after switching from 1 levothyroxine product to another. One tablet from 1 of the patient's levothyroxine prescriptions was assayed, and its levothyroxine content was 74.5% of the label claim, a value outside of the United States Pharmacopeia requirements of 90-110%. DISCUSSION: Two patients with hypothyroidism had remained euthyroid and stable while receiving 1 levothyroxine product, but became symptomatic with dramatically increased serum TSH concentrations while receiving what were thought to be comparable dosages of another levothyroxine product. Therapeutic control was reestablished in both patients after therapy with the original levothyroxine product was reinstated. CONCLUSIONS: Clinical pharmacists and other healthcare professionals should remain cognizant of possible product quality differences within or bioequivalency differences between levothyroxine products. These differences necessitate close monitoring of hypothyroid patients, counseling these patients about the clinical signs of sub- and supratherapeutic levothyroxine dosages, and prudence when switching patients with stable hypothyroidism to alternative levothyroxine products. If there are inconsistencies between levothyroxine products, resultant deleterious effects on the therapeutic stability of patients with hypothyroidism may undermine cost savings that might be incurred by such a change. If these patients are switched to alternative levothyroxine products, it is recommended that thyroid function tests be repeated after equilibration to the new product. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP COPELAND, PM (reprint author), SALEM HOSP,N SHORE MED CTR,81 HIGHLAND AVE,SALEM,MA 01970, USA. NR 20 TC 14 Z9 15 U1 0 U2 2 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAY PY 1995 VL 29 IS 5 BP 482 EP 485 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QX389 UT WOS:A1995QX38900005 PM 7655130 ER PT J AU PAN, M WASA, M LIND, DS GERTLER, J ABBOTT, W SOUBA, WW AF PAN, M WASA, M LIND, DS GERTLER, J ABBOTT, W SOUBA, WW TI TNF-STIMULATED ARGININE TRANSPORT BY HUMAN VASCULAR ENDOTHELIUM REQUIRES ACTIVATION OF PROTEIN-KINASE-C SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 106th Annual Session of the Southern-Surgical-Association CY DEC 04-07, 1994 CL PALM BEACH, FL SP SO SURG ASSOC ID NITRIC-OXIDE SYNTHESIS; RELAXING FACTOR; CELLS; DIFFERENTIATION; BIOSYNTHESIS; HYPOTENSION; INHIBITION; ISOENZYMES; METABOLISM; FAMILY AB Objective The authors determined the endothelial arginine transport mechanism and the potential role of a tumor necrosis factor (TNF)-alpha-mediated signal transduction pathway involving protein kinase C (PKC) in regulating this transport in cultured endothelial cells. Summary Background Data The vascular endothelium metabolizes arginine to generate nitric oxide (NO), and an increase in NO production can be stimulated by several cytokines. The mechanism(s) responsible for the accelerated arginine transport are poorly understood. Methods Arginine transport was assayed in confluent human umbilical vein endothelial cells in the presence of TNF +/- the PKC inhibitor chelerythrine chloride. Results Carrier-mediated arginine transport was accomplished by two Na+-independent transporters, System y(+) (80% of total transport) and System b(0,+) (20% of transport). Tumor necrosis factor (0.1-2 ng/mL) increased System y(+)-mediated arginine transport in a time- and dose-dependent manner by augmenting System y(+) transport maximal capacity (control V-max,, = 1325 +/- 60 pmol/mg protein/minute vs. TNF V-max = 3015 +/- 110 pmol/mg protein/minute, p < 0.01) without affecting transporter affinity (control Km = 30 +/- 1.4 mu M vs. 34 +/- 1.3 mu M arginine, p = NS). Stimulation was maximal at the 8-hour time point and was inhibited by both actinomycin D and cycloheximide. In addition, inhibition of PKC with chelerythrine abrogated the TNF-augmented arginine transport. Similarly, incubation of cells with the direct PKC activator TPA (phorbol ester 12-myristate 13-acetate) stimulated System y(+)-mediated arginine transport nearly fivefold, secondary to an increase in transporter V-max (TPA V-max = 5349 +/- 310 pmol/mg protein/minute, p < 0.001 vs. control), with no change in Km. This TPA-induced stimulation of arginine transport also was blocked by cheierythrine Cl, actinomycin D, and cycloheximide. Incubation of TNF-stimulated cells with two NO synthase inhibitors did not reduce transport activity, suggesting that the arginine transporter and the NO synthase enzyme may, in part, be independently regulated. Tumor necrosis factor and TPA only slightly increased System b(0,+)-mediated arginine transport. Treatment of cells with dcAMP (dibutyryl cyclic adenosine monophosphate, a protein kinase A activator) did not alter arginine transport activity, indicating that PKA activation was not required for the response to occur. Conclusions These data indicate that TNF stimulates arginine transport in human umbilical vein endothelial cells via a process that requires activation of the intracellular messenger PKC, which in turn signals de novo protein synthesis, possibly of the yi arginine transporter protein itself. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV FLORIDA,COLL MED,DEPT SURG,GAINESVILLE,FL. FU NHLBI NIH HHS [R01 HL44986] NR 29 TC 42 Z9 42 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 1995 VL 221 IS 5 BP 590 EP 601 DI 10.1097/00000658-199505000-00017 PG 12 WC Surgery SC Surgery GA QX810 UT WOS:A1995QX81000017 PM 7538287 ER PT J AU CENDAN, JC SOUBA, WW COPELAND, EM LIND, DS AF CENDAN, JC SOUBA, WW COPELAND, EM LIND, DS TI CHARACTERIZATION AND GROWTH-FACTOR STIMULATION OF L-ARGININE TRANSPORT IN A HUMAN COLON-CANCER CELL-LINE SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 47th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 17-20, 1994 CL HOUSTON, TX SP Soc Surg Oncol DE ARGININE; MEMBRANE TRANSPORT; EPIDERMAL GROWTH FACTOR; TRANSFORMING GROWTH FACTOR ALPHA ID AMINO-ACID-TRANSPORT; ENDOTHELIAL-CELLS; NITRIC-OXIDE; FACTOR-ALPHA; FACTOR-BETA; HEPATOCYTES; EXPRESSION; CULTURE; SYSTEM AB Background: Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are potent mitogens that contribute to abnormal growth regulation in colon cancer. Growth factors have been shown to regulate transmembrane nutrient uptake as an adaptive response to support cellular proliferation. Methods: The transport of L-arginine by the SW480 primary human colon adenocarcinoma cell line was characterized by assaying the uptake of [H-3]L-arginine in the presence and absence of sodium, Kinetic studies were performed over a range of L-arginine concentrations to determine transport affinity (Km) and maximal transport velocity (Vmax). To further characterize the specific transporters, [H-3]L-arginine uptake was measured in the presence of selected amino acids, hormones, and under conditions of varying external pH. To investigate the effects of EGF and TGF alpha, cells were incubated with increasing doses of growth factors (1, 10, 50 ng/ml) and L-arginine transport was measured at various time intervals (8, 12, 24 h). Proliferation was assessed by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay 3 days after growth factor stimulation, Results: The majority of carrier-mediated L-arginine transport was via a sodium-independent process (65-70%), whereas the remainder was sodium-dependent (28-30%). Diffusion contributed a small amount to total L-arginine uptake (2%). Kinetic studies of arginine transport revealed a single high-affinity Na+-independent transporter with a Km = 55.8 +/- 5.8 mu M and a Vmax = 710.6 +/- 87.3 pM/mg protein/30 s. Na+-independent arginine uptake was pH-insensitive and markedly inhibited by system y(+) substrates L-homoarginine, L-lysine, and L-ornithine. A single Na+-dependent transporter with a Km = 19.8 +/- 2.3 mu M and a Vmax = 159.1 +/- 8.9 pM/mg protein/30 s was identified. Na+-dependent arginine uptake was inhibited by system B-O,B-+ substrates L-lysine, L-ornithine, L-leucine, L-cysteine, and L-glutamine, but not by 2-methylaminoisobutyric acid. In addition, Na+-dependent arginine uptake was pH- and hormone-insensitive. Incubation with EGF or TGF alpha had no effect on Na+-independent L-arginine uptake; however, Na+-dependent uptake was enhanced 60% by EGF (10 ng/ml, p < 0.05) and 100% by TGF alpha (10 ng/ml, p < 0.05), whereas cellular proliferation was increased 27% by EGF (10 ng/ml, p < 0.05) and 37% by TGF alpha (10 ng/ml, p < 0.01). Conclusions: L-arginine transport in the SW480 colon cancer cell line is principally mediated by the Na+-independent system y(+) and to a lesser extent by the Na+-dependent system B-O,B-+. Furthermore, EGF and TGF alpha preferentially stimulate L-arginine uptake via the Na+-dependent transporter, ostensibly to accommodate for the mitogenic stimulus. C1 UNIV FLORIDA,COLL MED,DEPT GEN SURG,GAINESVILLE,FL 32610. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV SURG ONCOL,BOSTON,MA. RI Cendan, Juan/F-2303-2011 OI Cendan, Juan/0000-0002-2744-4838 FU NCI NIH HHS [T32-CA90605-03] NR 28 TC 15 Z9 15 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAY PY 1995 VL 2 IS 3 BP 257 EP 265 DI 10.1007/BF02307033 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA QZ071 UT WOS:A1995QZ07100013 PM 7641023 ER PT J AU GROSS, ME GIRON, KP SEPTIMUS, JD MASON, EO MUSHER, DM AF GROSS, ME GIRON, KP SEPTIMUS, JD MASON, EO MUSHER, DM TI ANTIMICROBIAL ACTIVITIES OF BETA-LACTAM ANTIBIOTICS AND GENTAMICIN AGAINST PENICILLIN-SUSCEPTIBLE AND PENICILLIN-RESISTANT PNEUMOCOCCI SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID STREPTOCOCCUS-PNEUMONIAE; MENINGITIS; THERAPY; INVIVO AB The MICs of penicillin and cefotaxime for a range of penicillin-susceptible and penicillin-resistant isolates of Streptococcus pneumoniae were unchanged by the addition of gentamicin. In time-kill studies the rate of killing was greater for 18 of 20 isolates in the presence of gentamicin. However, mean differences in killing after 6 h of incubation were modest, not exceeding 1 log(10) unit. C1 DEPT VET AFFAIRS MED CTR,INFECT DIS SECT,MED SERV,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MICROBIOL IMMUNOL,HOUSTON,TX 77030. NR 10 TC 19 Z9 19 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 MAY PY 1995 VL 39 IS 5 BP 1166 EP 1168 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA QW019 UT WOS:A1995QW01900026 PM 7625807 ER PT J AU SOHIER, R AF SOHIER, R TI THE DYADIC INTERVIEW AS A TOOL FOR NURSING RESEARCH SO APPLIED NURSING RESEARCH LA English DT Article C1 MASSACHUSETTS GEN HOSP,INST HLTH PROF,GRAD PROGRAN NURSING,BOSTON,MA. NR 20 TC 3 Z9 3 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0897-1897 J9 APPL NURS RES JI Appl. Nurs. Res. PD MAY PY 1995 VL 8 IS 2 BP 96 EP 101 DI 10.1016/S0897-1897(95)80562-1 PG 6 WC Nursing SC Nursing GA RB630 UT WOS:A1995RB63000009 PM 7598524 ER PT J AU PRAKASH, P OZTURK, E MACLAUGHLIN, DT SCHIFF, I LOUGHLIN, KR AGARWAL, A AF PRAKASH, P OZTURK, E MACLAUGHLIN, DT SCHIFF, I LOUGHLIN, KR AGARWAL, A TI INTERLABORATORY INTERPROTOCOL COMPARISON OF INDIRECT IMMUNOBEAD ASSAY FOR SPERM-ASSOCIATED ANTIBODIES IN SERUM SO ARCHIVES OF ANDROLOGY LA English DT Article DE ANTISPERM ANTIBODIES; COMPARISON; HUMAN SPERMATOZOA; IMMUNOBEAD TEST; SERUM ID ANTISPERM ANTIBODIES; SPERMATOZOA; IMMOBILIZATION; ABILITY; SURFACE AB This investigation was designed to study the effect of two different protocols on the indirect sperm-associated antibody test on serum performed using Bio-Rad immunobead (IBT) at two andrology laboratories. Aliquots of 31 serum samples from infertile couples were analyzed by both protocols. The IBT was negative by both protocols (100% concordance) for 18 serum samples. Seven of the 13 remaining samples were positive by both protocols (greater than or equal to 10% bead attachment by protocol A and greater than or equal to 20% bead attachment by protocol B), for a concordance of 54%. The remaining six samples were positive by one of the two protocols. The overall concordance for positive and negative results was 81% (25 of 31 samples). Protocol A detected a higher percentage of bead attachments for IgG and IgA, while protocol B detected a higher percentage of bead attachments for IgM. The discordance in the results of IgA attachment obtained by the two protocols was statistically significant (p < .05). A standardized, uniform protocol for the indirect IBT is needed. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,REPROD ENDOCRINOL LAB,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV UROL,BOSTON,MA 02115. RP PRAKASH, P (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,VINCENT MEM RES LAB,FRUIT ST,BOSTON,MA 02114, USA. NR 16 TC 0 Z9 0 U1 0 U2 2 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0148-5016 J9 ARCH ANDROLOGY JI Arch. Androl. PD MAY-JUN PY 1995 VL 34 IS 3 BP 133 EP 139 PG 7 WC Andrology SC Endocrinology & Metabolism GA QZ262 UT WOS:A1995QZ26200003 PM 7625876 ER PT J AU XU, XP DOCKERY, DW CHRISTIANI, DC LI, BL HUANG, HY AF XU, XP DOCKERY, DW CHRISTIANI, DC LI, BL HUANG, HY TI ASSOCIATION OF AIR-POLLUTION WITH HOSPITAL OUTPATIENT VISITS IN BEIJING SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article ID EMERGENCY ROOM ADMISSIONS; DAILY MORTALITY; TIME-SERIES; REGRESSION; MODELS AB Data collected at a community-based hospital in Beijing, China, were analyzed in an assessment of the association of air pollution with daily outpatient visits. Total suspended particle (TSP) measurements were available for 210 d (mean, 388 mu g/m(3); maximum, 1 255 mu g/m(3)), and sulfur dioxide (SO2) measurements were available for 2 d (mean, 119 mu g/m(3); maximum, 478 mu g/m(3)). The average number of daily hospital outpatient visits was 1 386; approximately 8.5% of these visits were to the surgery department, 7.9% were to the pediatrics department, and 20.6% were to the internal medicine department. A large increase in nonsurgery outpatient visits was observed in association with increases in both SO2 and TSP in linear regression models, after adjusting for temperature, humidity, season, and day of the week. The estimated effects (in which the most polluted days were compared with the least polluted days) on nonsurgery outpatient visits were increases of 20% (SE = 5%) and 17% (SE = 4%) in association with increases in SO2 and TSP, respectively. In a department-specific analysis, the association was found to be 1.5- to 2.0-fold stronger for pediatrics and internal medicine visits than for other types of visits. The separate associations of SO2 and TSP with internal medicine visits remained statistically significant when and TSP were considered simultaneously and when adjustment was made for both SO2 surgery visits. SO2 and TSP were found to be significant, independent predictors of internal medicine visits in both winter and summer. The association between outpatient visits and air pollution appeared to be stronger in summer than in winter, although the summer daily mean SO2 concentration was only 17 mu g/m(3) (maximum, 51 mu g/m(3)). These data, together with data obtained in previous studies, provide coherent evidence that current air-pollution levels in Beijing are associated with adverse health outcomes, and they also suggest that air pollution in Beijing needs to be controlled more effectively. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PULM & CRIT CARE UNIT,BOSTON,MA. BEIJING UNION MED COLL,BEIJING,PEOPLES R CHINA. INST MED INFORMAT & HOSP MANAGEMENT,BEIJING,PEOPLES R CHINA. RP XU, XP (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,655 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIEHS NIH HHS [ES-00002] NR 25 TC 56 Z9 74 U1 2 U2 9 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 MAY-JUN PY 1995 VL 50 IS 3 BP 214 EP 220 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA RL502 UT WOS:A1995RL50200006 PM 7618954 ER PT J AU BAER, L RAUCH, SL BALLANTINE, HT MARTUZA, R COSGROVE, R CASSEM, E GIRIUNAS, I MANZO, PA DIMINO, C JENIKE, MA AF BAER, L RAUCH, SL BALLANTINE, HT MARTUZA, R COSGROVE, R CASSEM, E GIRIUNAS, I MANZO, PA DIMINO, C JENIKE, MA TI CINGULOTOMY FOR INTRACTABLE OBSESSIVE-COMPULSIVE DISORDER - PROSPECTIVE LONG-TERM FOLLOW-UP OF 18 PATIENTS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PSYCHOSURGERY AB Background: The purpose of this study was to assess prospectively long-term change in obsessive-compulsive disorder (OCD) symptoms in patients with an OCD diagnosis that was confirmed by structured interview and with documented unsuccessful trials of multiple medications and attempts at behavior therapy. Methods: We conducted an unblinded preoperative and follow-up assessment of comorbid diagnosis; OCD, depressive, and anxiety symptoms; and functional status in 18 patients who underwent cingulotomy. Results: At a mean follow-up of 26.8 months, five patients (28%) met conservative criteria for treatment responders, and three others (17%) were partial responders. The group improved significantly in mean functional status, and few serious adverse events were found. Improvement in OCD symptoms was strongly correlated with improvement in depressive and anxiety symptoms. Conclusions: The rate of clinical improvement was consistent with a previous retrospective study in the same setting, indicating that 25% to 30% of the patients who previously were unresponsive to medication and behavioral treatments are significantly improved after cingulotomy. Cingulotomy remains a last resort treatment for severely incapacitated patients who have not responded to all other state-of-the-art pharmacological and behavioral treatments for OCD and is not to be taken lightly. C1 MASSACHUSETTS GEN HOSP EAST,DEPT NEUROSURG,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. MCLEAN HOSP,BOSTON,MA. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. RP BAER, L (reprint author), MASSACHUSETTS GEN HOSP EAST,DEPT PSYCHIAT,BLDG 149,BOSTON,MA 02129, USA. NR 39 TC 134 Z9 136 U1 0 U2 0 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 MAY PY 1995 VL 52 IS 5 BP 384 EP 392 PG 9 WC Psychiatry SC Psychiatry GA QX404 UT WOS:A1995QX40400006 PM 7726719 ER PT J AU DREYER, EB CHATURVEDI, N ZURAKOWSKI, D AF DREYER, EB CHATURVEDI, N ZURAKOWSKI, D TI EFFECT OF MITOMYCIN-C AND FLUOROURACIL-SUPPLEMENTED TRABECULECTOMIES ON THE ANTERIOR SEGMENT SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID GLAUCOMA FILTERING SURGERY; ENDOTHELIAL-CELL-DENSITY; FILTRATION SURGERY AB Objectives: To determine whether there is increased risk to the corneal endo thelium when mitomycin C is used in trabeculectomy surgery instead of fluorouracil, and whether these agents play a role in accelerating cataract formation. Design, Settings, and Participants: We analyzed the corneal endothelium and the lens preoperatively and postoperatively in 30 eyes of 21 patients who underwent either a fluorouracil- or mitomycin C-supplemented trabeculectomy. Results: No significant differences were found between these two groups in the rate of cataract progression, magnitude of endothelial cell loss, or appearance of endothelial sell morphologic characteristics. Endothelial cell loss accounted for approximately 7% to 8% of the preoperative counts in both groups. In addition, four (27%) of 15 eyes in each group showed evidence of cataract progression as graded by the Lens Opacities Classification System II. Conclusion: Fluorouracil- and mitomycin C-supplemented trabeculectomies cause similar changes in the lens and corneal endothelium. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. RP DREYER, EB (reprint author), MASSACHUSETTS EYE & EAR INFIRM,GLAUCOMA CONSULTAT SERV,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [R01-EY10009] NR 21 TC 37 Z9 39 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 MAY PY 1995 VL 113 IS 5 BP 578 EP 580 PG 3 WC Ophthalmology SC Ophthalmology GA QY407 UT WOS:A1995QY40700018 PM 7748126 ER PT J AU SIEBERT, JD MCCLURE, SP BANKS, PM GULLEY, ML AF SIEBERT, JD MCCLURE, SP BANKS, PM GULLEY, ML TI HODGKINS-DISEASE, MIXED CELLULARITY TYPE, WITH A B-CELL IMMUNOPHENOTYPE - REPORT OF A CASE AND LITERATURE-REVIEW SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Note ID REED-STERNBERG CELLS; IMMUNOGLOBULIN GENE REARRANGEMENTS; LYMPHOCYTE PREDOMINANCE TYPE; MONOCLONAL-ANTIBODIES; H VARIANTS; DIAGNOSIS; LYMPHOMAS; IMMUNOPEROXIDASE; EXPRESSION; ANTIGEN AB The origin of the Reed-Sternberg cell, the neoplastic cell of Hodgkin's disease, has not been defined. We evaluated a case of Hodgkin's disease, mixed cellularity type, which presented in the retroperitoneum of a 45-year-old woman. Reed-Sternberg cells and Hodgkin's cells expressed the characteristic markers CD15 and CD30. In addition, they expressed the B-cell antigens CD19 and CD20, as well as CD45/leukocyte common antigen. Clonal rearrangement of the immunoglobulin heavy chain gene was detected by Southern blot analysis. These results suggest that some cases of Hodgkin's disease ave derived from an activated cell of lymphoid origin. This case documents a close relationship between Hodgkin's disease and non-Hodgkin's lymphoma, and it demonstrates that even when newer ancillary techniques are employed these two entities can have overlapping features. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. CITY HOSP,DEPT PATHOL & LAB MED,AKRON,OH. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NR 38 TC 7 Z9 7 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 1995 VL 119 IS 5 BP 474 EP 479 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA QX384 UT WOS:A1995QX38400023 PM 7538289 ER PT J AU HOWARD, JP DRAKE, TR KELLOGG, DL AF HOWARD, JP DRAKE, TR KELLOGG, DL TI EFFECTS OF ALTERNATING-CURRENT IONTOPHORESIS ON DRUG-DELIVERY SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID THERAPEUTIC PEPTIDES; PROTEINS; DEVICES AB Objective: The duration of direct current (DC) iontophoresis is limited to 10- to 15-minute periods because of electrochemical burns from hydrogen and hydroxide ions generated by the DC current, A new iontophoretic device, the Lectro Patch, uses a low-frequency alternating current (AC), AC current is theorized to generate H+ ions during one phase and OH- when the current reverses polarity, thus possibly neutralizing pH changes and avoiding burns, This study examined this possibility and evaluated drug delivery with AC iontophoresis, using hydroxocobalamin. Design: A known amount of hydroxocobalamin dissolved in 6mL of water was loaded in Lectro Patches, two of which were then taped on the forearms of 10 patient volunteers, One patch was activated to deliver drug by AC iontophoresis, The second patch was not activated and served as a control for delivery by diffusion, Trials were run for 2 and 4 hours, with both 1,000 mu g/mL and 2,000 mu g/mL concentrations, Setting: Study was conducted with inpatients in an extended care setting using volunteers, Main Outcome Measures: Amounts of hydroxocobalamin remaining in the Lectro Patches after iontophoresis were assayed by spectrophotometry, Data were analyzed by ANOVA, Results: No burns occurred, Significantly greater losses occurred with 4 hours of iontophoresis than with 2 hours (p < 0.05), There was no significant effect of changing the concentration of hydroxocobalamin. Conclusions: AC iontophoresis avoids electrochemical burns; charged drugs can be delivered by AC iontophoresis; and delivery of drug increases with duration of application. (C) 1995 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,GRECC,SAN ANTONIO,TX 78284. FU NIA NIH HHS [AG00230] NR 20 TC 26 Z9 26 U1 1 U2 3 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 MAY PY 1995 VL 76 IS 5 BP 463 EP 466 DI 10.1016/S0003-9993(95)80579-6 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA QX808 UT WOS:A1995QX80800013 PM 7741619 ER PT J AU STRUYK, L HAWES, GE CHATILA, MK BREEDVELD, FC KURNICK, JT VANDENELSEN, PJ AF STRUYK, L HAWES, GE CHATILA, MK BREEDVELD, FC KURNICK, JT VANDENELSEN, PJ TI T-CELL RECEPTORS IN RHEUMATOID-ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Review ID SYNOVIAL-FLUID LYMPHOCYTES; V-GENE USAGE; SECONDARY ENCEPHALITOGENIC EPITOPE; MAJOR HISTOCOMPATIBILITY COMPLEX; POLYMERASE CHAIN-REACTION; BETA-CHAIN; ANTIGEN RECEPTOR; ALPHA-CHAIN; PERIPHERAL-BLOOD; BASIC-PROTEIN C1 UNIV LEIDEN HOSP,DEPT INNUNOHEMATOL & BLOOD BANK,2300 RC LEIDEN,NETHERLANDS. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA. FU NCI NIH HHS [CA-51345]; NHLBI NIH HHS [HL-43793] NR 76 TC 86 Z9 86 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1995 VL 38 IS 5 BP 577 EP 589 DI 10.1002/art.1780380502 PG 13 WC Rheumatology SC Rheumatology GA QX392 UT WOS:A1995QX39200001 PM 7748212 ER PT J AU Whatley, VJ Brozowski, SJ Whiting, PJ Harris, RA AF Whatley, V. J. Brozowski, S. J. Whiting, P. J. Harris, R. A. TI Microtubule depolymerization disaggregates GABA(A) receptor clustering and inhibits GABA(A)ergic function in stably transfected cells SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract C1 Univ Colorado, Sch Med, Denver VAMC, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Pharmacol, Denver, CO 80262 USA. Merck Sharp & Dohme Neurosci Res, Harlow, Essex, England. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD MAY PY 1995 VL 6 SU 1 BP 118 EP 118 DI 10.1097/00008877-199505001-00136 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA V26ZP UT WOS:000208583800137 ER PT J AU ROBINSON, DR KNOELL, CT URAKAZE, M HUANG, R TAKI, H SUGIYAMA, E XU, LL YEH, ETH OLESIAK, W GUO, M COLVIN, RB AURON, PE AF ROBINSON, DR KNOELL, CT URAKAZE, M HUANG, R TAKI, H SUGIYAMA, E XU, LL YEH, ETH OLESIAK, W GUO, M COLVIN, RB AURON, PE TI SUPPRESSION OF AUTOIMMUNE-DISEASE BY OMEGA-3-FATTY-ACIDS SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 653rd Meeting of the Biochemical-Society-of-London CY SEP 13-16, 1994 CL UNIV SUSSEX, BRIGHTON, ENGLAND SP Biochem Soc London HO UNIV SUSSEX ID DIETARY FISH-OIL C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02114. RP ROBINSON, DR (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,ARTHRIT UNIT,BULFINCH 165,FRUIT ST,BOSTON,MA 02114, USA. RI Taki, Hirofumi/I-6284-2012 NR 4 TC 10 Z9 10 U1 0 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD MAY PY 1995 VL 23 IS 2 BP 287 EP 291 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RE085 UT WOS:A1995RE08500017 PM 7672312 ER PT J AU ROSENBAUM, JF BIEDERMAN, J BOLDUCMURPHY, E FARAONE, S CHALOFF, J KAGAN, J AF ROSENBAUM, JF BIEDERMAN, J BOLDUCMURPHY, E FARAONE, S CHALOFF, J KAGAN, J TI DEVELOPMENT OF HUMAN ANXIETY SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD MAY 1 PY 1995 VL 37 IS 9 BP 593 EP 593 DI 10.1016/0006-3223(95)94412-P PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QX037 UT WOS:A1995QX03700003 ER PT J AU NIERENBERG, AA PHILLIPS, KA UEBELACKER, LA ALPERT, JE WORTHINGTON, JJ FAVA, M AF NIERENBERG, AA PHILLIPS, KA UEBELACKER, LA ALPERT, JE WORTHINGTON, JJ FAVA, M TI BODY DYSMORPHIC DISORDER IS COMORBID WITH MAJOR DEPRESSION SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BROWN UNIV,DEPT PSYCHIAT,PROVIDENCE,RI 02906. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD MAY 1 PY 1995 VL 37 IS 9 BP 611 EP 611 DI 10.1016/0006-3223(95)94480-K PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QX037 UT WOS:A1995QX03700071 ER PT J AU YOVELL, Y SIEVER, L TRESTMAN, R MITROPOULOU, V ERDOS, J GELERNTER, J AF YOVELL, Y SIEVER, L TRESTMAN, R MITROPOULOU, V ERDOS, J GELERNTER, J TI TRYPTOPHAN-HYDROXYLASE POLYMORPHISM IS ASSOCIATED WITH IMPULSIVE AGGRESSION SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MT SINAI SCH MED,BRONX,NY 10468. BRONX VET AFFAIRS MED CTR,BRONX,NY 10468. YALE UNIV,SCH MED,NEW HAVEN,CT 06516. W HAVEN VET AFFAIRS MED CTR,NEW HAVEN,CT 06516. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD MAY 1 PY 1995 VL 37 IS 9 BP 644 EP 644 DI 10.1016/0006-3223(95)94596-O PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QX037 UT WOS:A1995QX03700187 ER PT J AU BERGMAN, A ROITMAN, SL OSGOOD, G CORNBLATT, B SIEVER, L AF BERGMAN, A ROITMAN, SL OSGOOD, G CORNBLATT, B SIEVER, L TI ATTENTIONAL DYSFUNCTION IN SCHIZOTYPAL PERSONALITY-DISORDER SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 ST JOHNS UNIV,JAMAICA,NY. MT SINAI MED CTR,NEW YORK,NY 10029. BRONX VET ADM MED CTR,BRONX,NY 10468. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD MAY 1 PY 1995 VL 37 IS 9 BP 645 EP 645 DI 10.1016/0006-3223(95)94600-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QX037 UT WOS:A1995QX03700191 ER PT J AU HAMNER, MB ARVANITIS, LA MILLER, BG LINK, C HONG, WW AF HAMNER, MB ARVANITIS, LA MILLER, BG LINK, C HONG, WW TI THE EFFECTS OF SEROQUEL (ICI-204.636) ON PLASMA PROLACTIN IN PATIENTS WITH SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 RALPH H JOHNSON VA MED CTR,DEPT PSYCHIAT,CHARLESTON,SC 29401. ZENECA PHARMACEUT,CNS CLIN RES,WILMINGTON,DE 19897. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD MAY 1 PY 1995 VL 37 IS 9 BP 683 EP 683 DI 10.1016/0006-3223(95)94734-E PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QX037 UT WOS:A1995QX03700325 ER PT J AU OGUCHI, S WALKER, WA SANDERSON, IR AF OGUCHI, S WALKER, WA SANDERSON, IR TI IRAN SATURATION ALTERS THE EFFECT OF LACTOFERRIN ON THE PROLIFERATION AND DIFFERENTIATION OF HUMAN ENTEROCYTES (CACO-2 CELLS) SO BIOLOGY OF THE NEONATE LA English DT Article DE LACTOFERRIN; INTESTINAL EPITHELIAL CELLS; IRON SATURATION ID INTESTINAL BRUSH-BORDER; THYMIDINE INCORPORATION; DNA-SYNTHESIS; TRANSFERRIN; IRON; LACTOTRANSFERRIN; BINDING; GROWTH; RECEPTORS; SERUM AB Recent studies have indicated that lactoferrin may act as a cell mitogen. The effect of human and bovine lactoferrins on the proliferation and differentiation of a human intestinal epithelial cell Line (Caco-2) was investigated and compared with that of human transferrin. Caco-2 cells were cultured in serum-free media supplemented with both iron-unsaturated and -saturated forms of the iron-binding proteins. Cell proliferation and differentiation were evaluated by examining growth curves and measuring sucrase and alkaline phosphatase activities of brush border membrane fractions, respectively. The iron-binding status of lactoferrins and transferrin affected the proliferation of Caco-2 cells. The iron-saturated forms of human (S-hLf), bovine (S-bLf) lactoferrins and human transferrin (S-hTf) enhanced cell proliferation, while iron-unsaturated forms (U-hLf, U-bLf, and U-hTf) suppressed it. Iron-binding status also determined the effect oflactoferrin and transferrin on cellular differentiation, but this effect differed for different brush border enzymes, S-hTf enhanced sucrase activity more than S-hLF or S-bLf. Both U-hLf and U-bLf markedly suppressed sucrase activity. U-hTf suppressed alkaline phosphatase activity appreciably, while the other iron-binding proteins showed no significant effect on it, Lactoferrin and transferrin may modulate the proliferation and differentiation of intestinal epithelial cells, but their efficacy depends on their saturation with iron. C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,DEV GASTROENTEROL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NICHD NIH HHS [HD 12437, HD 31852] NR 32 TC 39 Z9 40 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0006-3126 J9 BIOL NEONATE JI Biol. Neonate PD MAY PY 1995 VL 67 IS 5 BP 330 EP 339 PG 10 WC Pediatrics SC Pediatrics GA RG883 UT WOS:A1995RG88300003 PM 7662812 ER PT J AU THORPE, WP TONER, M EZZELL, RM TOMPKINS, RG YARMUSH, ML AF THORPE, WP TONER, M EZZELL, RM TOMPKINS, RG YARMUSH, ML TI DYNAMICS OF PHOTOINDUCED CELL PLASMA-MEMBRANE INJURY SO BIOPHYSICAL JOURNAL LA English DT Article ID ANTIBODY-TARGETED PHOTOLYSIS; PHOTODYNAMIC THERAPY; CHLORIN; INVITRO; PHOTODESTRUCTION; PROTOPORPHYRIN; SENSITIZER; SYSTEMS; WATER AB We have developed a video microscopy system designed for real-time measurement of single cell damage during photolysis under well defined physicochemical and photophysical conditions. Melanoma cells cultured in vitro were treated with the photosensitizer (PS), tin chlorin e6 (SnCe6) or immunoconjugate (SnCe6 conjugated to a anti-ICAM monoclonal antibody), and illuminated with a 10 mW He/Ne laser at a 630 nm wavelength. Cell membrane integrity was assessed using the vital dye calcein-AM. In experiments in which the laser power density and PS concentration were varied, it was determined that the time lag before cell rupture was inversely proportional to the estimated singlet oxygen flux to the cell surface. Microscopic examination of the lytic event indicated that photo-induced lysis was caused by a point rupture of the plasma membrane. The on-line nature of this microscopy system offers an opportunity to monitor the dynamics of the cell damage process and to gain insights into the mechanism governing photolytic cell injury processes. C1 RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08855. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. FU NIGMS NIH HHS [T32 GM08339] NR 24 TC 40 Z9 40 U1 1 U2 8 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 1995 VL 68 IS 5 BP 2198 EP 2206 PG 9 WC Biophysics SC Biophysics GA RH658 UT WOS:A1995RH65800061 PM 7612864 ER PT J AU ZHAO, S OOI, SL PARDEE, AB AF ZHAO, S OOI, SL PARDEE, AB TI NEW PRIMER STRATEGY IMPROVES PRECISION OF DIFFERENTIAL DISPLAY SO BIOTECHNIQUES LA English DT Note ID MESSENGER-RNA; POLYMERASE; CDNA; PCR AB To increase the reproducibility and to reduce the false positives in the initial mRNA differential display, modified long composite primers were developed based on both mRNA differential display and RNA arbitrarily primed PCR fingerprinting methods. Ten-base nucleotides were added at the 5' ends of the primers used in the initial mRNA differential display. These included a restriction site to aid cloning. PCR began with one low-stringency cycle (40 degrees C for annealing) followed by 35 high-stringency cycles (60 degrees C for annealing). The mollified method significantly improved the reproducibility and sensitivity of the mRNA differential display while still keeping the characteristics of the original method. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP ZHAO, S (reprint author), DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA61232] NR 10 TC 95 Z9 104 U1 1 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAY PY 1995 VL 18 IS 5 BP 842 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QX422 UT WOS:A1995QX42200028 PM 7619490 ER PT J AU WENGLER, G GORLIN, JB WILLIAMSON, JM ROSEN, FS BING, DH AF WENGLER, G GORLIN, JB WILLIAMSON, JM ROSEN, FS BING, DH TI NONRANDOM INACTIVATION OF THE X-CHROMOSOME IN EARLY LINEAGE HEMATOPOIETIC-CELLS IN CARRIERS OF WISKOTT-ALDRICH SYNDROME SO BLOOD LA English DT Article ID HUMAN PERIPHERAL-BLOOD; LINKED AGAMMAGLOBULINEMIA; T-CELLS; MARKER; IDENTIFICATION; LINKAGE; DEFECT; GROWTH; LOCUS AB The Wiskott-Aldrich syndrome (WAS) is an X-linked (Xp11.22) recessive immunodeficiency syndrome characterized by susceptibility to opportunistic and pyogenic infections. thrombocytopenia, and eczema. Previous studies of obligate carriers of WAS documented that nonrandom inactivation of the X chromosome carrying the defective gene is observed in all peripheral blood cells, The existence of both abnormal platelets and lymphocytes is consistent with a defect that affects early hematopoietic precursors. We isolated CD34(+) hematopoietic progenitor cells collected from obligate carriers of WAS by apheresis and used polymerase chain reaction analysis of a polymorphic variable number of repeats (VNTR) within the X-linked androgen receptor to document nonrandom inactivation. These data show that nonrandom inactivation of the X-chromosome in WAS-obligate carriers occurs early during hematopoietic differentiation. (C) 1995 by The American Society of Hematology. C1 CHILDRENS HOSP,CTR BLOOD RES,DIV HEMATOL,BOSTON,MA. CHILDRENS HOSP,CTR BLOOD RES,DIV IMMUNOL,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NCRR NIH HHS [2M01RR02172-12]; NIAID NIH HHS [1UO1AI31541] NR 28 TC 103 Z9 103 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 MAY 1 PY 1995 VL 85 IS 9 BP 2471 EP 2477 PG 7 WC Hematology SC Hematology GA QW602 UT WOS:A1995QW60200022 PM 7537115 ER PT J AU MATULONIS, UA DOSIOU, C LAMONT, C FREEMAN, GJ MAUCH, P NADLER, LM GRIFFIN, JD AF MATULONIS, UA DOSIOU, C LAMONT, C FREEMAN, GJ MAUCH, P NADLER, LM GRIFFIN, JD TI ROLE OF B7-1 IN MEDIATING AN IMMUNE-RESPONSE TO MYELOID-LEUKEMIA CELLS SO BLOOD LA English DT Article ID ANTIGEN-PRESENTING CELLS; TUMOR-CELLS; T-CELLS; INTERLEUKIN-2 PRODUCTION; LYMPHOCYTES-T; TRANSFERRIN RECEPTORS; ACTIVATION ANTIGEN-B7; ANTITUMOR IMMUNITY; COUNTER-RECEPTOR; HUMAN-MELANOMA AB A costimulatory signal from B7-1 (CD80) to its counter-receptor CD28 is required for T-cell activation. Many tumors, including most human leukemias, lack expression of B7-1, and this has been suggested to contribute to the failure of immune recognition of these diseases. A murine leukemia model system was developed to assess the potential role of B7-1 in the induction immunity to leukemia cells. The nonleukemic 32Dc13 myeloid cell line was transformed by transfection of the BCR/ABL gene, generating a subline (32Dp210/clone 26) that was leukemic and rapidly lethal to syngeneic, immunocompetent C3H/HeJ mice or T-cell-deficient nude mice. B7-1-modified leukemic cells remained lethal in nude mice, but caused only a transient, nonlethal leukemia in C3H/HeJ mice. After a single exposure to live, nonirradiated B7-1-modified leukemic cells, C3H/HeJ mice developed protective immunity against subsequent challenge with B7-1(-) leukemic cells. Further, hyperimmunization with B7-1(+) leukemic cells prolonged the survival of mice previously injected with a lethal number of B7-1(-) leukemic cells. These results indicate that myeloid leukemic cells may be attractive candidates for B7-1 gene transfer. (C) 1995 by The American Society of Hematology. RP MATULONIS, UA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA47843, CA36167, CA34183] NR 49 TC 119 Z9 121 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 MAY 1 PY 1995 VL 85 IS 9 BP 2507 EP 2515 PG 9 WC Hematology SC Hematology GA QW602 UT WOS:A1995QW60200027 PM 7537118 ER PT J AU REDDY, SV KUZHANDAIVELU, N ACOSTA, LG ROODMAN, GD AF REDDY, SV KUZHANDAIVELU, N ACOSTA, LG ROODMAN, GD TI CHARACTERIZATION OF THE 5'-FLANKING REGION OF THE HUMAN TARTRATE-RESISTANT ACID-PHOSPHATASE (TRAP) GENE SO BONE LA English DT Article DE 5'-FLANKING SEQUENCE; TRANSCRIPTION FACTORS; TARTRATE-RESISTANT ACID PHOSPHATASE; PROMOTER; POLYMERASE CHAIN REACTION; INTRON ID TYPE-5; MOUSE; UTEROFERRIN; CLONING AB Tartrate-resistant acid phosphatase (TRAP) is expressed at high levels in osteoclasts and may play an important role in the bone resorptive process, However, factors regulating human TRAP gene expression have not been clearly defined. Therefore, we isolated a genomic clone (CL-9) for TRAP containing a 14-kb insert, A restriction map was generated for this insert, and a 2,6-kb ApaI fragment containing the 5'-flanking region was subcloned, Sequence analysis of this fragment revealed the presence of candidate transcription factor-binding sequences for H-APF-1, SP1, GATA2, and the c-Myc proto-oncogene, PCR analysis of RNA isolated from human osteoclastomas and pagetic bone revealed a 276-bp intron at -1 bp to -276 bp relative to the ATG and a transcript originating from this intron. Rapid amplification of the 5' end of the human TRAP mRNA by PCR indicated the presence of a 93-bp untranslated region 5' from the intron. Promoter activity was detected in the DNA fragment from +1 bp to -1903 bp relative to the ATG initiation codon, which drove the transient expression of a luciferase reporter gene when transfected into HRE H9 rabbit endometrial cells. Comparison of the human TRAP 5'-flanking region with mouse TRAP and uteroferrin revealed 41% and 47% homology, respectively. This suggests that regulation of human TRAP gene expression may differ from that for the murine TRAP gene. C1 UNIV TEXAS,AUDIE MURPHY VET ADM HOSP,HLTH SCI CTR,DEPT MED HEMATOL,RES SERV 151,SAN ANTONIO,TX 78284. FU NIADDK NIH HHS [AM 35188]; NIAMS NIH HHS [AR 41336, AR 39539] NR 18 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD MAY PY 1995 VL 16 IS 5 BP 587 EP 593 DI 10.1016/8756-3282(95)00086-S PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RB640 UT WOS:A1995RB64000014 PM 7654474 ER PT J AU CAVINESS, VS TAKAHASHI, T AF CAVINESS, VS TAKAHASHI, T TI PROLIFERATIVE EVENTS IN THE CEREBRAL VENTRICULAR ZONE SO BRAIN & DEVELOPMENT LA English DT Article DE NEOCORTEX; PROLIFERATION; CEREBRAL VENTRICULAR ZONE; CELL CYCLE ID CELL-CYCLE; NEOCORTEX; MOUSE; CORTEX; PHASE; GOLGI; MICE AB The neocortex varies vastly in size and complexity yet its cytology, laminar architecture, and general plan of cytoarchitectonic organization are closely similar across mammalian species, These similarities of structure and organization emerge in the course of a closely similarly developmental history, Thus, the neocortex in all species arises in the course of a discrete neuronogenetic interval (NI) from a pseudostratified ventricular epithelium (PVE) located at the margin of the developing cerebral wall, Once their terminal cell division in this epithelium has been completed the young neurons migrate across the cerebral wall to the neocortex where they grow, differentiate, and become synaptically incorporated into cerebral neural systems, The neurons forming the deepest cortical layers are the earliest to be formed while progressively later formed neurons arise at progressively later times in development, In experiments in mice, we have determined that it is the relation of total cell cycle number, occurring in the course of the NI, to the cell cycle output function, Q, which is regulatory to the duration of NI and to the rate of neuron production, Cell cycle number appears largely to be regulated by progression in the length of the G(1) phase of the cycle, We propose that regulation is mediated by cell external substances, acting upon the proliferating cell during G(1) phase. C1 KEIO UNIV,DEPT PEDIAT,TOKYO,JAPAN. RP CAVINESS, VS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114, USA. NR 35 TC 57 Z9 58 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0387-7604 J9 BRAIN DEV-JPN JI Brain Dev. PD MAY-JUN PY 1995 VL 17 IS 3 BP 159 EP 163 DI 10.1016/0387-7604(95)00029-B PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA RG199 UT WOS:A1995RG19900001 PM 7573753 ER PT J AU CAMPOSNETO, A MENGEL, JO OLIVEIRASILVA, DA BONINI, PV TAKETOMI, E STASHENKO, PP AF CAMPOSNETO, A MENGEL, JO OLIVEIRASILVA, DA BONINI, PV TAKETOMI, E STASHENKO, PP TI POTENT STIMULATION OF MURINE B-CELLS TO PROLIFERATE AND TO SECRETE IMMUNOGLOBULINS BY A LIPOTEICHOIC ACID-LIKE MOLECULE PRODUCED BY CLOSTRIDIUM-BOTULINUM-C AND CLOSTRIDIUM-BOTULINUM-D SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE CLOSTRIDIUM BOTULINUM MITOGEN; LIPOTEICHOIC ACID; B CELL ACTIVATION ID MAMMARY-TUMOR VIRUS; BACTERIAL TOXINS; CHOLERA-TOXIN; T-CELLS; BINDING; ACTIVATION; RESPONSES; GANGLIOSIDE-GM1; SUPERANTIGENS; RECEPTOR AB Bacterial products have served as important immunological tools to study lymphocyte activation. The lipopolysaccharides of the Gram-negative bacteria are well known to be potent activators of B lymphocytes. Several Gram-positive bacteria produce exotoxins that are superantigens for T cells. In the present study, we demonstrate that the Gram-positive bacteria Clostridium botulinum C and D produce a high molecular weight mitogen (Cb mitogen) that is a potent activator of murine B lymphocytes. The Cb mitogen was discovered as a consequence of our attempt to investigate a possible superantigen activity present in the botulinum exotoxins. We observed initially that mouse spleen cells were strongly stimulated to proliferate by culture supernatants of C. botulinum C and D. However, the characterization of the responding cell ruled out superantigen because only the B lymphocytes were stimulated to proliferate and to secrete immunoglobulins, and they did so independent of T cell help. In addition, the molecular characterization of the Cb mitogen demonstrated that the purified botulinum toxin was devoid of mitogenic activity. In contrast, the fractionation of the culture supernatant of C, botulinum C in an FPLC Superose 12 column indicated that the Cb mitogen was present in the void volume of the column (MW greater than or equal to 300 kDa) which had no toxigenic activity. However, the fractions containing molecules of 150 kDa were highly toxic for mice and had no mitogenic activity. The possibility that LPS was present as a contaminant in the Cb mitogen preparations was excluded because spleen cells from the LPS nonresponder C3H/HeJ mice responded well to the Cb mitogen, and the antibiotic polymyxin B, which is an inhibitor of LPS, had no effect on the Cb mitogen activity. However, an anti-lipoteichoic acid monoclonal antibody (3-1 mAb) inhibited to a great extent the proliferation of spleen cells induced by the Cb mitogen but had no effect on the LPS or concanavalin A stimulation of these cells. Moreover, the Cb mitogen was specifically adsorbed and eluted from a protein G Sepharose column to which the anti-lipoteichoic acid 3-1 mAb had been conjugated. These results support the view that lipoteichoic acid is a selective B cell mitogen. C1 UNIV SAO PAULO,FAC MED RIBEIRAO PRETO,DEPT IMUNOL,BR-14049900 RIBEIRAO PRET,BRAZIL. UNIV FED UBERLANDIA,DEPT PATOL,BR-30130100 UBERLANDIA,MG,BRAZIL. YALE UNIV,SCH MED,NEW HAVEN,CT 06520. FORSYTH DENT CTR,DEPT CYTOKINE BIOL,BOSTON,MA 02115. NR 35 TC 1 Z9 1 U1 0 U2 0 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD MAY PY 1995 VL 28 IS 5 BP 575 EP 584 PG 10 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA RG222 UT WOS:A1995RG22200011 PM 8555978 ER PT J AU HUNCHAREK, M KLASSEN, M CHRISTIANI, D AF HUNCHAREK, M KLASSEN, M CHRISTIANI, D TI MESOTHELIOMA OF THE TUNICA VAGINALIS TESTIS WITH POSSIBLE OCCUPATIONAL ASBESTOS EXPOSURE SO BRITISH JOURNAL OF UROLOGY LA English DT Note ID MALIGNANT MESOTHELIOMA C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PULM & CRIT CARE MED,BOSTON,MA. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. RP HUNCHAREK, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,COX BLDG,BOSTON,MA 02114, USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1331 J9 BRIT J UROL JI Br. J. Urol. PD MAY PY 1995 VL 75 IS 5 BP 679 EP 680 DI 10.1111/j.1464-410X.1995.tb07437.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA QW884 UT WOS:A1995QW88400031 PM 7613813 ER PT J AU FISHER, CM AF FISHER, CM TI BRAIN HERNIATION - A REVISION OF CLASSICAL CONCEPTS SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Review ID TRANSTENTORIAL HERNIATION; COMPUTED-TOMOGRAPHY; CONSCIOUSNESS; DISPLACEMENT; LEVEL AB This paper is an update on evolving ideas about brain herniations. Following observations on cerebellar pressure coning that raised doubts about its reputed lethal connotations, herniation at the tentorium was re-examined for its role in critically damaging the brain stem. Combining clinical, pathologic, computed tomography and magnetic resonance imaging data, it is concluded that temporal lobe herniation is not the means by which the midbrain sustains irreversible damage in acute cases, but rather lateral displacement of the brain at the tentorium is the prime mover and herniation a harmless accompaniment. Transtentorial herniation has been investigated with computed tomography using the three calcification relationship and descent through the tentorial opening could not be documented. Bilateral brain stem compression in acute bilateral cases must be distinguished from herniation. Upward cerebellar herniation is only the sign of an overfull posterior fossa. Subfalcial herniation is tolerated unless lateral displacement is excessive. RP FISHER, CM (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114, USA. NR 31 TC 19 Z9 19 U1 0 U2 0 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD MAY PY 1995 VL 22 IS 2 BP 83 EP 91 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA QX959 UT WOS:A1995QX95900001 PM 7627921 ER PT J AU RALL, CJN RUSTGI, AK AF RALL, CJN RUSTGI, AK TI CD44 ISOFORM EXPRESSION IN PRIMARY AND METASTATIC PANCREATIC ADENOCARCINOMA SO CANCER RESEARCH LA English DT Note ID SPLICE VARIANTS; HOMING RECEPTOR; CELLS; RAT; CARCINOMAS; BEHAVIOR; CANCER; PROTEINS; HOMOLOG; FORMS AB CD44 is the transmembrane adhesion molecule which binds hyaluronate. The gene encoding CD44 is found on chromosome lip and comprises 20 exons. Differential splicing of the 10 extracellular juxtamembranous exons (v1-10) generates the major isoforms of CD44. The major CD44 isoform found on hematopoetic cells (CD44s) contains none of the variably expressed exons, while the major isoform expressed on epithelial cells [CD44(v8-10)] contains exons v8-10. Metastasis-specific isoforms of CD44 were first documented in a model of rat pancreatic adenocarcinoma [CD44(v4-7), CD44(v6-7)] and subsequently in other cancers. This study is the first characterization of CD44 isoforms in primary and metastatic human pancreatic adenocarcinomas. CD44 isoforms were analyzed in specimens of 15 primary and 6 metastatic pancreatic adenocarcinomas as well as in 6 specimens of control pancreata by two different methods. Radiolabeled reverse transcriptase-PCR coupled with 8% PAGE allowed analysis of the major isoforms of CD44, while Southern blot hybridization with [alpha-P-32]dCTP-labeled probes permitted analysis for metastasis-specific CD44 isoforms containing CD44(v6) or CD44(v8-10). No differences in the expression of CD44(v8-10) and CD44s were found among the primary and metastatic pancreatic adenocarcinomas, and control specimens of pancreata. However, a novel CD44(v6) isoform was found in metastatic lesions and may represent the human homologue of the rat pancreatic adenocarcinoma metastasis-associated CD44 isoform. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. FU NCI NIH HHS [K08 CA01586-04]; NIDDK NIH HHS [DK 07191-20, NIDDK 43351] NR 29 TC 48 Z9 55 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 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1995 VL 55 IS 9 BP 1831 EP 1835 PG 5 WC Oncology SC Oncology GA QV015 UT WOS:A1995QV01500007 PM 7537174 ER PT J AU NELSON, HH WIENCKE, JK CHRISTIANI, DC CHENG, TJ ZUO, ZF SCHWARTZ, BS LEE, BK SPITZ, MR WANG, M XU, XP KELSEY, KT AF NELSON, HH WIENCKE, JK CHRISTIANI, DC CHENG, TJ ZUO, ZF SCHWARTZ, BS LEE, BK SPITZ, MR WANG, M XU, XP KELSEY, KT TI ETHNIC-DIFFERENCES IN THE PREVALENCE OF THE HOMOZYGOUS DELETED GENOTYPE OF GLUTATHIONE-S-TRANSFERASE-THETA SO CARCINOGENESIS LA English DT Note ID LUNG-CANCER; HUMAN-LEUKOCYTES; ETHYLENE-OXIDE; HUMAN BLOOD; CLASS-MU; SUSCEPTIBILITY; RISK; MARKER; POLYMORPHISM; EXPRESSION AB In humans the glutathione S-transferase (GST) genes encode four classes of proteins (GST) important in the detoxification of reactive electrophiles. Recently, a gene deletion polymorphism was discovered within the GST class theta locus that leads to a functional deficiency in GST theta activity within circulating red blood cells. In this study we have examined the ethnic distribution of this polymorphism using a polymerase chain reaction (PCR)-based genotyping method. Five different ethnic groups were studied: North American Caucasians, African-Americans, Mexican-Americans, Chinese and Koreans. The prevalence of the null genotype was highest among Chinese (64.4%), followed by Koreans (60.2%), African-Americans (21.8%) and Caucasians (20.4 %), whereas the prevalence was lowest among Mexican-Americans (9.7%). Interestingly, the prevalence of the deleted genotype in Caucasians differed significantly when 257 individuals drawn from a nation wide organization were compared with 185 people from the New England area (23.7 versus 15.7%, P < 0.05, chi(2) test). These results indicate that there are major differences in the prevalence of this trait attributable to ethnicity and that ethnic origin even among Caucasians should be considered in studies of gene-environment interaction involving this polymorphism. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT EPIDEMIOL & BIOSTAT,MOLEC EPIDEMIOL LAB,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH PUBL HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,DIV OCCUPAT HLTH,BALTIMORE,MD 21205. SOONCHUNHYANG UNIV,DEPT PREVENT MED,CHONAN,SOUTH KOREA. UNIV TEXAS,MD ANDERSON HOSP,DEPT EPIDEMIOL,HOUSTON,TX 77030. WUHU MED COLL,INST ENVIRONM & OCCUPAT EPIDEMIOL,WUHU,PEOPLES R CHINA. RI Cheng, Tsun-Jen /D-3495-2012; Kelsey, Karl/I-1252-2014; OI CHENG, TSUN-JEN/0000-0002-2613-8230 FU NIEHS NIH HHS [P42 ES04705, R01 ES06717]; PHS HHS [P01 06409] NR 26 TC 275 Z9 283 U1 0 U2 5 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1995 VL 16 IS 5 BP 1243 EP 1245 DI 10.1093/carcin/16.5.1243 PG 3 WC Oncology SC Oncology GA QZ456 UT WOS:A1995QZ45600040 PM 7767992 ER PT J AU KAUFMAN, JA WALTMAN, AC RIVITZ, SM GELLER, SC AF KAUFMAN, JA WALTMAN, AC RIVITZ, SM GELLER, SC TI ANATOMICAL OBSERVATIONS ON THE RENAL VEINS AND INFERIOR VENA-CAVA AT MAGNETIC-RESONANCE ANGIOGRAPHY SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE INFERIOR VENAE CAVAE; VENA CAVA; MAGNETIC RESONANCE ANGIOGRAPHY AB Purpose: To describe the renal vein and inferior vena cava (IVC) anatomy found at abdominal magnetic resonance (MR) angiography. Methods: Gadolinium-enhanced, three-dimensional, time-of-flight MR angiograms of 150 patients were evaluated for the number and configuration of the renal veins, and the number, configuration, and dimensions of the IVC. Data were analyzed with the Student's t-test. Results: Retroaortic left renal veins were found in 7% of patients, circumaortic left renal veins in 5%, multiple right renal veins in 8%, and duplicated IVCs in 0.7%. The length of the infrarenal IVC averaged 94 mm in females and 110 mm in males (p<0.00001). The length of the infrarenal IVC in patients with circumaortic and retroaortic left renal veins averaged 76 mm and 46 mm, respectively. The mean maximal caval diameter was 23.5 +/- 4 mm. No megacavae (diameter of the mid-IVC > 28 mm) were identified. Conclusion: Variant renal vein and IVC anatomy can be identified at MR angiography. RP KAUFMAN, JA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 0 TC 25 Z9 25 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD MAY-JUN PY 1995 VL 18 IS 3 BP 153 EP 157 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA RC384 UT WOS:A1995RC38400005 PM 7648590 ER PT J AU DUFFY, FH MCANULTY, GB ALBERT, MS AF DUFFY, FH MCANULTY, GB ALBERT, MS TI TEMPOROPARIETAL ELECTROPHYSIOLOGICAL DIFFERENCES CHARACTERIZE PATIENTS WITH ALZHEIMERS-DISEASE - A SPLIT-HALF REPLICATION STUDY SO CEREBRAL CORTEX LA English DT Article ID BRAIN ELECTRICAL-ACTIVITY; ACTIVITY MAPPING BEAM; VISUAL EVOKED-POTENTIALS; SENILE DEMENTIA; FREQUENCY-ANALYSIS; EEG ANALYSIS; TOPOGRAPHY; TOMOGRAPHY; PARAMETERS; DIAGNOSIS AB One hundred and eighty nine subjects were examined by quantified EEG (qEEG) during the resting awake state. Sixty subjects had probable Alzheimer's disease (AD) and were mild to moderately impaired. There were 129 healthy controls. Differences between patients and controls by topographic mapping demonstrated a pattern of group difference maximal posteriorly, primarily in posterior temporal and/or parietal regions, Frontal regions were much less frequently involved. Long-latency evoked potential derived difference showed similar spatial patterns of difference, By EEG spectral analysis, theta was increased and beta decreased for the AD patients. In addition, the qEEG measures were significantly correlated with neuropsychological test scores related to abilities that are impaired in the early stages of disease, such as delayed recall and verbal fluency, To assess replicability the population was split in half. Regions of interest derived from the first half provided numerical measures for discriminant function analysis. A discriminant function, derived from the first half, correctly identified 86% of all second-half subjects (91% controls, 77% AD). C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. RP DUFFY, FH (reprint author), CHILDRENS HOSP,DEPT NEUROL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIA NIH HHS [P01-AG04953]; NICHD NIH HHS [P30-HD18655] NR 52 TC 15 Z9 15 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAY-JUN PY 1995 VL 5 IS 3 BP 215 EP 221 DI 10.1093/cercor/5.3.215 PG 7 WC Neurosciences SC Neurosciences & Neurology GA QX048 UT WOS:A1995QX04800003 PM 7613077 ER EF